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Right ventricular (RV) failure has a significant adverse impact on pulmonary hypertension (PH) prognosis. None of the currently used parameters directly assess whether RV fails to provide enough energy output to propel the blood through diseased pulmonary vascular system. Furthermore, most of the current parameters are affected by the volume status of the patient. We aimed to explore whether RV energy failure has a predictive power for mortality on top of the established prognostic risk parameters in patients with PH. We screened 723 cases from our database. A total of 3 sets of binary regression analyses were executed to determine the hazard ratios (HRs) of RV energy failure for 5-year mortality in clinical, echocardiographic, and hemodynamic context, using adjustment variables chosen according to previous studies. The final study population encompassed 549 cases. A total of 77 patients died during the 5-year follow-up (14%). RV energy failure was observed in 146 of 549 patients (26.6%). In the univariate model, RV energy failure strongly associated with increased long-term mortality (HR 4.25, 95% confidence interval [CI] 2.58 to 7.00, p

The perinatal period is a time when provision of responsive care offers a life course opportunity for positive change to improve health outcomes for mothers, infants and families. Australian perinatal systems carry the legacy of settler-colonialism, manifesting in racist events and interactions that First Nations parents encounter daily. The dominance of a western risk lens, and conscious and unconscious bias in the child protection workforce, sustains disproportionately high numbers of First Nations infants being removed from their parents' care. Cascading medical interventions compound existing stressors and magnify health inequities for First Nations women. Critical discourse was informed by Indigenous ways of knowing, being and doing via targeted dialogue with a group of First Nations and non-Indigenous experts in Australian perinatal care who are co-authors on this paper. Dynamic discussion evolved from a series of yarning circles, supplemented by written exchanges and individual yarns as themes were consolidated. First Nations maternity services prioritise self-determination, partnership, strengths and communication and have demonstrated positive outcomes with, and high satisfaction from First Nations women. Mainstream perinatal settings could be significantly enhanced by embracing similar principles and models of care. The Australian Anti-racism in Perinatal Practice (AAPP) Alliance calls for urgent transformations to Australian perinatal models of care whereby non-Indigenous health policy makers, managers and clinicians take a proactive role in identifying and redressing ethnocentrism, judgemental and culturally blind practices, reframing the risk narrative, embedding strength-based approaches and intentionally prioritising engagement and connectedness within service delivery. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.]

The Covid-19 pandemic led to a global food crisis. Like previous food crises how the debate is framed by food policy actors can have a bearing on policy outcomes. This study researches how the policy responses to migrant horticultural labour shortages, due to the pandemic, were framed in the Italian print media and how this relates to longer-term food policy making. Data were gathered from the six highest-circulation Italian daily newspapers. The coverage was dominated by left-leaning outlets and peaked in relation to Covid-19 recovery policies and political processes. Farmer industry bodies were the most quoted group, and the legalisation of undocumented migrant workers was the most frequently discussed policy response. A frames analysis was conducted and identified three principal frames: food security, worker exploitation and immigration. The worker exploitation and immigration frames were most frequently used by left-leaning newspapers, while centre-right papers used the food security frame the most often. The results suggest that media framing could contribute to both policy change, helping to open policy windows, as well as policy lock-ins, side-lining certain debates, actors and policy solutions. The research aims to contribute to growing empirical work which seeks to understand the impact of Covid-19 on migrant agricultural workers and food policy.

Oral and Maxillofacial research has utilised predominantly quantitative research approaches and qualitative methodologies have been applied with very narrow scope. Although qualitative surgical research is increasing in popularity there is a lack of patient voice within extant research and important aspects of patients’ experiences including preparation, perceptions of well-being and functional outcomes are potentially overlooked. This provides researchers with significant opportunities to devise approaches that expand our understanding of the social contexts surrounding surgical interventions and associated outcomes and to develop better-informed approaches to research and practice. Reflecting on a novel research project involving OMFS patients this paper seeks to outline some distinct advantages of qualitative research based on researcher reflections. Firstly, we contend that understanding patients as collaborators within the research process helps to establish a research design that reflects the context and complexities of the phenomenon under investigation and in-creases the precision of the concepts being addressed. Secondly, interactive group-based data col-lection approaches create a space in which patients are able to explore aspects relating to OMFS. Thirdly, we suggest that patient interaction optimizes the quality of data by providing participants with the opportunity to engage in conversation with those who understand the treatment processes. The final advantage concerns the intentional involvement of patients within the data analysis phase. We contend that interactive approaches to data collection and analysis where data are collected, analysed, compared and refined as new data are acquired helps to develop a conceptual explanation for the phenomenon in question that is both significant and relevant to the setting being studied. We conclude with recommendations for future research.

In the early stages of the pandemic, Saudi Arabia and other countries in the Arab Gulf region relied on non-pharmaceutical therapies to limit the effect of the pandemic, much like other nations across the world. In comparison to other nations in the area or globally, these interventions were successful at lowering the healthcare burden. This was accomplished via the deterioration of the economy, education, and a variety of other societal activities. By the end of 2020, the promise of effective vaccinations against SARS-CoV-2 have been realized, and vaccination programs have begun in developed countries, followed by the rest of the world. Despite this, there is still a long way to go in the fight against the disease. In order to explore disease transmission, vaccine rollout and prioritisation, as well as behavioural dynamics, we relied on an age-structured compartmental model. We examine how individual and social behaviour changes in response to the initiation of vaccination campaigns and the relaxation of non-pharmacological treatments. Overall, vaccination remains the most effective method of containing the disease and resuming normal life. Additionally, we evaluate several vaccination prioritisation schemes based on age group, behavioural responses, vaccine effectiveness, and vaccination rollout speed. We applied our model to four Arab Gulf nations (Saudi Arabia, Bahrain, the United Arab Emirates, and Oman), which were chosen for their low mortality rate compared to other countries in the region or worldwide, as well as their demographic and economic settings. We fitted the model using actual pandemic data in these countries. Our results suggest that vaccinations focused on the elderly and rapid vaccine distribution are critical for reducing disease resurgence. Our result also reinforces the cautious note that early relaxation of safety measures may compromise the vaccine's short-term advantages.

Widely shared traumas have the potential to both improve and impair our relationships with others. During COVID-19 anxiety has been seen as a major individual vulnerability associated with relationship change, as have the wider economic, situational factors facing families and communities. In this national sample of 997 Japanese respondents we assessed perceived relationship changes in couple relations, neighbourhood relations, and wider relations with Japanese nationals, alongside anxiety, exposure to previous mass traumas, household economics, education, and vulnerability to COVID-19. Whilst most respondents reported little change in their relationships during this year there was a small overall improvement in couple relationships and a decline in relations with wider communities. Participant's economic resources were positively associated with an improvement in couple relationships, while anxiety was associated with a decline in relations with both the neighbourhood and the wider society. While neither prior experience of mass trauma, nor education or health vulnerability to COVID-19, were associated with relationship change, having time to talk, and younger age, was positively associated with improvement in couple relations. Findings suggest that anxiety can function to distance relationships during a time of stress, but perceived changes in relationships are little effected by experience of previous trauma. Relationship growth is likely to be greatest in those with better economic conditions. Practitioners need to be mindful of the impact of enhanced anxiety during the pandemic on interpersonal relations, and a potential threat to the relationships of older couples during this time of pandemic threat.

Background: Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution.Methods: We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings: In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5.Interpretation: Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes.Funding: Bill & Melinda Gates Foundation.

Objective To elicit what information and clinical decision-making processes physiotherapists use in the assessment and management of paediatric shoulder instability.\ud \ud Design Qualitative study. A modified nominal focus group technique, involving three clinical vignettes, was used to elicit physiotherapists' decision-making processes.\ud \ud Setting Physiotherapy departments from across four separate clinical sites.\ud \ud Subjects Twenty-five physiotherapists, (18F:7M), ranging from two to 29 years post qualification.\ud \ud Outcomes measures Thematic analysis. The initial round of coding was used to draw up a quantitative assessment of the diagnoses and map information used for clinical decision-making against the International Classification of Functioning (ICF) framework.\ud \ud Results The themes identified related to 'Differences in diagnoses, classification and diagnostic processes', 'Diagnostic process occurs over a long period of time', 'Management and prognosis are influenced by a number of factors' and 'Diagnostic test choices and prognosis influenced by factors beyond the patient injury' .\ud \ud Conclusion Current methods of assessment are prone to bias and error and may lead to inconsistent or delayed provision of essential care. Further work is needed to develop methods of measurement and frameworks which can accurately identify relevant physiological mechanisms and personal factors associated with shoulder instability as a part of the assessment/diagnostic process. (C) 2022 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The public and patients can be powerful sensors for shaping and powering healthcare research. They are joining research teams as investigators and collaborators to co-produce evidence for the practical use of interventions in clinical practice. While clinicians and researchers are encouraged by funders and policymakers to involve the public and patients as partners in research, knowledge on what involvement consists of is limited, and the continuum between consultation, collaboration and co-production are not clearly defined. In this article, we explore Patient and Public Involvement (PPI) and introduce greater involvement through research co-production. Co-production describes ways that research partnership can work through public and patient involvement and we outline the similarities of co-production to "The Commons", a strategy utilized by economists to increase effective use of resources. We share examples of how public and patient involvement have used co-production, to demonstrate financial and health benefits. We then outline practical challenges at system, social and cultural levels and consider how others have worked to resolve them. [Abstract copyright: Copyright © 2021 Elsevier B.V. All rights reserved.]

Rheumatoid arthritis (RA) is an inflammation-involved disorder and features the disruption of CD4+ T lymphocytes. Herein, we describe that microRNA-10b-5p (miR-10b) promotes RA progression by disrupting the balance between subsets of CD4+ T cells. MiR-10b-deficient mice protected against collagen antibody-induced arthritis (CAIA) model. RNA sequencing results indicated that disordered genes in miR-10b−/− CAIA model are closely associated with CD4+ T cells differentiation. Moreover, miR-10b mimics promoted Th1/Th17 and suppressed Th2/Treg cells differentiation, whereas miR-10b inhibitor induced contrary effects. In addition, GATA3 and PTEN was confirmed as two targets of miR-10b, and GATA3 siRNA could increase Th1 and reduce Th2 cells meanwhile PTEN siRNA could increase Th17 and decrease Treg cells. Furthermore, miR-10b inhibitor significantly ameliorated collagen-induced arthritis (CIA) development by attenuating the dysfunctional CD4+ T cell subpopulations. The present findings suggest that miR-10b could disrupt the balance of CD4+ T subsets, while suppressed miR-10b could attenuate the severity of experimental arthritis, which provided us a novel mechanistic and therapeutic insight into the RA.

Background Treatment of established depression is the dominant approach to care of older adults, but prevention holds much promise. Self-help interventions are a feasible preventive approach, since they are scalable and low cost. There are few trials in this area. Behavioral Activation (BA) is a credible candidate psychological approach, which has been shown to work in therapist led care but not been trialled in a self-help form. Aim To test the effectiveness of an unguided self-help intervention based on BA for older adults. Methods We compared a self-help intervention based on BA for older people (n = 172) to usual care (n = 160) in a pragmatic randomized controlled trial. Outcomes were depression status and severity (PHQ9) and health related quality of life (SF12). The primary timepoint of the primary outcome was depression at 4 months, with longer term follow up at 12 months to test sustained impact of the primary outcome. Results At 4 months adjusted PHQ-9 scores for BA self-help were 0.79 lower (95% CI: -1.70 to 0.13; p = 0.09) and the proportion of participants with case-level depression was significantly reduced (BA 31/137 (22.6%) versus usual care 41/141 (29.1%); Odds Ratio 0.48; 95% CI: 0.26–0.92; p = 0.03). There was no PHQ-9 difference at 12 months or for health related quality of life at any point (4 or 12 months). Discussion Self-help using BA for older people at risk of depression is a feasible and scalable intervention with potential short-term benefits in preventing depression.

This “Year in review” presents a selection of research themes and individual studies from the clinical osteoarthritis (OA) field (epidemiology and therapy) and includes noteworthy descriptive, analytical-observational, and intervention studies. The electronic database search for the review was conducted in Medline, Embase and medRxiv (15th April 2020 to 1st April 2021). Following study screening, the following OA-related themes emerged: COVID-19; disease burden; occupational risk; prediction models; cartilage loss and pain; stem cell treatments; novel pharmacotherapy trials; therapy for less well researched OA phenotypes; benefits and challenges of Individual Participant Data (IPD) meta-analyses; patient choice- balancing benefits and harms; OA and comorbidity; and inequalities in OA. Headline study findings included: a longitudinal cohort study demonstrating no evidence for a harmful effect of non-steroidal anti-inflammatory drugs (NSAIDs) in terms of COVID-19 related deaths; a Global Burden of Disease study reporting a 102% increase in crude incidence rate of OA in 2017 compared to 1990; a longitudinal study reporting cartilage thickness loss was associated with only a very small degree of worsening in pain over 2 years; an exploratory analysis of a non-OA randomised controlled trial (RCT) finding reduced risk of total joint replacement with an Interleukin -1β inhibitor (canakinumab); a significant relationship between cumulative disadvantage and clinical outcomes of pain and depression mediated by perceived discrimination in a secondary analysis from a RCT; worsening socioeconomic circumstances were associated with future arthritis diagnosis in an innovative natural experiment (with implications for unique research possibilities arising from the COVID-19 pandemic context).

Background Studies of racial disparities in care of patients admitted with an out-of-hospital cardiac arrest (OHCA) in the setting of acute myocardial infarction (AMI) have shown inconsistent results. Whether these differences in care exist in the universal healthcare system in United Kingdom is unknown. Methods Patients admitted with a diagnosis of AMI and OHCA between 2010 and 2017 from the Myocardial Ischaemia National Audit Project (MINAP) were studied. All patients were stratified based on ethnicity into a Black, Asian, or minority ethnicity (BAME) group vs a White group. We used multivariable logistic regression models to evaluate the predictors of clinical outcomes and treatment strategy. Results From 14,287 patients admitted with AMI complicated by OHCA, BAME patients constituted a minority of patients (1185 [8.3%]), compared with a White group (13,102 [91.7%]). BAME patients were younger (median age [interquartile range]) for BAME group, 58 [50-70] years; for White group, 65 [55-74] years). Cardiogenic shock (BAME group, 33%; White group, 20.7%; P < 0.001) and severe left ventricular impairment (BAME group, 21%; White group, 16.5%; P < 0.003) were more frequent among BAME patients. BAME patients were more likely to be seen by a cardiologist (BAME group, 95.9%; White group, 92.5%; P < 0.001) and were more likely to receive coronary angiography than the White group (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.2-1.88). The BAME group had significantly higher in-hospital mortality (OR 1.26, 95% CI 1.04-1.52) and re-infarction (OR 1.52, 95% CI 1.06-2.18) than the White group. Conclusions BAME patients were more likely to be seen by a cardiologist and receive coronary angiography than White patients. Despite this difference, the in-hospital mortality of BAME patients, particularly in the Asian population, was significantly higher., Graphical abstract

Pneumonia is a leading cause of mortality in limited resource settings (LRS), which are common in low- and middle-income countries (LMICs). Accurate referrals can reduce the devastating impact of pneumonia, especially in LRS. Discriminating pneumonia from other respiratory conditions based only on symptoms is a major challenge. Machine learning has shown promise in overcoming the diagnostic difficulties of pneumonia (i.e., low specificity of symptoms, lack of accessible diagnostic tests and varied clinical presentation). Many scientific papers are now focusing on deep-learning methods applied to clinical images, which is unaffordable for initial patient referral in LMICs. The current study used a dataset of 4500 patients (1500 patients affected by bronchitis, 3000 by pneumonia) from a middle-income country, containing information on subject population characteristics, symptoms and laboratory test results. Manual feature selection was performed, focusing on clinical symptoms that are easily measurable in LRS and in community settings. Three common machine learning methods were tested and compared: logistic regression; decision tree and support vector machine. Models were developed through a holdout process of training-validation and testing. We focused on six clinically relevant, easily interpreted patient symptoms as best indicators for pneumonia. Our final model was a decision tree, achieving an AUC of 93%, with the advantage of being fully intelligible and easily interpreted. The performance achieved suggested that intelligible machine learning models can enhance symptom-based referral of pneumonia in LRS and in community settings.

Background Heart failure (HF) is a chronic disease associated with a significant burden to patients, families, and health services. The diagnosis of HF can be easily missed owing to similar symptoms with other conditions especially respiratory diseases. Methods and Results We conducted a systematic review to determine the rates of HF and cardiomyopathy misdiagnosis and explored the potential causes. The included studies were narratively synthesized. Ten studies were identified including a total of 223,859 patients. There was a lack of definition of HF misdiagnosis in the studies and inconsistent diagnostic criteria were used. The rates of HF misdiagnosis ranged from 16.1% in hospital setting to 68.5% when general practitioner referred patients to specialist setting. The most common cause for misdiagnosis was chronic obstructive pulmonary disease (COPD). One study using a COPD cohort showed that HF was unrecognized in 20.5% of patients and 8.1% had misdiagnosis of HF as COPD. Another study suggests that anemia and chronic kidney disease are associated with an increase in the odds of unrecognized left ventricular systolic dysfunction. Other comorbidities such as obesity, old age, atrial fibrillation, and ischemic heart disease are prevalent in patients with a misdiagnosis of HF. Conclusions The misdiagnosis of HF is an unfortunate part of everyday clinical practice that occurs with a variable rate depending on the population studied. HF is frequently misdiagnosed as COPD. More research is needed to better understand the missed opportunities to correctly diagnose HF so that harm to patients can be avoided and effective treatments can be implemented.

Introduction The phase 3 FAST-Forward trial reported outcomes for 26 and 27 Gy schedules delivered in 5 fractions over 1 week versus 40 Gy in 15 fractions over 3 weeks in 4000 patients. We discuss concerns raised by the radiotherapy community in relation to implementing this schedule. Ipsilateral Breast Tumour Relapse (IBTR) Published estimated 5-year IBTR with 95% CI after 40 Gy in 15 fractions was 2.1% (95% CI 1.4–3.1), 1.7% (1.2–1.6) after 27 Gy and 1.4% (0.2–2.2) after 26 Gy, emphatically showing non-inferiority of the 5-fraction regimens. Subgroup analyses comparing IBTR in 26 Gy versus 40 Gy show no evidence of differential effect regarding age, grade, pathological tumour size, nodal status, tumour bed boost, adjuvant chemotherapy, HER2 status and triple negative status. The number of events in these analyses is small and results should be interpreted with caution. There was only 1 IBTR event post-mastectomy. Normal tissue effects The 26 Gy schedule, on the basis of similar NTE to 40 Gy in 15 fractions, is the recommended regimen for clinical implementation. There is a low absolute rate of moderate/marked NTE, these are predominantly moderate not severe change. Subgroup analyses comparing clinician-assessed moderate or marked adverse effect for 26 Gy versus 40 Gy show no evidence of differential effects according to age, breast size, surgical deficit, tumour bed boost, or adjuvant chemotherapy. Radiobiological considerations The design of the FAST-Forward trial does not control for time-related effects, and the ability to interpret clinical outcomes in terms of underlying biology is limited. There could conceivably be a time-effect for tumour control. A slight reduction in α/β estimate for the late normal tissue effects of test regimens might be a chance effect, but if real could reflect fewer consequential late effects due to lower rates of moist desquamation. Conclusion The 26 Gy 5-fraction daily regimen for breast radiotherapy can be implemented now.

PURPOSE: Musculoskeletal problems are the leading cause of chronic disability. Most patients in the UK seek initial care from general practitioners (GPs), who are struggling to meet demand. Patient direct access to National Health Service physiotherapy is one possible solution. The purpose of this study was to understand the experiences of patients, GPs, physiotherapists and clinical commissioners on direct access in a region in England with it commissioned. \ud \ud METHODS: The study was informed by Normalisation Process Theory (NTP). Data collection was via semi-structured individual face-to-face and telephone interviews with 22 patients and 20 health care professionals (HCPs). Data were analysed thematically using NPT. \ud \ud RESULTS: Three themes emerged: understanding physiotherapy and the direct access pathway; negotiating the pathway; making the pathway viable. HCPs saw direct access as acceptable. Whilst patients found the concept of direct access, those with complex conditions continued to see their GP as first point of contact. Some GPs and patients reported a lack of clarity around the pathway, reflected in ambiguous paperwork and inconsistent promotion. Operational challenges emerged in cross-disciplinary communication and between HCPs and patients, and lack of adequate resources. \ud \ud CONCLUSION: Direct access to NHS musculoskeletal physiotherapy is acceptable to patients and HCPs. There is need to ensure: effective communication between HCPs and with patients, clarity on the scope of physiotherapy and the direct access pathway, and sufficient resources to meet demand. Patient direct access can free GPs to focus on those patients with more complex health conditions who are most in need of their care.

\ud Background: Relationship between physical activity and fasting glucose in people with abnormal glucose metabolism is not well-known. This study was to investigate dose-response association between physical activity (PAT) and fasting glucose from two independent surveys among Chinese adults with abnormal glucose metabolism.\ud \ud Methods: 9419 adults with abnormal glucose metabolism from two independent surveys among Chinese adults were analyzed. Demographics, level of fasting glucose and PAT (in Met Score) were measured. Dose-response relationship between fasting glucose and PAT was assessed by natural cubic spline model. Certain threshold point was identified, and linear regression models were then used within each threshold interval to assess the liner relationship functions. Models were adjusted for confounding factors and were stratified in subgroup analyses by the main population characteristics including survey site, gender and age-group.\ud \ud Results: Overall the relationship between PAT and fasting glucose was not in a linear association (Linearity test: p < 0.0001). Level of fasting glucose was not associated with amount of PAT until a threshold point (square-rooted Met Score 66.6 (original Met score: 4436 MET-minutes per week), 95% confidence intervals (65.2-69.3 (4,251-4,802 MET-minutes per week)). After this threshold, an inverse association was observed: each increase of every standard deviation of square-rooted Met Score 29.8 (888 MET-minutes per week) was associated with a 0.25 mmol/L decrease in fasting glucose, with adjustment for confounding factors. The patterns of relationship were tested to be consistent in subgroup analyses by survey site, gender and age group.\ud \ud Conclusions: Our study indicated that among adults with abnormal glucose metabolism the level of fasting glucose was only inversely associated with square-rooted Met Score beyond a certain square-rooted Met Score amount.

Background The mental health toll of a second lockdown during the COVID-19 pandemic has not been yet examined. The purpose of the study was to examine psychological predictors before the second lockdown and their impact on the prediction of ICD-11 probable Adjustment Disorder (AjD) after the second lockdown.\ud \ud Methods Using a longitudinal design we surveyed a national representative sample of the Israeli population before and after the second lockdown. In wave 1, 1029 were surveyed (Response Rate (RR) = 76.17%) and in Wave 2, 764 were surveyed (RR = 74.24%). Participants answer a questionnaire tapping COVID-19 stressful related events, uncertainty, probable depression predicting ICD-11 and probable AjD.\ud \ud Results The main predictors of AjD after the second lockdown were sex (OR = 1.868; p ≤0.01), having a COVID-19 occupational related stressful event (OR = 2.855; p

Primary cardiac angiosarcomas are rare malignant tumors with a very poor prognosis. We present a case of a 48-year-old man with no previous cardiac history who developed an incessant focal atrial tachycardia complicated by tachycardia-mediated cardiomyopathy as a consequence of cardiac angiosarcoma. (Level of Difficulty: Beginner.), Central Illustration

Objective To determine the effect of patient and treatment parameters on 19 embryo morphokinetic parameters using pronuclear fading as time zero. Design Single-site, retrospective cohort analysis. Setting Fertility treatment center. Patients(s) Patients undergoing treatment between September 2014 and January 2016 (n = 639) whose embryos were cultured in the EmbryoScope for 6 days (n = 2,376). Intervention(s) None. Main Outcome Measure(s) Multiple regression analysis of body mass index; maternal age; infertility diagnosis; treatment type; suppression protocol on time to each cellular division (tn): t2, t3, t4, t5, t6, t7, t8, t9, time to start of compaction (tM), start of blastulation (tSB), full blastocyst (tB); and interval measurements: s2, s3, cc2, cc3, cc4, t9-tM, tM-tSB, and tSB-tB. Beta coefficients were analyzed to quantify any significant effects. Result(s) Embryos appeared to be subtly affected by patient and treatment parameters, exhibiting complex relationships between various morphokinetic parameters and specific patient and treatment factors, rather than a systemic effect. Conclusion(s) These findings outline the need for the consideration of confounding factors when assessing an embryo’s ability to achieve implantation. Although morphokinetic parameters have been related to embryo viability, it is likely that this will vary depending on the embryo’s origin.

Objectives\ud The aim of the study was to assess the magnitude of wealth inequalities in the development of diarrhoea among under-five children in low- and middle-income countries (LMICs) and to identify and quantify contextual and compositional factors' contribution to the inequalities.\ud \ud Design\ud This is a cross-sectional study.\ud \ud Methods\ud We used cross-sectional data from 57 Demographic and Health Surveys conducted between 2010 and 2018 in LMICs. Descriptive statistics were used to understand the gap in having diarrhoea between the children from poor and non-poor households and across the selected covariates using Fairlie decomposition techniques with multivariable binary logistic regressions at P = 0.05.\ud \ud Results\ud Of the 57 countries, we found a statistically significant pro-poor odds ratio in only 29 countries, 7 countries showed pro-non-poor inequality and others showed no statistically significant inequality. Among the countries with statistically significant pro-poor inequality, the risk difference was largest in Cameroon (94.61/1000), whereas the largest pro-non-poor risk difference in diarrhoea was widest in Timor-Leste (−41.80/1000). Important factors responsible for pro-poor inequality varied across countries. The largest contributors to the pro-poor inequalities in having diarrhoea are maternal education, access to media, neighbourhood socio-economic status, place of residence, birth order and maternal age.\ud \ud Conclusion\ud Diarrhoea remains a major challenge in most LMICs, with a wide range of pro-poor inequalities. These disparities were explained by both compositional and contextual factors, which varied widely across the countries. Thus, multifaceted geographically specific economic alleviation intervention may prove to be a potent approach for addressing the poor and non-poor differentials in the risk of diarrhoea with policies tailored to country-specific risk factors. There is a need for further investigation of factors that drive pro-non-poor inequalities found in 9 of the LMICs.

BackgroundThe COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic.MethodsThis national death registry included all adult (aged ≥18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death.FindingsBetween 2nd March and 30th June 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25,611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15,938 deaths; a proportional increase of 21%) with the remainder occurring at home (16,190 deaths; a proportional increase of 39%). At home, only 14% of 16,190 excess deaths were related to COVID-19, with 5,963 deaths due to cancer and 2,485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25,611 excess deaths were related to COVID-19, 5,539 of which were due to respiratory disease and most of these (4,315 deaths) involved COVID-19. In hospital, there were 16,174 fewer deaths than expected which did not involve COVID-19, and there were 4,088 fewer deaths due to cancer and 1,398 fewer deaths due to cardiac disease than expected.InterpretationThe COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions.FundingThe study is unfunded.

Anxiety, perceived control and trust in information sources have all been shown to significantly influence health and social behaviours during pandemics. We measured these factors in a nationally representative on-street survey collected across five regions of Thailand (N = 1000, May 2020, response rate 82.6%). Anxiety was positively associated with stocking up on food (OR 2.62 (95% CI 1.88–3.66)) and taking vitamins (OR 2.37 (1.59–3.54)); perceived control with (recommended) coughing into an elbow (OR 2.42 (1.80–3.26)), checking on others (OR 1.52 (1.00–2.31)), and negatively with stockpiling (OR 0.72 (0.55-0.96)). Those relying on family/friends, doctors online or foreign sources were more likely to take vitamins (ORs 4.11, 2.88. 2.82), respondents using TV news less likely to stock up on food (OR 0.57 (0.37-0.86)) and to wear a mask for self-protection (OR 0.27 (0.10-0.73)). Comparing findings with analogous cross-sectional data on anxiety collected at the start of the pandemic (Feb 2020, Goodwin et al., 2020) there was no significant difference between personal anxiety in the two surveys (F (1, 1197) = 0.72, p = .40)) but perceived control was lower in the later survey (F (1, 1197) = 6.72 p = .01)). Findings suggest reduced perceived control as the pandemic developed and illuminate possible negative impacts of anxiety and low sense of control on pandemic behaviours.

Infectious diseases remain one of the major causes of human mortality and suffering. Mathematical models have been established as an important tool for capturing the features that drive the spread of the disease, predicting the progression of an epidemic and hence guiding the development of strategies to control it. Another important area of epidemiological interest is the development of geostatistical methods for the analysis of data from spatially referenced prevalence surveys. Maps of prevalence are useful, not only for enabling a more precise disease risk stratification, but also for guiding the planning of more reliable spatial control programmes by identifying affected areas. Despite the methodological advances that have been made in each area independently, efforts to link transmission models and geostatistical maps have been limited. Motivated by this fact, we developed a Bayesian approach that combines fine-scale geostatistical maps of disease prevalence with transmission models to provide quantitative, spatially explicit projections of the current and future impact of control programs against a disease. These estimates can then be used at a local level to identify the effectiveness of suggested intervention schemes and allow investigation of alternative strategies. The methodology has been applied to lymphatic filariasis in East Africa to provide estimates of the impact of different intervention strategies against the disease., Comment: 48 pages

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Background The patient characteristics, therapy received and outcomes after one or more implantable cardioverter defibrillator (ICD) generator changes from contemporary practice is not well known. Methods We conducted a health service evaluation of patients who underwent ICD implantation and generator change. Patients who had generator changes from February 2016 to October 2019 were identified from our database and electronic records were reviewed for patient characteristics, number of generator changes, receipt of therapy and death. Results Our database included 88 patients with a generator change. A total of 22 patients (25.0%) received dual chamber ICD, 10 patients (11.4%) received single chamber ICD, 54 patients (61.3%) received cardiac resynchronization therapy defibrillator and 2 patients (2.3%) received subcutaneous ICD. A second generator change occurred in 18 patients and a third generator changes was performed in 6 patients. There were 29 deaths and a follow up period of 9.4 ± 2.9 years. From implant to initial generator change 39 patients had appropriate antitachycardia pacing (ATP), 6 patient had inappropriate ATP, 29 patients had appropriate shocks and 5 patients had an inappropriate shock. Between the 1st and 2nd generator change and the 2nd and 3rd there were no cases of inappropriate ATP or shock. Overall, 42 patients out of the 88 had appropriate therapy (47.7%) and 7 patients had inappropriate therapy (8.0%). Conclusions Most patients with ICDs do not receive therapy and a minority have inappropriate therapy which typically occur before the first generator change as we observed no inappropriate therapy beyond the first generator change.

Questions What are the experiences of physiotherapists delivering care for people with knee osteoarthritis? How do these experiences align with the national Clinical Care Standard? Design A qualitative study using individual interviews. Participants Twenty-two Australian physiotherapists (mean age 34 years, 50% female) with experience in providing care for people with knee osteoarthritis. Methods Physiotherapists participated in semi-structured individual telephone interviews. Questions were informed by seven quality statements from the national Knee Osteoarthritis Clinical Care Standard. Thematic analysis was undertaken, with themes/subthemes inductively derived. Interview data were also deductively analysed according to the Clinical Care Standard. Results Five themes emerged. First, physiotherapists focused on biomedical assessment with little psychosocial consideration. They managed ‘mechanical’ aspects of knee osteoarthritis, aiming to restore functional ability. Second, physiotherapists’ perceived their role as primarily providing goal-orientated personalised exercise via short-term episodic care. Knee surgery was considered a last option, but physiotherapists ‘prepped’ patients who decided on surgery. Third, clinical challenges included patient comorbidity, unsatisfactory patient adherence and a patient’s desire for a ‘quick fix’. The other two themes were: physiotherapists described a mismatch between what they know and what they do regarding imaging, weight management and manual therapy; and physiotherapists viewed weight loss, medication and surgical advice as outside of their professional role. Conclusion Physiotherapists’ reported experiences of delivering care for people with knee osteoarthritis were mostly consistent with the quality care standard. Care may be improved by increasing the focus on psychosocial aspects of care, offering longer-term reviews, and being more proactive with advice and/or referral regarding weight loss, pain medications and knee surgery. By describing the potential benefits and harms of common osteoarthritis medications and surgical interventions, physiotherapists will ensure that their patients are fully informed about all their treatment options.

Summary Background Sciatica has a substantial impact on individuals and society. Stratified care has been shown to lead to better outcomes among patients with non-specific low back pain, but it has not been tested for sciatica. We aimed to investigate the clinical and cost-effectiveness of stratified care versus non-stratified usual care for patients presenting with sciatica in primary care. Methods We did a two-parallel arm, pragmatic, randomised controlled trial across three centres in the UK (North Staffordshire, North Shropshire/Wales, and Cheshire). Eligible patients were aged 18 years or older, had a clinical diagnosis of sciatica, access to a mobile phone or landline number, were not pregnant, were not currently receiving treatment for the same problem, and had no previous spinal surgery. Patients were recruited from general practices and randomly assigned (1:1) by a remote web-based service to stratified care or usual care, stratified by centre and stratification group allocation. In the stratified care arm, a combination of prognostic and clinical criteria associated with referral to spinal specialist services were used to allocate patients to one of three groups for matched care pathways. Group 1 was offered brief advice and support in up to two physiotherapy sessions; group 2 was offered up to six physiotherapy sessions; and group 3 was fast-tracked to MRI and spinal specialist assessment within 4 weeks of randomisation. The primary outcome was self-reported time to first resolution of sciatica symptoms, defined as “completely recovered” or “much better” on a 6-point ordinal scale, collected via text messages or telephone calls. Analyses were by intention to treat. Health-care costs and cost-effectiveness were also assessed. This trial is registered on the ISRCTN registry, ISRCTN75449581. Findings Between May 28, 2015, and July 18, 2017, 476 patients from 42 general practices around three UK centres were randomly assigned to stratified care or usual care (238 in each arm). For the primary outcome, the overall response rate was 89% (9467 of 10 601 text messages sent; 4688 [88%] of 5310 in the stratified care arm and 4779 [90%] of 5291 in the usual care arm). Median time to symptom resolution was 10 weeks (95% CI 6·4–13·6) in the stratified care arm and 12 weeks (9·4–14·6) in the usual care arm, with the survival analysis showing no significant difference between the arms (hazard ratio 1·14 [95% CI 0·89–1·46]). Stratified care was not cost-effective compared to usual care. Interpretation The stratified care model for patients with sciatica consulting in primary care was not better than usual care for either clinical or health economic outcomes. These results do not support a transition to this stratified care model for patients with sciatica. Funding National Institute for Health Research.

Objectives To investigate ethnic differences in falls and road traffic injuries (RTIs) in Scotland. Study design A retrospective cohort of 4.62 million people, linking the Scottish Census 2001, with self-reported ethnicity, to hospitalisation and death records for 2001–2013. Methods We selected cases with International Classification of Diseases–10 diagnostic codes for falls and RTIs. Using Poisson regression, age-adjusted risk ratios (RRs, multiplied by 100 as percentages) and 95% confidence intervals (CIs) were calculated by sex for 10 ethnic groups with the White Scottish as reference. We further adjusted for country of birth and socio-economic status (SES). Results During about 49 million person-years, there were 275,995 hospitalisations or deaths from fall-related injuries and 43,875 from RTIs. Compared with the White Scottish, RRs for falls were higher in most White and Mixed groups, e.g., White Irish males (RR: 131; 95% CI: 122–140) and Mixed females (126; 112–143), but lower in Pakistani males (72; 64–81) and females (72; 63–82) and African females (79; 63–99). For RTIs, RRs were higher in other White British males (161; 147–176) and females (156; 138–176) and other White males (119; 104–137) and females (143; 121–169) and lower in Pakistani females (74; 57–98). The ethnic variations differed by road user type, with few cases among non-White motorcyclists and non-White female cyclists. The RRs were minimally altered by adjustment for country of birth or SES. Conclusion We found important ethnic variations in injuries owing to falls and RTIs, with generally lower risks in non-White groups. Culturally related differences in behaviour offer the most plausible explanation, including variations in alcohol use. The findings do not point to the need for new interventions in Scotland at present. However, as the ethnic mix of each country is unique, other countries could benefit from similar data linkage-based research., Highlights • Ethnic inequalities in injuries are demonstrated in Scotland based on a large sample size and a fine ethnic granularity. • White minority ethnic groups had the highest risks of fall-related injuries in Scotland. • Fall-related injuries were the least likely in the Pakistani population. • Ethnic differences in road traffic injuries varied by the type of road user. • Ethnic differences in injuries were not explained by socio-economic status or country of birth.

Objectives To determine which ultrasound measurement for predicted fetal macrosomia most accurately predicts adverse delivery and neonatal outcomes. Study Design Four biomedical databases searched for studies published after 1966. Randomised trials or observational studies of women with singleton pregnancies, resulting in a term birth who have undergone an index test of interest measured and recorded as predicted fetal macrosomia ≥28 weeks. Adverse outcomes of interest included shoulder dystocia, brachial plexus injury (BPI) and Caesarean section. Results Twenty-five observational studies (13,285 participants) were included. For BPI, the only significant positive association was found for Abdominal Circumference (AC) to Head Circumference (HC) difference > 50 mm (OR 7.2, 95 % CI 1.8–29). Shoulder dystocia was significantly associated with abdominal diameter (AD) minus biparietal diameter (BPD) ≥ 2.6 cm (OR 4.2, 95 % CI 2.3–7.5, PPV 11 %) and AC > 90th centile (OR 2.3, 95 % CI 1.3–4.0, PPV 8.6 %) and an estimated fetal weight (EFW) > 4000 g (OR 2.1 95 %CI 1.0–4.1, PPV 7.2 %). Conclusions Estimated fetal weight is the most widely used ultrasound marker to predict fetal macrosomia in the UK. This study suggests other markers have a higher positive predictive value for adverse outcomes associated with fetal macrosomia.

As UNAIDS 90-90-90 targets for people living with HIV are increasingly being reached in many contexts, health-related quality of life (HRQoL), the ”fourth 90”, warrants special attention. HIV-related stigma and discrimination remain major barriers for overall HRQoL despite impressive clinical and virological improvements in HIV care. We reviewed original publications examining the impact of interventions to reduce stigma as experienced by people living with HIV in all income settings between 2010–2018. Our search identified a lack of well-designed intervention studies that documented stigma reduction and few studies that specifically assessed the impact of stigma on HRQoL. Further, few interventions targeted discrimination from providers outside HIV-specific care or involved people living with HIV in both the design and implementation. Lastly, evidence on methods to reduce stigma among several underrepresented key populations and geographic regions was limited and research on intersectional stigma, i.e. the convergence of multiple stigmatized identities, needs further attention.

Objectives: To describe and compare trends in the frequency of opioid prescribing/dispensing in English and Swedish patients with osteoarthritis prior to total knee replacement (TKR). Methods: 49,043 patients from an English national database (Clinical Practice Research Datalink) and 5,955 patients from the Swedish Skåne Healthcare register undergoing TKR between 2015 and 2019 were included, alongside 1:1 age-, sex-, and practice (residential area) matched controls. Annual prevalence and prevalence rates ratio (PRR) of opioid prescribing/dispensing (any, by strength) in the 10 years prior to TKR (or matched index date for controls) were estimated using Poisson regression. Results: In England and Sweden, the prevalence of patients with osteoarthritis receiving any opioid prior to TKR increased towards the date of surgery from 24% to 44% in England and from 16% to 33% in Sweden. Prescribing in controls was stable, resulting in an increasing PRR (1.6–2.7) between 10 and 1 years prior to index date in both countries. No relevant cohort or period effect was observed in either country. Prevalence of opioid prescribing was higher in English cases and controls; weaker opioids were more commonly prescribed in England, stronger opioids in Sweden. Conclusions: Temporal prevalence patterns of opioid prescribing between cases and controls are similar in England and Sweden. Opioids are still commonly used in TKR cases in both countries highlighting the lack of valid alternatives for OA pain management.

Spiral ligament fibrocytes of the cochlea play homoeostatic roles in hearing and their degeneration contributes to hearing loss. Culturing fibrocytes in vitro provides a way to evaluate their functional characteristics and study possible therapies for hearing loss. We investigated whether in vivo characteristics of fibrocytes could be recapitulated in vitro by modifying the culture substrates and carried out proof of concept studies for potential transplantation of culture cells into the inner ear. Fibrocytes cultured from 4 to 5-week old CD/1 mice were grown on 2D substrates coated with collagen I, II, V or IX and, after harvesting, onto or into 3D substrates (hydrogels) of collagen I alone or mixed collagen I and II at a 1:1 ratio. We also assessed magnetic nanoparticle (MNP) uptake. Cell counts, immunohistochemical and ultrastructural studies showed that fibrocytes grown on 2D substrates proliferated, formed both small spindle-shaped and large flat cells that avidly took up MNPs. Of the different collagen coatings, only collagen II had an effect, causing a reduced size of the larger cells. On hydrogels, the cells were plump/rounded with extended processes, resembling native cells. They formed networks over the surface and became incorporated into the gel. In all culture formats, the majority co-expressed caldesmon, aquaporin 1, S-100 and sodium potassium ATPase, indicating a mixed or uncharacterised phenotype. Time-course experiments showed a decrease to ∼50% of the starting population by 4d after seeding on collagen I hydrogels, but better survival (∼60%) was found on collagen I + II gels, whilst TEM revealed the presence of apoptotic cells. Cells grown within gels additionally showed necrosis. These results demonstrate that fibrocytes grown in 3D recapitulate in vivo morphology of native fibrocytes, but have poorer survival, compared with 2D. Therefore hydrogel cultures could be used to study fibrocyte function and might also offer avenues for cell-replacement therapies, but need more optimization for therapeutic use. Fibrocyte function could be modified using MNPs in combination, for example, with gene transfection.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Telemonitoring of circadian and sleep cycles could identify shift workers at increased risk of poor health, including cancer and cardiovascular diseases, thus supporting personalized prevention.The Circadiem cross-sectional study aimed at determining early warning signals of risk of health alteration in hospital nightshifters (NS) versus dayshifters (DS, alternating morning and afternoon shifts). Circadian rhythmicity in activity, sleep, and temperature was telemonitored on work and free days for one week. Participants wore a bluetooth low energy thoracic accelerometry and temperature sensor that was wirelessly connected to a GPRS gateway and a health data hub server. Hidden Markov modelling of activity quantified Rhythm Index, rest quality (probability, p1-1, of remaining at rest), and rest duration. Spectral analyses determined periods in body surface temperature and accelerometry. Parameters were compared and predictors of circadian and sleep disruption were identified by multivariate analyses using information criteria-based model selection. Clusters of individual shift work response profiles were recognized.Of 140 per-protocol participants (133 females), there were 63 NS and 77 DS. Both groups had similar median rest amount, yet NS had significantly worse median rest-activity Rhythm Index (0·38 [IQR, 0·29-0·47] vs. 0·69 [0·60-0·77], p0·0001) and rest quality p1-1 (0·94 [0·94-0·95] vs 0·96 [0·94-0·97], p0·0001) over the whole study week. Only 48% of the NS displayed a circadian period in temperature, as compared to 70% of the DS (p=0·026). Poor p1-1 was associated with nightshift work on both work (p0·0001) and free days (p=0·0098). The number of years of past night work exposure predicted poor rest-activity Rhythm Index jointly with shift type, age and chronotype on workdays (p= 0·0074), and singly on free days (p=0·0005).A dedicated analysis toolbox of streamed data from a wearable device identified circadian and sleep rhythm markers, that constitute surrogate candidate endpoints of poor health risk in shift-workers.French Agency for Food, Environmental and Occupational HealthSafety (EST-2014/1/064), University of Warwick, Medical Research Council (United Kingdom, MR/M013170), Cancer Research UK(C53561/A19933).

The theory of critical slowing down states that a system displays increasing relaxation times as it approaches a critical transition. These changes can be seen in statistics generated from timeseries data, which can be used as early warning signals of a transition. Such early warning signals would be of value for emerging infectious diseases or to understand when an endemic disease is close to elimination. However, in applications to a variety of epidemiological models there is frequent disagreement with the general theory of critical slowing down, with some indicators performing well on prevalence data but not when applied to incidence data. Furthermore, the alternative theory of critical speeding up predicts contradictory behaviour of early warning signals prior to some stochastic transitions. To investigate the possibility of observing critical speeding up in epidemiological models we characterise the behaviour of common early warning signals in terms of a system’s potential surface and noise around a quasi-steady state. We then describe a method to obtain these key features from timeseries data, taking as a case study a version of the SIS model, adapted to demonstrate either critical slowing down or critical speeding up. We show this method accurately reproduces the analytic potential surface and diffusion function, and that these results can be used to determine the behaviour of early warning signals and correctly identify signs of both critical slowing down and critical speeding up.

Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.

Actions to address different forms of malnutrition are typically managed by separate communities, policies, programmes, governance structures, and funding streams. In contrast, double duty actions, which aim to simultaneously tackle both undernutrition and problems of overweight, obesity and diet-related non-communicable diseases (DR-NCDs) have been proposed as a way to effectively address malnutrition in all its forms in a more holsitic way. This paper identifies ten double duty actions that have strong potential to reduce the risk of both undernutrition and obesity/DR-NCDs. It does so by : 1) summarizing evidence on common drivers of different forms of malnutrition; 2) documenting examples of unintended harm caused by some undernutrition-focused programmes on obesity/DR-NCDs; and 3) highlighting a few examples of first double duty actions undertaken to tackle multiple forms of malnutrition. We find that undernutrition and obesity/DR-NCDs are intrinsically linked through early life nutrition; dietary quality; food environments; and socioeconomic factors. There is some evidence that undernutrition-focused programs have raised risks of poor quality diets and obesity/DR-NCDs, especially in countries undergoing a rapid nutrition transition. The paper builds on this evidence to develop a framework to guide the design of double duty approaches and strategies, and defines the first steps needed to deliver them. With a clear package of double duty actions now identified, there is an urgent need to move forward with double duty actions to address malnutrition in all its forms.

Background:\ud Total knee replacement (TKR) is the commonest joint arthroplasty procedure worldwide. Despite excellent outcomes, some studies have reported dissatisfaction in up to 20% of patients.\ud \ud There is evidence of an association between the biochemical stress response to surgery and outcomes. The objective of this study is to describe the stress biomarker profile for TKR, and correlate this with patient outcomes.\ud \ud Methods:\ud A prospective cohort study of 50 patients undergoing primary TKR was conducted. Serum IL-6, TNF-α, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were measured immediately pre- and post-operatively, and on Days 1 and 3. Follow-up questionnaires including the Oxford Knee Score (OKS) and EuroQol five dimensions (EQ-5D) were completed at 12-months.\ud \ud Univariate analysis was completed using a linear regression model (p

Objective\ud Treat-to-target in rheumatoid arthritis (RA) recommends targeting remission, with low disease activity (LDA) being an alternative goal. When deciding to target remission or LDA, important considerations are the likelihood of attaining them, and their impacts on function and healthrelated quality of life (HRQoL). We have addressed this by studying: (a) the frequency of remission and LDA/remission; (b) DAS28-ESR trends after remission; (c) ability of remission vs. LDA to identify patients with normal function (HAQ ≤0.5) and HRQoL (EQ-5D ≥ the normal population).\ud \ud Methods\ud We studied 571 patients in two clinical trials, and 1,693 patients in a 10-year routine care cohort. We assessed the frequency and sustainability of remission and LDA/remission, variability in DAS28-ESR after remission, and sensitivity/specificity of remission and LDA/remission at identifying patients with low disability levels and normal HRQoL using Receiver Operator Characteristic (ROC) curves.\ud \ud Results\ud Point remission and remission/LDA were common (achieved by 35-58% and 49-74% of patients, respectively), but were rarely sustained (sustained remission and remission/LDA achieved by 5-9% and 9-16% of patients, respectively). Following attaining remission, DAS28-ESR levels varied substantially. Despite this, of those patients attaining point remission, the majority (53-61%) were in remission at study end-points. Whilst remission was highly specific at identifying patients with low disability (85-91%) it lacked sensitivity (51-57%); similar findings were seen for normal HRQoL (specificity 78-86%; sensitivity 52-59%). The optimal DAS28-cut-off to identify individuals with low disability and normal HRQoL was around the LDA threshold.\ud \ud Conclusions\ud Our findings support both the treat-to-target goals. Attaining remission is highly specific for attaining low disability and normal HRQoL, although many patients with more active disease also have good function and HRQoL. Attaining a DAS28-ESR ≤3.2 has a better balance of specificity and sensitivity for attaining these outcomes, with the benefit of being more readily achievable. Although sustaining these targets over time is rare, even attaining them on a oneoff basis leads to better function and HRQoL outcomes for patients.

Background Case-mix adjustment is an established method to take account of variations across cohorts in baseline patient factors, when comparing health outcomes. Although commonplace, there is a lack of evidence as to the most appropriate case-mix adjustment model to use to enable fair comparisons of PROM data in musculoskeletal services. Objectives To conduct a systematic review summarising evidence of the development, validation, and performance of musculoskeletal case-mix adjustment models, and to make recommendations for future methods. Data Sources Searches included; AMED, CINAHL, EMBASE, HMIC, MEDLINE, and grey literature. Eligibility Criteria Studies; from January 1992-May 2017, English language, musculoskeletal adult population, developing or validating a case-mix adjustment model, using a relevant PROM, and using patient factors feasible for clinical collection. Data Synthesis Two reviewers evaluated selected papers. The CASP Cohort Tool was used to assess quality. Results Fourteen studies were included; eight US studies on the Focus on Therapeutic Outcomes model (pooled n = 546,726 patients (with pre/post treatment data)) and six UK studies related to the UK National PROMs Programme model (pooled n = 282,424 patients (with pre/post treatment data)). The majority used retrospective data, restricted to complete datasets. Both US and UK models showed good predictive ability (R2 18-42%). Common model variables were; baseline PROM score, age, sex, comorbidities, symptom duration, and surgical history. Reduced quality scores were mainly due to acceptability of patient recruitment, and completeness and length of patient follow up. Conclusion Significant methodological crossover was found. Further studies are however needed to externally validate and develop models across musculoskeletal settings. PROSPERO database(CRD42017055948).

Swearing produces effects that are not observed with other forms of language use. Thus, swearing is powerful. It generates a range of distinctive outcomes: physiological, cognitive, emotional, pain-relieving, interactional and rhetorical. However, we know that the power of swearing is not intrinsic to the words themselves. Hence, our starting question is: How does swearing get its power? In this Overview Paper, our aim is threefold. (1) We present an interdisciplinary analysis of the power of swearing (‘what we know’), drawing on insights from cognitive studies, pragmatics, communication, neuropsychology, and biophysiology. We identify specific effects of swearing, including, inter alia: emotional force and arousal; increased attention and memory; heightened autonomic activity, such as heart rate and skin conductance; hypoalgesia (pain relief); increased strength and stamina; and a range of distinctive interpersonal, relational and rhetorical outcomes. (2) We explore existing (possible) explanations for the power of swearing, including, in particular, the hypothesis that aversive classical conditioning takes place via childhood punishments for swearing. (3) We identify and explore a series of questions and issues that remain unanswered by current research/theorising (‘what we don’t know’), including the lack of direct empirical evidence for aversive classical conditioning; and we offer directions for future research.

Introduction\ud This study sought to identify the availability of automated external defibrillators (AEDs) in schools in the region served by West Midlands Ambulance Service University NHS Trust (WMAS), United Kingdom, and the number of out-of-hospital cardiac arrests (OHCA) that occurred at or near to schools. A secondary aim was to explore the cost effectiveness of school-based defibrillators.\ud \ud Methods\ud This observational study used data from the national registry for OHCA (University of Warwick) to identify cases occurring at or near schools between January 2014 and December 2016 in WMAS region (n = 11,399). A school survey (n = 2,453) was carried out in September 2017 to determine the presence of AEDs and their registration status with WMAS. Geographical Information System mapping software identified OHCAs occurring within a 300-metre radius of a school. An economic analysis calculated the cost effectiveness of school-based AEDs.\ud \ud Results\ud A total of 39 (0.34%) of all OHCAs occurred in schools, although 4,250 (37.3%) of OHCAs in the region were estimated to have occurred within 300 metres of a school. Of 323 school survey responses, 184 (57%) had an AED present, of which 24 (13.0%) were available 24 h/day. Economic modelling of a school-based AED programme showed additional quality-adjusted life years (QALY) of 0.26 over the lifetime of cardiac arrest survivors compared with no AED programme. The incremental cost-effectiveness ratio (ICER) was £8,916 per QALY gained.\ud \ud Conclusion\ud Cardiac arrests in schools are rare. Registering AEDs with local Emergency Medical Services and improving their accessibility within their local community would increase their utility.

Although ascites is the most frequent first decompensating event in cirrhosis, the clinical course after ascites as theA total of 622 patients with cirrhosis presenting with grade 2/3 ascites as theThe mean age was 57 ± 11 years, and most patients were male (n = 423, 68%) with alcohol-related (n = 366, 59%) and viral (n = 200,32%) liver disease as the main aetiologies. In total, 323 (52%) patients presented with grade 2 and 299 (48%) with grade 3 ascites. The median Child-Pugh score at presentation was 8 (IQR 7-9), and the mean model for end-stage liver disease (MELD) was 15 ± 6. During a median follow-up period of 49 months, 350 (56%) patients experienced further decompensation: refractory ascites (n = 130, 21%), hepatic encephalopathy (n = 112, 18%), spontaneous bacterial peritonitis (n = 32, 5%), hepatorenal syndrome-acute kidney injury (n = 29, 5%). Variceal bleeding as an isolated further decompensation event was rare (n = 18, 3%), whereas non-bleeding further decompensation (n = 161, 26%) and ≥2 concomitant further decompensation events (n = 171, 27%) were frequent. Transjugular intrahepatic portosystemic shunt was used in only 81 (13%) patients. In patients presenting with grade 2 ascites, MELD ≥15 indicated a considerable risk for further decompensation (subdistribution hazard ratio [SHR] 2.18;Further decompensation is frequent in patients with ascites as aDecompensation (the development of symptoms as a result of worsening liver function) marks a turning point in the disease course for patients with cirrhosis. Ascites (

Globally, 4.4% of the world's population suffer from depressive disorder, and 3.6% from anxiety disorder. Previous work found considerable negotiation between providers and patients about the nature of mental health problems and frequent patient resistance to treatment. However, how doctor-patient shared understanding of the problem is reflected in treatment recommendations and whether this is consequential for patient acceptance of treatment is poorly understood. This study explored shared understanding of the problem and patient acceptance of treatment using conversation analysis. In 52 U.K. video recorded primary care consultations (collected July 2014-April 2015), 33 treatment recommendations for medication or talking therapy were identified. Shared understanding was explored focusing on: whether the patient presented the mental health problem as their primary initial concern and how they characterised the concern; whether the mental health concern was raised by the patient; and how the doctor aligned with the patient's earlier characterisation of the problem in the treatment recommendation itself. These phenomena were coded for each treatment recommendation and the impact on treatment acceptance was explored. Patients accepted the recommendation immediately in 38% cases and actively resisted in 62% cases. However, two communication behaviors were associated with patient acceptance: recommending treatment for the patient's initial focal concern and doctors' turn design in the recommendation itself, i.e., using the patient's earlier words from the initial problem presentation to describe and characterise the problem. Given the global burden of mental health problems and frequent patient resistance to treatment, understanding how professionals can engage more closely with the patient's perspective is important. When doctors use the patient's precise words from the initial problem presentation in the treatment recommendation, this displays an understanding of the patient's perspective and personalisation of treatment based on the underlying biomedical or social causes, which then impacts on patient acceptance of treatment.

Objectives Accurate and timely diagnosis of pneumonia complicating stroke remains challenging and the diagnostic accuracy of chest X-ray (CXR) in the setting of stroke-associated pneumonia (SAP) is uncertain. The overall objective of this study was to evaluate the use of pulmonary computed tomography (CT) in diagnosis of suspected SAP. Materials and Methods Patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH) were recruited within 24h of clinically suspected SAP and underwent non-contrast pulmonary CT within 48h of antibiotic initiation. CXR and pulmonary CT were reported by two radiologists. Pulmonary CT was used as the reference standard for final diagnosis of SAP. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and diagnostic odds ratio (OR) for CXR were calculated. Results 40 patients (36 IS, 4 ICH) with a median age of 78y (range 44y-90y) and a median National Institute of Health Stroke Scale score of 13 (range 3-31) were included. All patients had at least one CXR and 35/40 patients (88%) underwent pulmonary CT. Changes consistent with pneumonia were present in 15/40 CXRs (38%) and 12/35 pulmonary CTs (34%). 9/35 pulmonary CTs (26%) were reported normal. CXR had a sensitivity of 58.3%, specificity of 73.9%, PPV of 53.8 %, NPV of 77.2 %, diagnostic OR of 3.7 (95% CI 0.7 - 22) and an accuracy of 68.5% (95% CI 50.7% -83.1%). Discussion CXR has limited diagnostic accuracy in SAP. The majority of patients started on antibiotics had no evidence of pneumonia on pulmonary CT with potential implications for antibiotic stewardship. Conclusions Pulmonary CT could be applied as a reference standard for evaluation of clinical and biomarker diagnostic SAP algorithms in multi-center studies.