No

Introduction

It is widely acknowledged that medicine can be a high-stress profession. The reasons behind this observation have been the focus of research over recent years, because concerns over the welfare of doctors have grown due to its relevance to burnout of individuals and safeguard of healthcare systems. However, a recent survey of hospital doctors still showed that 80% experienced workplace stress, and the junior doctors surveyed suffered significantly higher burnout rates than their consultants.¹ Separate research has specifically found that junior doctors have a poor work-life balance, a composite measure of individual factors affecting wellbeing.² There seem to be differences in the wellbeing of doctors in different specialities studied – a study in 2016 showed higher levels of leisure time enjoyed by general practitioners compared to doctors working in other specialities.³ Another survey showed that psychiatrists experienced lower levels of burnout than surgeons did.⁴ Furthermore, different burnout rates have been observed between consultants and junior doctors working in Psychaitry.⁵

We sought to build on existing research by studying the work-life balance of junior doctors and how some factors might affect that. We also decided to explore what factors might contribute to the differences in wellbeing between medical specialties and professional grades.

Method

Junior doctors working across an English county in general practice, medical and surgical specialities (the “non-psychiatric setting”), and in psychiatric specialities (the “psychiatric setting”), were recruited into a cross-sectional study between September and December 2019. To enable appropriate comparison between groups, junior doctors must have worked between the level of Foundation Year 2 (FY2) and consultant in their relevant speciality. This was necessary because the on-call responsibility of Foundation Year 1 (FY1) doctors in this locality varies significantly from that of more senior doctors.

All doctors were required to complete the SWING (Survey Work-home Interaction-NijmeGen), questionnaire⁶; a validated instrument measuring four aspects of work-home interaction. This questionnaire is split into negative (questions 1-12) and positive (questions 13-22) subscales, where lower and higher scores are better respectively. For each question four responses ranging from never to always could be returned. Demographic information was also collected to assess participant group similarity and identify any effect of these variables. These included age, gender, and whether they have children under the age of 18. No identifying information was requested to allow for staff anonymity, and no incentive was offered for participating.

Ethical approval for the study was granted by the local Medical Education Departments. Data from completed questionnaires was recorded in an Excel spreadsheet, which was used for collation and analysis. Significance of the between-group differences was calculated using the Chi-Squared test, with the threshold for statistical significance set at p<0.05. In order to allow comparison between the answers given for each questionnaire item, 1, 2, and 3 points were respectively allocated to each “sometimes”, “often”, or “always” response. The sum of these points for each question gave the “overall question score”, with lower and higher scores reflecting better work-life-balance on negative and positive subscales respectively. Overall question scores were also calculated as percentages of the maximum possible score for each question or subscale (i.e. if every respondent had answered “always”).

Results

Questionnaires were returned by 99 junior doctors (54 working in the non-psychiatric setting, and 45 working in the psychiatric setting). Demographic details are shown in Table 1. Not all respondents returned demographic details. There were no significant differences in the ages and genders of respondents between the two settings, but there were significantly more doctors with children <18 years in the psychiatric setting.

Table 1

Table 2

Questionnaire responses are shown in Table 2, along with calculated overall question scores and overall subscale scores for each subscale in both settings. Differences in overall question scores between settings are shown in Figure 1 and Figure 2.

Figure1

Figure 2

Overall question scores across the negative subscale were generally high, indicating a high incidence of negative work-home interaction among all respondents. Scores for questions 1-8, which ask about negative impact of work on home life, showed little/no difference between the two settings. Questions 9-12, which ask about negative impact of home life on work, recorded much lower scores in both settings, but there was separation between the settings, with scores in the psychiatric setting being higher than those in the non-psychiatric setting.

In the positive subscale, questions 13-17 ask about positive impact of work on home life, and questions 18-22 ask about positive impact of home life on work. Overall, there was a much more clear separation in scores between the two settings than that seen in the negative subscale. Aside from question 13, scores in the psychiatric setting being consistently higher than those in the non-psychiatric setting.

Main findings of this study can therefore be summarised as:

• High negative impact of work on home life in both settings
• Lower levels of negative impact of home life on work, but higher in the psychiatric setting
• Higher positive impact of home life on work, and work on home life, in the psychiatric setting than in the non-psychiatric setting

Discussion

There has been a great interest in the wellbeing of junior doctors in recent years, resulting in a number of changes in working patterns, such as the move away from the old “firm” structure to medical training, and the introduction of the European Working Time Directive.⁷ However, the perceived wellbeing of junior doctors in the UK seems to still be poor, and has resulted in a so-called “Drexit” of junior doctors to other countries, such as Australia, providing a better quality of life or away from medicine altogether.⁷ One survey shockingly revealed that almost half of UK junior doctors have considered leaving the National Health Service, citing concerns over wellbeing.⁷ It is, therefore, unsurprising that in 2018, only 38% of FY2 doctors continued into speciality training.⁸

Various aspects of junior doctor wellbeing and contributory factors have been researched. For example, a large survey of Australian junior doctors published in 2020 showed that those working only a few more hours than the average were more than twice as likely to report common mental disorders.⁹ Many interacting themes have been qualitatively identified, such as those found in a recent Australian qualitative survey.¹⁰ These ranged from institutional issues such as discouragement to claim overtime, to cultural issues such as not wanting to ask for assistance, to personal issues such as time for personal care. Another study found multiple factors to be correlated with higher rates of burnout in hospital doctors, including male sex, younger age, and lower years of practice.¹

It seems that wellbeing in junior doctors is a highly complex, multifactorial issue with many interacting contributory factors. In addition to considering the individual factors at work, it is also necessary to consider how these factors interact on a larger scale. One way which researchers have done this, and which we have replicated, is to consider the concept of “work-life balance”, which explores the interaction between work and home life, and vice-versa. Existing research in junior doctors has found work-life balance to be particularly poor in those with children and in women, who frequently cited that this had resulted in a change in career direction.²

Unsurprisingly, we have found high levels of work negatively impacting on home life in both psychiatric and non-psychiatric settings. Since work-life balance involves many interacting components, we speculated that it may differ between junior doctors working in different medical specialities. Indeed, we detected such differences, with the reported negative impact of home life on work being higher among those trainees in the psychiatric setting than those in the non-psychiatric setting. In a cross-sectional study like ours, it is not possible to comment on causality but we noted that there were significantly more trainees in the psychiatric setting who had children. This correlates with previous findings,² and raises the possibility of a causative relationship between having children under 18 and negative impact on work. A study of stress in psychiatrists which gathered responses from 449 participants found that sickness of children and arranging childcare were among the top five stressors identified.¹¹

Trainees in the psychiatric setting have consistently reported higher levels of positive impact of work on home life and vice-versa. One possible explanation is that the nature of psychiatry is inherently different to other areas of medicine, with a focus on promoting the quality of patient interaction, and training time dedicated to exploring this in detail. Supervision of patient contact is also conducted more thoroughly than in other specialities, which may lead to a greater sense of being supported in clinical decision making when trainees work in psychiatry.

Strengths and limitations

Regarding strengths of this study, we used an innovative method in seeking to compare trainees across two different settings. The questionnaire used was validated and holistic in examining bidirectional interaction between work and home life. Groups were well-matched in terms of the selection of trainees with broadly similar working rotas, and in their age and sex, which have been shown to be important variables which can affect work-life balance. We also used an innovative method in analysing the questionnaire responses which enabled us to compare directly between the two settings.

There are several limitations with this methodology which identify possible interesting and important areas for future research. For example, we did not investigate for differences in work-life balance between staff working in inpatient and community settings. Additionally, it was not possible to make conclusions about causality with this cross-sectional methodology, and the use of a longitudinal method with a more detailed exploration of demographic factors may provide interesting insights in the future. Due to local factors in the way psychiatric and general healthcare services are set up in our area, it was not practical to measure participant engagement with the study, and this would have presented a barrier making this study impossible. There were however 99 responses included in this study, with similar representation in both healthcare settings, which relative to the local population of doctors in the settings studied represents a good sample.

There will inherently be local differences in working patterns, and therefore the results of this study are not directly generalizable to a national or international population. The non-psychiatric setting is broad in its scope and includes trainees undertaking varied forms of medical and surgical training, and therefore there are likely to be more subtle variations which were missed in this approach.

Conclusion

This study adds to the literature on work-life balance in junior doctors, which is an important area of research in order to promote the wellbeing of the current and future medical workforce. It also explores how factors affecting wellbeing might interact on a higher level than when studied in isolation, and how these interactions may differ depending on the medical speciality in which the respective doctors work.

Because of the local variations in working patterns, we would suggest a replication of this research in other areas in the UK and abroad. We would also suggest that an interesting area for future research may be the exploration of differences in work-life balance between narrower groups of trainees, which may aid developmental policy generation in supporting doctors to maintain a healthy work-life balance across different specialities. The group we feel would benefit from further research in particular is the trainees with young children, as we found a possible negative association between this and impact of home life on work.

A 40 years old non-alcoholic and non-diabetic agricultural laborer presented with skin lesions around his neck, forearms and feet (sun exposed areas) along with glossitis. Pellagra was suspected because of Casal's necklace (i.e., erythematous, hyperpigmented, scaly lesions around his neck- arrow mark in figure 1). However he did not have diarrhea or neurological manifestations. Pellagra is due to Niacin (Vitamin B3) deficiency. Typical cases of pellagra are associated with 3 Ds - Dermatitis, Diarrhea, Dementia, (and if not treated, the 4^th D- Death).^1,2  Not many will have all the three Ds. Most commonly involved is skin – dermatitis (Pelle-skin; agra -rough). The patient belonged to poor socioeconomic status.² His vital parameters and basic investigations were all within normal limits and HIV-ELISA was negative.

The diagnosis of a pellagra-like dermatitis was entertained.³ He was treated with multivitamin capsules which included Niacinamide.²  

The skin lesions had disappeared dramatically at the time of follow-up after one month (figure 2).

Figure 1: Casal's necklace before treatment

Figure 2: Improvement after treatment

It welled up from my eyes
and dripped down on my
comatose condition.

Like Earth bathing in the sun’s light,
I warmed myself in the poet’s words.
I felt alive again
and wiped my tears.

I owe something
to this poet that awakened
me in this ward.

Ah, I must never forget
that once
I was a mass of terracotta.

INTRODUCTION

The most recent outbreak of severe acute respiratory syndrome (SARS) has been caused by coronavirus-2 (SARS-CoV-2) – a new single-strand, positive-sense-RNA beta-coronavirus first reported in 2019 in Wuhan, China. The virus has spread to nearly all countries across the world.^1-4

SARS-CoV-2 infection, also known as Coronavirus Disease 2019 (COVID-19), replicates mainly in the upper and lower respiratory tract. The transmission of COVID-19 from symptomatic and asymptomatic patients is usually through respiratory droplets, generated by coughing and sneezing or through contact with contaminated surfaces.^4,5 The disease has an incubation period of approximately 5.2 days.⁶

Most infections are mild and uncomplicated.⁴ After one week of the onset of disease, 5-10% of patients tend to develop pneumonia, needing hospitalisation.^4,6 Some of these patients develop further complications, often leading to death.^4,6 The overall case fatality rate is 1.4%, with a noticeably higher rate after the sixth decade of life.⁴

People aged ≥ 60 years, especially with underlying medical conditions – such as cardiovascular disease, hypertension, diabetes mellitus (DM), chronic respiratory disease, cancer, immunodeficiency, obesity – and those of male-sex, have an increased risk of dying.^4,7-12 Risk of severe adverse outcome is also associated with an increased number of associated co-morbidities.¹⁰

The impact of active cancer, endocrine disorders, autoimmune inflammatory rheumatic diseases etc. on COVID-19 outcomes has been investigated widely.^13-18 Divergent views have emerged regarding the role of renin angiotensin aldosterone system (RAAS) inhibitors, steroids, and immunomodulators in COVID-19 mortality.

The objective of our study was to evaluate the risk posed by epidemiological and demographic variables in our local population. We also sought to analyse the impact of co-morbidities on in-hospital mortality in confirmed COVID-19 patients.

METHODS

Study design:

We conducted a retrospective analysis of demographics characteristics (age and sex) and medical co-morbidities – hypertension, chronic heart failure, ischaemic heart disease, DM, thyroid disorders, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m2), chronic liver disease, active malignancy, immunosuppression, post-transplant status, chronic inflammatory arthritis and other rheumatic disorders – in all patients with confirmed COVID-19, who were admitted in two peripheral district general hospitals under a single National Health Service (NHS) trust serving primarily the rural population of western England.

Inclusion and Exclusion Criteria:

To determine COVID-19 status, nose and throat-swab specimens were obtained for real-time reverse transcription polymerase chain reactions (rt-PCR) in all adult (≥18 years) patients, attending one of the two district general hospitals (Royal Shrewsbury Hospital, Shrewsbury; and Princess Royal Hospital, Telford) under Shrewsbury & Telford Hospitals NHS Trust (SaTH) in the period from 1^st March to 15^th May 2020.

Patients who tested positive (either by N gene and ORF1ab gene positive / ORF1ab gene positive or N gene positive) and required subsequent in-hospital management were included in the study. Patients who were discharged after initial senior review (usually by a consultant physician), or brought in as a cardiac-respiratory arrest, were excluded. Re-admissions to the hospital beyond 48 hours following hospital discharge due to COVID-19 were excluded from the study. Patients diagnosed solely on radiological or clinical findings without a positive rt-PCR test were not included in our study.

We analysed the data based on the index-admission (including failed-discharge: re-admission within 48 hours following hospital discharge). No follow-up data was collected post-hospital discharge of these patients.

Data collection & analysis:

A list of all confirmed COVID-19 patients over a 76-day period was identified from the trust microbiology database. A search of the electronic patient records was completed by four members of our team. Supplementary data was gleaned from existing hospital paper records. Patient demographics, presenting symptoms, associated co-morbidities, medications, admission and discharge dates, intensive therapy unit (ITU) admissions, renal profile, referral source and outcomes were recorded in the specifically designed electronic datasheet.

Study Outcome:

The impact of epidemiological and demographic characteristics, and pre-existing medical conditions on the mortality of confirmed COVID-19 patients requiring in-hospital treatment was analysed.

RESULTS

A total of 303 confirmed COVID-19 (rt-PCR positive) samples were collected over a 76-day period. Five patients had been tested twice, and this was accounted for. Thirty-five patients were excluded from the study: twenty-four of them discharged after initial senior review without requiring in-hospital treatment, seven brought in with cardio-pulmonary resuscitation (CPR) in progress, three had inadequate data, and one was <18 years old. Of the 263 patients admitted, 70 (26.6%) died in hospital (Figure-1).

Figure-1: Flowchart of sampling and analysis

We stratified the mortality rates among the admitted patients by age (Table-1). A chi-square test of independence revealed that the mortality rate was significantly related to an advanced age (χ² =27.078, p<0.001). The age and sex distributions of admissions and mortality are shown in Figure-2 (a, b, c).

Table-1: Medical admissions and mortality stratified by age

N: number of patients, m: male, f: female.

Figure-2 (a,b,c): Age, Sex, Admission and Mortality pyramids

We considered two age cohorts - below 60 and ≥60 years of age and other relevant demographic parameters (sex and residence in own-home/care-home) to analyse the impact on mortality rates (Table-2). Of the admitted patients, 159 (60.5%) were male, and 104 (39.5%) were female. The mortality rate was strongly associated with advanced age ≥60 years (χ² =17.120, p<0.001) but independent of sex distribution (χ² =1.784, p=0.182). However, it was also affected by the care facility (χ² =18.146, p<0.001) with a higher mortality rate among the group of patients with residence in a long-term care-home.

Table-2: Admission and Mortality stratified by demographic variables

N: Number of patients; Care-home: Long-term care in residential or nursing home.

To identify the strength of the associations, we conducted a univariate logistic regression analysis with mortality as the dependent variable and the demography and presence/absence of the co-morbidities as the independent variable (Table-3). We found that age as a continuous predictor had an odds ratio of 1.058 (p<0.001), which translated to increased odds of dying by 5.8% for every year of advanced age. Using age as a categorical predictor with the other two categories, the odds of death for patients aged below 60 years was found to be 0.195 times the odds of death for the patients aged 60 years or above.

Table-3: Univariate logistic regression analysis of the demographic variables and co-morbidities

^*Cardiovascular: Hypertension, chronic heart failure, ischaemic heart disease, chronic arrhythmias; ^§Respiratory: Asthma, chronic obstructive pulmonary disease, interstitial lung disease, asbestosis; ^$DM & Endocrine: Diabetes Mellitus (DM), thyroid disorders, Addison's; ^£Renal: Chronic Kidney Disease (eGFR < 60 mL/min/1.73 m2), on dialysis, chronic nephritis, renal transplant; ^§§Rheumatic: Rheumatoid arthritis, inflammatory Polyarthritis, chronic vasculitis Syndrome, connective tissue disorders; ^±Liver & hepato-biliary: Fatty liver, non-alcoholic steatohepatitis, liver transplant; ^€Thyroid: Hypothyroidism, hyperthyroidism, post-thyroidectomy; ^€€Long-term oral steroids: Prednisolone, hydrocortisone, dexamethasone; ^$$Immunomodulators: Methotrexate, tacrolimus, sirolimus, mycophenolate, dapsone, sulfasalazine and azathioprine.

Based on the Charlson Comorbidity Index (CCI) score, the severity of co-morbidities was categorised into four cohorts: mild/no co-morbidity (CCI:0), moderate (CCI:1-2), severe (CCI:3-4), and very severe (CCI≥5) [Table-4(4a)].

Table-4: Impact of CCI score and specific medical-conditions on admission and mortality
4a) Admission and mortality stratified by CCI score based cohorts

4b) Admission and mortality stratified by specific medical-conditions

N: Number of patients; DM: Diabetes Mellitus; *RAAS-inhibitors; ^§Non RAAS-inhibitors.

The impact of CCI score-based cohorts on mortality are shown in Figure-3 (a-f). CCI value also predicted significant association with odds ratio 1.255 (p<0.001). If the CCI score was utilised as a categorical predictor with the other two parameters (age and place of primary care), it remained a significant predictor with the odds of death for the patients with CCI-scores between 0-4 turning out to be 44.8% (p=0.005) of the odds of death for the patients with CCI scores ≥5 (Table-3).

Figure-3(a - f): Pie-chart representing impact of CCI score-based cohorts on mortality


a) Overall admitted patients: discharge and mortality; b) CCI score 0: discharge and mortality; c) CCI score 1-2: discharge and mortality; d) CCI score 3-4: discharge and mortality; e) CCI score ≤4: discharge and mortality; f) CCI score ≥5: discharge and mortality.

Interestingly, the eGFR at presentation turned out to be a significant predictor of mortality (OR=0.961, p<0.001). Of the co-morbidities, pre-existing renal disease was found to be an important predictor of mortality with OR=1.996 (p=0.027). Long-term oral steroids were another significant predictor of mortality, with the odds of death for the patients with long-term oral steroids use being 341.2% (p=0.016) of the odds of death for the patients without such medication. Patients with no background medical conditions (OR=0.181, p=0.022) fared better, with significantly lower odds of death compared to patients with at least one known medical condition (Table-3).

We also analysed the mortality of our patients with specific medical condition-based cohorts [Table-4(4b)]. A high mortality of 52.9% [OR (95%CI): 4.053(1.091–15.063), p=0.037] was observed in patients who were on long-term oral steroids. A 33.3% [OR (95%CI):1.510(0.791–2.883), p=0.212] mortality rate was observed among in-patients with known diabetes on pharmacotherapy.

Many of the demographic variables and the co-morbidities were inter-related – the odds of death for a patient coming from their own-home was only 26% (OR=0.263, p<0.001) of the odds for those residing in a long-term care-home (Table-3). To offset the possibility of any confounding effect, we utilised multiple logistic regression analysis with all the important variables taken together (Table-5). Taking consideration of confounding effects, only age, care facility, presence of active malignancy and long-term oral steroids were found to be significant predictors of mortality. Interestingly, the presence of active malignancy was found to have a lower risk of death – this is possibly due to a bias on account of a relatively small number of patients in that subset of our study. Age was the most significant predictor of mortality, followed by a primary area of the care facility and the presence of active malignancy.

Table-5: Multiple logistic regression analysis of the demographic variables and co-morbidities

DM: Diabetes Mellitus

DISCUSSION

COVID-19 has taken 800,000 lives world-wide as reported by the World Health Organisation (WHO) on August 30, 2020. A recent systematic review and meta-analysis have reported the association of COVID-19 with a severe disease course in about 23% of infected patients and has a mortality of about 6%.¹⁹ The mortality rate varies in different geographical areas. In-hospital mortality was significantly higher in the United States of America (USA) (22.23%) and Europe (22.9%) compared to Asia (12.65%) – (p<0.0001).²⁰ However, there was no significant difference when compared to each other (p=0.49).²⁰ Our study showed a 26.6% in-hospital mortality.

The mean age of the patients in our study was 68.74 years (SD:16.89) – 60.5% of them were male and 39.5% female. 70.7% of these patients were aged ≥60 years. Univariate analysis showed that the mortality rate was significantly age-dependent (OR=1.058, p<0.001) – mortality (33.9%) was higher in patients aged ≥60 years, rising sharply ≥80 years to 44.0% (χ² =27.078, p<0.001). Our results were consistent with other studies.²¹

Among the demographic characteristics, mortality-risk was independent of sex distribution (χ² =1.784, p=0.182) in our study. This is in contrast to a meta-analysis, which reported the association between male-sex and COVID-19 mortality (OR =1.81; 95%CI:1.25–2.62).²² Multicentric studies in the United Kingdom (UK) would be warranted to see the trend in the local population.

Long-term care-home residents suffered 50.0% mortality (χ² =18.146, p<0.001). The London School of Economics report on May 14, 2020, estimated that the COVID-19 related deaths of care-home residents contributed to 54% of all excess deaths in England and Wales. Our study findings indicate long-term care-homes as hot-spots requiring shielding and protective measures against COVID-19 – a conclusion corroborating other studies.²³

We aimed to define the predictive-role of co-morbidities on COVID-19 mortality, an aspect that has been probed earlier as well.^7-12 The CCI score remains a reliable method to measure co-morbidity.²⁴ For admission to intensive care, NICE recommended CCI-score ≥ 5 requires critical care advice to help in treatment decision regarding the essential benefit of organ support for seriously unwell COVID-19 patients. We examined the predictive mortality-risk of CCI scores among the admitted patients.

The mortality rate in cohorts with CCI ≤4 and CCI scores ≥5 were 20.3% and 36.2% respectively. The odds of death for CCI ≤4 cohort was less than half (44.8%) compared with CCI scores ≥5 cohort. Based on this finding, we strongly recommend CCI scoring as a clinical risk-stratification tool in COVID-19.

We examined the impact of organ specific co-morbidities on in-hospital mortality in our study as well. Patients with no background medical conditions showed a low mortality rate 6.9% [OR (95%CI): 0.181(0.042–0.782), p=0.022] and had better outcomes with significantly lower odds of death, compared to patients with at least one medical condition on univariate logistic regression analysis (Table-3). The mortality rate was 3.2% in CCI-0 cohort [Table 4(4a)].

The impact of COVID-19 on patients with CKD, glomerulo-nephropathies, on dialysis dependent patients and post renal transplant patients remains unclear. Patients with SARS-CoV-2 infection were frequently found to have renal dysfunction – the latter was associated with greater complications and in-hospital mortality.²⁵ A mortality rate of 3.6%, was reported in patients attending an outpatient haemodialysis centre.²⁶ Another study has concluded 3.07-fold (95%CI:1.43–6.61)mortality among renal failure patients.²⁷ We found, the pre-existing renal disease to be a cause of significant concern with 37.7% mortality [OR(95%CI): 1.996(1.082 – 3.681), p=0.027] with the eGFR at presentation being a significant predictor (OR=0.961, p <0.001) (Table-3).

The use of steroids in COVID-19 continues to be explored.The RECOVERY trial in UK, after evaluation at 28 days, concluded that dexamethasone reduced deaths by one-third in ventilated patients [age-adjusted rate ratio (RR) 0.65; 95% CI: 0.48–0.88; p=0.0003], and by one-fifth in other patients receiving supplemental oxygen with or without non-invasive ventilation (RR 0.80; 95%CI: 0.67 to 0.96; p=0.0021), although no benefit was observed in mild or moderate cases not requiring oxygen support (17.0% vs.13.2%; RR 1.22; 95% CI, 0.93e1.61; p¼0.14). In contrast, a systematic review concluded that the results from retrospective studies are heterogeneous, and it was difficult to assign a definite protective role of corticosteroids in this setting.²⁸ We found long-term oral steroids use to be a significant predictor of mortality – 52.9% [OR(95%CI): 3.412(1.261–9.23), p=0.016] – this was 341.2% of the odds of death for the patients without any long-term oral steroids use (Table-3). The sample size of this cohort was relatively small with 9 deaths out of 17 patients. However, based on our results, it may be safe to suggest that further population-based studies would be required to determine the impact of long-term oral corticosteroid use in COVID-19.

A major proportion of endocrine disorders are of autoimmune aetiology. The impact of thyroid disorders on COVID-19 is yet to be studied widely.^15,16 We found no increased risk of mortality [OR (95%CI): 0.914 (0.285–2.934), p=0.880] in patients with thyroid disorders. However, 33.33% [OR(95%CI): 1.510(0.791–2.883), p=0.212] mortality was seen among the diabetic patients on pharmacotherapy in our study [Table-4(4b)].

Pre-existing hypertension is an accepted risk factor for COVID-19 mortality.^26,27 However, the role RAAS-inhibitors and upregulation of ACE-2 receptors in COVID-19 mortality call for targeted clinical research for further clarification.²⁹ A meta-analysis of four studies showed that patients treated with RAAS-inhibitors had a lower risk of mortality [RR: 0.65(95%CI:0.45–0.94), P=0.20].³⁰ We did not observe any significant mortality-risk difference between RAAS-inhibitors treatment group [OR(95%CI): 0.760(0.365–1.586), p=0.465] and non RAAS-inhibitor treatment groups [OR(95%CI): 0.704(0.253–1.964), p=0.503] [Table-4(4b)]. We recommend the continuation of RAAS-inhibitors during COVID-19 unless there exist other compelling medical reasons for their discontinuation.

A prospective study in the UK concluded that the mortality from COVID-19 in cancer patients appeared to be driven principally by age, gender, and co-morbidities.¹³ The study could not identify evidence suggesting cancer patients on cytotoxic chemotherapy, or other anticancer treatment, were at an increased risk of mortality from COVID-19 compared to the general population.¹³ We also did not detect any increased risk of mortality in patients with active malignancy [OR(95%CI): 0.078(0.008–0.725), p=0.025)] (Table-5).

The impact of various non-specific immunomodulators in COVID-19 outcome remains inconclusive.¹⁴ Our study did not reveal any significant predictive mortality-risk with the use of long-term immunomodulators (methotrexate, tacrolimus, sirolimus, mycophenolate, dapsone, sulfasalazine and azathioprine) on multiple logistic regression analysis. We reached the same conclusion with patients suffering from chronic rheumatic disorders on similar analysis (Table-5).

Our study had some unique characteristics. We analysed all the eligible samples over a consecutive 76-day period at the initial peak of the pandemic. The study was conducted across two district general hospitals, allowing an insight into two differently located rural populations. We conducted univariate and multiple logistic regression analysis of the demographic variables and co-morbidities to examine the predictive-risk of contributing factors in COVID-19 mortality. The association between CCI scores and in-hospital mortality was also analysed in detail. We included demographic characteristics such as age, sex and residence in a long-term care-home while factoring in the associations.

Our study was not without limitations, though. We were unable to study the predictive-risk of obesity, socioeconomic status and ethnicity due to inadequate data. The “White British” group consisted of 80.61% of admitted patients, and no ethnicity was documented in 17.11% of our patients (Table-6, Figure-4).

Table-6: Medical admissions and mortality stratified by ethnicity

N: Number of patients

Figure-4: Bar charts showing Admission and Mortality stratified by Ethnicity

We relied solely on electronic database and hospital records to conduct the study retrospectively. The few subsets of patients such as those on prescribed long-term oral steroids, immunomodulators, thyroid disorders, chronic liver disease, and active malignancy had relatively small sample sizes with possible introduction of bias. We did not categorise diabetic patients into insulin dependent/non-insulin dependent or well/poorly glycaemic control cohorts. We did not aim to split the respiratory group into well or poorly controlled asthma or COPD subsets. Patients on a long-term steroid inhalation treatment were not included in the steroid cohort – a more extensive population-based study may be better suited for such an analysis.

CONCLUSIONS

Patients aged ≥ 60 years, residence in a long-term care-home, pre-existing renal disease, multiple co-morbidities (especially those with CCI ≥ 5), and patients on long-term oral steroids need to be considered as having a high risk of dying from COVID-19, along with other established risk factors such as hypertension, diabetes and chronic respiratory disease. RAAS-inhibitors need not be discontinued due to COVID-19. Further studies are necessary to establish links between long-term oral steroids use, chronic rheumatic disease, non-specific immunomodulators and COVID-19 mortality.

What is the MTI scheme?

The Medical Training Initiative (MTI) is a training programme to assist doctors with proven capability in anaesthesia/Intensive Care/Pain Medicine from low and middle income countries to undertake further anaesthesia training in the UK, for a maximum of 24 months¹.

Why MTI?

It offers an opportunity not only to fine-tune their clinical acumen, but also to assimilate non-clinical skills (medical education, leadership and management, quality improvement projects) ². The exposure most of the MTIs receive overseas is heterogeneous - in terms of level of supervision/independence, access to modern equipment and medications, lines of management, level of expectations and communication or interaction with patients. Funding received by training hospitals overseas can be variable thereby impacting on the resources available to provide standardised training. Under the MTI scheme, anaesthetic trainees can also take the FRCA examination.

From home to UK

A general awareness of the scheme helps the department to provide the MTIs with an appropriate support system. Details of the MTI scheme are available on the Royal College of Anaesthetists (RCoA) website.

It takes about 3-6 months after verification of the educational qualification by Educational Commission for Foreign Medical Graduates (ECFMG) via Electronic Portfolio of International Credentials (EPIC). The planning involves resignation from the current job, applying for a Tier 5 Visa to be in time for the GMC identity check (3 month deadline) and collecting the Biometric Residence Permit to be able to start work in the UK.

Medical staffing has more paperwork, one of which is the Disclosure and Barring Service (DBS). Prior intimation to the MTIs on the need for police verification from their home country would be of great benefit to make the process smoother. Hospital accommodation should be offered and organised in advance.

Acquaintance with the system

The MTI trainees often join at a time that doesn’t coincide with the UK training programme. Hence, a one-to-one induction customised towards overseas doctors will be beneficial. In addition to a named Educational supervisor (a mandatory requirement stipulated by the RCoA), the MTIs will benefit from having a nominated mentor within the department. The trainees can also get familiarised to the new healthcare system via the RCoA approved training courses – ‘Simulation for MTIs’ and ‘New to NHS’.

Allocating MTIs to theatre lists with only a select number of consultants in the initial stages helps them to settle in a new healthcare environment before they commence on-call (out of hours) duties. The MTIs should be encouraged to attend resuscitation courses like Advanced Life Support (ALS) as most of them follow the Advanced Cardiac Life Support (ACLS). They should be encouraged to document their progress like any other UK trainee via the RCoA Lifelong Learning Platform (LLP).

Anaesthetic training in the UK is very structured. The three stages of training (core, intermediate and higher/advanced) are well defined. The curriculum is well laid out and assists trainees to not only develop clinical but also gain non-technical skills. A six-monthly ARCP (Annual Review of Competence Progression) like assessment with annual anonymised multi-source feedback helps to create professional development plans, monitor progress and put supportive plans in place (if needed ) for a struggling trainee. The curriculum provides an opportunity for all-round development to every overseas trainee.

Gaining experience in non-technical skills (leadership and management, medical education and QI/audit projects) can be lacking in some home countries as the curriculum back home could be heavily biased towards the development of clinical acumen only.

What to expect from an MTI?

The MTIs have at least 3-5 years (may be more) of anaesthetic experience. The NHS benefits from their skills and experience. Their experience helps the department to allocate them to provide out of hours work (on-call) sooner than a UK trainee after an appropriate period of induction. The journey of patient experience also improves with the presence of experienced staff on the shop floor.

Departments gain from increased service provision too. As an example, after obtaining the initial assessment of competency (IAC), the MTI anaesthetists can be allocated to do solo theatre lists with a named supervising consultant anaesthetist present within the theatre suite. The reliance on locum staff is reduced thereby reducing unnecessary cancellations of theatre lists for lack of permanent staff. It reduces the financial burden on the NHS as staffing the department with locums can add to increased costs.

Patient safety is of paramount importance in any healthcare setting. Since the MTIs have a two year working contract, they are familiar with the department policies and guidelines unlike a locum doctor who does the odd shift in a hospital.

Equally, new skills gained by the MTIs are ultrasound guided regional anaesthesia, using a fibre-optic scope and different airway gadgets, ICU training, experience in geriatric and bariatric anaesthesia, total intravenous anaesthesia (TIVA) / target controlled infusion (TCI) alongside access to new medications like remifentanil, sugammadex which may not be available in low to middle income countries. The NHS provides excellent opportunities in simulation training and teaching courses.

However, a system of protocols can be unnerving to the MTIs. One may find them taking a step back when it comes to ‘decision making’ as they are not sure if it would be approved or criticised. At times, some of the MTIs may come across as unyielding despite adequate teaching. It is essential to remember that the process of unlearning to re-learning takes time, and therefore, patience is the key. This is where the concept of teaching experienced medical practitioners with knowledge comes in handy.

Training learners with knowledge

Medical education comprises three inter-linked domains - knowledge, skills and attitude.³ Though trainees may differ in terms of their motivation for learning, it can manifest only after the basic needs are satisfied - the external barriers to motivation such as life events and transitions, opportunities, and barriers to learning or obtaining information are addressed and they feel respected in the educational environment. The MTIs are essentially adult learners with pre-existing knowledge, who bring a great deal of first-hand experience to any work-place. Learning should, therefore, be integrative, which forms the basis of constructivism theory of learning⁴. New knowledge and skills should be integrated into the existing bank of knowledge. They also have pre-set strong tastes and habits which can be a real asset or a hindrance to effective learning. The educational supervisor should be able to encourage or curb them accordingly⁵.

Being adults, MTIs enter training situations with a self-image as independent, mature beings as they have already passed the qualifying exams in their home country. They can direct their own learning, including decision making and plans for taking examinations. The supervisors should engage with the trainees in activities that create a sense of self-responsibility to facilitate better learning opportunities.

Many adult learners suffer from a fear of failure and living up to expectations⁶ and thus, educational supervisors should be cautious to avoid unnecessary criticism. Instead the focus should be to offer constructive positive feedback. Any educational plan for them should start with an awareness of their prior acquired knowledge, an assessment of their educational needs along with room for motivation and reflection. This helps the trainees retain the original “frame of reference” while continuing to constantly challenge and transform practice via reflection on-action and reflection in-action. The educational supervisors need to provide a supporting educational environment, a structured guide for reflection and constructive feedback to develop the trainees’ reflective practice⁷.

A simple multi-step approach involving active participation from both the trainee and the educational supervisor can be summarised into a model as below (Figure 1) ⁸. This model begins with the trainee’s prior knowledge.

Figure 1: Multi-step approach to training

The RCoA LLP, work-place based assessments and multi-source feedback along with the six-monthly meeting with educational supervisor are useful tools to deliver a holistic learning experience. It helps to refine the existing knowledge, reflect and provide constructive feedback. The supervisor can provide advance structures upon which the MTI can continue to build opportunities and gain confidence to rehearse and apply their new knowledge.

Summary

An organised induction programme, a period of familiarisation and good mentorship with patience helps to remove the barriers to learning for the MTI trainees. A dynamic trainee-supervisor relationship to accommodate the changing educational goals and an appropriate mix of strategies can help the MTI trainees attain medical competence, which is defined as “the habitual and judicious use of communication, knowledge, technical skills, clinical reasoning, emotions, values and reflection in daily practice for the benefit of the individual and the community being served³.”

Introduction

Lung carcinoma the most common malignancy worldwide, presents as a metastatic disease in majority of the cases. The most frequent sites of distant metastases are liver, adrenal glands, bones, and brain. Skeletal muscle metastasis is an unusual presentation of lung adenocarcinoma.

Case report

A fifty three year old male patient, labourer by occupation, beedi smoker for twenty five years, admitted to tertiary care hospital with pain and swelling over left arm, cough and expectoration for the past two months, accompanied with significant weight loss. There was no evidence of chest pain or haemoptysis. On local examination there was hard swelling over extensor compartment of left upper limb with mild tenderness, no loss of sensation and mild restriction of range of movements on flexion at elbow. Respiratory and other systemic examination was within normal results. Plain CT of thorax defined multilobulated lesion in right perihilar location in right middle lobe (Figure 1).

Figure 1: CT of Thorax: Well defined multi-lobulated lesion in right perihilar location in right middle lobe measuring 2.9 x 2.4 cm.

USG of left arm showed an irregular heterogenous soft tissue lesion noted within the triceps muscle with few areas of intra-lesional necrosis, MRI of left arm showed lobulated lesion in posteromedial aspect of mid and distal arm, involving triceps muscle, medial aspect of brachialis, encasing brachial artery, veins and median nerve (Figure 2).

Figure 2: MRI of Left arm: Well defined irregular lobulated enhancing T1 hypo intense, T2 and T2 flair hyperintense lesion in the posteromedial aspect of mid and distal arm.

PET scan showed enhancing nodular soft tissue lesion noted in middle lobe of right lung, 2.9 x 2.4 centimetres. Biopsy revealed metastatic adenocarcinoma. For further studies Immunophenotyping was done which showed negative for EGFR and ALK. Patient was treated with palliative RT, Pem-Carbo f/b Pemtrexed maintenance and recently 3# of Gemcitabine. The patient died of metastasis to brain within eight weeks of diagnosis.

Discussion

Lung carcinoma is a leading cause of cancer-related mortality. The most common sites of distant metastasis in lung carcinoma are brain, bones, the liver, and the adrenal gland¹. The most common tumours that cause skeletal muscle metastasis are tumours originating from thyroid, oesophagus, stomach, pancreas, colon, rectum, bladder, breast, ovary, and prostateand skeletal muscle metastasis of lung carcinoma was first reported by Fisher ER². Willis RA reported four skeletal muscle metastases in their autopsy series composed of 500 lung carcinoma patients³. Skeletal muscle metastasis is a rare occurrence for any tumour with a reported incidence lees than one percent^4-5. The most common sites of muscle metastasis are thigh muscles, iliopsoas, and paraspinous muscles⁶.

The mechanism of skeletal muscle metastasis is unclear. Despite its rich vascular blood supply and a large mass in the body, it is resistant to haematogenous metastases. Organs that are frequently metastasized, including liver, lung, and bone have rich capillary networks and blood supply. As a result of the muscle metabolism, substances such as lactic acid, free oxygen radicals, and low pH in the environment constitute an infertile medium for proliferating tumour cells. In addition, mechanical insults due to contractions, high tissue pressure, and widely alternating blood flow are also against the survival of tumour cells⁷.

There are several hypotheses proposed for skeletal muscle metastasis in lung carcinoma. The most widely accepted hypothesis is the haematogenous route. In this hypothesis, it is believed that tumour cells are formed through tumour embolism. Some authors suggested that skeletal muscle metastases might originate from abnormal lymph nodes found in the muscle. In a study by Bocchino M et al. 1754 lung carcinoma patients treated between 2007 and 2012 were analyzed and forty six (2.6%) had skeletal muscle metastasis⁸. Despite the variations between different studies in terms of the association between histological subtypes and skeletal muscle metastasis, forty patients in that study (87%) had non small cell lung carcinoma and six had (13%) small cell lung carcinoma. Among non small cell lung carcinoma patients, twenty four (60%) had adenocarcinoma. The most common initial manifestation of skeletal muscle metastasis is a pain. Pain can be accompanied by extremity swelling. The case presented herein also applied with pain and swelling. Diagnostic methods for skeletal muscle metastasis are not specific. Direct films usually show only soft tissue shadows. MRI usually reveals hypointense signal in T1 and hyperintense signal in T2. MRI is preferred to distinguish soft tissue metastasis from an abscess, sarcoma, and other conditions⁹, similarly; our patient had hypointense signal on T1 and the hyperintense signal on T2 series. The optimum treatment and prognosis of skeletal muscle metastasis from lung cancer is unclear. Depending on the clinical characteristics, treatment options include observation, surgery, chemotherapy and radiotherapy.

Conclusion

Lung carcinoma with skeletal muscle metastasis should be considered as a potential differential diagnosis in patients presenting with an intramuscular mass.

Acknowledgements

Authors acknowledge the immense co-operation received by the patient and the help received from the scholars whose articles are cited and included in references of this case report. The authors also acknowledge the authors/editors/publishers of all those articles, journals and books from where the literature for this case report has been reviewed and discussed.

Introduction

World COVID-19 cases exceed 20 million as of today and the number of deaths surpass 733103. Behind these statistics is a great deal of pain and suffering. It is now increasingly getting recognized that COVID-19 is not just a respiratory disease at all. The face of COVID-19 is changing from a pulmonary disease to an inflammatory disease which particularly affects the blood vessels, the coronary vessels, the kidneys, the liver, brain and elsewhere. Its duration is also much longer with long term impact than initially speculated. Sufferers report a huge spectrum of problems beyond the three NHS-approved symptoms (persistent cough, fever and loss of taste or smell). These include fatigue, breathlessness, muscle aches, joint pain, 'brain fog,' memory loss, lack of concentration, and depression.

More morbidity is recognised in cases of infections among the aged populations and patients with suppressed immunity. The high incidence of complications among ethnic minority apparently points toward environmental factors of immunity rather than genetic factors. Underactive immune responses in cooler temperature and diminished synthesis of vit D and the genetic factors linked with these anomalies might explain only part of the higher incidence of COVID-19 among Black, Asian, and Minority Ethnic (BAME) communities.

Research on the first British patients to contract COVID-19 has shown that BAME people are more prone to critical impacts and care compared to white people. This research, conducted by the Intensive Care National Audit and Research Centre, observed that of nearly 2,000 COVID-19 patients, 35% were non-white, though people of BAME heritage only comprise 13% of the UK’s population.¹ The study included data drawn from 286 critical care units across the UK and collected until 3 April 2020. According to another study from the UCL Institute for Global Health, Bangladeshi, Pakistani, Indian, Black African and Black Caribbean ethnic groups all had a substantially increased risk of death in comparison to white British and white Irish groups. Cook et al. pinpointed that of 119 NHS staff who died from COVID-19, 64 were from ethnic minority backgrounds.² They also noted fewer deaths among critical care staff, highlighting PPE’s usefulness.

The UK BAME population’s mortality rate for the 2009 influenza A (H1N1) epidemic was nearly twice that of the white population.³ The Pakistani and Bangladeshi ethnic groups are now 1.8 times more likely to have a COVID-19-related morbidity than white males of a similar age, when other sociodemographic and health characteristics were compared.⁴Studies have also specified that Black men are 4.2 and Black women 4.3 times more likely to die from a COVID-19-related death than white people.⁵ Doherty et al. suggested that socioeconomic disadvantages and other circumstances only partially explicate this discrepancy, and that there are missing gaps that have not yet been expounded.⁶

There is some confusion regarding the cause of this higher incidence of morbidity and mortality among the BAME community, due to media propaganda failing to assess this relation’s intricacies. Higher morbidity and mortality have been observed among first-generation migrants to the UK, but not necessarily among the second generation, who were born and raised in the UK. Five months is a short period to develop any form of genetic immunity or susceptibility to a new viral infection. Each person’s genetic code differs only by 1% of 25,000 genes. The gene cluster largely responsible for our health is called the human leukocyte antigen (HLA), also known as the major histocompatibility complex (MHC). It also takes much longer for any sort of adaptation or mutation to occur. Suppressed general immunity due to various factors appears to be the main reason for the higher COVID-19 incidence among the BAME population. The following discussion examines the possible factors responsible for this anomaly.

a. Immunity and Temperature

Some data has suggested that immune cells are more active in higher temperatures, as supported by the fact that fevers are a bodily mechanism activated by the immune system to defend against pathogens. It has been established that if the body temperature is increased by 1°C, immunity instantly increases 5–6 times. Likewise, if the body temperature is reduced by 1°C, immunity decreases 5–6 times. This observation has some value in explaining the higher incidence of COVID-19 infection and mortality among BAME groups who were born and raised in warmer areas, then migrated to colder regions.

Temperature-dependent immune responses are linked to genetics. One probable explanation is that BAME individuals’ immune cells are genetically wired to function better in hot weather and are unable to optimally function in cold weather. Such a genetically determined immunological build-up means that their immune cells are slow to react to viral invaders. BAME individuals’ immune cells are well-adapted to warm weather but not so to cold weather, in comparison to white individuals who were born and raised in colder climates and adapted to lower temperatures. BAME individuals’ immune cells may even become underactive in cold weather. Though COVID-19 thrives equally well in hot and cold weather, the BAME population has immunity shortcomings in surviving colder months; this insight might prompt them to take special precautions in future cold seasons.

Low temperatures have been recognized as immunosuppressive. It has been observed that even coldblooded animals migrate to warmer places when they become ill. An increase in body temperature has long been a defence mechanism against infection and inflammation. The generation and differentiation of the lymphocytes CD8+ cytotoxic T-cells are enhanced by hyperthermia. Elevated body temperature changes T-cells’ membranes, which may help mediate micro-environmental temperature’s effects on cell function. Sub-thermoneutral laboratory housing temperature was shown to induce immunosuppression in mice experiments: when the mice were housed at a thermoneutral ambient temperature, striking reductions in tumour formation, growth rate and metastasis were observed.⁷

Mice experiments with antigens demonstrated that mice with antigen-induced raised temperatures showed a greater number of the CD8 T-cells capable of destroying infected cells.^8,9 Parallels were observed in teleost fish.¹⁰ Higher temperatures also seem to interfere with microbe replication. This is particularly noticeable when a host has a high fever and their immune system temporarily enhances as their temperature rises. Hong Kong’s persistent cold weather was attributed to the rapid spread of SARS in 2003. BAME communities whose immune mechanisms are genetically evolved for survival in higher temperatures are compromised in Western countries’ lower temperatures. The cold weather puts additional stress on their immune cells, which give in to viral invaders.

This argument is further supported by the spread of the flu. During flu season, immune cells become less efficient and flu viruses, unaffected by low temperatures, are in an advantageous position to defeat these cells. Such a hypothesis explains the higher incidence of flu in the winter and challenges the misconception that the flu virus is killed by hot weather and thrives in cold weather. The 1918 Spanish flu that broke out in the United States in the winter seemed to ease off during the summer, but returned with a deadlier strain in the autumn, and a third wave followed the next year. The problem then seems to be in humans, as viruses are unaffected by seasonal temperature variations.

b. Diminished Vitamin D Synthesis

Other mitigating factors can explain the higher COVID-19 incidence among BAME people. Nearly all immune cells have vitamin D receptors that connect to vitamin D networks in the immune system. Vitamin D helps regulate both the innate and adaptive immune systems, and is critical for balancing immune function. Vitamin D has been demonstrated to reduce the production of pro-inflammatory cytokines associated with lung damage caused by acute viral respiratory infections, such as influenza and COVID-19.¹¹ BAME communities are prone to vitamin D deficiency because higher melanin levels in their skin cause lower vitamin D absorption. Consequently, prolonged exposure to sunlight is required to accrue the equivalent vitamin D quantity produced in the white population. This is further exacerbated in colder countries like the UK, which see less sunlight, meaning BAME individuals spend more time indoors without much opportunity to absorb vitamin D. So, there may be a connection between lower vitamin D levels and more frequent COVID-19 cases in BAME communities, though there is no firm data defending this link.

Virtually all immune cells have vitamin D receptors, indicating vitamin D interacts with the immune system. Vitamin D is required to regulate both the innate and adaptive immune systems and its deficiency is associated with immune dysregulation. Many of the ways this vitamin affects the immune system are directly relevant to the body’s ability to defend against viruses. For example, vitamin D triggers the production of cathelicidin and other defensins, which are natural antivirals capable of preventing viruses from replicating and entering cells. Vitamin D also increases the number of CD8+ T-cells, which play a critical role in clearing acute viral infections in the lungs. Further, vitamin D suppresses pro-inflammatory cytokines and may also alleviate the cytokine storms occurring in the most severe COVID-19 cases. This vitamin plays an essential role as well in glucose homeostasis, insulin sensitivity and the regulation of adipokines, such as leptin and inflammatory cytokines.¹²

Evidence from randomized controlled trials suggested that regular vitamin D supplements may help protect against acute respiratory infections. Admittedly, the direct evidence of vitamin D’s role against COVID-19 is still scant. One study from the United States and another from Asia found a strong correlation between low vitamin D and severe COVID-19 infection. It is well-recognized that the elderly and people with pre-existing conditionsare more vulnerable to COVID-19. Notably, people with existing medical conditions are also often vitamin D–deficient. Studies assessing ICU patientshave reported these patients’ low vitamin D levels even before COVID-19. It appears logical to hypothesize a link between the high COVID-19 infection rates in UK and US BAME groups and their observed lower vitamin D levels. Moreover, it is not possible to gain a sufficient vitamin D supply through food alone, making exposure to sunlight indispensable.

c. Weakened Immunity

COVID-19’s spread in the UK is disproportionately high compared to its spread in the countries of origin of many BAME communities. BAME people should be mindful of their genetics in a new environment. These demographics also have higher rates of cardiovascular disease, type-2 diabetes and hypertension, conditions that have been linked to severe COVID-19 symptoms and complications. There may also be other genetic links that warrant further exploration.

Current evidence has illustrated that chronic stress can increase infection susceptibility by suppressing the T-helper 1 immune response in favour of the T-helper 2 immune response.⁴⁰ Stress management, lifestyle changes and career management may reduce infection susceptibility in turn. When people are less mobile, food becomes a distraction and they can overindulge. Obesity is also an adaptation to cold weather, as fat protects against low temperatures. Black and South Asian populations in the UK have 3–5 times the prevalence of type-2 diabetes compared to the white population and are diagnosed 10–12 years sooner on average.¹³

Human immunity is generally fixed by age 5, as contributed to by bacterial flora, among other factors. Several trillion bacteria exist within our body, with the gut considered this bacterial colony’s front yard. We have 25,000 genes, but up to 3 million bacterial flora genes are the real immune cell trainers.¹⁴Bacterial worlds came into existence well before humans evolved. When people migrated to Western countries from tropical regions, their bacteria had to adjust to their host’s new lifestyle, with some even replaced. Others may not have survived at all; consequently, these individuals’ immunity may have weakened.

The high incidence of diabetes and coronary heart disease in the British Asian population has been well-recognized, along with many other risk factors and comorbidities, including obesity, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and age. These may partly account for this population’s increased COVID-19 mortality^15,16, but warrant further exploration. Vitamin D level is also likely to drop with rising BMI and age.¹⁷Obesity is strongly associated with vitamin 19-22D deficiency.¹⁸ Admittedly, there are weaknesses in these data collections and interpretations, which are theoretical speculations yet to be confirmed, modified or falsified. 

There are diverse genetically linked immune responses in a given population, and the spread and survival of complications in a pandemic like this are not well-defined. Research has suggested that people living in close communities, like certain regions of Lombardy, Italy, have a poor genetically linked immune response to COVID-19. Like our fingerprints, immunity genetics contribute to our physical identity, but our immunity is not permanently fixed by genetics. There thus remain many unknowns in immunity research.

It is now increasingly recognized that immune ageing and organismal ageing are intimately inter-related. Aging weakens the immune system and immunity decline further accelerates the aging process. Immune system protects the individuals against viruses and bacteria and it also helps identify and remove cancer cells and toxins. The potential for these elements to cause damage in the body increases as age advances. Critical cells in the immune system decrease in number and become less functional as people get older. COVID-19 affects seriously the aging people of the BAME community as in the case of general population, but they are more disadvantaged in terms of health care access.

d. Social Factors

Alongside these factors, many BAME individuals work in fields that carry a high risk of infection, such as healthcare, transport services and retail. In the UK, 40% of doctors, 20% of nurses and a large number of social care and unskilled migrant workers belong to BAME backgrounds. Another reason why these infections may become more prevalent among ethnic minorities is that BAME community members tend to spend more time indoors clustered together, often in cramped accommodations, which increases the likelihood of person-to-person transmission. A multigenerational family set-up is not helpful either to social distancing in a pandemic, so this lifestyle could contribute to higher infection rates. Some people living in this arrangement may also become stressed and obese due to unhealthy nourishment.

Migrant communities tend to visit and keep in contact with their country of origin, which involve international air travel and thus increased infection risk. Family studies demonstrate that BAME people living in the colder countries develop COVID-19 at a faster rate, but most of their family members living in the tropical climate in the countries of birth are spared from the infection. Such an observation point towards extrinsic factors like lifestyle and weather conditions rather than intrinsic genetic links-nurture than genetics. The second-generation immigrant population are less affected and the mixed-race individuals because of diversity of immune cells appear more resilient to the viral pandemic. There appears to exist an epidemiological trend of transmission concentrations within BAME communities living in colder countries, such a situation runs the risk of racial stigmatisation and discrimination and also risks to social cohesion.

BAME individuals should be cognizant of the additional risks and take preventive and precautionary measures. They should also adapt to balance their immunity. Enough sleep, healthy diet, moderate exercise, abstaining from excess alcohol and smoking and de-stressing are the cornerstones of enhancing immunity. Immunity is not absence of a specific disease or illness; rather, it is a balanced physiological and psychological state, the most sophisticated and elegant system of human physiology. Vaccines are pathogen-specific, and they do not bestow an overall balanced immunity.

Supporting Immunity

To defeat the tiger, one may need to become stronger than the tiger. To do this with COVID-19, we may need to foster our existing immune system, which can be done in many subtle ways. We all must grapple with the unprecedented threat posed by COVID-19, and frontline health workers must be mindful of their own immune systems when advising their patients to do the same. Unreasonable fear of COVID-19 only weakens the immune system, and fear attracts that which is feared. According to many COVID-19 survivors, remaining positive is a crucial factor in combatting this illness. Knowledge about the enemy and our potential resources lessens fears and helps us to plan strategies to defeat the adversary. With a quarter of the world’s population in the grip of COVID-19, it is a highly challenging period to learn to survive and strengthen our body and mind and enhance our immune system, even using the wisdom of unconventional medicines and faith traditions. We will have to battle with this invisible enemy until an effective vaccine is identified. Anything that fosters self-immunity should be encouraged in this time of a global medical emergency.

The two functions of immune system are defending the body’s health and maintaining health.The immune system is depicted as having two components: the innate and adaptive immune responses. The innate system is the more primitive and less specific. It is the body’s first line of defence against foreign substances that may lead to disease. The adaptive system, found only in vertebrates, is a much more specific, delayed response and requires sanction from the innate system to be instigated. Though considered separate, each interacts with the other in critical and complex manner. A basic understanding of both responses facilitates to clarify and further substantiate the significance of immune balance.

There are many myths surrounding immunity enhancement. Enrichment of the immune system is possible so that it becomes vigilant and active in the event of an invasion by pathogens and it may possibly prevent immunity anomalies. It is defending the defenders of the body. Immune system is our protective shield. Metaphorically, immune cells are the guardian angels of the body. Balancing of immunity can be achieved by focussing on ample sleep, healthy diet, moderate exercise, weight monitoring, restricting alcohol, free of smoking and destressing.In the nutshell, it warrants lifestyle changes- one size may not fit all and immune balancing has to be adjusted on an individual basis.

a. Restful Sleep

One healthy habit vital to preventing sickness is getting a full eight hours of sleep each night, which may help regulate immune function.¹⁹ Studies reveal that people who are deprived of quality sleep are more likely to get sick after being exposed to a virus. Respiratory infection has been linked to poor sleep.²⁰ One study of over 22,000 people, for example, found that those who slept less than six hours per night or had a sleep disorder were more likely to suffer colds and other respiratory infections.²¹ Lack of sleep can affect immune system adversely.

During sleep, immune system releases cytokines, some of which even help promote sleep. Certain cytokines need to increase during an infection, or under stress. Sleep deprivation may decrease production of these protective cytokines. In addition, infection-fighting antibodies and cells are reduced during periods when person is deprived of ample sleep. Sleep and the circadian system are strong regulators of immunological processes.²² There is a bidirectional communication between CNS and immune system. This is mediated by shared signals though neurotransmitters, hormones and cytokines and direct innervations of the immune system by the autonomic nervous system. Differentiated immune cells with immediate effect or functions, like cytotoxic NK cells and terminally differentiated CTL, peak during the wake period. ²³ These chemicals permit an efficient and fast combat of obtrusive antigens and reparation of tissue damage. The more slowly evolving adaptive immune response is initiated during nocturnal sleep and undifferentiated or less differentiated cells like naïve and central memory T cells peak during the night.

It is during sleep, the immune system heals, repairs, and prepares for the challenges of wakeful periods. During the deep stages of NREM sleep, the body repairs and recuperates, and this deep sleep also reinforces immunological memories of previous pathogens.²³ The endocrine milieu during early sleep critically supports (a) the interaction between APC and T cells, as evidenced by an enhanced production of IL-12, (b) a shift of the Th1/Th2 cytokine balance towards Th1 cytokines and (c) an increase in Th cell proliferation and (d) probably also facilitates the migration of naïve T cells to lymph nodes.²² A feeling of lethargy when fighting an infection may be a signal from the body—which produces chemicals that act on the brain—to sleep, so that the body can recover. A single night of poor sleep can lead to a dramatic reduction in NK cells, the first line of defence against viruses and cancer cells, which negatively impacts other immune cells.

b. Nutrition

The size of the inoculum, the virulence of the exposure, the immune response of the host, and the health of the host are the four vulnerability factors of an infection. The former three ingredients are beyond the control of the host and the fourth one is within the control of the host and is very much based on the nutritional status. Food is generally viewed in terms of calories, but nutritionists have started appreciating the noncaloric micronutrients in the food, including those that are neither vitamins nor minerals, but phytochemicals (plant-chemicals) that strengthen and support normal immune function. The recent research discovery that food is not only a calorie supplier, but also adds to disease resistance and longevity benefits, has rekindled an interest in phytochemicals that support defensive and self-reparative functions. Modern diet consists of processed food mixed with additives, colouring agents, and preservatives; there is no room for unrefined vegetables in the dietary pie. Nutritional excellence can be achieved through green vegetations and friuts.

Antioxidants are vitamins, minerals and phytochemicals that support the clearance of free radicals and controlling its production in the body. Free radicals are molecules that contain an unpaired electron which causes them to be highly chemically reactive and these unstable molecules are destructive as they come in contact with structures and other molecules within the cells.²⁴ Antioxidants are the natural enemy of free radicals which creates inflammation leading to dysfunctional immune system and to premature aging. Vitamin C, E, folate, selenium, and alpha and beta-carotene, as well as various other phytochemicals have antioxidant properties. They are available in plentiful amounts in vegetables and fruits and consumption of them enhances the immune functions. The Namboothiri caste of Kerala are famous for their strict vegetarian dietary habits and disease-free life, and longevity. The nutritional status of the host is critical in permitting or prophylaxis against viral and bacterial infections as well as the nutritional deficiencies in the host allow mutation of viruses into more lethal forms. ²⁴ This is evident in the meat-eating food markets where the SARS-Cov-2 initially began to breed and mutate.

Pro-inflammatory foods can sabotage the immune system and should thus be checked in its quantity of consumption. Thirty minutes after they are consumed, carbohydrates may begin suppressing the immune system, and this effect may last for up to five hours. Foods with extreme diuretic properties also have detrimental effects on the immune system, which functions better when well hydrated. Drinking plenty of water facilitates efficient cell operation and allows the body to process food and eliminate waste. Following a diet rich in antioxidants is also essential to supporting the immune system, so eating fruits and vegetables is recommended. Fruits and vegetables are rich in antioxidants that combat free radicals—chemical by-products known to damage DNA and suppress the immune system.²⁵ Choosing healthy fats—such as the omega-3 fatty acids found in oily fish, flaxseed and krill oil—over the saturated fats found in meat and dairy products is generally recommended by health authorities. These oils may help increase the body’s production of compounds involved in regulating immunity.²⁶

Dietary supplements and medicines may be required for people who suffer from micronutrient deficiencies. Vitamin D is linked with a healthy immune system, and a large body of well-established data highlights its antiviral effects; it not only directly interferes with viral replication but also has immunomodulatory and anti-inflammatory effects.^27-29 A research study in the U.S. suggests that having low levels of vitamin D doubles the risk of death due to heart attack compared to having higher levels.³⁰ It is therefore recommended that all UK citizens take a vitamin D supplement between October and March to help maintain healthy levels during less sunny months. Such supplements are available in several forms, including capsules, sublingual sprays, and liquid drops, that are usually oil-based, as the vitamin is fat-soluble.

Nutritional excellence is in one’s own individual control. An over-boosted immune system, however, can lead to autoimmune reactions, so it is important to balance supplements and not over-boost. Moreover, vitamin D toxicity can cause hypercalcemia, which may lead to excess calcium deposits in the kidneys, lungs, or heart. A well-balanced diet is crucial in balancing immunity. An ideal immunity diet maintains caloric balance and consists of healthy fats, phytonutrients, fibre, quality carbs and diverse protein sources. Multiple micronutrients, including lutein, lycopene, folate, bioflavonoids, riboflavin, zinc, selenium, and many others have immune modulating functions.³¹ In general, the Mediterranean diet pattern has been praised as anti-inflammatory and good for fortifying immunity.³² The Mediterranean diet is associated with older age, as well as increased activity and reduced stress

c. Hygiene

Simply keeping the hands clean is one of the best ways to ward off illness, according to the Centres for Disease Control and Prevention (CDC). By washing the hands for 20 seconds using warm water and soap before preparing food or eating, as well as after coughing, sneezing, using the bathroom, or touching public surfaces can prevent the invasion of several pathogens. Hygiene hypothesis in medicine is quite often misinterpreted and misunderstood. It does not suggest that having more infections during childhood would be an overall benefit.

The hygiene hypothesis promulgates the view that early childhood exposure to particular microorganisms such as the gut flora and helminth parasites shields against allergic diseases by contributing to the maturation of the immune system. Lack of exposure is thought to lead to defects in the establishment of immune tolerance. The time period for exposure to microbes commences in utero and probably terminates at school age.

d. In Praise of Microbes and Nature

The preindustrial lifestyle that made available for the daily intake of trillions of friendly microbes is now replaced by a world of sanitisers and wet wipes. Alternative medicine takes into account the friendly bacterial flora inhabiting human body and we ought to be mindful of their role in balancing immunity. Even though humans are controlled by 25000 genes, the genes of the microbes cohabiting with ours are taken into account, it would be more than 3 million. In fact, these genes of the microbes are the immunity trainers and coaches of human immunological genes. Conventional medicine also takes into account the existence of intestinal microbes and their role in health and illness. Approximately, 95 percent of the total number of cells in the human body are constituted by these GI tract microflorae and play a prominent role in the health of our immune system. In fact, these guts bacterial flora is the meeting point of alternative medicine and modern medicine.³³

The intestinal microflora serve several useful functions that may include the supplementation of the digestive process, produce vitamins, short-chain fatty acids, protect against the overgrowth of pathogenic bacteria and yeasts, strengthen immune abilities and generate beneficial nutrients that stop weight gain. ²⁴ Pathogenic bacteria, on the other hand, produce toxic substances, become bacterial invaders, cause digestive disturbances, trigger immune system dysfunctions, and even stimulate weight gain.

Modern urban life is at a low level on microbial variety and has poor contact with helpful environmental microbes.³⁴ Asthma and allergies are found to be much less among children brought up in farm and drunk farm milk.³⁵ People living in urban areas are more susceptible to allergies and inflammatory diseases. Children exposed to outdoor microbes have more robust immunity. Obese people with 30% fewer intestinal microbes tend to gain more weight. ³⁶

People should enjoy the smell of green grasses and appreciate the healing powers of mother nature. Ecopsychology, which is the study that explores the connection between the world of nature and the world of humans, is a new branch of psychology. Studies have revealed that spending some time outdoors, in the nature, can actually reduce stress, as well as improve our overall emotions and feelings of happiness and wellbeing, raise the levels of energy, and enhance immunity. It is healthier to do exercises outdoors than indoors. A lifestyle admirably adapted to mother nature alone can guarantee robust mental and physical health.

e. Antibiotic Overuse

Research findings suggest that antibiotic abuse can result in damage to the immune system, and memory problems caused by a lack of growth in new brain cells. Overusing antibiotics, which happens when antibiotics are overprescribed or prescribed inappropriately, has many negative outcomes. In the first place there is no relief of symptoms or rationale in prescribing antibiotics for a viral rather than bacterial infection. It results in disruption of the normal, healthy flora in the digestive system, which can take nearly two years to correct and lead to other infections. Antimicrobial resistance is another established complication of overprescribing antibiotics. Antibacterial adverse effects are attributed to 25% of all drug reactions in hospital patients.³⁷

Even a single course of antibiotics has a detrimental effect on the gut flora and can result in harmful alterations in the composition and diversity of gut flora disrupting ecosystem. ³⁸ Antibiotic exposure in children have long standing impact on the health and is linked with increased risk of immune system disorders. Antibiotic induced autoimmunity has been reported. Low levels of antibiotic administration lead to fatter mice by up to 40%.³⁹

f. Physical Activity

To enjoy a good night sleep, one has to be pleasantly tired. Being active reduces stress and causes individuals to feel more energetic and alert, thereby helping the body prepare for better sleep. The main principle underlying exercise is keeping the body moving. Stress hormones are slowly released during exercise, which has a favourable effect on the immune system.⁴⁰ Physical activity can also facilitate clearing of bacteria from the pulmonary system and can alter levels of white blood cells and antibodies. It is believed that during exercise, leucocytes and antibodies move faster in the circulatory system, allowing them to detect internal threats and diseases sooner; however, there is not yet proof that infections are prevented by these changes. Bacterial growth may also be blocked by the increased body temperature during and after exercise, which may help the body fight infection in a way similar to a fever.

Keeping muscles active releases high levels of interleukin 7 into the blood, which helps to stop the thymus from shrinking. This would help production of new T cells and balance our immunity. Maintaining a healthy basal metabolic rate is crucial. Walking is the simplest but highly effective exercise. Regular walks strengthen our immune system. It improves the mood and energizes the body. Walking in green spaces could give a big mood boost Walking has no set rules and can be carried out in the busiest cities and in the sprawling countryside. Too much of exercise can become a stressor for the body and turn out to be counterproductive.

g. Immunity and Obesity

Obesity is the result of a disruption of energy balance that leads to weight gain and metabolic disturbances that cause tissue stress and dysfunction. ⁴¹Metabolic syndrome is a cluster of metabolic disorders and is rampant in the 21^st century. It results in conditions combining diabetes, hypertension, and obesity. Metabolic syndrome is also linked to several types of cancers and it has strong inflammatory underpinnings linked to dysregulated immunity.

Obesity and immunity are inversely related. It has been observed, for example, that the same amount of vaccine generates different immune responses from obese and lean people. Obesity has been identified as a modifiable risk factor of severe COVID-19, but weight loss also brings other health benefits. Having a healthy body weight is important in maintaining strong immunity because the presence of too many fat cells suppresses immunity. Obesity can depress the immune system by reducing the body’s ability to produce leucocytes, generate antibodies and locate infection sites. Persistently enlarged fat cells place a body in a constant state of inflammation, keeping the immune system permanently on the go. Maintaining the right amount of body fat is crucial to immunity and health.

h. Alcohol Impairs Immune Cells

Much remains unclear about the impact of alcohol consumption to immune system. Alcohol abuse result in diminished liver and pancreas functioning which can lead to immune system problems. Chronic alcohol abuse and pneumonia are linked. Alcohol has an immunosuppressant effect, and binge drinking is particularly detrimental. One study reports that after four shots of vodka within a 20-minute period, blood samples reveal initial ramping of the immune system followed by sluggish immune responses a few hours later. Acute and chronic alcohol use impedes cellular immune function, placing binge drinkers at greater risk for bacterial and viral infections. A multi-layered interaction between alcohol and immunity exists, and alcohol abuse has negative effects on both innate and adaptive immunity.⁴²

Drinking alcohol immoderately can cause damage to the immune system in two ways. First, it reduces the availability of nutrients, thus depriving the body of resources that strengthen immunity. Second, it can hinder the ability of white blood cells to destroy microbes. It is well recognised that excessive alcohol consumption suppresses white blood cell replication, inhibits the action of killer white cells on cancer cells and hampers macrophages’ production of tumour necrosis factors. Immune system damage increases in proportion to the quantity of alcohol consumed. While wine promoters assert that one daily glass of red wine may be helpful to maintaining health, any amount of alcohol large enough to cause intoxication is also large enough to suppress immunity.

There is a perilous myth circulating among the inner quarters of the public that consuming high-strength alcohol can kill the COVID-19 virus and it has stemmed from fear and helplessness and is totally unfounded. Consuming any alcohol poses health risks, but consuming high-strength ethyl alcohol (ethanol), particularly if it has been adulterated with methanol, can result in severe health consequences, including death. Alcohol consumption is associated with a range of communicable and noncommunicable diseases and mental health disorders, which can make a person more vulnerable to COVID-19. In particular, alcohol compromises the body’s immune system as described above and increases the risk of harmful health effects. Though there is still limited data on the link between alcohol and COVID-19, past evidence shows alcohol consumption can worsen the outcomes from other respiratory illnesses by damaging the lungs and gut and impairing the cells responsible for immune function.

i. Avoiding Substance Use

Marijuana, cocaine, heroin, and other opiates are widely used illegal drugs. Drug abuse compromises immunity, so it is imperative to stay clear of illicit drugs during a pandemic. Numerous clinical reports indicate the association between infectious diseases and the use of illegal drugs. These drugs alter not only neurophysiological and pathophysiological responses but also immunity responses. Thus, it is vital to determine the mechanisms through which drugs compromise immune responses both independently and in concert with immunosuppressive viruses.⁴³

Snorting cocaine harms mucous membranes in the nasopharynx and pulmonary areas. This increases the chance of upper respiratory infections.⁴⁴Marijuana affects several kinds of cells in the body, which can ultimately harm the immune system. Smoking marijuana reduces the body’s ability to resist infections from viruses, bacteria, fungi, and protozoa. Because of the suppressed ability of the immune system, it may also reduce the ability of an immune system to be able to destroy cancer cells. Drugs of abuse include heroin, morphine, fentanyl, opium, and prescription painkillers. While all narcotics have some effect on the immune system, injecting drugs into the veins increases the risk of viral infections like HIV and hepatitis B or C (due to sharing needles) and bacterial or fungal infections. This is especially dangerous in people whose immune systems are already compromised. Crushing and snorting narcotic drugs can also increase the risk of upper respiratory infections due to damage to the mucous membranes in the nasopharyngeal regions. Morphine and related opioids have been found to directly impact white blood cells, which can reduce the ability of the immune system to react to diseases.⁴⁵

j. Pulmonary Health

As with marijuana and crack cocaine, smoking cigarettes can lead to upper respiratory problems and a lowered immune system response to infections in the pulmonary system.⁴⁶ Studies indicate that smoking increases the risk of more severe lung disease in cases of SARS-CoV-2 infection. It has been argued that exposure to cigarette smoke increased the number of infected and apoptotic cells in the airway and that SARS-CoV-2 prevented the usual repair response to airway injury.⁴⁷ SARS-CoV-2, the causative agent of the COVID-19, infects cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor present on host cells. ACE2 is highly expressed in ciliated cells of the upper airways. Smoking is linked with both a negative progression and adverse outcomes of COVID-19.⁴⁸

Smokers touch their lips frequently, which may accidentally pass the virus to their mouths, and they tend to have existing respiratory conditions consequent to their smoking habit. These factors make them more vulnerable to viral respiratory infections and more prone to COVID-19-related complications. Indeed, smoking has been linked to a plethora of respiratory diseases and poor disease prognosis.⁴⁹ Smokers are more vulnerable to infectious diseases because smoking harms the immune system, adversely affecting how it responds to infections.⁵⁰ During the previous MERS-CoV epidemic, for example, smokers were found to have high mortality rates.⁵¹ One retrospective analysis of 78 patients in China found that smoking was correlated with greater COVID-19 severity and poorer prognosis. Though analytical studies conflict,⁵² smoking continues to be linked with higher risk.⁵³

k. Balancing Bodily Temperature

It has been recognised that an increase in body temperature by 1°C than normal would result in an instantaneous increase of immunity by 5 to 6 times. On the contrary, as soon as the body temperature drops, the activity of white blood cells will be retarded, resulting in a decrease in immunity. Low temperature is well recognised as immunosuppressive. It is an accepted fact that fever is the body’s defence mechanism that activates the immune system in response to inflammation. The immune system functions optimally at higher comfortable temperatures and becomes underactive in cold environments. This is why seasonal infectious diseases like influenza are more prevalent during lower temperatures. Warm temperature restricts viral replication through type I IFN-dependent and -independent mechanisms in vitro.⁵⁴ In addition, both humidity and temperature affect the frequency of influenza virus transmission among guinea pigs.⁵⁵ One way to warm the body is to be metabolically active while keeping a relatively high room temperature and/or wearing warm clothes. The significance of thermal balancing to maintain healthy immunity has been discussed in preceding paragraphs.

l. Destressing

Good relationships protect mental health and wellbeing. People who are more socially connected are happier, physically healthier and have longevity. One should put more time aside to connect with friends and family, learn to live in the present and switch out of work mode whenever possible. It is important to invest time on and value relationships and make them a priority, listen to others, and speak openly about feelings. People should be good listeners and concentrate on the needs of other people. Happiness is the reflection of what one does for others. People should make an effort to be surrounded by positive individuals and allow themselves to be listened and supported. The key to destressing and happiness is being honest and respecting others.

Severe anxiety suppresses the immune system and the coronavirus may thus literally feed on fear. Relaxing and focussing on the present, however, can improve mental health and counteract negative feelings. Various forms of meditation and progressive muscle relaxation techniques, for example, can help one unwind from the assault of daily stressors, and such post-work relaxation may enhance the immune system. Incorporating relaxing practices like meditation, yoga or deep breathing into a daily routine has been found to be helpful. Psychological health and immunity are causally related. The current pandemic is forcing us all to adjust to new and strange ways of life, which can adversely affect mental wellbeing.

While short-term exposure to stressors can accelerate immune defence, prolonged stress may wear down the immune system, increasing vulnerability to illness. ⁵⁶ In this way, chronic stress can be a killer. Immuno-psychiatry is a fledgling sub-speciality which deals with the immunological components of psychosis and depression.⁵⁷ The autoimmune aetiology of schizophrenia is gaining ground ^58-60 and the neurotoxic effects of cytokine storm due to COVID-19 have recently caught high attention.

Extra-physiological Immunity?

The chemical effects of allopathic medicines are a scientific reality, but their therapeutic effects are also partially due to placebo effect. Placebos are aimed at the symptomatic relief of illnesses. Disease and illness have different connotations; disease is understood scientifically in terms of pathophysiology and illness is understood phenomenologically, as a lived experience. ⁶¹ It is increasingly being recognized that what we call the ‘placebo effect’ may involve changes in brain chemistry induced by quantum bioenergy fields. That implies the placebo effect may be a quantum reality that is created by the mobilisation of quantum bioenergy fields.⁶² The placebo effect is believed to be brought about when the subjective mind produces medicinal agents and accelerates the healing process. It is estimated that up to 40 per cent of the effects of medicinal drugs may be a placebo effect. The placebo effect often seems to be associated with measurable changes in brain chemistry and there have been observed quantifiable changes in neurotransmitters, hormones, and immune regulators. ⁶³ Placebos also relate to the disposition to heal, no matter what treatment is offered, if those being treated believe the treatment is helpful. ⁶⁴ Regarding the effects of drugs, expectations appear to have a significant influence. The very existence of placebos offers an indirect proof for the existence of extrasomatic energy system and we need to incorporate their effect in the immune balancing. A quantum conceptual model of placebo is essential to understand certain hidden channels of medical sciences. The placebo component of immunity is highly significant and needs further evaluation.

Immunity is not a single entity; it is a system, and for a system to function well, it requires balance and harmony. Not everything about the immune system is known to science, and according to integrated medicine, immunity may not be confined to physiology alone, but may have non-physiological aspects as well. Numerical age and physiological age are two different things. This is particularly so if extra-physiological energy system is brought into the equation of immunity. It is true that the existence of extra-physiological systems is not scientifically well established, but they are strong hypothetical possibilities.

Studies of quantum bioenergy fields should be an integral part of the science of human physiology and homeostasis should be redefined as the state of steady internal physical and chemical conditions maintained by different regulators, including extrasomatic energy fields.⁶⁵ Humans are multidimensional or psycho-spiritual entities with several layers of energy bodies with increasing subtilty.⁶⁶ Complementary medicines work on the assumption that humans are associated with a subtle energy system, in addition to their material body. Even though such extrasomatic energy systems are not recognised in the modern medical sciences, there are energy fields that cannot be explained by the classic Maxwell–Schrodinger equation.

The material body and energy bodies are in a complementary relationship: if the material body is the container, vital energy is the content.⁶⁷ Beverly Rubik postulated that biological systems may be regarded as complex, non-linear, dynamic, self-organising systems of energy and field phenomena^68,69 Many researchers have attempted to bring the existence of extrasomatic energy fields into the arena of mainstream sciences.^70--73 If such quantum bioenergy fields really exist, they may play a major role in maintaining homeostasis in the human physiology, and it would be of great clinical interest to evaluate their role in immune system functionality, as long as they do not overrun the scientifically accepted views. To bring the concept of extra-physiological immunity into immunology, we may also have to accept the possibility of ‘nano immune cells’ and a ‘nano-level immune mechanism’.

Conclusion

The high incidence of complications among ethnic minority points toward the thermal conditioning and the role of immunogeneticsgenetics. Underactive immune responses in cooler temperature and diminished synthesis of vit D and the genetic factors linked with these anomalies might explain part of the higher incidence of COVID-19 among BAME. It is the physically and psychologically resilient people of a community who normally migrate to overseas countries. If migrants are to develop mental health problems, it would manifest within 6 months of migration, but physical health problems come about any time of their stay abroad as the weakening of immunity is a slow process. COVID-19 has a direct impact on co-existing disease processes worsening them because of the added immunity impairment. There are still missing gaps in the pervasive occurrence of this viral affliction among the BAME people. They should be mindful of the vulnerability factors and special precautionary measures should be adapted to prevent the infection.

COVID-19 appears to be a test of self-immunity. To combat COVID-19, efficient tests, novel treatments, and vaccines are the three means. An effective and safe vaccine would drastically change the pandemic situation for good. Vaccination and developing novel form of medication would take some time to become available. In such circumstances, one way of protecting from COVID-19 is by balancing one’s own immune mechanisms. It is a good thing that there is ample promotion of preventive measures of the contagion, there should be more awareness of improving personal immunity. More research works are warranted in immunology including extra-physiological immunity. Strengthening immunity is achievable for everybody if sufficient attention is paid. A safe and effective vaccine with long term immunological properties would drastically change the pandemic situation for good. Thus far, the research findings of the pandemic are inconsistent, and many dimensions of this pandemic warrant further clarification. COVID-19 will have a serious impact on virology and the neurotoxic effects of cytokine storm may be a stimulus for the growth of immuno-psychiatry.

Science is good enough to study the physical and visible, but it has obvious limitations when it comes to the unphysical and non-physical. Unphysical is undetectable only because they cannot be identified with the present-day instrumentation but can become detectable when our technology advances and their presence should not be stubbornly denied. The well-established placebo effects may point towards the existence of quantum bioenergy fields. Existence of extrasomatic energy system indirectly support the concept of extra-physiological immunity. Placebo effects are not psychological artefacts, but quantum manifestations. If extra-physiological immunity exists, it may be guarding and supervising the physiological immune system.

Introduction

Across the UK there has been a reduction in the number of children and young people (CYP) presenting acutely to hospital during the COVID-19 pandemic. This was highlighted in a recent survey of consultant paediatricians in the UK and Ireland¹. It showed that not only were fewer children being brought to emergency departments, but there were also delays in acute presentation of critical illness (such as sepsis and diabetic ketoacidosis) and reductions in referrals for cancer treatment and child protection assessments¹.

The reasons for the reduced attendance are thought to be related to the initial government messaging of Stay Home, Protect the NHS, Save Lives². However, as it became clear that not only parents, but other potential patients were not presenting even if warranted, the government adjusted the messaging to make it clear that the NHS was still open for urgent care that was not just COVID-19 related.

In CYP the cause of delayed presentations were likely to be manifold: parents following the initial governmental message; families concerned that hospitals were unsafe; the initial presumption that COVID-19 in CYP would present in the same manner as in adults potentially leading to primary care and NHS 111 pathways channelling them to domestic isolation. It may be that some delays in hospital presentations may be due to reduced referrals from primary care, and that in turn may be influenced by fewer CYP accessing their local General Practice facility. The ‘Take the Temperature’ survey which assessed the views of 1535 respondents (predominantly aged 16-25 years) found, “85% knew that they shouldn’t go to a doctor if they got the virus”³. However, it is possible that CYP and parents may not be able to make the often challenging differentiation between symptoms of COVID-19 and what may be another illness in need of medical attention.

There has been a significant increase in pressure on many aspects of the health service, including on primary care. Automated telephone messages have been used as a tool by General Practice to direct service users to the correct service or point of care for some time. As such, it is unsurprising that automated messages may be used to try to address some questions about the pandemic prior to speaking to a call handler at a practice. In addition to this, significantly limiting face to face contact with patients during the pandemic in Primary Care has been essential to prevent the potential spread of the virus and closure of services. We aimed to review the initial advice that parents and carers may be receiving from their first point of contact when telephoning their local General Practice and whether this considered CYP specifically.

Methods
All General Practices within four Clinical Commissioning Groups (CCGs) in NHS Sheffield CCG, NHS Manchester CCG, NHS Leeds CCG and NHS Birmingham and Solihull CCG were identified using the NHS website. These were chosen as they are large cities, with diverse populations.

Practices were only contacted within their standard opening hours by three of the authors, within a four-day time period (7^th July 2020 to 10^th July 2020). The data collected is shown in table 1. All practices were telephoned and identified as to whether they had the following (see table 1):

Table 1: Questions asked during data collection

Percentages, means, standard deviation, and standard error of the mean were calculated. Proportions were compared using Fisher’s Exact test to calculate statistical significance of some data.

Table 2: Reasons for exclusion from analysis

In total, 549 practices were listed under these four CCGs. 12 practices were excluded (see table 2), leaving 537 practices from which we could obtain results.

Table 3: Analysis of results from 537 GP practices

Table 3 demonstrates that of the 537 practices, 81.9% (n=440) had an automated message. When an automated message was present, the mean length was 54.1 seconds (SD = 26.9).
Of all of the practices with an automated message, 65.9% (n=290) mentioned ‘coronavirus’ or ‘COVID-19’ in their message, 34.8% (n=153) gave specific advice to stay away from the practice if the caller had symptoms of COVID-19, 27.3% (n=120) gave advice about self-isolating with COVID-19 symptoms, and 38.4% (n=169) re-directed callers to telephone NHS 111 or visit the NHS 111 website for advice on worsening symptoms. Only 1.1% (n=5) practices mentioned children specifically. Of these, two said that the advice about self-isolating also applied to children, and the other three said the following:
“…anyone with a new continuous cough or fever of 37.8 degrees centigrade or higher must self-isolate for 7 days. This includes children. Travel history is now irrelevant. Anyone with these symptoms who are well are to stay at home and do not need to ring 111 or be tested. Anyone with these symptoms who are unwell should go to NHS 111 online for advice. You must not come to the surgery…”
“…anyone with a new continuous cough and/or a high temperature should stay at home and self-isolate for the next 7 days. This includes children. All other members of your household will need to self-isolate for 14 days even if they remain asymptomatic. Do not attend the university health service, hospital, pharmacy or other NHS service in person. If you have these symptoms, use the NHS 111 online coronavirus service to find out what to do. Do not call NHS 111 unless you cannot get help online…”

“…anyone with a new continuous cough, a fever of 37.8 degrees or higher, or a loss or change to your sense of smell or taste must self-isolate for 7 days. This includes children. Anyone with these symptoms who are well must stay at home and order a COVID-19 test… Anyone with these symptoms who are unwell should go to 111 online for advice. You must not come to the surgery…”

Sheffield CCG had the fewest number of automated messages compared with all the other CCGs:

• Sheffield CCG (n=75, 70.8%) vs Leeds CCG (n=119, 88.8%) p<0.0005;
• Sheffield CCG (n=75, 70.8%) vs Manchester CCG (n=74, 81.3%) p=0.0974;
• Sheffield CCG (n=75, 70.8%) vs Birmingham and Solihull CCG (n=172, 83.5%) p=0.012.
• Sheffield CCG had the most automated messages with advice to stay away from the practice compared with the other CCGs:
• Sheffield CCG (n=44, 58.7%) vs Leeds CCG (n=34, 28.6%) p<0.0001;
• Sheffield CCG (n=44, 58.7%) vs Manchester CCG (n=26, 35.1%) p=0.0052;
• Sheffield CCG (n=44, 58.7%) vs Birmingham and Solihull CCG (n=49, 28.5%) p<0.0001.
• Manchester CCG had the fewest messages with advice to self-isolate compare with the other CCGs: Manchester CCG (n=9, 12.2%) vs Leeds CCG (n=30, 25.2%) p=0.0415;
• Manchester CCG (n=9, 12.2%) vs Sheffield CCG (n=26, 34.7%) p=0.0018;
• Manchester CCG (n=9, 12.2%) vs Birmingham and Solihull CCG (n=55, 32%) p=0.0009. See Table 4.

Table 4: Breakdown of results for individual CCGs

Automated messages were all in English (although a small number of practices provided a translation in other languages after the message) and orated by a mixture of computerised voices, doctors or staff from the practice. Many automated messages indicated a range of options for the caller to be re-directed to a different line (such as to arrange an urgent appointment or to obtain a repeat prescription) but for the purposes of this study, the key data points listed in table 2 were the only parts of the message which were recorded.

There was no statistically significant difference in mean message length between the four CCGs. Sheffield CCG 51.7 seconds (95% confidence interval 46.5 to 56.8); Leeds CCG 55.7 seconds (95% confidence interval 51.2 to 60.1); Manchester CCG 58.0 seconds (95% confidence interval 52.2 to 63.7); Birmingham and Solihull CCG 52.4 seconds (95% confidence interval 48.7 to 56.0) (p<0.05).

Discussion

This study found that very few practices specifically mentioned children in their automated messaging in relation to the current pandemic. 81.9% of the practices contacted had automated telephone messaging. Of these, 65.9% mentioned COVID-19 in their message but only 1.1% (n=5) specifically mentioned children in their message.

38.4% of practices re-directed callers to either the NHS website or NHS 111 telephone advice line. The website advice states, "Call 111 if you're worried about a baby or child under 5. If your child seems very unwell, is getting worse or you think there's something seriously wrong, call 999”⁴. There is also further advice particularly focussed upon babies and very young children on the website. This is helpful advice for parents or carers of an unwell child and it is important that it is emphasised. However, it relies upon parents and carers to make an assessment as to when something may be getting worse or is ‘seriously wrong’. Whilst this would increase the workload for primary care, it perhaps would be more beneficial for CYP, particularly those under 5 years to be triaged by a call handler at the local practice and have a much lower threshold for a telephone consultation with a clinician at the surgery or advice to attend hospital.

This study provides a timely representation of first point of care health advice which is being provided in England during the current pandemic. It seeks to look specifically at automated advice given to CYP and whether this may contribute the delays in presentation to secondary care for acutely unwell CYP which have been seen.

It is difficult to know for certain how this may be directly attributable to the reported delays in presentation of serious illness.

Practices from within only four CCGs were contacted in this study. However, this covered a sizable number of different practices, 537 in total, all of which were in large cities and towns in England. It is notable that we did not assess any advice that may have been given by those answering the telephone call. Once the automated message had been completed there may have been opportunity to provide targeted advice. Also, for the 18.1% (n=97) practices where there was no automated message, we do not know if any further advice is relayed by those answering the call. It may have been at this point when age specific advice might have been received.

To our knowledge there have been no other studies looking at the spectrum of automated messages in General Practice during the COVID-19 pandemic.

This study highlights the need for tailored and consistent advice for CYP specifically during the COVID-19 pandemic.

There is significant variation in the advice being given by different General Practices. The Royal College of General Practitioners (RCGP) states that ‘as with all patients, children should be triaged prior to any face to face consultation’ and ‘every effort should be made to avoid face to face assessment’⁵. It is very important to note that the pandemic has been an extremely challenging time for General Practice with rapid adaptations to working being made in a very short time period. There have been repeated changes in guidance which highlight the challenges faced by General Practice in providing the most up to date information. Since 18^th February 2020, patients with a travel history or suspected symptoms were advised to call NHS 111 and to not go to their local General Practice, pharmacy or hospital⁶. On 5^th March 2020, General Practitioners (GPs) were advised by NHS England to switch to a telephone-only triage system, to reduce the change of potentially infected patients attending the practice⁷. The latest NHS England Standard operating procedure for General Practice (at the time of writing; 24 June 2020, Version 3.3)⁸ offersspecific advice for GPs regarding children; “Prolonged illness and/or severe symptoms should not be attributed to COVID-19 and should be evaluated as usual”. The rapidly changing advice, coupled with large amounts of uncertainty and anxiety among staff in Primary Care may have contributed to the challenges of providing consistent, standard information for service users such as through automated messaging. For some practices, a telephone triage service was a completely novel way of working, making this large process change over a very limited time frame must have been extremely challenging.

Logistically, the ability to alter automated telephone messaging is often not straightforward and, in many cases, requires outsourcing of this to external companies. This requires an already pressured service to keep up to date with rapidly altering advice whilst arranging for a staff member to formulate a new script and then arrange for this recording to be amended. A process which would have been required to be repeated multiple times over the preceding months, due to regularly changing government messaging.

Although evidence continues to emerge, we know that COVID-19 is less likely to develop into serious illness in healthy children and adolescents compared to adults⁹.

There have been concerns regarding a serious but rare complication of COVID-19 infection in children PIMS-TS (paediatric inflammatory multisystem syndrome temporarily associated with SARS-CoV-2). A recent paper in the Lancet¹⁰ reviewing children admitted to PICUs in the UK between 1^st April 2020 and 10^th May 2020 suggested that incidence of PIMS-TS requiring intensive care was around 1.5%. However, at the time only hospitalised patients were being tested for COVID-19 in the UK, so this does not take into account the number of children who may have had COVID-19 but were not tested. As a result, it is likely to be an overestimation. Whilst this condition can be serious, the likelihood of a child progressing to PIMS-TS after developing Covid-19 remains low. The greater concern is delayed presentation of other serious illness.

As other publications have suggested, there is a greater risk that children may delay in presenting to hospital or be delayed in being referred to secondary care for important investigations due to the widespread ‘stay away’ advice, seen in both the UK¹¹ and in Europe¹².

We suggest that adapting the messaging that parents or carers receive when they first contact their GP to include CYP would be possible and may reduce the number of unwell CYP who have delays in receiving medical care. It would also be important to aim to have consistent messaging across different practices, advice which perhaps should be standardised at a national level. This could greatly assist those working in Primary Care to be able to provide accurate and up to date messaging for their patients. Any adaptations required could be made by individual CCGs to take account of local differences.

Increased amounts of wider public health messaging directed towards encouraging parents and carers to seek medical advice if they are worried about their child, despite the pandemic, are paramount to aid in getting this vital message to those caring for CYP. It is important that additionally where appropriate, this advice is also available in languages other than English.

This study does not prove a direct link between the advice provided at the first point of contact in Primary Care and the delays in CYP presenting to hospital with serious illness. We do not know what influence the advice on automated messages has over CYP and their parents in their decision making about accessing care. Future research should seek to answer this question specifically, perhaps involving directly interviewing CYP and their parents or carers.

BACKGROUND

General Practice is the first point of contact for most patients who ask for professional medical advice in the United Kingdom (UK) National Health Service (NHS)¹. Primary care makes up around 90% of all NHS activity and, as a result of increasing populations overtaking the number of newly qualified General Practitioners (GPs), the burden of tasks from patients has increased exponentially. GPs characterise their workload as “unmanageable” or “unsustainable” and 93% have reported that patient care has been subsequently affected.¹ Funding into General Practice from the NHS expenditure has fallen by almost 20% which has halted the expansion of new practices and recruitment of substantial GPs. The growth of new GPs increased by 0.2% only, between 2009-2014, and this has indirectly pressured existing doctors to care for more patients. This is reducing job morale as well as patients’ satisfaction with services. The main causes of increased workload are increased administrative load, high patient expectations and increased risk of litigation.²

Four years ago, there were four doctors at our practice. As time passed, one doctor emigrated, another doctor passed away and the third had retired. This has left two doctors at the practice at this current time. The practice currently employs locum GPs to cover the pressures of daily patient appointments as, according to new studies, there are now on average an astonishing 2,100 registered patients per GP.³ The loss of permanent doctors in this practice may be due to the location of the GP surgery. Barnsley, according to uSwitch in 2015, was ranked 122 out of 138 local areas across the UK based on 26 factors such as household income, life expectancy, hours of sunshine and the cost of essential goods including food bills, fuel costs and energy bills.⁴ Adding to the lack of permanent GPs, recruitment into General Practice as a specialty has been scarce. Studies have shown that medical graduates chose medical careers that they considered as more stimulating and interesting. One study mentions that medical students are attracted to technical or biomedical forms of medical practice, as opposed to a holistic view of medicine such as that of General Practice.⁵

Non-permanent GPs in the practice are keen on taking on flexible working hours, which meant the permanent doctors are left with a majority of the work including all of the on-call tasks. These tasks include dealing with patient requests that come through to the receptionist such as booking appointments, patient referrals, prescribing medication and issuing sick notes. We aim to identify the prevalence of specific tasks and evaluate ways to reduce the tasks performed by the doctor. We intend to analyse the number of prescribed acute medication that can be placed on a repeat or variable repeat prescription.

METHODS

Data was collected from a single NHS England GP Centre. This centre utilizes the Egton Medical Information Systems (EMIS) web platform for recording consultations, tracking investigation results, prescribing medications, and communicating within the practice.⁶ Using EMIS, we collected all the tasks of the on-call doctor for a single month. In this month, there were no school or public holidays. These tasks are sent to the on-call doctor from the receptionist who receives them directly from patients. At this centre, all tasks from 2pm on a particular day form part of the following days’ workload. Therefore, the tasks of each day were recorded from 2pm the previous day until 2pm that day.

We separated tasks by allocating them into 1 of 5 categories: medication request; request for appointment, advice, or test results; request for a referral; request for sick note; and other which included all miscellaneous tasks.

RESULTS

Total task distribution

A total of 969 tasks were performed in the month. The proportion of tasks over 4 weeks was as follows: week 1 had 26.7% (n=259) of the total tasks; week 2 had 25.6% (n=248); week 3 had 25.1% (n=243); and week 4 had 22.5% (n=218).

Figure 1: Total number (n) of tasks per day across each week for the four weeks of the month

Further to this, regarding the proportion of tasks over the days of the week: Monday had 23.1% (n=224) of the total tasks; Tuesday had 19.8% (n=192); Wednesday had 17.0% (n=165); Thursday had 18.0% (n=174); and Friday had 22.1% (n=214). Figures 1 and 2 show the number and percentage of task distribution respectively across the days and weeks for the month.

Figure 2: Percentage (%) of task distribution per day-of-the-week across each week for the four weeks of the month.

Type of task

The tasks for the month were separated unevenly across the five categories: medication tasks were 50.9% (n=493) of the total tasks; requests for appointments, results and advice were 35.9% (n=348) of the total tasks; referrals were 2.4% (n=24) of the total tasks; sick note were 4.6% (n=45) of the total tasks; and other tasks made up the remaining 6.1% (n=59) of the month. Figure 3 shows the distribution of tasks for the month.

Figure 3: Distribution of tasks/requests according to task-type for the month (total tasks n=969).

We recorded the type of tasks completed per week. Figure 4 shows the distribution of tasks according to task-type for weeks 1, 2, 3, and 4, respectively. Of the total 260 tasks recorded for week 1, 55.8% (n=145) were tasks involving medication; followed by 29.2% (n=76) request for appointments, results and advice; referrals made up 4.2% (n=11); sick notes were 7.3% (n=19); and miscellaneous tasks came to 3.5% (n=9).

The second week had a total of 248 tasks. Of these, 51.6% (n=128) were medication tasks; 34.7% (n=86) were requests for appointments, results and advice; referrals made up 2.4% (n=6); sick notes made up 2.8% (n=7); and miscellaneous tasks were 8.5% (n=21).

The third week had a total of 243 tasks. Of these, 44.4% (n=108) were medication tasks; 45.7% (n=111) were requests for appointments, results and advice; referrals made up 1.2% (n=3); sick notes made up 3.3% (n=8); and miscellaneous tasks were 5.3% (n=13).

The fourth week had a total of 218 tasks. Of these, 51.4% (n=112) were medication tasks; 34.4% (n=75) were requests for appointments, results and advice; referrals made up 2.8% (n=6); sick notes made up 5.0% (n=11); and miscellaneous tasks were 6.4% (n=14).

Figure 4: Comparison of distribution of tasks/requests according to task-type for week 1, 2, 3, and 4, respectively.

Medication tasks

Focusing on the medication category, we had a look at whether medication requests sent to the on-call doctor were drug prescriptions that should have been on a repeat/variable repeat prescription rather than on acute. Out of a total 493 medication tasks for the month, 49.1% (n=242) medication requests could have been on repeat prescription rather than being acutely prescribed. A further analysis of this data yielded comparable findings per week. In the first week, there were 145 total medication tasks, about 50.3% (n=73) of drug prescriptions could have been on repeat. In the second week, out of 128 medications, 46.1% (n=59) of medication could have been on a repeat or variable repeat prescription. In the third week, out of 108 medications, 39.8% (n=43) of drug prescriptions could have been on a repeat or variable repeat prescription. In the fourth week, out of 112 medications, 59.8% (n=67) could have been on a variable repeat or repeat prescription. Table 1 represents the total number of medication tasks that could have been on repeat or variable repeat prescription per day. Figure 5 represents the percentage of medication tasks that were on acute prescription but could have been on repeat or variable repeat prescription across each week.

Table 1: Total medication tasks that could have been on repeat or variable repeat prescription, per day across each week for the four weeks of the month.

Figure 5: Percentage (%) of medication tasks that could have been on repeat or variable repeat prescription, across each week for the four weeks of the month.

DISCUSSION

SUMMARY

The total number of tasks did not differ significantly day-to-day: each day per week (Monday-Friday) held about 15-25% of the total weeks’ tasks. The medication requests contributed to the majority of the total tasks (50.9%); followed by requests for appointments, results and advice (35.9%). Upon further analysis of the medication category, 10-25 medication tasks per day could have been avoided by having certain drugs on repeat prescription rather than being acutely prescribed. Taking into account that a GP would typically spend 2 minutes per task, this could save 20-50 minutes per day, which amount to 100-250 minutes per week, and 400-1000 minutes or 6.5-16 hours per month.

The drug prescriptions that we thought should have been on repeat or variable repeat prescription, rather than on acute prescription, included requests for drugs that patients typically take long-term. This included Proton Pump Inhibitors (PPIs) such as Omeprazole, statins such as Simvastatin, and Angiotensin Converting Enzyme Inhibitors (ACEIs) such as Ramipril. These are for chronic conditions such as gastric reflux, hypercholesterolemia, and hypertension, respectively. Other drugs that we considered would be more feasible if put on repeat or variable repeat prescription were those for palliative patients in care homes that require a constant need for laxatives such as Senna or Lactulose, or drugs such as Paracetamol. These are for constipation or pain management, respectively.

The medication requests that could not have been on repeat or variable repeat prior to the request being sent were drugs that were required acutely, such as for short-lived infection, transient pain relief, changing of drug doses, and prescribing of alternative drugs due to a possible manufacturing problem or unavailability from the pharmacy. These are tasks that we deem necessary to be sent to the GP so that drug doses are changed based on clinical judgement, and not merely on a request sent to the receptionist. This upholds a standard of drug-control and patient safety within the practice.

STRENGTHS & LIMITATIONS

This retrospective study provides an in-depth analysis of the on-call doctors’ day-to-day tasks in terms of the nature and number of tasks. This is a study involving a large number of tasks collected from a month in a single GP surgery which has produced significant results. As non-GPs collected all the data, including data in the medication category, this eliminated bias in reporting acute medication that could have been prescribed as repeat or variable repeat medication. Limitations include the sample size being considered as a relatively small number which cannot be representative of all on-call GPs’ tasks in the rest of England. In addition, this study took place in the month of September and the tasks can be distinctly different when looking into other months.

COMPARISON WITH EXISTING LITERATURE

To date, the existing literature that looks at GP tasks from this perspective is limited. Most studies look at the receptionists’ role in handling patient requests or focus on scrutinizing the technology that GPs rely on to issue repeat or variable repeat prescriptions.

Our study included the number of tasks completed in a single month as well the stratification of tasks done within the month. We separated our results week per week to see if there were any differences between them. In 2014, a quantitative analysis of incoming calls into three GP surgeries described basic numbers of calls and type of patient enquiries that came into the practice. They had received a total of 2,780 calls and found that the most dominant type of request was making a doctor’s appointment. The main finding in the study is that it identifies an aspect of non-effective communication in GP receptionists’ encounters with patients. It describes how some receptionists failed to meet the initial requests of the patient by directing the telephone call forward or even closing calls prematurely before understanding the problem. This increased ‘patient burden’ and lead to lower patient satisfaction score when recorded. Effective receptionists understood and summarized the patients’ requests as well as making alternative actions to help the patients enquiry.⁷

Repeat prescriptions are defined as those that are printed by a practice computer from its repeat prescribing program⁸. In the UK, repeat prescriptions account for up to three quarters of all drugs prescribed, and four fifths of drug costs in General Practice.^9,10 Repeat prescriptions are mostly done as a technology-supported practice that requires collaboration between clinical and administrative staff to ensure patient safety.¹¹ Two conflicting opinions exist around repeat prescribing: the first is that the increased automation aids in improving safety; the second is that the process as a whole may be weakened if assumptions built into the technology do not take full account of the nature of healthcare work such as real life demands like time, space, and resource constraints.^11,12 It is important that the GPs at our practice are aware of the risks involved in potentially putting more drugs onto repeat prescription, and consequently monitor this closely.

IMPLICATIONS FOR RESEARCH AND/OR PRACTICE

The findings collected in our study demonstrate the increasingly demanding role of the on-call GP outside of consultation hours. According to recent surveys, the GP occupation has had its lowest job satisfaction since 2001 because of a higher workload which indirectly lowers quality of patient care and increases negative patient experiences.^13,14 This should be taken with paramount importance, as this can cause harm to both patients and GPs. As results have described the huge number of tasks, it is important to find a way to avoid unnecessary tasks telephoned into the GP surgery. The results of our study were presented to all of the staff in the practice and the underlying message was well received. Medications that are prescribed by the doctors are double checked by the Clinical Commissioning Group pharmacist in the practice to ensure that drugs are safely given to patients.

CONCLUSION

As the funding formula has changed in the last decade, the government budget into the NHS primary care has decreased more than in secondary care even with the ever-growing pressures on primary care services.¹³ Some strategies, such as telephone triage, have been introduced at the practice to reduce workload crisis. However recent evidence has shown this is not effective.¹⁵ In 2015, the primary care workforce commission laid out recommendations to restructure primary care services as the current model for primary care was under doubt. The underlying message in the report was that continuity of care was important for the majority of GPs - the GPs understood patients better when they had been under their care for many years.¹⁶ With this, extra tasks can be avoided if GPs know their patients well. At a glance of primary care, from literature and our findings, it seems that General Practice may follow an unsustainable path. The pressures of workload include increasing patient lists, higher public expectations and growing bureaucracy.¹⁷ Our data collection has proven that there are a lot of tasks to be done in a month by an on-call doctor, however the amount of time that could be saved by prescribing repeat or variable repeat rather than acute medication can save significant time. From our positive results in the medication task section, we hope this can inspire further research into other areas of the GP surgery that can help optimize the time of the doctors. Furthermore, we would like to repeat our retrospective study in one year’s time with the suggestion implemented (appropriate acute medications changed to repeat or variable repeat prescriptions) over a longer period of time. With limitations corrected for, we want to re-analyse the number and type of tasks completed to determine whether this has truly optimized the time of the overworked on-call doctor.

Introduction

Since 2005, there has been an increase of 10% in hospital admissions with acquired brain injury (ABI), with 348,453 United Kingdom (UK) admissions in 2016-17.¹ With improvements to both medical and surgical management, a higher proportion of patients survive to hospital discharge, resulting in more people with complex physical and cognitive disabilities reaching the community.^2,3

Prolonged disorders of consciousness (PDOC) can occur following ABI. This can vary from coma, to vegetative state (VS), and minimally conscious state (MCS). Following acute stabilisation, the treating team must provide the correct diagnosis, prognosis, and management. Ethical and legal issues, such as best interests decision-making (considering patient wishes, advanced decisions, and best possible quality of life), deciding when appropriate to provide end-of-life care, and understanding the legal framework around these issues can further complicate the process.

Whilst there is currently no national registry for patients with PDOC, information taken from patients in nursing homes in the UK give an estimated 4000 – 16000 patients in VS, and up to three times this many in MCS.⁴

Early and ongoing assessment of the patient is vital, as is good communication with those close to the patient, and an understanding of the legal requirements of the treating clinician. These are likely to present even more of a challenge to General Practitioners (GP) in the community who are managing these patients as part of their larger responsibilities.

This review article summarises guidance from the Royal College of Physicians (RCP) and British Medical Association (BMA), in conjunction with our own clinical experience, to improve understanding surrounding the assessment, long term management, and the ethical and legal issues in patients with PDOC, aiming to improve the confidence of clinicians managing these patients.^5,6

Identifying Patients

Consciousness requires a combination of wakefulness and awareness (self and environment). Patients with significant deficits in either of these can be said to have a disorder of consciousness. Various brain injuries can result in disorders of consciousness (see Table 1).

Table 1: Aetiology of acquired brain injury.⁵

This article focuses on acute causes of PDOC rather than those with primary neurodegenerative conditions, as they present separate clinical entities with different issues affecting prognosis and management choices.

Disorders of consciousness, like a sliding scale, vary from coma, to VS, and MCS:

• Coma - unrousable unresponsiveness. Patients cannot be roused, lack a sleep-wake cycle, exhibit no purposeful movement, and do not respond to stimuli.
• VS - wakefulness but not awareness. Patients have a sleep-wake cycle and open their eyes spontaneously, but lack awareness of self or their environment. These patients can exhibit spontaneous and reflexive movements, and external stimuli can produce arousal responses.
• MCS - wakefulness but reduced or inconsistent awareness. Patients have a sleep-wake cycle and demonstrate reproducible but inconsistent awareness of self, and ability to interact with others and their environment.

Diagnosis

As per RCP guidance 2020, patients with impaired consciousness for over 4 weeks are deemed to have PDOC.⁵ It is first important to differentiate possible VS / MCS from other conditions:⁵

• Abnormalities on electroencephalography (EEG) can aid diagnosis of coma. These patients tend to progress to VS or death within weeks, so assessments of consciousness are not appropriate during this period.
• Patients with locked-in syndrome have wakefulness and awareness, but paralysis of the limbs and majority of facial musculature, preventing communication by these means. EEG in locked-in syndrome is usually normal, and patients may be able to communicate using eye movements.
• Patients with brainstem death have loss of all brainstem reflexes and respiratory effort, and organ survival is only temporarily achieved with life support machines.

Once ‘mimic’ conditions are ruled out, making a diagnosis of VS or MCS in patients with a suspected disorder of consciousness follows a 3-step process with input of clinicians trained in the management of PDOC:

1. Establishing a cause

This can be straightforward in some cases, such as those with direct trauma to the brain, or acquired brain infections or inflammation causing structural damage to the brain. In other cases this can be more difficult, and it may not possible to reach an exact diagnosis. The treating clinician must establish that the patient’s current condition is due to a brain injury, and take reasonable steps to determine the cause.

2. Reversible causes should be excluded

This includes reviewing medications to stop sedative medications whenever possible, blood tests to look for infection or metabolic / electrolyte abnormalities, up-to-date imaging to rule out new onset hydrocephalus, or performing an EEG to rule out subclinical seizures needing antiepileptic medication. This step also includes establishing that neurological pathways are intact, so that any assessment of consciousness provides an accurate reflection of the patient’s condition. Briefly, this involves examination and investigations to confirm that sensory, visual, auditory, and motor pathways are intact.

3. Structured assessment

There are several tools available which can confirm the diagnosis of VS or MCS. All of these require a trained assessor and an appropriate environment. These tools provide a structured method of assessing the patient to:

• Observe spontaneous behaviours.
• Observe the patient’s reaction to stimuli from different sensory modalities.
• Document the findings of family / friends / members of the healthcare team following their interactions with the patient.

Tools available include the Wessex Head Injury Matrix (WHIM), the JFK Coma Recovery Scale-Revised (CRS-R), and the Sensory Modality Assessment and Rehabilitation Technique (SMART), amongst others. As per RCP guidance, the CRS-R should be the primary assessment tool, and WHIM or SMART can be used to provide additional information. Furthermore, assessments need to be performed on at least 10 occasions, at several different times of the day, and over the course of a 2-3 week period.^5,7-9

The 2020 RCP guidance also addresses how to manage patients that do not present through the acute hospital pathway.⁵ In these ‘late assessment’ cases, formal assessment is still required to establish their level of consciousness and guide management. These patients should be referred to an experienced PDOC assessor to establish the cause of PDOC, rule out reversible causes, and arrange formal evaluation. This should ideally be achieved by outreach assessments, but if this is not possible, structured interviews should be held with family and care staff to complete the CRS-R. If these measures do not provide a definite diagnosis, admission to a PDOC centre can be considered.^5,8

Vegetative State & Minimally Conscious State

Patients in VS are unable to interact with their surroundings or those around them (no voluntary behaviours / communication / purposeful movements), and show no evidence of awareness of self. The patient may demonstrate reflexive behaviour (such as increased heart rate or startle response to noise), or spontaneous, purposeless movements (such as eye movements, teeth grinding, or limb movements). These behaviours can be misleading, which is why an objective and structured assessment method is vital.

Patients in MCS have some evidence of awareness of self or their environment, on a reproducible but inconsistent basis. Patients demonstrate behaviours such as: following simple commands, verbalisation, and purposeful behaviour MCS which is further classified based on the level of responsiveness:

• MCS-minus - less complex behaviours such as orientation to noxious stimuli, or purposeful eye movements.
• MCS-plus - more complex behaviours such as following instructions or interacting with objects.

Prognosis depends on cause, time since brain injury, and the trajectory of improvement (better prognosis for those who quickly progressed from VS to MCS). Those with traumatic brain injury are more likely to regain awareness and have a longer window for potential recovery. The majority of VS patients that regain consciousness tend do so within 12 months in traumatic cases, and 3 months in non-traumatic cases. The majority of MCS patients that regain consciousness do so within 2 years post injury, although others can emerge at up to 4 years. Whilst these are the expected outcomes, there are, however, rare case reports of patients emerging later than this.

VS / MCS-minus are classed as ‘continuing’ at >4 weeks post brain injury, and ‘chronic’ at >3 months for non-traumatic cases, or >12 months in traumatic cases. MCS-plus is classed as ‘continuing’ at >4 weeks post brain injury, and ‘chronic’ at >9 months for non-traumatic cases, or >18 months in traumatic cases. Chronic VS / MCS can be classed as ‘permanent’ when there has been no further change in trajectory of serial CRS-R for 6 months. In permanent PDOC it is predicted that consciousness is highly improbable to recover. It is important to remember these time frames, and their implications during discussions with family, when making best interests decisions and planning further assessments of consciousness.^5,10,11

With the longer time period for potential emergence, and improved survival rate compared to VS, GPs are more likely to come across these patients in the community. Figure 1 outlines the key time points for assessment of VS and MCS.¹²

Figure 1: Timeline for assessment of VS & MCS.⁵

Emergence

A patient is considered to have ‘emerged’ from PDOC if they are able to consistently demonstrate awareness of self and surroundings. The RCP advise that patients who have emerged are able to do at least one of the following:⁵

• Functional interactive communication (accurate yes/no responses to 6/6 basic questions on 2 consecutive evaluations).
• Functional use of objects (intelligent use of ≥2 objects on 2 consecutive evaluations).
• Consistent discriminatory choice-making (correct identification between 2 pictures, 6/6 times, on 2 consecutive evaluations).

Specialist Involvement

Early specialist input from a neurological rehabilitation team is recommended. The Royal College of Physicians Guideline Development Group advise that those with an ongoing disorder of consciousness at 4 days (Glasgow Coma Scale ≤10/15) should be referred for assessment, and advice regarding neurological disability and prevention of complications.^5,13 At 2 weeks the patient should be referred for specialist neurological evaluation to identify the cause of the disorder of consciousness, assess the primary neurological pathways, and advise on further investigations.

Patients with ongoing disorder of consciousness at 4 weeks should have regular input from a specialist neurological rehabilitation team, led by a consultant in Rehabilitation Medicine. Once stable the patient should ideally be transferred to a specialist neurorehabilitation unit for multidisciplinary care, objective assessment of level of consciousness, formal best interests decision-making, and discharge planning.

Following this initial period, the patient should be placed in a unit away from the acute setting, where they can be monitored until it is evident that they are likely to remain in VS / MCS. These ‘slow-stream’ rehabilitation units, are designed to deliver care to patients with complex neurological disability, and provide appropriate maintenance therapy to manage physical disability. Medical input is usually provided by the GP surgery covering the area, although units should also have access to rehabilitation medicine physicians with experience in managing PDOC.

If it is agreed that a patient has permanent VS / MCS, then longer-term of care can be provided in a nursing home or, if appropriate, in the patient’s own home. A skilled assessor should review the patient yearly, with formal assessment of consciousness until either the patient emerges or dies.

Medicolegal & Ethical Issues

Capacity Assessments

By definition a person in PDOC lacks capacity to make decisions about medical treatment. The Mental Capacity Act 2005 requires this to be formally documented in the medical notes. A Deprivation of Liberty Safeguard should be put in place during hospital admission or nursing / residential home stay, providing that restraint and restrictions are in the patient’s best interests.¹⁴

Identifying Advance Decisions

The team providing care need to identify as early as possible whether the patient has a valid and relevant Advance Decision, Health and Welfare Lasting Power of Attorney, or Court-appointed Welfare Deputy. If one of these is in place, the team need to request to see the relevant documentation to understand what exactly it entails.

Best Interests Meetings

All medical treatment provided must be in the patient’s best interests. In the UK, the treating clinician must by law identify those people close to the patient that can provide insight into the patient’s beliefs / previous expressed wishes / likely wishes, and take part in best interests meetings. If there is nobody to fulfil this role then an Independent Mental Capacity Advocate must be appointed. An initial best interests meeting should be held to discuss the diagnosis, likely prognosis, and to plan treatment. Further meetings should be held at planned regular intervals, for major medical decisions, and following repeat assessments to decide future management, discharge planning, and ceilings of care.

Ceiling of Care Discussions:

Many relatives may not feel comfortable bringing up these topics themselves, so it is advisable to make the discussion part of a routine review as standard for PDOC patients.

In patients with PDOC, cardiopulmonary resuscitation (CPR) has a very low success rate, and will likely result in further brain injury due to hypoxia. For the majority of patients where emergence is not expected, or if it is felt that the patient would not accept their level of quality of life, CPR could be considered to be futile. This is because CPR would not provide a perceivable benefit to the patient, but would carry significant risks of harm (worsening brain injury, injury related to the CPR itself, undignified end of life). Decisions regarding ceiling of care or appropriateness of resuscitation should either follow the instructions set out in existing advanced directives, or be discussed together with the treating multidisciplinary team (MDT). It is highly advisable to involve close family / friends in discussions, but ultimately it is a medical decision.

For similar reasons, it should be considered whether hospital admission for treatment of acute deterioration is in the patient’s best interests. For example in a patient with permanent VS, treating an acute chest infection may improve their lungs, but will not improve the patient as a whole in a way that can be perceived and appreciated by that patient, so may be considered futile. Additionally, it may be considered appropriate to stop medications not aimed at providing comfort, or stop performing observations and investigations. As with all major medical decisions, this should be discussed within the MDT and with those close to the patient. Although patients with PDOC have absent / reduced awareness, care should be taken to maximise patient comfort, and if appropriate consider input from the palliative care team.

Decisions relating to withdrawing clinically assisted nutrition and hydration (CANH) have previously been managed differently than withdrawal of life-sustaining treatment. Until recently, the decision to withdraw CANH could not be made without referring to the Court of Protection (COP). More recent guidance published by the BMA advises that in PDOC this is not always necessary. The treating team should first establish whether there are any valid and relevant advance directives / health and welfare attorney with relevant power, and then follow a best interests decision-making process. If all parties are agreed that withdrawal of CANH is in the patient’s best interests, then a second opinion should be obtained (from an independent, expert PDOC physician); if they also agree, then CANH can be withdrawn. If there is any doubt or disagreement about the decision, then an application to the COP is required. Now in the UK, it is essential to have best interests meetings to decide whether provision or continuation of CANH is of benefit to the patient, rather than deciding whether to withdraw it. If CANH is determined to not be of overall benefit to the patient, then it should not be continued. Prior to the withdrawal of CANH, an appropriate end-of-life care plan should be agreed and be ready to put in place.⁶

Conclusion

Disorders of consciousness can occur following brain injury, and vary from coma to MCS. If the disorder of consciousness continues for 4 weeks, it is described as a PDOC. Diagnosis requires structured assessment by trained clinicians, once the patient is medically optimised and reversible causes are excluded. Ongoing assessment is crucial to monitor recovery, guide prognosis, and establish when the disorder is permanent.

There are many ethical and medicolegal issues involved in managing patients with PDOC, which are mainly centred on the patient’s loss of mental capacity to make decisions. The cost implications of providing care as outlined in these guidelines can be quite significant. This article reflects our experience working within the National Health Service (NHS) within the UK, which provides free healthcare to all at the point of delivery. Therefore the costing is less relevant to the patients, although this does need to be considered when commissioning services. In other private healthcare settings, costs may vary widely based on hospital and wider multidisciplinary team costs, and this may need to be taken into account when commissioning services. Also, we appreciate that in other countries there are likely to be different laws surrounding PDOC, and varying views regarding the ethical decisions discussed.

Currently, these guidelines are based on expert opinion from the Royal College of Physicians Guideline Development Group. In future, management of patients with PDOC could be improved with the establishment of a national registry, further studies into PDOC, and better integration with community services. Furthermore, an improved education about PDOC and the issues surrounding it, as we have aimed to outline in this article, will help physicians understand their responsibilities and provide the best possible patient care.

Introduction

The Royal College of Psychiatrists and NICE Guidelines both stress the importance of carrying out physical examination on psychiatric in-patients due to their high level of physical health issues. Carrying out and carefully documenting these physical examinations at the time of admission allows physical health issues to be appropriately taken into account when creating management and medication plans and, in more severe cases, to allow diversion for medical treatment if that is required or the underlying cause of the presentation.

Monitoring physical health of patients in psychiatric settings is vital and is recommended by NICE in its guidelines; documentation of physical health assessment carried out at the right place is also imperative. According to Louth/Meath Mental Health Services Admission Policy, 2016, all psychiatric patients admitted should have their Physical Examination completed and recorded on Physical Examination Proforma.

Psychotropic medications can effect on physical health of psychiatric patients¹. Patients with medical co-morbidities are more at risk from psychotropic medications compare to normal healthy population². In addition, depression is considered as an independent risk factor for cardiac events in patients with coronary artery disease³. Adding that, depression may also possibly increase the risk of cardiovascular disease in population without medical co-morbidities. Hence, psychotropic medications are carefully chosen for treatment of individual patients to avoid any adverse events¹. Depression is not the only risk factor for medical co-morbidities; other psychiatric problems also make patients vulnerable for physical health issues¹. Moreover, prevalence of medical problems is relatively high in psychiatric patients compared to cohorts without mental health disorders⁴. The risk of medical co-morbidities do not always increase after prescribing psychotropic medications; the risk of cardiovascular disease also increases for patients suffering from anxiety and not necessarily using medications⁵.

Psychiatric patients receiving psychotropic medications should have their physical health monitored regularly as recommended by NICE⁶.

Methods

The audit cycle was completed in St Brigid’s Complex, Ardee. The audit cycle comprised initial audit (phase 1), implementing changes following recommendations and re-audit to compare results with initial audit. All patients in Unit 1, which is an acute admission ward, were included for the audit and re-audit. Patients admitted in another ward, which is a long stay ward, were excluded in the audit cycle. The rationale for not including patients admitted in long stay ward was that these cohorts of patients are already well established on psychotropic medications and their physical health is regularly monitored. Data collection was carried out from physical health proforma completed upon admission and filed in notes. No patient identifiable data was collected during the audit cycle.

During phase1, a review of the notes of all in-patients on a specific day in Unit 1, St Brigid’s Complex, Ardee was carried out. Data was collected from physical health proforma of each patient. This data was then entered in Xl-spread sheet for the analysis purpose. Results were analysed and feedback obtained from non-consultant hospital doctors. The findings were presented during local teaching to both the consultant and NCHD bodies and means of improving compliance were discussed openly. These discussions led to a redesign of the proforma to make it shorter and simpler to complete. This proforma was then attached to an assessment booklet, whereas physical health proforma was not part of an assessment booklet. A re-audit was carried out during a single day on all in-patients in Unit 1 several months after the first phase of the audit. In-patients who remained in Unit 1 since the initial phase of the audit were excluded from the re-audit.

Results

The results of initial audit demonstrated only 50% (10/20) compliance with physical health proforma. Furthermore, in phase 1 the proformas were only partially completed with elements of the physical exam documented on the proforma. In addition, other components were documented elsewhere in the admission notes and many elements omitted altogether. Only 15% (3/20) of the proformas contained a complete, documented physical examination.

One of the sections on proforma that lacked information significantly was information about patient’s current circumstances. On the other hand, demographic details were recorded for only 50% of patients. However, admitting doctor’s details were recorded on 35% (7/20) of proformas, the details of professional carrying out physical information was also not available on large number (19/20) of proformas.

Table 1:

Data analysis of the re-audit shows that 80% (16/20) of the proformas were been completed. In overall, there was a huge improvement seen in the results of the re- audit and doctor’s details performing physical health was recorded on 75% of the proformas. Adding that, general examination section of the proforma demonstrated huge compliance of 80% along with Cardiovascular and Respiratory system.

Table 2:

Discussion

A total of 20 patients in each phase of the audit were included for data analysis. The number of patients included may seem small for a research study with a different design; however, quantitative number is not taken into account with this particular design used. On the other hand, number of patients admitted in any acute ward is similar.

During data collected, it was apparent that physical examination findings were recorded in the notes instead and proforma was not used for some of patients, which is evident through results. Even though physical examination may have been carried out, it was not possible to include in data analysis and results due to the study design.

The results of first phase demonstrated poor compliance with physical health proforma despite carrying out physical examinations and findings been recorded elsewhere in admission notes. It is an arguable fact that regardless of physical health proforma been filled, physical examination of patients are been carried out as per local and NICE guidelines. However, physical examinations documented elsewhere in the admission notes makes it difficult to locate; hence, a proforma is completed upon admission as a pre agreed standard procedure.

Once the results of initial audit were analysed, these results were presented in the local academic session to all the NCHDs and Consultant Psychiatrists. While all involved agreed the importance of carrying out physical examination on all patients upon admission; the design and complex nature of the initial proforma made very difficult for NCHDs to complete it. Adding that, some of the information, such as demographic details and personal information, was also repeated making it duplicate that had been recorded elsewhere in the notes. The physical health proforma was then redesigned and simplified to complete. Unnecessary and duplicate information was omitted in the new proforma and was attached with the initial psychiatric assessment booklet. The new physical health proforma was then implemented in the service after discussions with fellow NCHDs, Consultants and management.

Second phase of the audit cycle was conducted after number of months and redesigned physical health proforma been in circulation for some time. Data was again collected as per study design and methods and entered for analysis. These results demonstrated a huge improvement in compliance with physical health proforma after the change of practice. Although compliance with proforma has improved significantly, some gaps were noted to reach the desired outcome of 100% in practice. Case notes were studied to understand the reasons for not completing physical health proformas. Several themes emerged through case note reviews and one of the reasons was assumed that patient was transferred from medical ward of General Hospital after been medically cleared. Time and mode of admission also resulted in physical health proforma not been completed.

Conclusion

While all involved agreed that carrying out physical examination on all admissions was advisable; the length and complexity of the initial proforma contributed to poor completion rates by NCHDs. A combination of teaching to underline its importance and a redesign focused on usability and speed led to significantly increased completion of the proforma with attendant benefits for patient assessment and treatment.

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disease. It is associated with loss of dopamine leading to motor disorders ¹. However, non-motor symptoms such as anxiety, stress, and depression as well as cognitive impairment are also abundant among patients ². It has been hypothesized that non-motor symptoms can affect the quality of life in PD patients ³. The current therapeutic approach relies on dopamine substitution, which has no curative effect and does not improve non-motor symptoms. Studies have shown that meditation and other relaxation techniques can provide relief in non-motor symptoms. Mindfulness-based stress reduction (MBSR) is a technique used for improving stress-related symptoms in long-term conditions such as stroke, cancer, and PD ^4-6. It involves focused attention, open monitoring, and self-awareness of body movements in a non-judgemental state in the present moment. Studies have shown that mindfulness improves brain plasticity in some areas of interest. The areas of plasticity are involved in emotional regulation and processing ^{7, 8}. Thus, we hypothesized that mindfulness techniques could also have a positive effect on non-motor symptoms of PD patients which can enhance the quality of life after training sessions. This clinical trial aimed to investigate the impact of mindfulness training on the quality of life of PD patients.

Materials and Methods

Participants and Ethical issues

This randomized clinical trial was conducted at the neurology outpatient clinic of Imam Reza and Razi University-Hospital. Participants were 40 patients aged 67.95 ± 6.8 years (56-80) with a definite diagnosis of PD who were receiving dopaminergic drugs for at least one year. Twenty-seven of the patients were males, and 13 were females. They all were married, and 4 of them reported a family history of PD. Participants were randomly categorized into two experiment and control groups with 20 patients in each. For randomization, a list of random numbers was used based on the computer program and applied to the patients at the time of their neurologist visit at the clinic.

The inclusion criteria were: definite diagnosis of idiopathic PD based on UK Brain Bank criteria, mild and moderate forms of disease according to Hoehn and Yahr (HY) staging (1-3), stable and normal dosage of PD medications within last six months, normal cognitive function or mild cognitive impairment according to Mini-Mental State Examination (MMSE) score 17-30, enthusiasm and commitment to participate in mindfulness training sessions and to practice the required works at home.

The patients with the following criteria were excluded: focal neurologic deficit, abnormal brain imaging findings suggestive of brain lesions, other medical conditions that would affect the quality of life, use of antiepileptic drugs and symptoms of psychosis,

The protocol of the study was reviewed and confirmed by the local ethics committee of Tabriz University of Medical Sciences (IR.TBZMED.REC.1397.551). All patients received an informed written consent to participate in the study and to the use of their information. This trial was registered on the IRCT.ir website (IRCT20181007041258N1).

Mindfulness Training sessions

The interventions included 8-week mindfulness-based stress reduction (MBSR) sessions each for 2hours with a 15-minute break between the first and second hours. The sessions followed by a one-day retreat program between sixth and seventh sessions and took for 7 hours. The patients were asked to practice the requested homework at least for 30 minutes after each session. The protocol of the training sessions was conducted as per the steps described by Kabat-Zinn ⁹. The sessions were performed by a psychiatrist with over 5-year of experience in MBSR instructions. The instructions were based on the teaching of three techniques: body scanning, mindfulness meditation, and gentle yoga. The sessions focused on physical and mental awareness of body, how to diminish the physiological effect of pain and stress, how to perform less emotional reaction when facing distress, mental calmness in challenges through life, non-judgmental awareness, equity in stress management and joy of every moment.

Controls

The patients in the control group received eight 1-hour sessions during the same time as the experiment group. The sessions centered on basic information about PD based on brochures published by the American Parkinson Disease Association with topics: medications, symptoms of the disease, mood and sleep, and connecting with resources.

Assessments

All participant's general data, regarding age, gender, type of medication, and duration of disease were gathered according to patients' self-report and the information documented in patients' clinical records. Two neurologists assessed the HY stage, disease severity, and probable motor disturbance at baseline (within patient recruitment within one week before the initial session). The assessments of the quality of life were conducted at baseline (on the day of the first training session before the class), and after the experiment.

For the evaluation of the quality of life, the PDQ-39 questionnaire was used. PDQ-39 is a 39-item questionnaire based on the patient report of health status. It evaluates eight scales of daily activities including Mobility (MOB), Activities of daily living (ADL), Emotional well-being (EMO), Stigma (STI), Social support (SOC), Cognitions (COG), Communication (COM) and Bodily discomfort (BOD) and how these scales are being affected by PD. Participants are required to choose one of five orders of responses based on how often due to their disease, they have faced difficulties defined in each item. The final score of each item is calculated as a percentage score. The overall score is measured by calculating the mean percentage score of eight items as Parkinson`s disease summary Index(PDSI). The assessments were conducted in-person by the principal investigator (N.Gh) who was blinded about the group of study which patients were enrolled in.

Statistical Analysis

The scores of each item were described as mean ± SD. The between-group and within-group comparisons were made by the independent and sample T-test, respectively. The chi-square test was performed for the comparison of categorical variables. To investigate the change in the quality of life each PDQ-39 item scores and the PDSI scores were compared before and after the experiment in either control or experiment group by splitting the data into two study groups and comparing the mean scores of each item using independent T-test. All the analyses were performed using SPSS software version 19.0 (IBM Corp., Armonk, N.Y., USA). The boxplot figures were drawn using medCalc.ink software. Figures of the change in questionnaires' scores were provided by GraphPad.prism v.6.0.7 Ink software.

Results

All the 40 patients completed the training sessions in 8 weeks. The primary assessment was made after the last MBSR session and during their first neurologic visit at the clinic.

The general characteristics of the patients in each experiment and control group are shown in Table 1. The baseline characteristic data did not differ significantly between the two study groups.

As it is demonstrated in Table 2, at baseline, the PDQ-39 item scores did not differ significantly between two study groups, except for the SOC score, which was significantly higher in control subjects compared to the experiment group (35.80 ± 9.7 vs 29.11 ± 8.7, p = 0.02).

Quality of life assessment

The statistical analysis revealed a lower mean score in all PDQ-39 items in the experiment group compared to control subjects; however, the difference was insignificant for MOB, ADL, EMO, STI, COG, COM, and BOD and was only significant for SOC (34.13 ± 9.7 vs 26.19 ± 7.7 for control and experiment group, respectively. P = 0.007) (Table 2).

On the other hand, the within-group analysis yielded a significant improvement in the mean score of subjects in the experiment group. Their mean PDSI score was 31.88 ± 6.5 after one month compared to the baseline score of 33.93 ± 6.2 (p < 0.001). However, the mean scores of the participants in the control group did not significantly differ from the baseline.

A comparison of the delta values between the experimental and control groups showed MOB, ADL, and EMO to be significantly different.

The classification of the patients based on the stage of disease by HY revealed a significant improvement in PDSI score in patients in the experiment group at the severe stage (III). In contrast, the PDQ-39 item scores did not significantly differ (except for the ADL) after the training for mindfulness. The analysis also showed that patients in milder stages (I) have significant improvement after the experiment. However, the same improvement was noted in the control group (Table 3).

Table 1. Patients' demographic data in each study group

Note: Abbreviations: Female (F), Male (M), Hoehn Yahr (HY), Parkinson's disease (PD)

Table 2. PDQ-39 score items and PDSI before and after the mindfulness sessions in control and experiment group pf patients

Note: Abbreviations: Confidence Interval (CI), Mobility (MOB), Activities of daily living (ADL), Emotional well-being (EMO), Stigma (STI), Social support (SOC), Cognitions (COG), Communication (COM), Bodily discomfort (BOD), Parkinson`s disease summary Index (PDSI). ^ϯ: P value of the differences before and after the experiment in each group; ^*: P value of the differences between mean score of experiment and control group; ^€: 95% CI of the differences between mean score of experiment and control group.

Table 3. The quality of life in patients with different stages of PD before and after the mindfulness sessions in each experiment and control group

Note: Abbreviations: Confidence Interval (CI), Mobility (MOB), Activities of daily living (ADL), Emotional well-being (EMO), Stigma (STI), Social support (SOC), Cognitions (COG), Communication (COM), Bodily discomfort (BOD), Parkinson`s disease summary Index (PDSI)

Discussion

Significant improvement in the quality of life between the patients who received mindfulness training and the control group was observed in this clinical trial of people with Parkinson’s disease within eight weeks of trial.

Overall PDSI decreased modestly in the experiment group by 2.05 points and decreased in the control group by 0.27 points after the experiment.

Among the PDQ items, MOB, ALD, and EMO significantly improved in the experiment group compared to the control group. These results show that mindfulness training has a significant impact on not only motor symptoms of the disease but also the non-motor emotional wellbeing of the patients. The most significant effect of mindfulness training was on patients’ daily activity, which was also obvious in the severe cases of the disease.

Up to now, a few trials have been conducted on the effect of mindfulness training on PD ^10-13. The effect of mindfulness on different features of motor and non-motor symptoms has been measured. However, the outcome was discrepant regarding the time duration of the follow-up and improvement in the measured symptoms.

Similar to our findings, Geong son et al. found a significant difference in the quality of life and ADL of 33 experiment patients who received mindfulness training in comparison to 30 control subjects ¹³. Some other studies found mindfulness an effective modality for a few subscales of PDQ-39^{11, 12}.

In a clinical trial by Cash et al. 39 patients were enrolled in 8-week mindfulness sessions and their EMO and COG improved after the experiment¹¹. In a similar study conducted by Advocat et al., the effect of mindfulness training on the quality of life in 35 PD patients was compared with 37 control subjects within seven weeks and six months. In a two-step analysis, ADL was the only improved factor in experiment group ¹⁴.

In contrast, Dissanayaka et al. examined the effect of mindfulness on fourteen PD patients in the 8-week training program and compared the results with baseline at post-intervention assessment and 6-month follow up ¹⁵. Their results did not yield a significant improvement in any subscales of the quality of life in primary and secondary evaluation. Similarly, non-significant results were reported by Rodgers et al. and Pickut et al. ¹².

Birtwell et al. also assessed the long-term efficacy (16 weeks) of mindfulness training on STI and EMO in thirteen individuals with PD. They found an insignificant change in these two subscales of PDQ-39 ¹⁶.

In the present study, EMO and ADL were more subjective to the short-term effect of mindfulness training. The results of Rodger’s et al. study were consistent with our primary outcome. Their between-group analysis revealed a significant difference in depression subscale of DASS-21 after mindfulness intervention in PD patients ¹⁷. Cash et al. also found depression to improve after mindfulness interventions in PD patients ¹¹.

In contrary to our findings, the difference between PD experiment and control subjects was not meaningful in Pickut et al.'s study ¹². COG was unaffected to mindfulness training in our study. This finding was supported by the clinical trial of Cash et al. They found an insignificant change in PD patients' cognitive function in immediate pots-intervention assessment ¹¹.

On the other hand, Dissanayaka et al. found post-interventional improvement in PD patients' cognition by obtaining PD Cognitive Rating Scale (PDCRS), extended for six months ¹⁵.

Similarly, Geong son et al. showed a significant difference between experiments who received mindfulness training with controls in the mean score of Korean Montreal Cognitive Assessment ¹³.

As described above, there are discrepant results regarding the role of mindfulness stress reduction sessions on quality of life in PD patients. Our results were consistent with some studies and contrary to others. The main factors that might have affected these differences are the size of the sample, including a control group in the study, subjective mood changes in the patients, the severity of the disease, and the likelihood of practicing the Learned lessons at home.

Mindfulness-based interventions aim to improve the current wellbeing of the individuals by self-awareness of present emotions and body movements. It might also help individuals to manage daily stress, have a better judgment of their own, and adjust to daily life. There is also evidence suggesting that mindfulness training leads to neuroplasticity in the brain areas which are involved in emotions ¹⁸.

Studies have also suggested that early therapeutic interventions are more practical in terms of diminishing the probable severity of the disease in the future ^{13, 18}. In our study, patients in the early stages had improvement in their overall quality of life, which was also noted in controls of the same stage, too. However, a meaningful change in the quality of life of patients at the severe stage of PD was recorded after the training sessions. We suggest a long term follow up of the patients in each group and with different stages of the disease to find if the mindfulness training would help in diminishing the progress of the disease.

This study was a pilot study in which MBSR showed a great impact in improving the quality of life in PD patients. However, there were limitations in the study that must be considered. First, the sample size of the study was not large comparing to the prevalence of the disease, and it was constrained by other important factors such as disease severity and level of education. Patients needed to have a minimum level of education to be able to attend the sessions and apply them in their routine life. Second, the psychological nature of the intervention limited the blindness of the patients to the intervention.

We did not perform an intention to treat analysis or crossover randomization as all the randomly selected patients completed the trial, and none dropped out of the clinical trial.

Conclusion

In our study, mindfulness training improved the overall quality of life in PD patients. However, long-term follow up on a large-scale population is required to evaluate the impact of mindfulness-based stress reduction on each item.

Introduction

Nocardia sp. are aerobic, gram-positive microorganisms found mainly in soil and stagnant water. Nocardiosis commonly occur in immunocompromised patients, is often multi-systemic and easily mistaken for tuberculosis when involving the lungs ^{1 2}. We report a complex case of disseminated nocardiosis in a patient already suffering from Myasthenia Gravis (MG) and azathioprine-induced myelosuppression, in which selection of antimicrobials and management planning became complex.

Case Report

A 68-year old lady, known to have generalized MG for 12 years, presented to our centre following a week history of diarrhea and lethargy. She describes having loose stools, up to 8 times per day, chills and rigors, but denied per rectal bleeding or melaena. The patient was, on regular oral prednisolone (50mg a day). She had recently ceased her azathioprine 4 months prior due to severe anaemia, linked to myelosuppression following a bone marrow aspiration test revealing markedly reduced erythropoiesis, normal oesophageo-gastro-dudodenoscopy and colonosocopy, and having normal thiopurine methyltransferase levels prior to azathioprine initiation. The patient had several admissions in that 4 months due to her anaemia, requiring packed cell transfusions, and had recently sustained an interhemispheric subdural bleed two weeks prior following a mechanical fall. At the time, hemoglobin and platelet levels had returned within normal range. Clinical examination was unremarkable and her vitals on arrival included an oxygen saturation of 98% on room air with a normal chest radiography on arrival (Figure 1a). The patient was subsequently treated for infective gastroenteritis, and was started on metronidazole.

Figure 1: Chest radiography on (a) initial presentation and (b) 48-hours into admission, showing newly developed diffuse bilateral consolidation.

Unfortunately, 48 hours into her inpatient stay, the patient developed acute dyspnoea in which her oxygen saturation dropped to 77% under room air and examination revealed diffuse, coarse crepitations bilaterally. A repeat chest radiograph confirmed diffuse consolidation bilaterally (Figure 1b). She was subsequently treated for a hospital-acquired pneumonia, and had her antibiotics swapped to intravenous ceftriaxone. Unfortunately, the patient showed little improvement on the ward, which prompted further investigation. Her blood cultures revealed presence of nocardia farcinica which was resistant to ceftriaxone. In view of being immunosuppressed, a computed tomography (CT) imaging of the brain, thorax, abdomen and pelvis (Figure 2) was performed. Imaging showed extensive bilateral lung consolidation and reticulonodular opacities, predominantly in upper lobes. There was also evidence of sigmoid colon diverticulitis with a rim-enhancing collection adjacent to the posterior aspect of the proximal-to-mid sigmoid colon (2.9 x 2.6 x 2.6 cm).

Figure 2: Computed tomography (CT) imaging of (a) the brain, revealing inter-hemispheric hyperdensity consistent with a subdural haematoma, (b) the thorax, revealing extensive bilateral lung consolidation and reticulonodular opacities, predominantly in upper lobes, and (c) abdomen, showing sigmoid colon diverticulitis with a rim-enhancing collection adjacent to the posterior aspect of the proximal-to-mid sigmoid colon (2.9 x 2.6 x 2.6 cm).

Following consultation with our Infectious Disease team, the patient was treated for likely disseminated nocardiosis using intravenous trimethoprim/sulfamethoxazole as a recommended first line therapy. Unfortunately, following 72 hours of trimethoprim/sulfamethoxazole administration, the patient developed severe pancytopenia (haemoglobin 63 g/L, white cell count 2.0 x 10⁹/L and platelets 33 x 10⁹/L) requiring packed red cell and platelet transfusions, as well as immediate cessation of trimethoprim/sulfamethoxazole. Further decisions on antimicrobial proved difficult as it was noted that other effective alternatives against nocardiosis, including amikacin and fluoroquinolones may potentially exacerbate MG symptoms. Furthermore linezolid, another possible alternative, could potentially exacerbate her thrombocytopenia and worsen the pre-existing subdural haematoma. Thus, a decision was made to commence co-amoxiclav and meropenem concurrently despite neither being first-line therapy. The patient subsequently had an uneventful CT-guided drainage of the sigmoid abscess, with the assistance of our General Surgical colleagues, and was kept on prolonged intravenous antibiotic therapy for 3 months. Following improvement in clinical state, she was allowed discharge from hospital with ongoing oral co-amoxiclav and linezolid with regular bloods tests to monitor for myelosuppression as an outpatient, which has not occurred till this date. With support from clinical and radiological improvement, we aim for 12 months of therapy.

Discussion

Various cases of nocardia sp bacteraemia have been reported, in which immune system dysfunction was primarily due to chronic glucocorticoid therapy ^{1 3 4}. A retrospective review of 40 patients from a Chinese tertiary hospital revealed that half of patient with nocardiosis were on corticosteroids prior to infection onset ⁵. An even larger case series reported up to 94% of pulmonary nocardial infection being linked to use of immunosuppressants ⁶.

Management of nocardiosis can be challenging. Often, imipenem, trimethoprim/sulfamethoxazole, amikacin or a combination of these antibiotics are recommended, with treatment duration being guided by clinical and radiological improvement often extending up to a year ⁷. Bactericidal agents including carbapenems and amikacin are often recommended alongside trimethoprim/sulfamethoxazole in cases of disseminated nocardiosis to ensure greater success in treatment ^{7, 8}. The use of amikacin however should be cautioned in cases of MG, and reports have described management using linezolid as an alternative ^{1, 9}.

In our patient, the risk of worsening pancytopenia as illustrated following trimethoprim/sulfamethoxazole administration led to hesitance in using linezolid. Furthermore, the consequences of thrombocytopenia would have been devastating for the patient due to having residual subdural hematoma. Thus, the choice of antibiotics was limited to that of second-line agents including co-amoxiclav and meropenem on top of surgical drainage of existing abscesses, which has also been shown to be beneficial ^{1 5}. However, it should be noted that the risk of pancytopenia remains to be multifactorial in our patient, ranging from pre-exisitng myelosuppression to ongoing sepsis and initiation of culprit medications

Mortality of nocardiosis infections ranges depending on organ involved, rates being under 40% in cases of pulmonary spread, and up to 100% when disseminated to the central nervous system (CNS) ⁶. Unfortunately, nocardia farcinica, the subtype reported in our case, has been shown to be more resistant to antimicrobials and carries a greater risk of dissemination to the CNS, a point being greatly considered as our centre continues to manage the patient ¹⁰.

Conclusion

Nocardiosis, although not uncommon in immunocompromised individuals, poses a unique challenge in the MG population due to limitations in suitable antibiotics. Our case highlights the importance of a multi-disciplinary approach, involving various specialties including the infectious disease, neurology, general surgical and microbiology to ensure successful management of such complex cases.

Introduction

Convex probe EBUS-TBNA has been a major development in respiratory medicine. In the last decade we have seen numerous articles supporting the high diagnostic accuracy of EBUS-TBNA in the diagnosis of lung cancer, staging of lung cancer, diagnosis of extra-thoracic malignancies & benign conditions (e.g., TB & sarcoidosis)¹. Patients included in this study reflect the real-life referrals that we see as respiratory physicians in our daily practice. This shows that the trend of doing EBUS-TBNAs for non-cancer patients is rising. Lung cancer is a common cause of cancer death worldwide². Various guidelines (including NICE) have found this procedure safe & recommend it for the staging of lung cancer. In the last 10 years, lots of district general hospitals have started this service in UK & it is mainly delivered by respiratory physicians.

This has provided a specialist service for patients in their local area, which has reduced travelling and waiting times.

Setting & Methods

In this district general hospital under discussion, EBUS service was setup in 2018, under supervision of a tertiary care centre. We carried out 82 procedures during the first year of this service. All of these cases were reviewed for this article. Data was recorded on an excel spreadsheet (data included: number of cases, age, gender, lymph node stations sampled, complications, pathology & microbiology results of EBUS TBNA). Minimum of 4 passes were done at each lymph node station. Where EBUS was done for diagnostic purposes, stations to be sampled were at the discretion of the operator. Samples obtained via EBUS-TBNA were flushed into CytoLyt (methanol-water solution). EBUS-TBNAs were carried out in the absence of rapid on-site evaluation (ROSE). Where a cancer was suspected but EBUS-TBNA showed normal findings, samples were obtained via another modalities (e.g., CT biopsy) & FDG PET was carried out as well (if not done already). In cases of isolated mediastinal & hilar lymphadenopathy (IMHL), where EBUS-TBNA did not reveal any pathology, interval surveillance CTs were carried out for monitoring purposes. Where lymphadenopathy did not resolve, surveillance scans were carried out for a year. The outcomes of these surveillance CTs & PET CTs were also reviewed for this study. Diagnosis of reactive lymphadenopathy was made if EBUS-TBNA sample did not reveal any pathology, repeat CT did not show any change (or showed reduction/ resolution of lymphadenopathy) & the clinician did not consider the patient to have another diagnosis. EBUS-TBNA was labelled as false negative, if pathology result was negative, but node was positive on PET (in suspected cancer patients).

Results

Out of these 82 patients who underwent EBUS-TBNA, 55 (about 67%) were male & 27 were female (about 33%) (Figure 1).

The age range of patients at the time of procedure was 28 to 88 years. Majority of the patients were between the age of 52 – 88 years (80% of the cases) (Figure 2).

The 82 EBUS-TBNA procedures were carried out for the following main reasons (Figure 3):
A. 42 procedures for cancer reasons (i.e. 51% of the total procedures)
a. For diagnosis of lung cancer (38 procedures)
b. Diagnosis of suspected extra-thoracic cancer (3 cases)
c. Staging of lung cancer (1 case)
B. 40 procedures for IMHL (i.e. 49%)

The final diagnoses in 38 procedures carried out for “diagnosis of lung cancer” were as follows:
1. 25 patients were diagnosed with lung cancer (12 squamous cell cancers, 7 adenocarcinomas, 4 small cell cancers, 1 undifferentiated lung cancer & 1 neuroendocrine tumour)
2. Final diagnosis in 9 cases was reactive lymphadenopathy (repeat CT showed resolution of lymph nodes in 3 cases, reduction in the size in 1 case & stable nodes in 5 cases)
3. Extra-thoracic malignancies were diagnosed in 2 cases (1 metastatic prostate cancer & 2^nd was metastatic disease from primary parotid gland tumour)
4. We had false negative results in 2 cases (1 patient was diagnosed with small cell lung cancer on CT biopsy & 2^nd with adenocarcinoma on ultrasound biopsy)

It was found in 11 cases, where the clinicians initial suspicion was a possible lung cancer, that the final diagnoses were reactive lymphadenopathy and extra-thoracic malignancies.

Some of these patients had lung nodules as well (along with mediastinal & hilar lymphadenopathy). These nodules either resolved or remained stable. In the case of metastatic prostate cancer, prior MRI showed prostate confined disease & the clinician suspected this size significant lymphadenopathy to be due to a lung primary. In the case of metastatic parotid tumour, the initial diagnosis of parotid cancer was a very long time ago & metastatic disease was not expected.

Final diagnoses in 3 patients who had EBUS-TBNA for “extra-thoracic malignancies” were as follows:
1. Prostate cancer (here pelvic MRI showed locally advanced disease)
2. Colon cancer (known colon cancer)
3. Ovarian cancer (patient had ovarian mass & abdominal/pelvic lymphadenopathy)

As most of the surgical patients go directly to tertiary care centres (from this hospital), we therefore didn’t have many patients for staging purposes during the 1^st year of the service. We only had 1 patient for “staging EBUS-TBNA” during this time. In this case stations 4L, 7 & 12L were sampled. Only station 12L was PET positive & also positive on EBUS-TBNA sample. Station 4L & 7 were PET and EBUS-TBNA negative. There was no size significant nodes seen on staging CT in any other area, only 12L node was PET avid & we were not able to identify any size significant lymphadenopathy at any other station via EBUS as well. Sensitivity in this staging EBUS was 100%.

In these 42 diagnostic & staging procedures (carried out for cancers or suspected cancers), summary of the pathological diagnoses from lymph nodes aspirates is as follows:
1. Squamous cell carcinoma of lung 13 approximately (31%)
2. Adenocarcinoma of lung origin 7 approximately (17%)
3. Small cell lung cancer 4 approximately (9.5%)
4. Neuroendocrine tumour of lung origin 1 approximately (2.3%)
5. Undifferentiated lung cancer 1 approximately (2.3%)
6. Metastatic prostate cancer 2 approximately (4.75%)
7. Metastatic parotid gland cancer 1 approximately (2.3%)
8. Metastatic ovarian cancer 1 approximately (2.3%)
9. Metastatic colon cancer 1 approximately (2.3%)
10. False negative 2 approximately (4.75%)
11. Reactive lymphadenopathy 9 approximately (21.5%)

Out of the 40 procedures for IMHL, we were not able to get an adequate sample in 1 case and this patient underwent repeat EBUS-TBNA. Repeat sample showed granulomas; findings were consistent with the clinical diagnosis of sarcoidosis. Final diagnoses in these 40 cases are as follows:
1. Metastatic adenocarcinoma from pancreaticobiliary origin = 1 (2.5%)
2. Bronchogenic cyst = 1 (2.5%)
3. Insufficient sample = 1 (2.5%)
4. Tuberculosis = 3 (7.5%)
5. Granulomas = 16 (40%)
6. Reactive lymphadenopathy = 18 (45%)

Serious diagnoses were made in 10% cases of IMHL (4 out of 40). One patient had metastatic adenocarcinoma from pancreaticobiliary origin & didn’t have any abdominal symptoms or any abnormalities on CTs in the abdomen. 3 patients were diagnosed & later treated for active tuberculosis. Out of these 3 patients only 1 had features of active disease, but sputum negative. The other 2 patients had only mediastinal lymphadenopathy, no lung infiltrates & no sputum production.

A total of 122 lymph nodes were sampled. Details are as follows (figure 4):

Commonly sampled nodes were station 7 nodes. This is consistent with international literature published on EBUS-TBNA.

There were no complications from the procedures performed. None of our patients experienced significant airway bleeding (requiring admission or blood transfusion), mediastinal infection, pneumothorax, pneumo-mediastinum, haemo-mediastinum or airway lacerations.

Discussion

EBUS TBNA is one of the methods to access the mediastinal & hilar lymph nodes. This is a minimally invasive way to get samples from these nodes. Several invasive, minimally-invasive & non-invasive techniques are available to diagnose & stage lung cancers. Choice depends upon the extent of the disease. About 50% of lung cancer patients have evidence of metastatic disease at the time of presentation ³. Patients with intrathoracic disease undergo several investigations. Now we know that EBUS-TBNA should be considered as the initial investigation for patients with early stage suspected lung cancer ⁴. Research carried out has shown that EBUS-TBNA had a sensitivity of 90% ⁵. A recent national BTS audit on bronchoscopy & EBUS showed national diagnostic sensitivity of 90% for staging EBUS-TBNA. BTS quality standards statement sets target of 88% sensitivity for staging EBUS-TBNA⁶. As far as diagnostic EBUS-TBNA is concerned, we had 2 false negative results out of 41 (4.8%), that gives the sensitivity for diagnostic procedures of 95.2%.

There is significant evidence available that ROSE does not increase the diagnostic yield of even conventional TBNA ⁷. Trisolini et al demonstrated in this randomised controlled trial that ROSE did not give any significant diagnostic advantage & did not affect the percentage of adequate specimens. Articles have also shown that ROSE does not reduce the EBUS-TBNA procedure time ⁸. The use of immunohistochemistry on EBUS-TBNA reduces the rate of unclassified non-small cell lung cancer when compared with cytological diagnosis alone ⁹. EBUS-TBNA samples are sufficient to allow immunohistochemical and molecular analysis. I am happy to say that we were able to get ALK, EGFR & PDL1 testing on the EBUS-TBNA samples (where indicated), at our centre. The presence of a cytopathologist or cytotechnologist during the procedure for ROSE purposes can increase the cost significantly. This increased cost can have a significant impact on starting the service at the level of a district general hospital. Another issue which needs clarification, is the number of passes required before declaring the material is inadequate while using ROSE technique. Studies have shown that significant number of samples inadequate on ROSE were still able to give a diagnosis with the help of immunohistochemical analysis.

Here we have seen that 40 EBUS-TBNA procedures were carried out for IMHL. Unfortunately, in this group, one patient was diagnosed with unexpected malignancy, i.e., metastatic adenocarcinoma of pancreaticobiliary origin. In the remaining cases we had benign diagnoses. In the IMHL group about 45% cases had the diagnosis of reactive lymphadenopathy. Out of the total number of 82, about 33% cases were diagnosed with reactive lymphadenopathy. We made the diagnosis of reactive lymphadenopathy in patients where EBUS samples showed normal lymphocytes; these patients had surveillance CTs & clinical follow up as well. Clinicians’ impression & surveillance scans were also reviewed for the purpose of this diagnosis. In this IMHL group, 40% cases were diagnosed with sarcoidosis. In these cases, in addition to clinicians’ impressions, we reviewed cytology, microbiology & surveillance CT reports. Processing method for specimens impacts on the yield for granulomas. Cell block preparation, as carried out in this hospital, showed higher yield for granulomas ¹⁰.

During the first year of the EBUS service at this centre, there was no suspected or diagnosed lymphoma patient who underwent this procedure. International data suggests, for the diagnosis of lymphoma, EBUS-TBNA aspirates should be sent for cytopathology, immunohistochemistry, flow cytometry, cytogenetics and molecular studies ^11,12,13.

Conclusion

EBUS-TBNA is a safe & minimally invasive procedure. It is a first line investigation for lung cancer staging. EBUS-TBNA has been effective in diagnosing extra-pulmonary malignancies ¹⁴. In the last decade we have also seen that its utility has increased significantly in diagnosing benign conditions like sarcoidosis and TB.

We feel operators’ training is also very important in achieving excellent results. Mastering the complexity of this procedure is time consuming. Standardised training is mandatory to achieve high skill levels¹⁵ and we hope there will be a standardised approach to this in future.

Introduction

Lichtenstein tension-free mesh repair has been the standard practice in open inguinal hernia repair for many years. The procedure involves suture fixation of the mesh via an anterior approach to the inguinal canal. It is hypothesised that this invasive fixation contributes to the development chronic postoperative inguinal pain (CPIP), a condition which can cause significant morbidity.

A sound repair should restore the groin anatomy whilst minimising recurrence and not adversely affecting the patient quality of life. Considering the large number of these operations performed each year, reducing complications such as chronic postoperative pain will have a significant impact on healthcare resources.

The introduction of anatomical self-adhesive meshes such as Parietx ProGrip^TM addresses this concern in theory by obviating the need for mesh fixation. This mesh is a macro porous polyester mesh that utilizes polylactic acid micro grips (PLA) to aid placement within 60 seconds¹ without the need for additional fixation. The manufacturer does suggest, however, that additional fixation is left to the discretion of the operating surgeon.

We conducted a review of the literature to evaluate the reported outcomes of using this mesh in open inguinal hernia repair.

Methods

We conducted a PUBMED/MEDLINE search using the search words “Self-adhesive mesh”, “Lichtenstein repair”, “Open inguinal hernia repair” and “Self-gripping mesh” .We looked primarily at the outcomes of postoperative pain and recurrence. The result highlighted five well-structured meta-analyses and several RCTs and retrospective reviews.

Results

In a retrospective review of 211 patients who underwent open inguinal hernia repair with self-adhesive mesh, Tarchi P et al reported a recurrence rate of 0.5% at 1 year and 2.4% at 2 years. They incidence of chronic pain was less than 3%. There were no cases of seroma, testicular complications or mesh infection at 1, 2 and 3-year follow-up. The report highlighted the shorter operative duration with no effect on recurrence rates as a point in favour of self-adhesive mesh. The authors acknowledged the limitation of the study design and the need for randomised trials to address the issue.⁸ A few other small non-randomised trials draw similar conlusions.⁹

A randomised blinded trial from the Danish Multicentre DANGRIP Study Group allocated 163 vs 171 patients to self-adhesive and suture fixation respectively. There were no significant differences between the groups in postoperative complications (33.7 versus 40.4 %; P = 0·215), rate of recurrent hernia within 1 year (1.2 % in both groups) or quality of life. The 12 month prevalence of moderate or severe symptoms was 17.4 and 20.2% respectively (P = 0.573).

The study concluded that the avoidance of suture fixation using a self-gripping mesh was not accompanied by a reduction in chronic symptoms after inguinal hernia repair. ⁵

The FinnMesh trial is a randomised multicentre trial from Finland that Compared glue fixation, self-gripping mesh, and suture fixation of mesh. 625 patients were randomised to cyanoacrylate glue (Histoacryl, n = 216), self-gripping mesh (Parietex ProGrip, n = 202), or conventional non absorbable sutures (Prolene 2-0, n = 207) There was no significant differences postoperatively in pain response or need for analgesics between the study groups at 1 year follow up. The mean operative duration was lower in the self-adhesive mesh group.⁶

The HIPPO trial is a randomised double-blinded trial of 165 patients. The reported hernia recurrence rate after 24 months was 2.4% for the ProGrip mesh and 1.8% for the sutured mesh (P = 0.213).

The incidence of CPIP was 7.3% at 3 months declining to 4.6% at 24 months and did not differ between both groups. ⁷ The mean duration of surgery was significant shorter with the ProGrip mesh (44 vs 53 minutes, P < 0.001).

In a systematic review of 7 studies comparing self-gripping versus sutured mesh for inguinal hernia repair totalling 1353 patients, Zhang C et al found no difference in recurrence (risk difference -0.02 [95% confidence interval -0.07 to 0.03], P = 0.40) or chronic pain (risk difference -0.00 [95% confidence interval -0.01 to 0.01], P = 0.57). ² This review found no difference in wound infection, hematoma, and seroma formation. Self-adhesive mesh was again associated with a shorter mean operative duration. In its conclusion, the authors surmised that both mesh types are comparable in outcome but further long term analysis might be needed.

Pandanaboyana S published a meta-analysis of 5 RCTs and 1170 patients, that also found no significant difference in recurrence or chronic pain. Wound infection was lower in the self-gripping mesh group compared to sutured mesh but this was not statistically significant (risk ratio (RR) 0.57, 95% confidence interval 0.30-1.06, P = 0.08). The duration of operation was significantly shorter with self-gripping mesh compared to sutured mesh with a mean difference of -5.48 min [-9.31, -1.64] Z = 2.80 (P = 0.005).³

In another meta-analysis, Li J et al included 5 RCTs and 2 prospective comparative studies and 1353 patients. Statistically, there was no difference in the incidence of chronic pain [odds ratio = 0.74, 95% confidence interval (CI) (0.51-1.08)]. There was no statistical difference in the incidence of acute postoperative pain [odds ratio = 1.32, 95% CI (0.68-2.55)], hematoma or seroma [odds ratio = 0.89, 95% CI (0. 56-1.41)], wound infection [risk difference = -0.01, 95% CI (-0.02 to 0.01)], and recurrence [risk difference = 0.00, 95% CI (-0.01 to 0.01)]. The self-gripping mesh group was associated with a shorter operating time (1-9 minutes).¹⁰

In Ismail A et al’s meta-analysis of 12 randomized controlled trials and 5 cohort studies, 3722 patients were included in the final analysis. The two groups, using self-gripping mesh or sutured mesh fixation, did not differ significantly in terms of recurrence rate (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P = 0.54) or postoperative chronic groin pain (odds ratio = 0.75, 95% confidence interval 0.54-1.05; P = 0.09). The operative time was less in the self-gripping mesh group (mean difference = -7.85, 95% confidence interval -9.94 to -5.76; P < .0001). There were comparable risks between self-gripping mesh and sutured mesh fixation groups in terms of postoperative infection (odds ratio = 0.81, 95% confidence interval 0.53-1.23; P = 0.32), postoperative hematoma (odds ratio = 0.97, 95% confidence interval 0.7-1.36; P = 0.9), and urinary retention (odds ratio = 0.66, 95% confidence interval 0.18-2.44; P =0.54).¹¹

A more recent meta-analysis including 10 RCTs and 2541 patients also draws similar conclusions, with no significant difference in the incidence of chronic pain (odds ratio = 0.93; 95% confidence interval, 0.74-1.18), recurrence (odds ratio = 1.34; 95% confidence interval, 0.82-2.19), or foreign body sensation (odds ratio = 0.82; 95% confidence interval, 0.65-1.03).⁴ The mean operating time was significantly shorter (odds ratio = -7.58; 95% confidence interval, -9.58 to -5.58) in the self-gripping mesh group which is consistent with the reported literature.

Discussion

Open inguinal hernia repair is a routinely performed operation and chronic postoperative inguinal pain is a significant cause of morbidity that can impact negatively on patients’ quality of life. Eliminating the need for suture fixation seems theoretically a step in the right direction.

The published literature, however, seems to arrive at similar conclusions. Whilst using self-adhesive mesh results in a shorter operative duration and seemingly does not affect the outcome negatively otherwise, there is no evidence that it reduces postoperative chronic pain and therefore should not be advocated on this merit. A shortened operative time coupled with a non-inferior outcome does seem like a more reasonable evidence-based argument for its proponents.

The decision of which mesh fixation technique to use can be left to the discretion of the operating surgeon. Further long-term follow up data is required to arrive at more definitive conclusions as the mean follow up duration in the reviewed studies ranged from 4 months to 3 years. The cost implications involved in the choice of mesh used should also be taken into account in future studies.

Background

Tuberculosis (TB) involving the central nervous system (CNS) account for 2 to 5% of all TB cases¹. Commonly it manifests in three ways – meningo-encephalitis, tuberculomas or abscesses2. Treatment should be guided by histological evidence, which unfortunately can be difficult to obtained in those with CNS dissemination. We present a rare case of solitary basal ganglia tuberculous abscess, which provided a diagnostic dilemma and led to complex management planning.

Case Report

A 53-year old man, with no known medical illness, presented with a 5-day history of fever, vomiting and altered mental behaviour. His vital signs were stable, on arrival aside from being pyrexial at 38°C. There was, however, neck stiffness noted on clinical examination as well as evidence of increased tone on the right upper and lower limbs, with an upgoing right-sided plantar response. Power was preserved in all limbs.

An initial contrast-enhanced computed tomography (CT) imaging of the brain revealed a hypodense lesion measuring 1.6 cm x 2.1 cm x 1.8 cm in the left basal ganglia region, with rim enhancement, complicated by cerebral oedema causing mass effect and mild hydrocephalus (Figure 1). A lumbar puncture was performed, and cerebrospinal fluid (CSF) analysis suggested the possibility of bacterial infiltration (Table 1). Initial, Ziehl-Neelsen (ZN) staining, mycobacterium tuberculosis (MTB) cultures and Gene Xpert nucleic acid amplification test (NAAT) from CSF were negative and a HIV antibody serology was negative as well. A transthoracic echocardiogram and CT imaging of the thorax and neck were both performed, failing to identify a possible source of spread. Furthermore, there was no evidence of focal lung infection or collection, and no evidence of lymphadenopathy of note.

The patient was initially treated for 2 weeks with intravenous antibiotics, using intravenous Ceftriaxone 2g BD and Metronidazole 500mg TDS. Intravenous Dexamethasone was also commenced in view of the cerebral oedema. Unfortunately, the patient showed no clinical improvement, prompting repeat CT and Magnetic Resonance Imaging (MRI) which revealed an unchanged left basal ganglia enhancing lesion, with worsening obstructive hydrocephalus, perilesional oedema causing midline shift. The lesion was in contact with the lateral wall of the left lateral ventricle, with evidence of acute ventriculitis and involvement of the basal cisterns (Figure 2). A right-sided ventriculo-peritoneal shunt was inserted in view of the worsening hydrocephalus and persistent symptoms of headache and vomiting. Subsequently, stereotactic drainage and biopsy of the lesion was discussed but could not be performed in view of its deep location. A decision was thus made to initiate anti-tuberculosis therapy (ATT) empirically and to cease antibiotics. Subsequently, the patient’s clinical state improved with ongoing ATT and active inpatient rehabilitation, alongside improvement in the lesion, via radiological evidence (Figure 3).

Table 1: Cerebrospinal Fluid (CSF) test and other investigations performed during admission.

Figure 1: CT imaging of the brain on (a) axial and (b) saggital view, illustrating a well-circumscribed, rim-enhanced lesion in the left basal ganglia region, suspicious of an abscess

Figure 2: T2-sequence of MRI brain on axial view (a) pre- and (b) post-procedure involving ventriculo-peritoneal shunting, illustrating a well-circumscribed hyperdense basal ganglia lesion, with peri-lesional oedema, as well as evidence of hydrocephalus.

Figure 3: Non-contrasted CT brain on axial view, illustrating less apparent left basal ganglia lesion, with hypodensities in areas of previous oedema, as well as an in-situ ventriculo-peritoneal shunt.

Discussion

Basal ganglia abscesses are very rare, incidence varying between 0.9 to 4% of total brain abscesses³. These are often disseminated lesions from sources such as congenital heart disease infections, intrathoracic and abdominal sepsis, dental caries, otitis media or sinusitis^3-4. Solitary tuberculosis lesions, which includes tuberculous abscesses (TBA), in the basal ganglia are additionally more uncommon, even in endemic countries, as they normally have a predilection for the cerebellum and brainstem5. TBA has been seen in both the immunocompromised, or otherwise, where clinical presentation differs only slightly^6-9.

Similar to other brain abscesses, stereotactic aspiration remains the gold standard diagnostic tool but there is a risk of rupture into ventricles or the subarachnoid space (leading to ependymitis or meningitis), worsening neurological deficits and more importantly the possible need for repeated procedures in as many as 70% of patients⁹.

Although experts advocate the combination of both surgical and chemotherapeutic therapy in managing TBA, the former was limited by the location of the lesion, whereas the latter was due to lack of histological evidence. Furthermore, the lack of risk factors, negative yield from cultures, NAAT and ZN stain, and inability to biopsy made the decision-making complex in our patient. Fortunately, there are evidence to support presumptive ATT for diagnostic and therapeutic purposes, which was adopted in our case⁵. This, however, requires cerebrospinal fluid examination, lung CT imaging and brain MRI that can provide circumferential evidence for diagnosis and to monitor treatment progress, all of which were performed in our gentleman⁵. In fact, CT imaging of the thorax is considered mandatory in cases suspicious of asymptomatic and subclinical extra-neurological tuberculosis, although yield remains poor (detecting abnormalities in only 38 to 56%)¹⁰.

Conclusion

Although CNS involvement in extra-pulmonary tuberculosis is not uncommon, TBA in the basal ganglia region remains a unique entity which poses a challenge in terms of diagnosis, as histological evidence is often difficult to obtain. As adopted in the case highlight, empirical therapy using ATT remains a valid option, especially in areas limited by resources and appropriate skills to perform intracranial biopsies, which is a common occurrence in endemic areas globally.