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Introduction Injury is a major cause of morbidity and mortality in low- and middle-income countries. Effective trauma surveillance is imperative to guide research and quality improvement interventions, so an accurate metric for quantifying injury severity is crucial. The objectives of this study are (1) to assess the feasibility of calculating five injury scoring systems - ISS (injury severity score), RTS (revised trauma score), KTS (Kampala trauma score), MGAP (mechanism, GCS (Glasgow coma score), age, pressure) and GAP (GCS, age, pressure) - with data from a trauma registry in a lower middle-income country and (2) to determine which of these scoring systems most accurately predicts in-hospital mortality in this setting. Patients and methods This is a retrospective analysis of data from an institutional trauma registry in Mumbai, India. Values for each score were calculated when sufficient data were available. Logistic regression was used to compare the correlation between each score and in-hospital mortality. Results There were sufficient data recorded to calculate ISS in 73% of patients, RTS in 35%, KTS in 35%, MGAP in 88% and GAP in 92%. ISS was the weakest predictor of in-hospital mortality, while RTS, KTS, MGAP and GAP scores all correlated well with in-hospital mortality (area under ROC (receiver operating characteristic) curve 0.69 for ISS, 0.85 for RTS, 0.86 for KTS, 0.84 for MGAP, 0.85 for GAP). Respiratory rate measurements, missing in 63% of patients, were a major barrier to calculating RTS and KTS. Conclusions Given the realities of medical practice in low- and middle-income countries, it is reasonable to modify the approach to characterising injury severity to favour simplified injury scoring systems that accurately predict in-hospital mortality despite limitations in trauma registry datasets.

Abstract Background Obesity is a highly prevalent, complex, and chronic relapsing disease with a considerable unmet medical need. We aimed to identify perceptions, attitudes, behaviors, and barriers to effective obesity treatment among people with obesity (PwO) and physicians in Israel. Methods The ACTION-IO study was an online survey conducted in 11 countries, including Israel. Findings from the Israeli cohort are reported here. Israeli respondents were PwO (body mass index of ≥30 kg/m2 based on self-reported height and weight) and physicians primarily in direct patient care. Results In total, 750 PwO and 169 physicians completed the survey in Israel. Although most PwO (70%) and physicians (95%) perceived obesity as a chronic disease, the majority of PwO assumed full responsibility for their own weight loss (88%) compared with only 19% of physicians who placed the responsibility for weight loss on their patients with obesity. Many PwO (62%) and physicians (73%) agreed that a complete change in lifestyle would be required for PwO to lose weight and felt that treatment of obesity should be a team effort between different healthcare professionals (HCPs; 80 and 90%, respectively). Dietitians were considered by 82% of physicians to be the most effective professionals in helping PwO achieve their weight loss goals. Many PwO (69%) liked that their HCP initiated weight management discussions and 68% of those who had not previously discussed their weight would like their HCP to initiate the conversation. However, among PwO who had discussed their weight with an HCP, 59% considered the discussions to be a little helpful or not at all helpful. The beliefs that patients have little interest in or motivation for losing weight were identified by physicians as the main reasons (71 and 70%, respectively) for not initiating weight management discussions. Conclusions In line with the ACTION-IO international study, our Israeli dataset reveals a need to improve awareness, primarily among physicians, on the physiologic basis and clinical management of obesity, including how to approach weight and weight management discussions during patient consultations. Trial registration Registered at ClinicalTrials.gov , NCT03584191 . Data first posted on ClinicalTrials.gov : 12 July 2018 - ‘Retrospectively registered’.

Introduction: Exposure to food odors are known to increase food intake. Olfaction declines from age 50 years. Objective: We examined changes in the sense of smell, body weight, food preferences, and parameters of metabolic status, following the use of a specially designed nasal device. Methods: This is a randomized, placebo-controlled study. Participants wore a nasal device (soft silicone insert) for 5–12 h daily (device group) or inserted 2 drops of normal saline into each nostril daily (control group). Follow-up visits occurred every 2 weeks. All participants were given a 500 kcal/day reduced diet and instructed not to change their regular physical activity. Weight, food preferences, olfactory sensitivity, and blood tests were performed at baseline and after 12 weeks. Results: Of 156 participants, 65 (42%) completed the study. Sense of smell decreased in the device group (from 6.4 ± 0.9 to 4.4 ± 1.5, on a scale of 0–7, p < 0.001), and did not change in the control group. Weight loss decreased by 6.6 ± 3.7% (p = 0.001) and by 5.7 ± 3.5% (p = 0.001) in the respective groups (between-group difference, p > 0.05). Among participants aged ≤50 years, weight loss was greater in the device than in the control group (7.7 ± 4.2% vs. 4.1 ± 2.9%, p = 0.02). Insulin level and the homeostatic model assessment of insulin resistance (HOMA-IR) were significantly reduced in the device group (p = 0.02 and p = 0.01, respectively), but not in the control group. Food preferences for sugar (p < 0.02), sweet beverages (p < 0.001), and artificial sweeteners (p < 0.02) were significantly reduced in the device group compared to the control group. Conclusions: The use of a novel self-administrated nasal device led to reduced olfactory sensitivity, improved insulin sensitivity, weight loss, and lesser preference for sweets in adults aged ≤50 years.

Objective: Obesity is a major risk factor for becoming seriously ill with the 2019 novel coronavirus (COVID-19). One difficulty faced by clinicians and by patients is the unknown time frame of hospitalization until discharge of symptomatic patients. Methods: We followed 34 patients with laboratory-confirmed COVID-19 infection who recovered fromthe infection. All diagnoses were given using semi-quantitative RT-PCR on nasopharyngeal swabs. Envelope protein gene (E), RNA-dependent RNA polymerase gene (RdRP), and nucleocapsid gene (N) were measured by RT-PCR. Weight was measured and height was self-reported. Results: Mean ± SD age was 51.8 ± 16.7 years. Mean ± SD body mass index (BMI) was 27.4 ± 4.7 kg/m2. 26% (9/34) had obesity, with BMI above 30 kg/m2. Fifteen patients had BMI between 25 and 29.9 kg/m2. The mean length of hospital stay was longer for those with a BMI >25 kg/m2 (n = 24) than for those with a normal BMI (19.2 vs. 16.0 days, p = 0.08). Comparing people with obesity (BMI >30 kg/m2 or above) to those without obesity, the difference was larger (20.6 vs. 16.0 days, p = 0.06). A trend for correlation between body weight and the time to negative detection of RdRp gene was found (r = 0.33, p = 0.09). Conclusions: Our results highlight the need for priority of early detection and testing, and early therapy for people with obesity and COVID-19 infections.

Accumulating evidence suggests that obesity is a major risk factor for the initiation, progression, and outcomes of coronavirus disease 2019 (COVID-19). The European Association for the Study of Obesity (EASO), as a scientific and medical society dedicated to the promotion of health and well-being, is greatly concerned about the concomitant obesity and COVID-19 pandemics and their impact on health and society at large. In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity. Clearly, this has important implications for preventive measures, vaccination, and future therapeutic strategies to combat COVID-19. Furthermore, we will highlight important knowledge gaps and provide suggestions for future research and recommendations for policy actions. Since many new reports on COVID-19 rapidly appear, the present perspective should be seen as a focus for discussion to drive forward further understanding, research initiatives, and clinical management of COVID-19.

Abstract Background The RECIPE study aims to validate a risk prediction model for intrapartum caesarean delivery which has been developed by our group. The Genesis study was a prospective observational study carried out by the Perinatal Ireland Research Consortium across 7 clinical centres in Ireland between October 2012 and June 2015. Genesis investigated a range of maternal and fetal parameters in a prospective blinded study of 2336 singleton pregnancies between 39 + 0–41 + 0 weeks’ gestational age. This resulted in the development of a risk prediction model for Caesarean Delivery in nulliparous women at term. The RECIPE study now proposes to provide external validation of this risk prediction tool. Methods In order to externally validate the model, we aim to include a centre which was not involved in the original study. We propose a trial of risk-assignment for intrapartum caesarean amongst nulliparous women with a singleton pregnancy between 38 + 0 and 40 + 6 weeks’ gestational age who are planning a vaginal birth. Results of the risk prediction tool will be concealed from participants and from midwives and doctors providing labour care.. Participants will be invited for an ultrasound scan and delivery details will be collated postnatally. The principal aim of this study is to externally validate the risk prediction model. This prediction model holds the potential to accurately identify nulliparous women who are likely to achieve an uncomplicated vaginal birth and those at high prospect of requiring an unplanned caesarean delivery. Discussion Validation of the Genesis prediction model would enable more accurate counselling for women in the antenatal setting regarding their own likelihood of requiring an intrapartum Caesarean section. It would also provide valuable personalised information to women about the anticipated course of their own labour. We believe that this is an issue of national relevance that will impact positively on obstetric practice, and will positively empower women to make considered, personalised choices surrounding labour and delivery.

The World Health Organization declared COVID-19, the infectious disease caused by the coronavirus SARS-CoV-2, a pandemic on March 12, 2020. COVID-19 is causing massive health problems and economic suffering around the world. The European Association for the Study of Obesity (EASO) promptly recognised the impact that the outbreak could have on people with obesity. On one side, emerging data suggest that obesity represents a risk factor for a more serious and complicated course of COVID-19 in adults. On the other side, the health emergency caused by the outbreak diverts attention from the prevention and care of non-communicable chronic diseases to communicable diseases. This might be particularly true for obesity, a chronic and relapsing disease frequently neglected and linked to significant bias and stigmatization. The Obesity Management Task Force (OMTF) of EASO contributes in this paper to highlighting the key aspects of these two sides of the coin and suggests some specific actions.

Abstract Background Identifying patients with COPD at increased risk of poor outcomes is challenging due to disease heterogeneity. Potential biomarkers need to be readily available in real-life clinical practice. Blood eosinophil counts are widely studied but few studies have examined the prognostic value of blood neutrophil counts (BNC). Methods In a large population-based COPD registry in the East of Scotland (TARDIS: Tayside Allergic and Respiratory Disease Information System), BNC were compared to measures of disease severity and mortality for up to 15 years follow-up. Potential mechanisms of disease modification by BNC were explored in a nested microbiome substudy. Results 178,120 neutrophil counts were obtained from 7220 people (mean follow up 9 years) during stable disease periods. Median BNC was 5200cells/μL (IQR 4000-7000cells/μL). Mortality rates among the 34% of patients with elevated BNCs (defined as 6000-15000cells/μL) at the study start were 80% higher (14.0/100 person years v 7.8/100py, P

Background: Data about injury patterns and clinical outcomes are essential to address the burden of injury in low- and middle-income countries. Institutional trauma registries (ITRs) are a key tool for collecting epidemiologic data about injury. This study uses ITR data to describe the demographics and patterns of injury of trauma patients in Addis Ababa, Ethiopia in order to identify opportunities for injury prevention, systems strengthening and further research. Methods: This is an analysis of prospectively collected data from a sustainable ITR at Menelik II Specialized Hospital, a public teaching hospital with trauma expertise. All patients presenting to the hospital with serious injuries requiring intervention or admission over a 13 month period were included. Univariable and bivariable analyses were performed for patient demographics and injury characteristics. Results: A total of 854 patients with serious injuries were treated during the study period. Median age was 33 years and 74% were male. The most common mechanisms of injury were road traffic injuries (RTI) (37%), falls (30%) and blunt assault (17%). Over half of RTI victims were pedestrians. Median delay in presentation was 2 h; 17% of patients presented over 6 h after injury. 58% of patients were referred from another hospital or a clinic, and referrals accounted for 84% of patients arriving by ambulance. Median emergency center length of stay was 2 h and 62% of patients were discharged from the emergency center. Conclusion: This study highlights the utility of institutional trauma registries in collecting crucial injury surveillance data. In Addis Ababa, road safety is an important target for injury prevention. Our findings suggest that the most severely injured patients may not be making it to the referral centers with the capacity to treat their injuries, thus efforts to improve prehospital care and triage are needed. African relevance: Injury is a public health priority in Africa. Institutional trauma registries play a crucial role in efforts to improve trauma care by describing injury epidemiology to identify targets for injury prevention and systems strengthening efforts. In our context, pedestrian safety is a key target for injury prevention. Improving prehospital care and developing referral networks are goals for systems strengthening.

Abstract Background The growing prevalence of obesity and its complications pose a huge burden on the individual and health care systems worldwide. This study presents the frequency of multiple prevalent co-morbidities and estimated annual cost burden by body mass index (BMI) groups, age, and sex among the Israeli adult population to provide policy makers with further evidence to appropriately target interventions. Methods This cross-sectional study utilized population-based electronic medical records from the largest payer-provider health fund in Israel. The population included individuals ≥25 years as of 01/01/2014. A new approach assessing body system-related morbidity (BSRM) prevalence was assessed along with estimated annual cost burden for the year 2015 and presented across BMI group, age, and sex via heat maps. Results Among 1,756,791 adults, 65% had an elevated BMI (BMI > 25 kg/m2). Heat map analysis demonstrated a higher multi-BSRM prevalence and relative estimated annual cost burden among participants with obesity in all age groups. There was a notably higher multi-BSRM prevalence among men and women aged 25–29 with class III obesity (26 and 30%, respectively) compared to the corresponding BMI groups between 18·5-

Social distancing during the COVID-19 pandemic has presented millions of people with extraordinary challenges that are associated with significant amounts of stress. Emotion regulation is crucial during this crisis as people seek to mitigate the stress and uncertainty of the present moment. In this study, we surveyed a nationally representative sample of 297 adults from the United States on their levels of perceived stress related to the COVID-19 pandemic as well as their level of engagement of different emotion regulation strategies during the pandemic. We performed multiple linear regression analyses to assess which regulation strategies were associated with individual differences in perceived stress. Among all emotion regulation strategies, psychological distancing, which involves thinking about stressful circumstances in an objective, impartial way, was uniquely associated with reductions in perceived stress due to COVID-19 across individuals. This effect was not moderated by age, gender, socioeconomic status, race/ethnicity, or trait-related difficulty in regulating emotion. Conversely, situation modification was associated with significantly greater perceived stress overall. These results suggest the broad applicability and utility of psychological distancing during pandemic-related social distancing as part of an adaptive emotion regulation toolkit and motivate the investigation of interventions involving psychological distancing in this context.

Indigenous second language programs in K-12 schools contribute to culturally nourishing education and to the revitalization of Indigenous languages. Assessing Indigenous second language learning presents particular opportunities and challenges based on the linguistic, historical, political, cultural, and social contexts in and for which the Indigenous language is being taught and learned. The self-governing Inuit region of Nunatsiavut is concerned with developing effective and appropriate tools for assessing students’ Inuttitut in order to evaluate how well K-12 programs are working so far, identify the basis on which future K-12 Inuttitut curriculum may be developed, and support ongoing assessment of learning and for learning in Inuttitut classrooms. This article discusses ways in which Inuit teachers in Nunatsiavut and a curriculum evaluation team have developed and implemented assessment tools and practices to evaluate Inuttitut learning in Nunatsiavut area K-12 schools. We discuss how Indigenous language learning and assessment, even when it occurs as part of an official school program, can be anchored in families and community. Families and communities need to be part of establishing language learning goals. Inuit teachers are drawing in full community resources and building a community of practice including Elders, other language speakers, leaders, principals, and teachers, to support and create contexts for community-anchored Inuttitut learning and assessment.

BackgroundHome injuries are an important cause of morbidity and mortality in high-income countries. In Sub-Saharan Africa, including Cameroon, many people live in unplanned settlements with poorly constructed houses, predisposing them to home injuries. However, little is known about the epidemiology and care-seeking behaviors of the domestically injured. In this study, our objective was to determine the epidemiology and care-seeking behaviors of home injuries in the Southwest Region of Cameroon.MethodsA sub-analyses of a larger descriptive cross-sectional community-based study on injury epidemiology in the preceding 12 months was conducted. Sampling was done using three-stage cluster sampling technique. Differences between groups were evaluated using Chi-squared and Adjusted Wald tests.ResultsOf 8065 participants, 157 suffered home injuries giving an incidence of 19.6 (16.8-23.0 95% CI) cases per 1000-person years. Home injuries comprised 31.2% of all 503 injuries and affected more females (60.8%) and younger individuals (mean age (SE) 25.1 years (2.0)) than non-home injuries. The most common activity and mechanism of home injury was leisure/play (51%) and falls (37.9%) respectively. Amongst those with home injuries, 37.6% did not seek care from any care provider (versus 25.0% of non-home injuries, p = 0.004) and were more likely to seek treatment within the family or at home (p = 0.008) or at church (p = 0.010). Those with home injuries experienced a median of 14 disability days and 22.9% of families faced difficulties affording basic expenses (p = 0.001).ConclusionHome injuries comprise about a third of the Southwest Region of Cameroon's burden of injury and likely have a profound socioeconomic impact. Though these injuries cause severe disabilities, a large proportion of victims do not seek care from providers. Prevention efforts should address the design of homes and victims of home injury should be encouraged to utilize formal care services.

The galaxy cluster Zwicky 3146 is a sloshing cool-core cluster at z = 0.291 that in Sunyaev–Zel’dovich (SZ) imaging does not appear to exhibit significant pressure substructure in the intracluster medium. We perform a surface brightness fluctuation analysis via Fourier amplitude spectra on SZ (MUSTANG-2) and X-ray (XMM-Newton) images of this cluster. These surface brightness fluctuations can be deprojected to infer pressure and density fluctuations from the SZ and X-ray data, respectively. In the central region (Ring 1, r < 100″ = 440 kpc, in our analysis), we find fluctuation spectra that suggest injection scales around 200 kpc (∼140 kpc from pressure fluctuations and ∼250 kpc from density fluctuations). When comparing the pressure and density fluctuations in the central region, we observe a change in the effective thermodynamic state from large to small scales, from isobaric (likely due to the slow sloshing) to adiabatic (due to more vigorous motions). By leveraging scalings from hydrodynamical simulations, we find an average 3D Mach number ≈0.5. We further compare our results to other studies of Zwicky 3146 and, more broadly, to other studies of fluctuations in other clusters.

Background and objectives: New Zealand emergency medical service (EMS) crewing configurations generally place one (single) or two (double) crew on each responding ambulance unit. Recent studies demonstrated that double-crewing was associated with improved survival from out-of-hospital cardiac arrest (OHCA), therefore single-crewed ambulances have been phased out. We aimed to determine the association between this crewing policy change and OHCA outcomes in New Zealand. Methods: This is a retrospective observational study using data from the St John OHCA Registry on patients treated during two different time periods: the Pre-Period (1 October 2013–30 June 2015), when single-crewed ambulances were in use by EMS, and the Post-Period (1 July 2016–30 June 2018) when single-crewed ambulances were being phased out. Geographic areas identified as having low levels of double crewing during the Pre-Period were selected for investigation. The outcome of survival to thirty-days post-OHCA was investigated using logistic regression analysis. Results: The proportion of double-crewed ambulances arriving at OHCA events increased in the Post-Period (81.8%) compared to the Pre-Period (67.5%) (p ≤ 0.001). Response times decreased by two minutes (Pre-Period: median 8 min, IQR [6–11], Post-Period: median 6 min, IQR [4–9]; p ≤ 0.001). Thirty-day survival was significantly improved in the Post-Period (OR 1.63, 95%CI (1.04–2.55), p = 0.03). Conclusions: An association between improved OHCA survival following increased responses by double-crewed ambulances was demonstrated. This study suggests that improvements in resourcing are associated with improved OHCA outcomes.

ObjectiveTo assess the effect of linagliptin vs. standard therapy in improving clinical outcomes in patients hospitalized with diabetes and coronavirus disease 2019 (COVID-19).Materials and MethodsWe did an open-label, prospective, multicenter, randomized clinical trial in 3 Israeli hospitals between October 1, 2020, and April 4, 2021. Eligible patients were adults with type 2 diabetes mellitus and a diagnosis of COVID-19. A total of 64 patients, 32 in each group, were randomized to receive linagliptin 5 mg PO daily throughout the hospitalization or standard of care therapy. The primary outcome was time to clinical improvement within 28 days after randomization, defined as a 2-point reduction on an ordinal scale ranging from 0 (discharged without disease) to 8 (death).ResultsThe mean age was 67 ± 14 years, and most patients were male (59.4%). Median time to clinical improvement was 7 days (interquartile range (IQR) 3.5-15) in the linagliptin group compared with 8 days (IQR 3.5–28) in the standard of care group (hazard ratio, 1.22; 95% CI, 0.70–2.15; p = 0.49). In-hospital mortality was 5 (15.6%) and 8 (25.0%) in the linagliptin and standard of care groups, respectively (odds ratio, 0.56; 95% CI, 0.16–1.93). The trial was prematurely terminated due to the control of the COVID-19 outbreak in Israel.ConclusionsIn this randomized clinical trial of hospitalized adult patients with diabetes and COVID-19 who received linagliptin, there was no difference in the time to clinical improvement compared with the standard of care.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT04371978.

In 1990 Katie was diagnosed with a profound hearing loss at 26 months of age. Her communication skills were delayed and a hearing loss had been suspected earlier. Several months later, Katie received hearing aids. Her mother was also referred to the county's Birth to 3 Program. In Wisconsin, Birth to 3 Programs were based out of the Department of Health Services, and each county had its own program. Katie was the first deaf child on the service coordinator's caseload. Due to the significant language delay, the Individualized Family Service Plan (IFSP) team determined the need for early intervention. Neither the early interventionist nor the speech therapist on the team had ever worked with a deaf child. The speech therapist, however, knew 10 signs and was assigned to provide services to Katie. Several months later, at 3 years of age, Katie transitioned to the public school system with a vocabulary of 10 signs and behavioral issues stemming from lack of communication. Katie was bright and should have entered school with communication skills commensurate to her peers so that she was ready to learn within a classroom environment. Instead, she was linguistically delayed and behavioral challenges were evident. Fortunately for other deaf and hard of hearing children and their families in the state of Wisconsin, early intervention services there have undergone significant changes over the past 20 years. Wisconsin faced numerous issues in this evolution. Many of the county Birth to 3 Programs were not able to provide trained and/or experienced personnel to address the unique needs of a child with hearing loss. The low incidence of this population, the size and rural nature of the state, the lack of qualified personnel, and the structure of Wisconsin Birth to 3 services were contributing factors to the challenges in adequately serving this population. This article describes how these challenges were addressed to improve early intervention services in the state.

BackgroundUp-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013.MethodsEstimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries.FindingsDisease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013.InterpretationAgeing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.FundingBill & Melinda Gates Foundation.

PurposeThe purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.Methods and materialsA total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol.ResultsExisting models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study.ConclusionsPlan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.

IntroductionThe purpose of the study was to determine whether racial differences exist in the pattern of local disease progression among men treated with radical prostatectomy (RP) for localized prostate cancer (PCa), which is currently unknown. In this study we evaluated the pattern of adverse pathologic features in an identical cohort of African-American (AA) and Caucasian (CS) men with PCa.Patients and methodsThe overall cohort consisted of 1104 men (224 AA, and 880 CS) who underwent RP between 1990 and 2012. We compared preoperative factors and pathologic outcomes after RP across race groups. Multivariate analysis was used to identify factors predictive of adverse pathologic outcomes. The effect of race on adverse pathologic outcomes and biochemical control rate (BCR) was evaluated using multivariate regression model and Kaplan-Meier analysis.ResultsThe 10-year BCR was 59% versus 82% in AA and CS men, respectively (P = .003). There was no significant difference in extraprostatic spread (P = .14), positive surgical margin (P = .81), lymph node involvement (P = .71), or adverse pathologic features (P = .16) across race groups. However, among patients with ≥ 1 adverse pathologic features, AA men had higher rate of seminal vesicle invasion (SVI) compared with CS men (51% vs. 30%; P = .01). After adjusting for known predictors of adverse pathologic features AA race remained a predictor of SVI.ConclusionAA men have an increased risk of SVI after RP, particularly among men with Gleason ≤ 6 disease. This might represent racial differences in the biology of PCa disease progression, which contribute to poorer outcomes in AA men.

PurposeTo explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP).MethodsThe overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores.ResultsWith a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029).ConclusionsAA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment.

BackgroundVictims of violence are at significant risk for injury recidivism, including fatality. We previously demonstrated that our hospital-based violence intervention program (VIP) resulted in a fourfold reduction in injury recidivism, avoiding trauma care costs of $41,000 per injury. Given limited trauma center resources, assessing cost-effectiveness of interventions is fundamental to inform use of these programs in other institutions. This study examines the cost-effectiveness of hospital-based VIP.MethodsWe used a decision tree and Markov disease state modeling to analyze cost utility for a hypothetical cohort of violently injured subjects, comparing VIP versus no VIP at a trauma center. Quality-adjusted life-years (QALYs) were calculated using differences in mortality and published health state utilities. Costs of trauma care and VIP were obtained from institutional data, and risk of recidivism with and without VIP were obtained from our trial. Outcomes were QALYs gained and net costs over a 5-year horizon. Sensitivity analyses examined the impact of uncertainty in input values on results.ResultsVIP results in an estimated 25.58 QALYs and net costs (program plus trauma care) of $5,892 per patient. Without VIP, these values are 25.34 and $5,923, respectively, suggesting that VIP yields substantial health benefits (24 QALYs) and savings ($4,100) if implemented for 100 individuals. In the sensitivity analysis, net QALYs gained with VIP nearly triple when the injury recidivism rate without VIP is highest. Cost-effectiveness remained robust over a range of values; $6,000 net cost savings occur when 5-year recidivism rate without VIP is at 7%.ConclusionVIP costs less than having no VIP with significant gains in QALYs especially at anticipated program scale. Across a range of plausible values at which VIP would be less cost-effective (lower injury recidivism, cost of injury, and program effectiveness), VIP still results in acceptable cost per health outcome gained. VIP is effective and cost-effective and should be considered in any trauma center that takes care of violently injured patients. Our analyses can be used to estimate VIP costs and results in different settings.Level of evidenceEconomic and value-based evaluation, level 2.

Introduction Disease-modifying therapies (DMTs) are the mainstay of treatment for relapsing–remitting multiple sclerosis (RRMS). There is established evidence that DMTs are effective at reducing relapse rate and disease progression in RRMS, but there has been less consideration to the synthesis of MRI and neurocognitive outcomes, which play an increasingly important role in treatment decisions. The aim of this systematic review and network meta-analysis is to examine the relative efficacy, acceptability and tolerability of DMTs for RRMS, using MRI and neurocognitive outcomes.Methods and analysis We will search electronic databases, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, with no date restrictions. We will also search the websites of international regulatory bodies for pharmaceuticals and international trial registries. We will include parallel group randomised controlled trials of DMTs including interferon beta-1a intramuscular, interferon beta-1a subcutaneous, interferon beta-1b, peginterferon beta-1a, glatiramer acetate, natalizumab, ocrelizumab, alemtuzumab, dimethyl fumarate, teriflunomide, fingolimod, cladribine, ozanimod, mitoxantrone and rituximab, either head-to-head or against placebo in adults with RRMS. Primary outcomes include efficacy (MRI outcomes including new T1/hypointense lesions and T2/hyperintense lesions) and acceptability (all-cause dropouts). Secondary outcomes include gadolinium-enhancing lesions, cerebral atrophy and tolerability (dropouts due to adverse events). Neurocognitive measures across three domains including processing speed, working memory and verbal learning will be included as exploratory outcomes. Data will be analysed using a random-effects pairwise meta-analysis and a Bayesian hierarchical random effects network meta-analysis to evaluate the efficacy, acceptability and tolerability of the included DMTs. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement.Ethics and dissemination This protocol does not require ethics approval. Results will be disseminated in a peer-reviewed academic journal.PROSPERO registration number CRD42021239630.

Summary: This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.

BackgroundImproved clinical predictors for disease progression are needed for localised prostate cancer, since only a subset of patients develop recurrent or refractory disease after first-line treatment. Therefore, we undertook an unbiased analysis to identify RNA biomarkers associated with metastatic progression after prostatectomy.MethodsProstate cancer samples from patients treated with radical prostatectomy at three academic institutions were analysed for gene expression by a high-density Affymetrix GeneChip platform, encompassing more than 1 million genomic loci. In a discovery cohort, all protein-coding genes and known long non-coding RNAs were ranked by fold change in expression between tumours that subsequently metastasised versus those that did not. The top ranked gene was then validated for its prognostic value for metastatic progression in three additional independent cohorts. 95% of the gene expression assays were done in a Clinical Laboratory Improvements Amendments certified laboratory facility. All genes were assessed for their ability to predict metastatic progression by receiver-operating-curve area-under-the-curve analyses. Multivariate analyses were done for the primary endpoint of metastatic progression, with variables including Gleason score, preoperative prostate-specific antigen concentration, seminal vesicle invasion, surgical margin status, extracapsular extension, lymph node invasion, and expression of the highest ranked gene.Findings1008 patients were included in the study: 545 in the discovery cohort and 463 in the validation cohorts. The long non-coding RNA SChLAP1 was identified as the highest-ranked overexpressed gene in cancers with metastatic progression. Validation in three independent cohorts confirmed the prognostic value of SChLAP1 for metastatic progression. On multivariate modelling, SChLAP1 expression (high vs low) independently predicted metastasis within 10 years (odds ratio [OR] 2·45, 95% CI 1·70-3·53; p