Mapping the risk of infections in patients with multiple sclerosis: A multi-database study in the United Kingdom Clinical Practice Research Datalink GOLD and Aurum.

BACKGROUND: People with multiple sclerosis (pwMS) have an increased risk of infections; risk factors include underlying disease, physical impairment and use of some disease-modifying treatments. OBJECTIVE: To quantify changes in population-level infection rates among pwMS and compare these to the general population and people with rheumatoid arthritis (pwRA), and identify patient characteristics predictive of infections after MS diagnosis. METHODS: We conducted a multi-database study using data on 23,226 people with MS diagnosis from the UK Clinical Practice Research Datalink Aurum and GOLD (January 2000-December 2020). PwMS were matched to MS-free controls and pwRA. We calculated infection rates, and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) of predictors for infections ⩽ 5 years after MS diagnosis using Poisson regression. RESULTS: Among pwMS, overall infection rates remained stable - 1.51-fold (1.49-1.52) that in MS-free controls and 0.87-fold (0.86-0.88) that in pwRA - although urinary tract infection rate per 1000 person-years increased from 98.7 (96.1-101) (2000-2010) to 136 (134-138) (2011-2020). Recent infection before MS diagnosis was most predictive of infections (1 infection: IRR 1.92 (1.86-1.97); ⩾2 infections: IRR 3.00 (2.89-3.10)). CONCLUSION: The population-level elevated risk of infection among pwMS has remained stable despite the introduction of disease-modifying treatments.

Association between left atrial epicardial fat, left atrial volume, and the severity of atrial fibrillation.

AIMS: Left atrial (LA) volume and LA epicardial fat are both substrates for atrial fibrillation (AF), but may relate with AF at different (early vs. late) stages in the AF disease process. We evaluated associations between LA epicardial fat and LA volume in patients with sinus rhythm (SR), paroxysmal AF (PAF), and persistent/permanent AF. METHODS AND RESULTS: In total, 300 patients (100 with SR, 100 with PAF, and 100 with persistent/permanent AF) who underwent cardiac computed tomography angiography (CTA) were included. The epicardial fat mass posterior to the LA and the LA volume were quantified from CTA and compared between patients with SR, PAF, and persistent/permanent AF. Furthermore, four groups were created by classifying LA epicardial fat and LA volume into large or small according to their median. The mean age of the population was 58.9 ± 10.5 years and 69.7% was male. Left atrial epicardial fat mass was larger in patients with PAF compared with SR, but did not further increase from PAF to persistent/permanent AF. Left atrial volume increased significantly from SR to PAF and to persistent/permanent AF. Left atrial epicardial fat and LA volume were both concordantly large or small in 184 (61%) patients, and discordant in 116 (39%). When both were small, 65.2% of the patients had SR, 23.9% PAF, and 10.9% persistent/permanent AF. When the LA epicardial fat mass was large and the LA volume small (compared with both being small), patients were significantly more often in PAF (55.2 vs. 23.9, P < 0.05), less frequently in SR (32.8% vs. 65.2%, P < 0.05) but showed comparable rates of persistent/permanent AF (12.0% vs. 10.9%, P < 0.05). When the LA volume was large, most patients had persistent/permanent AF. CONCLUSION: Left atrial epicardial fat mass was larger in PAF vs. SR, possibly indicating a marker of early disease, while large LA volumes were associated with a high prevalence of persistent/permanent AF. Elevated LA epicardial fat mass without large LA volume may reflect the early AF disease process.

Diabetes and Incomplete Revascularisation in ST Elevation Myocardial Infarction.

BACKGROUND: Incomplete revascularisation is common and prognostically important. The degree to which incomplete revascularisation (IR) is associated with adverse cardiac outcomes in patients with diabetes and ST-elevation myocardial infarction (STEMI) is unknown. METHODS: Late outcomes (3.6 years) were evaluated in 589 consecutive STEMI patients treated with percutaneous coronary intervention in this observational study. Associations between incomplete revascularisation, and diabetes were assessed. A residual SYNergy Between Percutaneous Coronary Intervention With TAXus and Cardiac Surgery (SYNTAX) Score (rSS) >8 defined IR. The primary endpoint studied was cardiac death, myocardial infarction or cerebrovascular accident. RESULTS: Incomplete revascularisation occurred in 36% of patients with diabetes (46/127) and 32% of patients without diabetes (147/462); p=0.329. The primary endpoint occurred in 27% of patients with diabetes compared to 18% of patients without diabetes (p=0.042); and in 28% with a rSS>8 compared to 16% of patients with a rSS≤8 (p<0.001). The primary endpoint occurred in 35% of patients with both diabetes and a rSS>8, 27% without diabetes with a rSS>8, 22% with diabetes and a rSS≤8, and 14% of with patients neither factor (p<0.001), with cardiac death rates respectively of 22%, 9%, 6%, 2% (p<0.001). Patients with both IR and diabetes accounted for only 8% of STEMI patients but 30% of all cardiac deaths. On multivariable analyses diabetes and IR were independently associated with cardiac death, myocardial infarction and cerebrovascular accident; both p<0.05. CONCLUSIONS: Diabetes and IR contribute independently to late outcomes in STEMI patients. The prognostic impact of diabetes was not due to IR alone. Diabetes acts synergistically with incomplete revascularisation to worsen prognosis.

Left atrial function to identify patients with atrial fibrillation at high risk of stroke: new insights from a large registry.

Aims: Atrial fibrillation (AF) is an independent risk factor for ischaemic stroke. The CHA2DS2-VASc is the most widely used risk stratification model; however, echocardiographic refinement may be useful, particularly in low risk AF patients. The present study examined the association between advanced echocardiographic parameters and ischaemic stroke, independent of CHA2DS2-VASc score. Methods and results: One thousand, three hundred and sixty-one patients (mean age 65±12 years, 74% males) with first diagnosis of AF and baseline transthoracic echocardiogram were followed by chart review for the occurrence of stroke over a mean of 7.9 years. Left atrial (LA) volumes, LA reservoir strain, P-wave to A' duration on tissue Doppler imaging (PA-TDI, reflecting total atrial conduction time), and left ventricular (LV) global longitudinal strain (GLS) were evaluated in patients with and without stroke. The independent association of these echocardiographic parameters with the occurrence of ischaemic stroke was evaluated with Cox proportional hazard models. One-hundred patients (7%) developed an ischaemic stroke, representing an annualized stroke rate of 0.9%. The incident stroke rate in the year following the first diagnosis of AF was 2.6% in the entire population and higher than the remainder of the follow-up period. Left atrial reservoir (14.5% vs. 18.9%, P = 0.005) and conduit strains were reduced (10.5% vs. 13.5%, P = 0.013), and PA-TDI lengthened (166 ms vs. 141 ms, P < 0.001) in the stroke compared with non-stroke group, despite similar LV dimensions, LV ejection fraction, GLS, and LA volumes. Left atrial reservoir strain and PA-TDI were independently associated with risk of stroke in a model including CHA2DS2-VASc score, age, and anticoagulant use. Conclusion: The assessment of LA reservoir strain and PA-TDI on echocardiography after initial CHA2DS2-VASc scoring provides additional risk stratification for stroke and may be useful to guide decisions regarding anticoagulation for patients upon first diagnosis of AF.

The impact of incomplete revascularization on early and late outcomes in ST-elevation myocardial infarction.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) in patients with multivessel disease, there is a lack of consensus regarding the importance of complete revascularization and the timing of treatment of nonculprit stenoses. Our objective was to investigate the impact of incomplete revascularization in STEMI patients using the residual Synergy Between PCI with TAXUS and Cardiac Surgery score (rSS) to define completeness of revascularization. METHODS: This study examined associations between incomplete revascularization, determined by the rSS, and the combined outcome of cardiac death and myocardial infarction (MI). Patients were divided into groups: rSS = 0 (complete revascularization), rSS = 1-8 (incomplete revascularization with a low burden of residual disease), or rSS >8 (incomplete revascularization with a high burden of residual disease). RESULTS: The rSS score was calculated in 589 consecutive patients; 25% had an rSS of 0, 42% rSS 1-8, and 33% rSS >8. At median follow-up of 3.5 years, cardiac death and MI occurred in 5% of rSS = 0 patients, 15% rSS = 1-8, and 26% with rSS >8 (P < .001). The rSS was powerful independent predictor of cardiac death and MI (hazard ratio 5.05, CI 2.89-12.00, rSS >8 vs rSS 0, P < .001 and hazard ratio 2.96, CI 1.31-6.69, rSS = 1-8 vs rSS = 0, P = .009), respectively, and an independent predictor of mortality, MI, unplanned revascularization, and major adverse cardiovascular events. CONCLUSIONS: In patients with STEMI, the rSS independently predicts cardiac death and MI. Patients with an rSS >8 had substantially higher rates of cardiac death or MI. The rSS can be used to define incomplete revascularization in STEMI and predict adverse outcomes.

Harvest of lymph nodes in colorectal cancer depends on demographic and clinical characteristics of the patients.

PURPOSE: This study aims to study the impact of clinical factors on the lymph node sampling in a large cohort of patients with colorectal cancer. METHODS: A colorectal cancer database of 2298 patients in Queensland, Australia, was established. Zero-inflated regression method was used to model positive lymph node counts given the number of lymph nodes examined, with patient's demographic and clinical factors as covariates in the model. Sensitivity and survival analyses were performed to illustrate the applicability of the recommendation of the minimum number of lymph nodes need to be pathologically examined. RESULTS: Younger patients with a larger sized tumour located at the left colon or rectum require fewer lymph nodes to be pathologically examined. Overall, 45.9% of the patients require eight or nine lymph nodes and 31.5% needs ten or 11 lymph nodes to be harvested for pathological examination. A simple formula could be used to obtain the minimum number of lymph node sampling required in patients with colorectal cancer based on patients' age as well as site and dimension of the cancer. CONCLUSIONS: The findings provide practical information about that the minimum number of lymph nodes that could be harvested at the time of collection of lymph nodes for pathological examination for patients with colorectal cancer. The minimum number of lymph nodes harvested depends on demographic (age) and clinical (location and dimension of cancer) characteristics of the patients with colorectal cancer.

Evaluation of multidisciplinary strategies and traditional approaches in teaching pathology in medical students.

This study aims to evaluate the impact on the implementation of multiple strategies to improve medical student's pathology learning experience. In two consecutive years, medical students after a whole year of enrolling in pathology teaching, were invited to complete questionnaires rating and commenting on the personal learning experience of multiple teaching resources delivered in pathology. In both years, the overall score was high (mean score = 4.57 ± 0.63 /5) for the newly introduced sessions, namely histology lectures, clinical integrations and virtual microscopy pre-practical sessions. However, this was only marginally different from that of traditional practical (mean = 4.37 ± 0.68/5) and pathology lecture sessions (mean = 4.42 ± 0.61 /5). In addition, 53% positive correlation was noted for the overall responses between virtual microscopy guided pathology modules and practical sessions indicating the benefit of virtual microscopy in better preparing students for these sessions (P < 0.001). Qualitative comments suggested that the virtual microscopy sessions along with clinical scenario based learning were extremely useful for students' learning in pathology. To conclude, a multidisciplinary approach by clinical integration and flexibility in the mode of delivery by the use of virtual microscopy has the potential to better engage students to the learning of pathology.

Integrated imaging of echocardiography and computed tomography to grade mitral regurgitation severity in patients undergoing transcatheter aortic valve implantation.

AIMS: Quantitative mitral regurgitation (MR) grading remains challenging. This study evaluated the concept of integrating echocardiography and computed tomography for grading MR severity. Specifically, an integrated parameter was developed that combines the true cross-sectional mitral regurgitant orifice area (ROA) assessed with multi-detector row computed tomography (MDCT) with flow data from echocardiography. METHODS AND RESULTS: Systolic MDCT data of 73 patients, referred for transcatheter aortic valve implantation (TAVI) who also had MR, were evaluated. The MDCT systolic phase with the smaller left ventricular volume and the largest mitral regurgitant orifice was selected. Using planimetry, the mitral ROA was measured. The mitral ROA was multiplied with the velocity time integral of the MR jet on echocardiography for the calculation of the integrated regurgitant volume (RVol). MDCT analysis showed a mean mitral ROA of 11.3 ± 7.4 mm2 and a mean integrated RVol of 21.4 ± 14.7 mL/beat, whereas echocardiography showed a mean effective ROA and RVol of MR of 13.3 ± 8.2 mm2 and 23.9 ± 13.6 mL/beat, respectively. Compared with echocardiography, grading based on integrated mitral RVol resulted in reclassification of 10% of the patients from severe to non-severe MR and 14% of the patients from non-severe to severe MR. CONCLUSIONS: Integrated mitral RVol is a quantitative parameter of MR severity by combining the true cross-sectional mitral ROA assessed with MDCT and Doppler mitral haemodynamics which resulted in a significant reclassification of MR grade in patients with severe aortic stenosis undergoing TAVR.

Echocardiographic associates of atrial fibrillation in end-stage renal disease.

BACKGROUND: The prevalence of atrial fibrillation (AF) in end-stage renal disease (ESRD) patients is relatively high. The present study evaluated the association between left atrial (LA) remodelling, including an increased size and myocardial fibrosis, and slow LA conduction and the occurrence of AF. METHODS: In 171 ESRD patients enrolled in the Implantable Cardioverter Defibrillators in Dialysis patients (ICD2) trial, the LA dimensions, LA conduction delay [as reflected by the time difference between P-wave onset on surface electrocardiogram and A'-wave on tissue Doppler imaging (PA-TDI)] and LA function were compared between patients who exhibited AF versus patients without AF. Based on ICD remote monitoring or clinical records, the occurrence of AF was detected. RESULTS: Of 171 patients, 47 (27%) patients experienced AF. Despite comparable left ventricular ejection fraction and prevalence of significant mitral regurgitation, patients with AF had significantly larger LA volume index (mean ± standard deviation) (29 ± 11 versus 23 ± 10 mL/m2, P = 0.001), longer PA-TDI duration (144 ± 30 versus 131 ± 27 ms, P = 0.010) and reduced late diastolic mitral annular velocity (A') (7.1 ± 2.8 versus 8.2 ± 2.4 cm/s, P = 0.012) compared with patients without AF. On multivariable analysis, larger LA volume index [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08, P = 0.017], longer PA-TDI duration (OR 1.02, 95% CI 1.00-1.03, P = 0.025) and reduced A' (OR 0.84, 95% CI 0.72-0.98, P = 0.025) were independently associated with AF after adjusting for age and left ventricle diastolic relaxation. CONCLUSION: ESRD patients with AF show more advanced changes in the LA substrate than ESRD patients without AF.

Engineering enzyme-cleavable hybrid click capsules with a pH-sheddable coating for intracellular degradation.

The engineering of layer-by-layer (LbL) hybrid click capsules that are responsive to biological stimuli is reported. The capsules comprise a pH-sheddable, non cross-linked outer coating that protects enzyme-cleavable inner layers. Upon cellular uptake, the outer coating is released and the capsules are enzymatically degraded. In vitro cell degradation results in rapid capsule degradation (10 min) upon cellular internalization.

The value of serial echocardiography in risk assessment of patients with paroxysmal atrial fibrillation.

Progression from paroxysmal to persistent atrial fibrillation (AF) is associated with increased morbidity and mortality. We examined the association of left atrial (LA) remodeling by serial echocardiography, and AF progression over an extended follow-up period. Two-hundred ninety patients (mean age 61  ±  11 years, 73% male) who underwent transthoracic echocardiography performed at first presentation for non-valvular paroxysmal AF (PAF) and repeat echocardiogram 1-year later, were followed for progression to persistent AF. LA and left ventricular (LV) dimensions, volumes, LA reservoir, conduit and booster pump strains, LV global longitudinal systolic strain (GLS) assessed by 2D speckle tracking, and PA-TDI (time delay between electrical and mechanical LA activation- reflecting the extent of LA fibrosis) were compared on serial echocardiography. Sixty-nine (24%) patients developed persistent AF over a mean follow-up period of 6.3 years. At baseline, patients with subsequent persistent AF had larger LA dimensions (46 mm vs. 42 mm, p < 0.001), indexed LA volumes (41 ml/m2 vs. 34 ml/m2, p < 0.001), lower LA reservoir and conduit strain (17.6% vs. 27.6%, p < 0.001; 10.5% vs. 16.3%, p < 0.001; respectively) and longer PA-TDI (155 ms vs. 132 ms, p < 0.001) compared to the PAF group. Patients with subsequent persistent AF showed over time significant enlargement in LA volumes (from 37.7 ml/m2 to 42.4 ml/m2, p < 0.001), lengthening of PA-TDI (from 142.2 ms to 162.2 ms, p = 0.002), and decline in LA reservoir function (from 21.9% to 18.1%, p = 0.024) after adjusting for age, gender, diabetes and LV GLS. There were no changes in LA diameter, LA conduit or booster pump function. Conversely, the PAF group showed no decline in LA function. Patients who developed persistent AF had larger LA size and impaired LA function and atrial conduction times at baseline, compared to patients who remained PAF. Over the 1-year time course of serial echocardiographic evaluation, there was progression of LA remodeling in patients who subsequently developed persistent AF, but not in patients who remained in PAF.

Rationale and design of a randomized trial on the impact of aldosterone antagonism on cardiac structure and function in diabetic cardiomyopathy.

UNLABELLED: Development of a cardiomyopathy in diabetes mellitus is independent of traditional risk factors, with no clinical trials targeting specific therapeutic interventions. Myocardial fibrosis is one of the key mechanisms and aldosterone is a key mediator of myocardial fibrosis. We propose that aldosterone antagonism will improve cardiac function. We aim to evaluate the efficacy of selective aldosterone receptor antagonism with eplerenone added to optimal medical treatment in improving cardiac structure and function in diabetic cardiomyopathy. We will randomize 130 patients with type 2 diabetes mellitus, stable metabolic control and impaired left ventricular (LV) systolic or diastolic function, to either eplerenone (target dose 50mg) or matching placebo, in addition to optimal medical therapy for 12 months. The primary endpoints are changes in LV systolic and diastolic function, measured by echocardiographic 2-dimensional speckle tracking strain and strain rate and tissue Doppler imaging. The secondary endpoints include changes in echocardiographic markers and plasma biomarkers of collagen turnover; left atrial dimensions and function, incidence of atrial fibrillation and changes in exercise capacity and dyspnea score. The present study will assess whether specific aldosterone antagonism with eplerenone in addition to standard therapy will prevent progression or reverse cardiac dysfunction in diabetic cardiomyopathy using sensitive, robust and quantifiable echocardiographic measures that allow early detection of change. The study may offer a new direction in the management of this condition. TRIAL REGISTRATION: ACTRN12610001063000.

Effects of Using a Shoulder/Scapular Brace on the Posture and Muscle Activity of Healthy University Students during Prolonged Typing-A Randomized Controlled Cross-Over Trial.

Laptop use appears to contribute to poor working postures and neck pain among university students. Postural braces have the potential to improve upper back/neck posture and therefore might have a role as an ergonomic aid for this population. Therefore, the purpose of this study was to assess the short-term effects of scapular bracing on pain, fatigue, cervicothoracic posture, and the activity of the neck and upper-back muscles in healthy college students. A randomized controlled crossover trial was conducted to evaluate the self-reported pain and fatigue, the amplitude and median frequency of surface electromyography in neck extensors, upper trapezius, and lower trapezius, as well as the neck and shoulder sagittal alignment (measured by inertial sensors and digital photographs) during a 30-min typing task in a sample of young, healthy university students with or without a scapular brace. The brace condition resulted in significantly smaller levels of bilateral trapezius muscle activity (p < 0.01). Rounded shoulder posture was slightly better in the brace condition, but these differences were not significant (p > 0.05). There were no significant immediate differences in pain or fatigue scores, neck alignment, or the electromyographic activity of the other muscles tested between brace and non-brace conditions (all p > 0.05). However, bracing appears to immediately reduce the electromyographic activity of the lower trapezius muscles (p < 0.05). These findings shed some light on the possible advantages of scapular bracing for enhancing laptop ergonomics in this group of individuals. Future studies are warranted to evaluate the effects of different types of braces, the importance of matching the brace to the user, and the short- and long-term effects of brace use on computer posture and muscle activity.

Metachronous carcinomas in colorectum and its clinicopathological significance.

PURPOSE: The study was designed to examine the significance of colorectal metachronous carcinoma in a large cohort of patients. METHODS: Over a mean follow-up period of 10 years, the clinicopathological features, microsatellite instability (MSI) and clinical follow-up of 56 patients with metachronous colorectal carcinoma were analysed. RESULTS: The prevalence of metachronous colorectal carcinoma was 2.1 %. The metachronous colorectal carcinomas appeared between 7 and 246 months (mean = 66 months) after surgical resection of the index colorectal carcinomas. Thirty-six per cent (n = 20) of the metachronous carcinoma occurred more than 5 years after the operation of the index carcinoma. Of the 56 patients, 20 % (n = 11) of the metachronous colorectal carcinomas were mucinous adenocarcinoma. Cancers detected in the secondary operations (metachronous colorectal carcinomas), when compared with the primary index cancers, were smaller, showed higher proportions of mucinous adenocarcinoma and more often located in the proximal colon. Patients with metachronous colorectal cancers had higher prevalence of mucinous adenocarcinoma, loss of staining for MSI markers and better survival rates than other patients with colorectal cancers. CONCLUSIONS: Patients with metachronous colorectal carcinomas have characteristic features, and attention to these features is important for better management of this group of cancer.

Bio-click chemistry: enzymatic functionalization of PEGylated capsules for targeting applications.

All sorted: The enzyme Sortase A was used to catalyze functionalization of PEGylated capsules with an activation-specific anti-platelet single-chain antibody (scFv). This enzymatic method allows fast, covalent, and site-directed functionalization of delivery vehicles under mild conditions. Activation-specific anti-platelet scFv-coated PEGylated capsules exhibited a high level of selective binding to thrombi, thus suggesting their potential for thrombosis therapy.

Whole-Slide Imaging: Updates and Applications in Papillary Thyroid Carcinoma.

Whole-slide imaging (WSI) has wide spectrum of application in histopathology, especially in the study of cancer including papillary thyroid carcinoma. The main applications of WSI system include research, teaching, and assessment and recently pathology practices. The other major advantages of WSI over histological sections on glass slides are easier storage and sharing of information as well as adaptation of use in artificial intelligence. The applications of WSI depend on factors such as volume of services requiring WSI, physical factors (computer server, bandwidth limitation of networks, storages requirements for data), adaption of the WSI images with the laboratory workflow, personnel (IT expert, pathologist, technicians) adaptation to the WSI workflow, validation studies, ethics, and cost efficiency of the application(s).

Non-ST elevation myocardial infarction and ischaemic cardiomyopathy due to extrinsic tumour compression of left internal mammary artery graft-obtuse marginal with fibrosis due to chest wall radiation: a case report.

Background: Cardiovascular disease and cancer remain the most prevalent conditions worldwide. The relationship between the two is becoming increasingly recognized, with both sharing similar risk factors. Currently, there are no guidelines or substantial data for the management of this subset of patients. This case presents the management of a patient with advanced malignancy and ischaemic cardiomyopathy, exploring the difficult decision making process for revascularization, ensuring an individualized approach is used for each patient. Case summary: A 68-year-old man with Stage II lung cancer and overall poor prognosis with multiple comorbidities limiting his functional status presented with a non-ST elevation myocardial infarction and ischaemic cardiomyopathy due to extrinsic tumour compression and left internal mammary artery graft-obtuse marginal fibrosis due to chest wall radiation. He had a prolonged admission with the heart team discussions regarding optimal management. He subsequently underwent percutaneous coronary intervention to his native left circumflex chronic total occlusion. He was discharged home on dual antiplatelet and heart failure therapy. Discussion: This case reflects that the management of patients with cancer and coronary artery disease is complex. Many factors including patient comorbidities adversely impact on prognosis, and treatment goals need to be clearly defined. The evidence in the area is lacking but continues to grow; however, the care for such patients needs to be individualized.

Representation of Women in Internal Medicine Specialties in North America, the United Kingdom, and Australasia: Cardiology's Outlier Status and the Importance of Diversity.

Decades of research demonstrate the value of workplace diversity. Reports from individual countries show that women are underrepresented in internal medicine workforces. However, large pooled international studies are not available. This study investigates the current representation of women in the internal medicine workforce internationally and identifies specialties in which underrepresentation is evident. Peer-reviewed studies, government reports, and medical association reports were used to determine proportions of specialists and doctors training in internal medical specialties and in comparator surgical specialties. Data were available from Australia, Canada, England, New Zealand, the United States, Wales, Scotland, and Northern Ireland. A total of 380,263 doctors were studied, including 268,822 practicing specialist physicians (also known as attendings or consultants) and 53,226 doctors in internal medicine specialty training programs (also known as residents, fellows, advanced trainees, or specialist registrar trainees). Among practicing physician specialists, the rate of representation of women was 35% (95,195/268,822, p <0.001). Among trainees, the rate of representation of women was 43% (22,728/53,226, p <0.001). Among physician specialties evaluated, cardiology (15%, 4,152 of 27,328), gastroenterology (20%, 3,765 of 18,893), and respiratory/critical care (24%, 5,255 of 21,870) had the lowest representations of women compared with men (p <0.001 for all). Cardiology and particularly the subspecialty of interventional cardiology were clear outliers as the internal medicine specialties with the lowest representation of women at practicing specialist and trainee levels. In conclusion, this study is the largest international study of women in internal medicine specialties. It found that cardiology, gastroenterology, and respiratory/critical care specialties have the most substantial underrepresentation of women. These data are a global call to action to establish more successful strategies to provide a diverse and representative cardiology workforce.

Return to work after injury in Hong Kong: prospective multi-center cohort study.

PURPOSE: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong. METHODS: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis. RESULTS: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW. CONCLUSIONS: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03219424.

Assembly and degradation of low-fouling click-functionalized poly(ethylene glycol)-based multilayer films and capsules.

Nano-/micrometer-scaled films and capsules made of low-fouling materials such as poly(ethylene glycol) (PEG) are of interest for drug delivery and tissue engineering applications. Herein, the assembly and degradation of low-fouling, alkyne-functionalized PEG (PEG(Alk) ) multilayer films and capsules, which are prepared by combining layer-by-layer (LbL) assembly and click chemistry, are reported. A nonlinear, temperature-responsive PEG(Alk) is synthesized, and is then used to form hydrogen-bonded multilayers with poly(methacrylic acid) (PMA) at pH 5. The thermoresponsive behavior of PEG(Alk) is exploited to tailor film buildup by adjusting the assembly conditions. Using alkyne-azide click chemistry, PEG(Alk)/PMA multilayers are crosslinked with a bisazide linker that contains a disulfide bond, rendering these films and capsules redox-responsive. At pH 7, by disrupting the hydrogen bonding between the polymers, PEG(Alk) LbL films and PEG(Alk) -based capsules are obtained. These films exhibit specific deconstruction properties under simulated intracellular reducing conditions, but remain stable at physiological pH, suggesting potential applications in controlled drug release. The low-fouling properties of the PEG films are confirmed by incubation with human serum and a blood clot. Additionally, these capsules showed negligible toxicity to human cells.