Gongs galore: phaleristic study of the relative risk of a healing art related New Year Honour.

OBJECTIVES: To compare proportional representation of healthcare specialty workers, in receipt of New Year Honours (NYHs) and examine system bias. DESIGN: Observational study of UK honours system including comparative analysis of proportional representation of the UK medical workforce. PARTICIPANTS: Recipients of NYHs from 2010 to 2019. MAIN OUTCOME MEASURES: Absolute risk of receiving an NYH, related to medical specialty, gender and geographical region. Relative risk (RR) of receiving an NYH for services to healthcare related to specialty. RESULTS: 11 207 NYHs were bestowed, with 368 (3.3%) awarded to healthcare professionals: 212 (57.6%) women, 156 (42.4%) men. The RR of a healthcare professional receiving an NYH was 0.76 (95% CI 0.68 to 0.84, p<0.001) when compared with the remaining UK workforce. Doctors received most NYHs (n=181), with public health, clinical oncology and general medicine specialties most likely to be rewarded (RR 20.35 (95% CI 9.61 to 43.08, p<0.001), 8.43 (95% CI 2.70 to 26.30, p<0.001) and 8.22 (95% CI 6.22 to 10.86, p<0.001)), respectively; anaesthetists received fewest NYHs (RR 0.52 (95% CI 0.13 to 2.10), p=0.305). Men were more likely to receive NYHs than women (OR 0.44, 95% CI 0.36 to 0.54; p<0.001). Two hundred and fifty-four NYHs (69.0%) were bestowed on residents of England (60, 16.3% London), 49 (13.3%) Scotland (p=0.003), 39 (10.6%) Wales (p<0.001) and 26 (7.1%) Northern-Ireland (p<0.001). CONCLUSIONS: Relative risk of receiving an NYH varied over 150-fold by specialty, twofold by gender and threefold by geographical location. Public health physicians are perceived to be the pick of the parade.

Bronchoscopic intratumoral injections of cisplatin and endostar as concomitants of standard chemotherapy to treat malignant central airway obstruction.

STUDY PURPOSE: Malignant central airway obstruction (CAO) in non-small cell lung cancer (NSCLC) is associated with high morbidity and requires endobronchial palliative treatment to re-establish a free air passage. We investigate intratumoral therapy combining anti-angiogenic and cytotoxic as a feasible therapeutic modality to treat malignant CAO. STUDY DESIGN: Ten NSCLC subjects with symptomatic malignant CAO underwent endobronchial intratumoral cisplatin and Endostar co-injection after tumour debulking next to systemic cisplatin-based chemotherapy. Injection was performed immediately after debulking surgery and was then carried out on day 2, day 6 and day 10 past systemic chemotherapy. Nine subjects of control group constantly received traditional cisplatin-based chemotherapy. Bronchoscopy, CT scanning, histology, FEV1/FVC ratio, Karnofsky performance (KPS) and shortness of breath scores were analysed to assess therapeutic efficacy. RESULTS: All 10 subjects benefited from the intratumoral cisplatin and endostar co-injection and systemic chemotherapy combination therapy. Bronchoscopy and CT scanning analyses showed a massive airway widening after treatment. Increased KPS and reduced shortness of breath score were also observed. A substantial improvement of lung function was further confirmed by increased FEV1/FVC ratio. For subjects of control group, the improvement was moderate and obviously not as optimal as the 10 subjects with intratumoral injection. CONCLUSIONS: We have shown that the intratumoral injection of cytotoxic cisplatin plus anti-angiogenic Endostar is an effective and safe adjuvant therapeutic option to treat malignant CAO in clinical practice. This time-staggered local and systemic treatment combination improves quality of life and clinical parameters, thus may provide a feasible therapeutic option for symptomatic CAO.

Description of multimorbidity clusters of admitted patients in medical departments of a general hospital.

OBJECTIVE: We aim to identify patterns of disease clusters among inpatients of a general hospital and to describe the characteristics and evolution of each group. METHODS: We used two data sets from the CMBD (Conjunto mínimo básico de datos - Minimum Basic Hospital Data Set (MBDS)) of the Lucus Augusti Hospital (Spain), hospitalisations and patients, realising a retrospective cohort study among the 74 220 patients discharged from the Medic Area between 01 January 2000 and 31 December 2015. We created multimorbidity clusters using multiple correspondence analysis. RESULTS: We identified five clusters for both gender and age. Cluster 1: alcoholic liver disease, alcoholic dependency syndrome, lung and digestive tract malignant neoplasms (age under 50 years). Cluster 2: large intestine, prostate, breast and other malignant neoplasms, lymphoma and myeloma (age over 70, mostly males). Cluster 3: malnutrition, Parkinson disease and other mobility disorders, dementia and other mental health conditions (age over 80 years and mostly women). Cluster 4: atrial fibrillation/flutter, cardiac failure, chronic kidney failure and heart valve disease (age between 70-80 and mostly women). Cluster 5: hypertension/hypertensive heart disease, type 2 diabetes mellitus, ischaemic cardiomyopathy, dyslipidaemia, obesity and sleep apnea, including mostly men (age range 60-80). We assessed significant differences among the clusters when gender, age, number of chronic pathologies, number of rehospitalisations and mortality during the hospitalisation were assessed (p<0001 in all cases). CONCLUSIONS: We identify for the first time in a hospital environment five clusters of disease combinations among the inpatients. These clusters contain several high-incidence diseases related to both age and gender that express their own evolution and clinical characteristics over time.

Systematic review of interventions to improve gender equity in graduate medicine.

Women are substantially underrepresented in senior and leadership positions in medicine and experience gendered challenges in their work settings. This systematic review aimed to synthesise research that has evaluated interventions for improving gender equity in medicine. English language electronic searches were conducted across MEDLINE, CINAHL, Academic Search Complete, PsycINFO and Web of Science. Reference list screening was also undertaken. Peer-reviewed studies published between 2000 and March 2020 that evaluated interventions to improve gender equity, or the experiences of women, in academic or clinical medicine were reviewed. Dual reviewer data extraction on setting, participants, type of intervention, measurement and outcomes was completed. Methodological rigour and strength of findings were evaluated. In total, 34 studies were included. Interventions were typically focused on equipping the woman (82.4%), that is, delivering professional development activities for women. Fewer focused on changing cultures (20.6%), ensuring equal opportunities (23.5%) or increasing the visibility or valuing of women (23.5%). Outcomes were largely positive (87.3%) but measurement typically relied on subjective, self-report data (69.1%). Few interventions were implemented in clinical settings (17.6%). Weak methodological rigour and a low strength of findings was observed. There has been a focus to-date on interventions which Equip the Woman Interventions addressing systems and culture change require further research consideration. However, institutions cannot wait on high quality research evidence to emerge to take action on gender equity. Data collated suggest a number of recommendations pertaining to research on, and the implementation of, interventions to improve gender equity in academic and clinical settings.

Reviewing the use and quality of machine learning in developing clinical prediction models for cardiovascular disease.

Cardiovascular disease (CVD) is one of the leading causes of death across the world. CVD can lead to angina, heart attacks, heart failure, strokes, and eventually, death; among many other serious conditions. The early intervention with those at a higher risk of developing CVD, typically with statin treatment, leads to better health outcomes. For this reason, clinical prediction models (CPMs) have been developed to identify those at a high risk of developing CVD so that treatment can begin at an earlier stage. Currently, CPMs are built around statistical analysis of factors linked to developing CVD, such as body mass index and family history. The emerging field of machine learning (ML) in healthcare, using computer algorithms that learn from a dataset without explicit programming, has the potential to outperform the CPMs available today. ML has already shown exciting progress in the detection of skin malignancies, bone fractures and many other medical conditions. In this review, we will analyse and explain the CPMs currently in use with comparisons to their developing ML counterparts. We have found that although the newest non-ML CPMs are effective, ML-based approaches consistently outperform them. However, improvements to the literature need to be made before ML should be implemented over current CPMs.

Evaluation of a survey for acute care programme directors on the utilisation of point-of-care ultrasound.

PURPOSE: Point-of-care ultrasound (POCUS) is ultrasound brought to the patient's bedside and performed in 'real time' by the healthcare provider. The utility of POCUS to facilitate management of the acutely ill patient has been demonstrated for multiple pathologies. However, the integration of ultrasonography and echocardiography training into residency curriculum varies across the acute care specialties. STUDY DESIGN: After an institutional review board approval, anaesthesiology, emergency medicine, family medicine, internal medicine, paediatrics and general surgery programme directors (PDs) were surveyed. The survey consisted of 11 questions evaluating the primary bedside assessment tool for common acute care situations, POCUS topics that the PDs were comfortable practising and topics that the PDs felt were useful for their specialty. Barriers to POCUS use, certification and documentation were also surveyed. RESULTS: Overall, 270 PD surveys were completed. The preferred primary assessment tool for common acute care situations varied with specialty; emergency medicine PDs consistently responded that POCUS was the diagnostic modality of choice (p<0.0001). The majority of the PDs reported lack of educational opportunities as the primary barrier to learning POCUS (64%). Most PDs indicated that POCUS examinations should be documented (95.7%), and 39% reported that departmental certification would be sufficient. CONCLUSIONS: This study is the first to evaluate differences in the preferred initial bedside assessment tool between the acute care specialties. Although POCUS is a superior tool for evaluating acute pathologies, disconnect between education and utilisation remains. This study highlights the need to incorporate POCUS into the acute care specialty curriculum.

Deficient serum furin predicts risk of abdominal obesity: findings from a prospective cohort of Chinese adults.

BACKGROUND: As a key enzyme of natriuretic peptides system playing an integral role in energy homeostasis, furin may be a potential contributor to obesity. However, the association between furin and obesity has been scarcely studied. This study aims to examine the prospective association between serum furin and abdominal obesity. METHODS: Waist circumference (WC) was measured twice 4 years apart for a total of 892 Chinese adults free of abdominal obesity at baseline. Abdominal obesity was defined as WC over 85 cm for men and as WC over 80 cm for women. A Cox proportional hazard model was constructed to examine the association of baseline serum furin with incident abdominal obesity. RESULTS: After an average 4 years of follow-up, 184 participants developed new abdominal obesity. Baseline serum furin was significantly associated with dynamic body weight during follow-up (ß=-0.593, p=0.003). Participants with a higher level of serum furin at baseline were less likely to develop new abdominal obesity compared with those with a lower level of serum furin (HR=0.81, 95% CI 0.67 to 0.97). CONCLUSIONS: A lower level of serum furin predicts a higher risk of developing future abdominal obesity in Chinese adults. Furin deficiency may be a contributor to abdominal obesity but still needs further investigations.

Syncope in pulmonary embolism: a retrospective cohort study.

OBJECTIVE: To determine the prevalence of syncope or collapse in pulmonary embolism (PE). METHODS: A retrospective cohort study was conducted. We examined the frequency with which syncope or collapse (presyncope) occurred alone or with other symptoms and signs in an unselected series of 224 patients presenting to a district general hospital with PE between September 2012 and March 2016. Confirmation of PE was by CT pulmonary angiogram in each case. RESULTS: Our cohort of 224 patients comprised 97 men and 127 women, average age 66 years with age range of 21-94 years. Syncope or collapse was one of several symptoms and signs that led to a diagnosis of PE in 22 patients (9.8%) but was never the sole presenting feature. In descending order, these other clinical features were hypoxaemia (17 patients), dyspnoea (12), chest pain (9), tachycardia (7) and tachypnoea (7). ECG abnormalities reported to occur more commonly in PE were found in 13/17 patients for whom ECGs were available. Patients with PE presenting with syncope or collapse were judged to have a large clot load in 15/22 (68%) cases. CONCLUSION: Syncope was a frequent presenting symptom in our study of 224 consecutive patients with PE but was never the sole clinical feature. It would be difficult to justify routine testing for PE in patients presenting only with syncope or collapse.

Review on therapeutic targets for COVID-19: insights from cytokine storm.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been caused the greatest pandemic of our century. Many of the deaths related to it are due to a systemic inflammatory response, which has been called 'cytokine storm'. OBJECTIVES: We developed a comprehensive review of the pathophysiology mechanisms of COVID-19 and of the rationale for drugs and therapeutics that have been tested in clinical trials. METHODS: A narrative review of the literature was conducted using PubMed, SciELO, Bireme, Google Scholar and ClinicalTrials. RESULTS: SARS-CoV-2 has evolutive mechanisms that made it spread all around the globe, as a higher latency period and a lesser lethality than other coronaviruses. SARS-CoV-2 causes a delay in the innate immune response and it disarranges the immune system leading to an overwhelming inflammatory reaction (the 'cytokine storm'). In this scenario, high levels of interleukins (IL), notably IL-6 and IL-1, create a positive feedback of chemokines and immune responses, and powers pulmonary and systemic tissue damage, leading to capillary leakage and SARS, the main cause of death in patients with COVID-19. On 17 July 2020, there were 1450 entries on ClinicalTrials.gov of ongoing studies on COVID-19. The mechanisms of the main therapeutic approaches were comprehensively reviewed throughout the text. Therapies focus on blocking viral entry (remdesivir, umifenovir, among others) and blocking of immune system for cytokine storm control (IL-1 and IL-6 inhibitors, glucocorticoids, convalescent plasma, among others). CONCLUSIONS: Understanding of action mechanisms of SARS-CoV-2 enables us to direct efforts on effective therapeutic targets. This comprehensive review helps to interpret the clinical results of the several trials ongoing.

Normal-range emergency department serum phosphorus levels and all-cause mortality.

PURPOSE OF THE STUDY: Hypophosphataemia and hyperphosphataemia are frequently encountered in hospitalised patients and are associated with significant clinical consequences. However, the prognostic value of normal-range phosphorus levels on all-cause mortality and hospitalisations is not well established. Therefore, we examined the association between normal-range phosphorus levels, all-cause mortality and hospitalisations in patients presenting to the emergency department of a tertiary medical centre in Israel. STUDY DESIGN: A retrospective analysis of patients presenting to the Chaim Sheba Medical Center emergency department between 2012 and 2018. The cohort was divided into quartiles based on emergency department phosphorus levels: 'very-low-normal' (p ≥ 2 mg/dL and p ≤ 2.49 mg/dL), 'low-normal' (p ≥ 2.5 mg/dL and p ≤ 2.99 mg/dL), 'high-normal' (p≥  3 mg/dL and p≤3.49 mg/dL) and 'very-high-normal' (p ≥  3.5 mg/dL and p ≤ 4 mg/dL). We analysed the association between emergency department phosphorus levels, hospitalisation rate and 30-day and 90-day all-cause mortality. RESULTS: Our final analysis included 223 854 patients with normal-range phosphorus levels. Patients with 'very-low-normal' phosphorus levels had the highest mortality rate. Compared with patients with 'high-normal' phosphorus levels, patients with 'very-low-normal' levels had increased 30-day all-cause mortality (OR 1.3, 95% CI 1.1 to 1.4, p<0.001), and increased 90-day all-cause mortality (OR 1.2, 95% CI 1.1 to 1.3, p<0.001). Lower serum phosphorus levels were also associated with a higher hospitalisation rate, both for the internal medicine and general surgery wards (p<0.001). CONCLUSIONS: Lower phosphorus levels, within the normal range, are associated with higher 30-day and 90-day all-cause mortality and hospitalisation rate.

Vitamin D status and outcomes for hospitalised older patients with COVID-19.

PURPOSE: Older adults are more likely to be vitamin D deficient. The aim of the study was to determine whether these patients have worse outcomes with COVID-19. METHODS: We conducted a prospective cohort study between 1 March and 30 April 2020 to assess the importance of vitamin D deficiency in older patients with COVID-19. The cohort consisted of patients aged ≥65 years presenting with symptoms consistent with COVID-19 (n=105). All patients were tested for serum 25-hydroxyvitamin D (25(OH)D) levels during acute illness. Diagnosis of COVID-19 was confirmed via viral reverse transcriptase PCR swab or supporting radiological evidence. COVID-19-positive arm (n=70) was sub-divided into vitamin D-deficient (≤30 nmol/L) (n=39) and -replete groups (n=35). Subgroups were assessed for disease severity using biochemical, radiological and clinical markers. Primary outcome was in-hospital mortality. Secondary outcomes were laboratory features of cytokine storm, thoracic imaging changes and requirement of non-invasive ventilation (NIV). RESULTS: COVID-19-positive arm demonstrated lower median serum 25(OH)D level of 27 nmol/L (IQR=20-47 nmol/L) compared with COVID-19-negative arm, with median level of 52 nmol/L (IQR=31.5-71.5 nmol/L) (p value=0.0008). Among patients with vitamin D deficiency, there was higher peak D-dimer level (1914.00 µgFEU/L vs 1268.00 µgFEU/L) (p=0.034) and higher incidence of NIV support and high dependency unit admission (30.77% vs 9.68%) (p=0.042). No increased mortality was observed between groups. CONCLUSION: Older adults with vitamin D deficiency and COVID-19 may demonstrate worse morbidity outcomes. Vitamin D status may be a useful prognosticator.

Trends in the prevalence of cardiometabolic disease and cardiovascular events by body mass index category in adults from 1999 to 2016.

OBJECTIVES: An increasing percentage of the US population is obese. Cardiometabolic risk in the population increases with body mass index (BMI), but whether this correlation changes over time is unknown. We analysed the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016 to determine if the prevalence of cardiometabolic disease and cardiovascular events within each BMI category is changing over time as the BMI of the population is increasing. STUDY DESIGN: For each of the nine survey cycles covering this period, we divided the population by BMI category (normal, overweight, class 1 obesity, class ≥2 obesity) and subsequently by the presence of cardiovascular events or cardiometabolic disease. NHANES participants are a group of 5000 individuals/cycle selected to be representative of the US population. We used the weighted data sets to perform trend analyses for each risk/BMI group adjusted for relevant confounders. RESULTS: The distribution of the highest risk category (cardiovascular event) has not changed over time within any BMI category. The distribution of the lowest risk category (cardiometabolically healthy) increased significantly over time in all BMI categories. This was noted in the 18- to 45-year subgroup but not in the group aged >45 years. CONCLUSIONS: The increase in the prevalence of overweight and obese individuals might be associated with a 'healthy obesity' phenotype in those <45 years; however, individuals >45 years showed a proportional increase in associated cardiometabolic risk.

Personal historical perspective of HIV: part 11.

All animal life on earth is thought to have a common origin and have common genetic mechanisms. Evolution has enabled differentiation of species. Pathogens likewise have evolved within various species and mostly come to a settled dynamic equilibrium such that co-existence results (pathogens ideally should not kill their hosts). Problems arise when pathogens jump species because the new host had not developed any resistance. These infections from related species are known as zoonoses. COVID-19 is the latest example of a virus entering another species but HIV (and various strains of influenza) were previous examples. HIV entered the human population from monkeys in Africa. These two papers outline the underlying principle of HIV and the differing epidemiologies in Africa, the USA and in Edinburgh. The underlying immunosuppression of HIV in Africa was initially hidden behind common infections and HIV first came to world awareness in focal areas of the USA as a disease seemingly limited to gay males. The epidemic of intravenous drug abuse in Edinburgh was associated with overlapping epidemics of bloodborne viruses like hepatitis B, hepatitis C and HIV.

Smouldering ashes: burning questions after the outbreak of electronic cigarette or vaping-associated lung injury (EVALI).

In the summer of 2019, the Center for Disease Control and Prevention (CDC) declared an emergency of electronic cigarettes and/or vaping (vaping)-associated lung injury (EVALI) in the USA. The outbreak abated by January 2020, which the CDC attributed to heightened public awareness, 'user actions to reduce risk' and potentially the removal of vitamin E acetate (VEA) from vaping products (VEA is an oily chemical cutting agent, strongly associated with the disease). Even though the EVALI outbreak appears to be over, numerous epidemiological and medical questions are left still open. First, why were there practically no cases outside the USA, which represents nearly a quarter of the global vaping market? Comparative studies to map the differences in device/fluids/user habits between countries might be needed urgently. Second, what is the pathomechanism that sickens vapers irrespective of VEA exposure? VEA was only confirmed in about half of the cases and the presumed toxicity is yet to be determined. Aetiology/epidemiology focused research is needed to investigate/interpret the broader context to explain the outbreak. Third, could any socioeconomic/environmental factors have influenced the course of the outbreak? Finally, what should we expect in the years to come? Was EVALI a serious but reversible emergency medicine condition or is vaping as detrimental to long-term health as smoking? Besides the complex legislative, regulatory, ethical aspects of EVALI, biomedical research is also difficult: in-vitro experiments have limited inferential value to real real-life vaping due to its complexity; user habits are self-reported and under-researched; there is an active black market pouring unknown quality counterfeit products and, in the USA, federal restrictions limit cannabis research. Vaping is a toxicological, multidimensional conundrum; therefore, stringent quality control, transparent legal/ethical boundaries, meticulous international research and user education are paramount to prevent potential future outbreaks and determine the parameters safe vaping (if these exist).

Genomics in medicine: a novel elective rotation for internal medicine residents.

It is well recognised that medical training globally and at all levels lacks sufficient incorporation of genetics and genomics education to keep up with the rapid advances and growing application of genomics to clinical care. However, the best strategy to implement these desired changes into postgraduate medical training and engage learners is still unclear. We developed a novel elective rotation in 'Genomic Medicine and Undiagnosed Diseases' for categorical Internal Medicine Residents to address this educational gap and serve as an adaptable model for training that can be applied broadly across different specialties and at other institutions. Key curriculum goals achieved include increased understanding about genetic testing modalities and tools available for diagnosis and risk analysis, the role of genetics-trained allied health professionals, and indications and limitations of genetic and genomic testing in both rare and common conditions.

Guidelines for conducting epidemiological studies of blast injury.

Blast injuries are often caused by more than one mechanism, do not occur in isolation, and typically elicit a secondary multi-system response. Research efforts often do not separate blast injuries caused by blast waves from those caused by blunt force trauma and other mechanisms. 15 experts from nine different NATO nations developed in the HFM Research Task Group (RTG; HFM-234 (RTG)) 'Environmental Toxicology of Blast Exposures: Injury Metrics, Modelling, Methods and Standards' Guidelines for Conducting Epidemiological Studies of Blast Injury. This paper describes these guidelines, which are intended to provide blast injury researchers and clinicians with a basic set of recommendations for blast injury epidemiological study design and data collection that need to be considered and described when conducting prospective longitudinal studies of blast injury.

A long wait: barriers to discharge for long length of stay patients.

INTRODUCTION: Reducing long length of stay (LLOS, or inpatient stays lasting over 30 days) is an important way for hospitals to improve cost efficiency, bed availability and health outcomes. Discharge delays can cost hundreds to thousands of dollars per patient, and LLOS represents a burden on bed availability for other potential patients. However, most research studies investigating discharge barriers are not LLOS-specific. Of those that do, nearly all are limited by further patient subpopulation focus or small sample size. To our knowledge, our study is the first to describe LLOS discharge barriers in an entire Department of Medicine. METHODS: We conducted a chart review of 172 LLOS patients in the Department of Medicine at an academic tertiary care hospital and quantified the most frequent causes of delay as well as factors causing the greatest amount of delay time. We also interviewed healthcare staff for their perceptions on barriers to discharge. RESULTS: Discharge site coordination was the most frequent cause of delay, affecting 56% of patients and accounting for 80% of total non-medical postponement days. Goals of care issues and establishment of follow-up care were the next most frequent contributors to delay. CONCLUSION: Together with perspectives from interviewed staff, these results highlight multiple different areas of opportunity for reducing LLOS and maximising the care capacity of inpatient hospitals.