Search

Background: MAGnetic Expansion Control (MAGEC) rods can prevent repeated lengthening operations for scoliosis patients. However, there have been several Field Safety Notices issued, including a worldwide product recall due to actuator endcap separation. We aimed to review adverse events reported to the Food and Drug Administration (FDA) regarding MAGEC rods, focusing on MAGEC X., Methods: Reports submitted to the Manufacturer and User Facility Device Experience database in relation to MAGEC devices were accessed and analysed using R Statistical Software. Exclusion criteria included duplicate and literature review reports (n = 54). Free-text data were analysed using inductive content analysis., Results: 1016 adverse events were reported to 11/30/2023. 99.0% (1006) were submitted by the manufacturer. Reports primarily arose from the UK (465, 45.8%) or US (421, 41.4%). From free-text data the most frequent adverse events were distraction mechanism failure (573), device wear (272), and actuator seal damage (180). Rod fracture (n = 48) was not significantly associated with rod diameter (≤ 5.0 mm or > 5.0 mm), p = 0.736. 234 reports referenced MAGEC X devices; actuator endcap separation was identified in 41.9% (99). Other events include failure of distraction (63), surface damage (31), and rod fracture (15). On 06/30/2020 MAGEC X2 received FDA approval. Twenty reports reference devices manufactured after this date, seven describe distraction mechanism failure; notably there are no reports of endcap separation., Conclusion: These data represent the largest series of adverse events reported for MAGEC rods, including significant new data regarding MAGEC X. As well as endcap separation, failure of distraction, surface damage, and rod fracture were reported., Competing Interests: Declarations. Competing Interests: TJ undertakes expert witness work in relation to magnetic spinal rods with all monies paid to Newcastle University. JF and AB have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Background: Major depressive disorder (MDD) and alcohol use disorder (AUD) are leading psychiatric causes of burden of disease. Although research has found pronounced gender differences in these disorders, the magnitude of these differences varies substantially between settings. However, integrated analyses of both disorders are lacking, limiting the comparability of findings. Moreover, few studies conceptualize political and socio-cultural characteristics as separate macro-level determinants of gender differences. This paper analyzes the association between gender differences in the prevalence of both MDD and AUD with social policy expenditures and indicators of gender equality., Methods: Data for adults from the U.S. Behavioral Risk Factor Surveillance System 2006/2008 (n = 234,020) and the European Social Survey 2014 (n = 30,416) were used. Cross-sectional analyses were conducted using modified Poisson regression models adjusted for individual-level and macro-level covariates; multiplicative and additive interaction were evaluated., Results: Social policy expenditures and support for gender equality were negatively associated with gender differences in AUD in Europe (p < 0.001), with the male excess prevalence varying between 26.1 % at lowest and 9.4 % at highest observed levels of expenditures, and between 23.3 % at lowest and 6.8 % at highest levels of gender equality. In the U.S., state-level reproductive rights were negatively associated with gender differences in AUD (p = 0.036). No equivalent effects were observed for gender differences in MDD., Conclusion: The prevalence of AUD among men and women tends to converge in settings with higher levels of social policy generosity and gender equality, respectively. This effect does not seem to apply to gender differences in MDD in either setting., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Second wave feminist legal and educational reform contributed to the fourfold rise in the number of women doctors in the United States between 1970 and 1990, challenging the hierarchical medical workplace from within. At the same moment, the feminist women's health movement (FWHM) identified and protested gendered health disparities, changing medical practice from without. This article analyses five women doctors' autobiographical reflections of medical training published between 1976 and 1987, during this period of gendered upheaval. In these works, authors shared their experiences of entering a male-dominated profession, addressing second wave feminist concerns about women's workplace equality. They explored whether women could become full and equal members of the medical professional, but also how women should become members of a profession that mistreated female patients in ways the FWHM sought to address. Through autobiographical writing, women doctors shared experiences that amplified these reform imperatives, while reflecting on their position as agents within an unequal healthcare system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age., Methods: Records from the 2016-2020 National Inpatient Sample were used for our study. The sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in in-hospital complications between the two groups using multivariable regression., Results: The analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, of whom 57.3 % were in the 30-40 years cohort and 42.7 % in the 15-29 years group. The prevalence of cardiovascular risk factors such as smoking, obesity, hypertension, diabetes and lipid disorder was higher among women aged 30-40 years (p < 0.01). These patients also demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95 % CI 1.038-1.767, p = 0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95 % CI 0.688-0.901, p < 0.01) as compared to those aged 15-29 years during their hospitalisation with PPCM. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95 % CI 0.976-1.182, p = 0.143), acute pulmonary oedema (aOR 1.147, 95 % CI 0.988-1.332, p = 0.071) or in-hospital mortality (aOR 0.978, 95 % CI 0.742-1.290, p = 0.877)., Conclusion: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The reporting of adverse events (AEs) relating to medical devices is a long-standing area of concern, with suboptimal reporting due to a range of factors including a failure to recognize the association of AEs with medical devices, lack of knowledge of how to report AEs, and a general culture of nonreporting. The introduction of artificial intelligence as a medical device (AIaMD) requires a robust safety monitoring environment that recognizes both generic risks of a medical device and some of the increasingly recognized risks of AIaMD (such as algorithmic bias). There is an urgent need to understand the limitations of current AE reporting systems and explore potential mechanisms for how AEs could be detected, attributed, and reported with a view to improving the early detection of safety signals., Objective: The systematic review outlined in this protocol aims to yield insights into the frequency and severity of AEs while characterizing the events using existing regulatory guidance., Methods: Publicly accessible AE databases will be searched to identify AE reports for AIaMD. Scoping searches have identified 3 regulatory territories for which public access to AE reports is provided: the United States, the United Kingdom, and Australia. AEs will be included for analysis if an artificial intelligence (AI) medical device is involved. Software as a medical device without AI is not within the scope of this review. Data extraction will be conducted using a data extraction tool designed for this review and will be done independently by AUK and a second reviewer. Descriptive analysis will be conducted to identify the types of AEs being reported, and their frequency, for different types of AIaMD. AEs will be analyzed and characterized according to existing regulatory guidance., Results: Scoping searches are being conducted with screening to begin in April 2024. Data extraction and synthesis will commence in May 2024, with planned completion by August 2024. The review will highlight the types of AEs being reported for different types of AI medical devices and where the gaps are. It is anticipated that there will be particularly low rates of reporting for indirect harms associated with AIaMD., Conclusions: To our knowledge, this will be the first systematic review of 3 different regulatory sources reporting AEs associated with AIaMD. The review will focus on real-world evidence, which brings certain limitations, compounded by the opacity of regulatory databases generally. The review will outline the characteristics and frequency of AEs reported for AIaMD and help regulators and policy makers to continue developing robust safety monitoring processes., International Registered Report Identifier (irrid): PRR1-10.2196/48156., (©Aditya U Kale, Riya Dattani, Ashley Tabansi, Henry David Jeffry Hogg, Russell Pearson, Ben Glocker, Su Golder, Justin Waring, Xiaoxuan Liu, David J Moore, Alastair K Denniston. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.07.2024.)

This article examines historical trends in health inequalities over the 20th and 21st centuries. Drawing on studies from the United States, United Kingdom, Sweden, and Western Europe, it concludes that there is evidence of a u-shaped curve in (relative) health inequalities. These trends in health inequalities broadly parallel those identified by economists with regards to the u-shaped curve of income and wealth inequalities across the 20th and 21st centuries. The article argues that-as with income inequalities-health inequalities generally decreased across the twentieth century through to the early 1980s. They then started to increase and accelerated further from 2010, particularly in the United Kingdom and the United States. The article sets out four distinct policy periods that shaped the evolution of trends in health inequalities: the Interbellum Era, 1920-1950; the Trente Glorieuse, 1950-1980; Neoliberalism, 1980-2010; and the Crisis Age, 2010-present. The u-shaped curve of health inequalities over this period suggests that social policies, health care access, and political incorporation have driven changes over time. Taking this long view of changes in health inequalities emphasizes the importance of politics and policy for future health improvement., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Eating healthier is associated with a range of favorable health outcomes. Our previous model estimated the impact of dietary changes on life expectancy gains but did not consider height, weight, or physical activity., Objectives: We aimed to estimate the increase in life expectancy resulting from the transition from typical national dietary patterns to longevity-optimizing dietary changes, more feasible dietary modifications, and optimized vegan dietary changes in China, France, Germany, Iran, Norway, the United Kingdom, and the United States., Methods: Our modeling study used data from meta-analyses presenting dose-response relationships between intake of 15 food groups and mortality. Background mortality data were from the Global Burden of Disease Study. We used national food intake data and adjusted for height, weight, and physical activity level., Results: For 40-y-olds, estimated life expectancy gains ranged from 6.2 y (with uncertainty interval [UI]: 5.7, 7.5 y) for Chinese females to 9.7 y (UI: 8.1, 11.3 y) for United States males following sustained changes from typical country-specific dietary patterns to longevity-optimized dietary changes, and from 5.2 y (UI: 4.0, 6.5 y) for Chinese females to 8.7 y (UI: 7.1, 10.3 y) for United States males following changes to optimized vegan dietary changes., Conclusions: A sustained change from country-specific typical dietary pattern patterns to longevity-optimized dietary changes, more feasible dietary changes, or optimized vegan dietary changes are all projected to result in substantial life expectancy gains across ages and countries. These changes included more whole grains, legumes, and nuts and less red/processed meats and sugars and sugar-sweetened beverages. The largest gains from dietary changes would be in the United States., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop "Mechanisms and Barriers in Nanomedicine" in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, and students to trigger ideas and concepts to move the field forward.

Objective: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI., Methods: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort., Results: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac., Conclusions: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background & Aims: Autosomal dominant polycystic liver disease is a rare condition with a female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal dominant polycystic liver disease is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and US centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease., Methods: We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points., Results: Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication., Conclusions: Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although some male patients with congenital hypogonadotropic hypogonadism (CHH) undergo spontaneous reversal following treatment, predictors of reversal remain elusive. We aimed to assemble the largest cohort of male patients with CHH reversal to date and identify distinct classes of reversal., Methods: This multicentre cross-sectional study was conducted in six international CHH referral centres in Brazil, Finland, France, Italy, the UK, and the USA. Adult men with CHH (ie, absent or incomplete spontaneous puberty by age 18 years, low serum testosterone concentrations, and no identifiable cause of hypothalamic-pituitary-gonadal [HPG] axis dysfunction) were eligible for inclusion. CHH reversal was defined as spontaneous recovery of HPG axis function off treatment. Centres provided common data elements on patient phenotype, clinical assessment, and genetics using a structured, harmonised data collection form developed by COST Action BM1105. Latent class mixture modelling (LCMM) was applied to establish whether at least two distinct classes of reversal could be identified and differentially predicted, and results were compared with a cohort of patients without CHH reversal to identify potential predictors of reversal. The primary outcome was the presence of at least two distinct classes of reversal., Findings: A total of 87 male patients with CHH reversal and 108 without CHH reversal were included in the analyses. LCMM identified two distinct reversal classes (75 [86%] in class 1 and 12 [14%] in class 2) on the basis of mean testicular volume, micropenis, and serum follicle-stimulating hormone (FSH) concentration. Classification probabilities were robust (0·998 for class 1 and 0·838 for class 2) and modelling uncertainty was low (entropy 0·90). Compared with class 1, patients in class 2 had significantly larger testicular volume (p<0·0001), no micropenis, and higher serum FSH concentrations (p=0·041), consistent with the Pasqualini syndrome (fertile eunuch) subtype of CHH. Patients without CHH reversal were more likely to have anosmia (p=0·016), cryptorchidism (p=0·0012), complete absence of puberty (testicular volume <4 cm³; p=0·0016), and two or more rare genetic variants (ie, oligogenicity; p=0·0001). Among patients who underwent genetic testing, no patients (of 75) with CHH reversal had a rare pathogenic ANOS1 variant compared with ten (11%) of 95 patients without CHH reversal. Individuals with CHH reversal had a significantly higher rate of rare variants in GNRHR than did those without reversal (nine [12%] of 75 vs three [3%] of 95; p=0·025)., Interpretation: Applying LCMM to a large cohort of male patients with CHH reversal uncovered two distinct classes of reversal. Genetic investigation combined with careful clinical phenotyping could help surveillance of reversal after withdrawing treatment, representing the first tailored management approach for male patients with this rare endocrine disorder., Funding: National Institutes of Health National Center for Advancing Translational Sciences; Ministry of Health, Rome, Italy; Ministry of University, Rome, Italy; National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the Josiah Macy Jr Foundation., Translation: For the Italian translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Combined expression of the autophagy-regulatory protein AMBRA1 (activating molecule in Beclin1-regulated autophagy) and the terminal differentiation marker loricrin in the peritumoral epidermis of stage I melanomas can identify tumour subsets at low risk of -metastasis., Objectives: To validate the combined expression of peritumoral AMBRA1 and loricrin (AMBLor) as a prognostic biomarker able to identify both stage I and II melanomas at low risk of tumour recurrence., Methods: Automated immunohistochemistry was used to analyse peritumoral AMBRA1 and loricrin expression in geographically distinct discovery (n = 540) and validation (n = 300) cohorts of nonulcerated American Joint Committee on Cancer (AJCC) stage I and II melanomas. AMBLor status was correlated with clinical outcomes in the discovery and validation cohorts separately and combined., Results: Analysis of AMBLor in the discovery cohort revealed a recurrence-free survival (RFS) rate of 95.5% in the AMBLor low-risk group vs. 81.7% in the AMBLor at-risk group (multivariate log-rank, P < 0.001) and a negative predictive value (NPV) of 96.0%. In the validation cohort, AMBLor analysis revealed a RFS rate of 97.6% in the AMBLor low-risk group vs. 78.3% in the at-risk group (multivariate log-rank, P < 0.001) and a NPV of 97.6%. In a multivariate model considering AMBLor, Breslow thickness, age and sex, analysis of the combined discovery and validation cohorts showed that the estimated effect of AMBLor was statistically significant, with a hazard ratio of 3.469 (95% confidence interval 1.403-8.580, P = 0.007) and an overall NPV of 96.5%., Conclusions: These data provide further evidence validating AMBLor as a prognostic biomarker to identify nonulcerated AJCC stage I and II melanoma tumours at low risk of disease recurrence., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Repurposing existing drugs for use in oncology is more efficient, cost-effective and safe than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance. This study assessed the impact of calcium channel blockers (CCB) in pancreatic cancer., Methods: Retrospective population study of patients undergoing resection (curative intent) of pancreatic ductal adenocarcinoma (SEER-Medicare, 2007-2017). Cox models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, the impact of CCB was assessed separately in patients receiving neoadjuvant chemotherapy., Results: 6,223 patients were included, of whom 660 were prescribed CCB. In total, 591 received neoadjuvant chemotherapy; in this cohort CCB prescription was associated with improved overall survival when adjusting for multiple prognostic factors (aHR = 0.715, 0.514-0.996, P = 0.047). This effect was not observed in patients not receiving neoadjuvant chemotherapy (aHR = 1.082, 0.982-1.191, P = 0.112)., Conclusion: CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy, mirroring the chemosensitising effect in laboratory studies. This defines patients receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Across several sites in the United States, we examined whether kindergarten conduct problems among mostly population-representative samples of children were associated with increased criminal and related (criminal + lost offender productivity + victim; described as criminal + victim hereafter) costs across adolescence and adulthood, as well as government and medical services costs in adulthood., Methods: Participants (N = 1,339) were from two multisite longitudinal studies: Fast Track (n = 754) and the Child Development Project (n = 585). Parents and teachers reported on kindergarten conduct problems, administrative and national database records yielded indexes of criminal offending, and participants self-reported their government and medical service use. Outcomes were assigned costs, and significant associations were adjusted for inflation to determine USD 2020 costs., Results: A 1SD increase in kindergarten conduct problems was associated with a $21,934 increase in adolescent criminal + victim costs, a $63,998 increase in adult criminal + victim costs, a $12,753 increase in medical services costs, and a $146,279 increase in total costs. In the male sample, a 1SD increase in kindergarten conduct problems was associated with a $28,530 increase in adolescent criminal + victim costs, a $58,872 increase in adult criminal + victim costs, and a $144,140 increase in total costs. In the female sample, a 1SD increase in kindergarten conduct problems was associated with a $15,481 increase in adolescent criminal + victim costs, a $62,916 increase in adult criminal + victim costs, a $24,105 increase in medical services costs, and a $144,823 increase in total costs., Conclusions: This investigation provides evidence of the long-term costs associated with early-starting conduct problems, which is important information that can be used by policymakers to support research and programs investing in a strong start for children., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: The 2018 (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are evidence-based lifestyle recommendations which aim to reduce the risk of cancer worldwide. Sociodemographic factors modulate lifestyle behaviours, and both cancer incidence and survival are socio-economically patterned. We investigated adherence to these recommendations and examined patterns of adherence across sociodemographic subgroups in the UK Biobank cohort., Methods: We included 158 415 UK Biobank participants (mean age 56 years, 53% female). Total adherence scores were derived from dietary, physical activity and anthropometric data using the 2018 WCRF/AICR standardized scoring system. One-Way analysis of variance (ANOVA) was used to test for differences in total scores and in values for individual score components according to sociodemographic factors and Pearson's Χ2 test to investigate associations between sociodemographic factors according to tertiles of adherence score., Results: Mean total adherence score was 3.85 points (SD 1.05, range 0-7 points). Higher total scores were observed in females, and older (>57 years), Chinese or South Asian, and more educated participants. We found significant variations in adherence to individual recommendations by sociodemographic factors including education, Townsend deprivation index and ethnicity., Conclusions: Identifying and understanding lifestyle and dietary patterns according to sociodemographic factors could help to guide public health strategies for the prevention of cancers and other non-communicable diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health.)

Peptides continue to gain significance in the pharmaceutical arena. Since the unveiling of insulin in 1921, the Food and Drug Administration (FDA) has authorised around 100 peptides for various applications. Peptides, although initially derived from endogenous sources, have evolved beyond their natural origins, exhibiting favourable therapeutic effectiveness. Medicinal chemistry has played a pivotal role in synthesising valuable natural peptide analogues, providing synthetic alternatives with therapeutic potential. Furthermore, key chemical modifications have enhanced the stability of peptides and strengthened their interactions with therapeutic targets. For instance, selective modifications have extended their half-life and lessened the frequency of their administration while maintaining the desired therapeutic action. In this review, I analyse the FDA approval of natural peptides, as well as engineered peptides for diabetes treatment, growth-hormone-releasing hormone (GHRH), cholecystokinin (CCK), adrenocorticotropic hormone (ACTH), and α-melanocyte stimulating hormone (α-MSH) peptide analogues. Attention will be paid to the structure, mode of action, developmental journey, FDA authorisation, and the adverse effects of these peptides.

Background: The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based guidelines which aim to reduce cancer risk. This study investigated, in the UK Biobank, associations between an abbreviated score to assess adherence to these Recommendations and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with diet, adiposity, and physical activity., Methods: We used data from 288,802 UK Biobank participants (mean age 56.2 years), cancer-free at baseline. An abbreviated version of the 2018 WCRF/AICR Score was calculated to assess adherence to five Recommendations on (i) body weight, (ii) physical activity, (iii) fruits, vegetables, and dietary fiber, (iv) red and processed meat, and (v) alcohol. Multivariable Cox proportional hazards models were used to analyze associations between the abbreviated score (range, 0-5 points) and cancer incidence, adjusting for confounders., Results: During a median follow-up of 8.2 years (interquartile range, 7.4-8.9), 23,448 participants were diagnosed with cancer. The abbreviated score was inversely associated with risk of cancer overall [HR: 0.93; 95% confidence interval (CI): 0.92-0.95 per 1-point increment], and breast (HR: 0.90; 95% CI: 0.87-0.94), colorectal (HR: 0.86; 95% CI: 0.83-0.90), lung (HR: 0.89; 95% CI: 0.84-0.94), kidney (HR: 0.83; 95% CI: 0.76-0.90), pancreatic (HR: 0.86; 95% CI: 0.79-0.94), uterine (HR: 0.79; 95% CI: 0.73-0.86), esophageal (HR: 0.82; 95% CI: 0.75-0.90), stomach (HR: 0.89; 95% CI: 0.79-0.99), and liver (HR: 0.80; 95% CI: 0.72-0.90) cancers., Conclusions: Greater adherence to the Cancer Prevention Recommendations, assessed using an abbreviated score, was associated with reduced risk of all cancers combined and of nine site-specific cancers., Impact: Our findings support compliance to these Recommendations for cancer prevention., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: Duchenne muscular dystrophy (DMD) is a progressive, life-limiting, neuromuscular disorder. Clinicians play an important role in informing families about therapy options, including approved gene therapies and clinical trials of unapproved therapies., Objective: This study aimed to understand the perspectives of clinicians about gene therapy for DMD, which has not previously been studied., Methods: We conducted interviews with specialist clinicians treating patients with DMD in the United States (n = 8) and United Kingdom (n = 8). Interviews were completed in 2022, before any approved gene therapies, to gain insight into barriers and facilitators to implementing gene therapy and educational needs of clinicians., Results: Most respondents expressed cautious optimism about gene therapy. Responses varied regarding potential benefits with most expecting delayed progression and duration of benefit (1 year to lifelong). Concern about anticipated risks also varied; types of anticipated risks included immunological reactions, liver toxicity, and cardiac or renal dysfunction. Clinicians generally, but not uniformly, understood that gene therapy for DMD would not be curative. Most reported needing demonstrable clinical benefit to justify treatment-related risks., Conclusions: Our data demonstrate variability in knowledge and attitudes about gene therapy among clinicians who follow patients with DMD. As our knowledge base about DMD gene therapy grows, clinician education is vital to ensuring that accurate information is communicated to patients and families.

In the United States (U.S.), premature mortality in adulthood from suicide, alcohol-related disease, and substance overdoses has increased steadily over the past two decades. To better understand these trends, it is necessary to first examine the harmful behaviors that often precede these preventable deaths (i.e., suicidal ideation and attempts, and harmful alcohol and substance use). Representing critical developmental periods in which psychopathology is most likely to emerge, childhood and adolescence provide an informative lens through which to investigate susceptibility to harmful behaviors. This article synthesizes current evidence describing these rising U.S. mortality rates and the prevalence rates of harmful behaviors linked to these types of mortality. A brief selective review of longitudinal research on harmful behaviors in relation to the most relevant categories of child and adolescent psychopathology is then provided. Finally, recommendations for future research and implications for prevention are discussed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Cancer Prevention Recommendations are lifestyle-based recommendations which aim to reduce cancer risk. This study investigated associations between adherence, assessed using a standardised scoring system, and the risk of all cancers combined and of 14 cancers for which there is strong evidence for links with aspects of lifestyle in the UK., Methods: We used data from 94,778 participants (53% female, mean age 56 years) from the UK Biobank. Total adherence scores (range 0-7 points) were derived from dietary, physical activity, and anthropometric data. Associations between total score and cancer risk (all cancers combined; and prostate, breast, colorectal, lung, uterine, liver, pancreatic, stomach, oesophageal, head and neck, ovarian, kidney, bladder, and gallbladder cancer) were investigated using Cox proportional hazard models, adjusting for age, sex, deprivation index, ethnicity, and smoking status., Results: Mean total score was 3.8 (SD 1.0) points. During a median follow-up of 8 years, 7296 individuals developed cancer. Total score was inversely associated with risk of all cancers combined (HR: 0.93; 95%CI: 0.90-0.95 per 1-point increment), as well as breast (HR: 0.90; 95%CI: 0.86-0.95), colorectal (HR: 0.90; 95%CI: 0.84-0.97), kidney (HR: 0.82; 95%CI: 0.72-0.94), oesophageal (HR: 0.84; 95%CI: 0.71-0.98), ovarian (HR: 0.76; 95%CI: 0.65-0.90), liver (HR: 0.78; 95%CI: 0.63-0.97), and gallbladder (HR: 0.70; 95%CI: 0.53-0.93) cancers., Conclusions: Greater adherence to lifestyle-based recommendations was associated with reduced risk of all cancers combined and of breast, colorectal, kidney, oesophageal, ovarian, liver, and gallbladder cancers. Our findings support compliance with the Cancer Prevention Recommendations for cancer prevention in the UK., (© 2023. The Author(s).)

Background: A wave of expiring patents for first-generation insulin analogues has created opportunities in the global insulin market for highly similar versions of these products, biosimilar insulins. Biologics are generally large, complex molecules produced through biotechnology in a living system, such as a microorganism, plant cell, or animal cell. Since manufacturing processes of biologics vary, biosimilars cannot be exact copies of their reference product but must exhibit a high degree of functional and structural similarity. Biosimilarity is proven by analytical approaches in comparative assessments, preclinical cell-based and animal studies, as well as clinical studies in humans facilitating the accumulation of evidence across all assessments. The approval of biosimilars follows detailed regulatory pathways derived from those of their reference products and established by agencies such as the European Medicines Agency and the US Food and Drug Administration. Regulatory authorities impose requirements to ensure that biosimilars meet high standards of quality, safety, and efficacy and are highly similar to their reference product., Purpose: This review aims to aid clinical understanding of the high standards of development, manufacturing, and regulation of biosimilar insulins., Methods: Recent relevant studies indexed by PubMed and regulatory documents were included., Conclusions: Driven by price competition, the emergence of biosimilar insulins may help expand global access to current insulin analogues. To maximize the impact of the advantage for falling retail costs of biosimilar insulins compared with that of reference insulins, healthcare professionals and insulin users must gain further awareness and confidence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:Prof. Lutz Heinemann is member of an advisory board of Becton Dickinson, Convatec, Roche Diabetes Care, Sciarc and Member of the Board of Lifecare.Prof. Melanie Davies has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk, Sciarc, and Sanofi; an advisory board member and speaker for AstraZeneca; an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma Inc; and a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International, Inc. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca, and Janssen.Prof. Philip Home or institutions with which he is associated have received funding for his research, lecturing, or advisory activities from Viatris, Sanofi, Gan & Lee, Sciarc, and Merck Inc in regard of biosimilar insulins, and from Ely Lilly, Novo Nordisk, and Sanofi in regard of originator insulins.Prof. Thomas Forst is member of an advisory board of Astra Zeneca; Atrogi, Bayer; Cipla, Eli Lilly; Eyesense; Fortbildungskolleg; Novo Nordisk; Pfizer; Sanofi; Bayer; Remynd, Roche; Eyesense; Sciarc and member of the speaker Panel of Astra Zeneca; Boehringer Ingelheim, Berlin Chemie; Cipla, Daiichi-Sankyo, Eli Lilly; Fortbildungskolleg; MSD; Novartis, Novo Nordisk; SanofiProf. Tina Vilsbøll has served on scientific advisory panels and/or speakers’ bureaus or has served as a consultant to and/or received research support from AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, MSD/Merck, Mundipharma, Novo Nordisk, Sanofi, Sciarc, and Sun Pharmaceuticals.Prof. Oliver Schnell is a founder and CEO of Sciarc GmbH.

Background: The World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations are lifestyle-based guidelines that aim to reduce cancer risk. A systematic review and meta-analysis of studies investigating associations between a score for adherence to the 2018 Cancer Prevention Recommendations and cancer risk was conducted., Methods: MEDLINE, Embase, Web of Science, and Scopus were searched for studies published to November 28, 2022. In meta-analysis, the estimated risk ratios and 95% CIs for adherence score as a continuous (per 1-point increment) and categorical (highest vs. lowest score category) variable using random-effects models were estimated., Results: Eighteen studies (11 cohort; seven case-control) were included investigating incidence of breast (n = 7), colorectal (n = 5), prostate (n = 2), lung (n = 2), pancreatic (n = 1), endometrial (n = 1), unknown primary cancer (n = 1), chronic lymphocytic leukemia (n = 1), and overall (any) cancer (n = 1). The summary risk ratio per 1-point increment in adherence score was 0.89 (95% CI, 0.85-0.93; I 2  = 76.5%; n = 7) for breast cancer, 0.88 (95% CI, 0.84-0.91; I 2  = 26.2%; n = 4) for colorectal cancer, and 0.92 (95% CI, 0.86-0.98, I 2  = 66.0%; n = 2) for lung cancer. There were no significant associations with prostate or other cancers. Meta-analysis results using categorical adherence score variables were consistent with these findings., Conclusions: Greater adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations was associated with lower risk of breast, colorectal, and lung cancers. Future studies investigating associations with risk of other forms of cancer are warranted., Prospero Registration Number: CRD42022313327., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Citational practices reflect values and valuation in academia. Far from being merely consciously or unconsciously political, they reflect academic "upbringing" in complex ways, and, although one may be unhappy at how they were raised, it still may not be clear how to live better. In this article, I highlight aspects of my upbringing in anthropology, noting how I was instructed in citational practice by senior anthropologists from biological and social anthropology. In exploring my journey from naivete to an understanding of citational politics, I describe two figures, the giant and the mule. These figures illustrate the impacts of the practices I was taught. One comes to us from the history of great white men of Europe, the other from Black feminist anthropological fiction of the United States., (© 2023 The Author. Medical Anthropology Quarterly published by Wiley Periodicals LLC on behalf of American Anthropological Association.)

Background: The friction cost approach (FCA) offers an alternative to the dominant human capital approach to value productivity losses. Application of the FCA in practice is limited largely due to data availability. Recent attempts have tried to standardise the estimation of friction periods across Europe, but to date, this has not been attempted elsewhere. Our aim was to estimate friction periods for 17 Organisation for Economic Co-operation and Development (OECD) member countries between 2010 and 2021 based on routinely published data., Methods: We derived friction period estimates for Australia, Austria, Canada, Czechia, Finland, Germany, Hungary, Japan, Korea, Luxembourg, Norway, Poland, Portugal, Sweden, Switzerland, the United Kingdom and the United States. Vacancy stock and flow data was sourced from the OECD's short-term labour situation database from 2010 to 2021, and included the impact of Covid-19 on the labour market. The estimated friction periods were applied to cost cancer-related premature mortality for the United States as an illustrative case., Results: The average friction period in the five non-European countries (Australia, Canada, Korea, Japan and the United States) was 61.0 days (SD 9.4) (range between 44.8 days in Korea and 82.2 days in Canada) and the average friction period in the 12 European countries was 60.6 days (SD 14.8) (range between 34.1 days in Switzerland and 137.3 days in Czechia). In both cases, the outbreak of Covid-19 increased the length of the friction period. Our illustrative case revealed that productivity costs in the US were over a third lower using the study-specific friction period (56 days) compared with the conventionally assumed 90-day friction period applied in the literature as a default measure., Conclusions: Our results expand the potential application of the FCA outside of Europe and will support greater utilisation of the FCA and wider inclusion of productivity costs in societal-based economic evaluations based on the use of widely available and updated key labour market variables in our selected countries., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Between 40 and 50% of patients with Parkinson's disease (PD) experience anxiety and depression, associated with impaired physical function, high care dependency and mortality. Recently, the United States National Institutes of Health has urged the implementation of mindfulness practices in chronic illness care. Most research to date has examined the effects on chronically ill patients of complex interventions using a combination of mindfulness techniques. In PD patients, however, such complex modalities appear to hinder the technique mastery. Hence, the aim of this trial is to investigate the effects and underlying mechanism of individual mindfulness techniques among PD patients, as well as exploring participants' experience in using individual mindfulness techniques as a lifestyle intervention for stress and symptom management., Methods: We will conduct an assessor-blind three-arm randomized waitlist-controlled trial with a descriptive qualitative evaluation. Up to 168 PD patients will be recruited from community settings and out-patient clinics, and randomized to meditation, yoga, or usual care group. Meditation and yoga sessions of 90-minute are held weekly for 8 weeks. Primary outcomes include anxiety and depression. Secondary outcomes include PD-related motor and non-motor symptoms and quality-of-life; and level of mindfulness and biomarkers of stress and inflammatory responses will be measured as mediating variables. All outcome evaluations will be assessed at baseline, 8 weeks, and 24 weeks. Following the intention-to-treat principle, generalized estimating equation models and path analysis will be used to identify the treatment effects and the mediating mechanisms. A subsample of 30 participants from each intervention group will be invited for qualitative interviews., Discussion: The study would also generate important insights to enhance the patients' adaptation to debilitating disease. More specifically, symptom management and stress adaptation are highly prioritized healthcare agenda in managing PD. The research evidence will further inform the development of community-based, nurse-led compassionate care models for neurodegenerative conditions, which is complementary to existing health services., Trial Registration: WHO Primary Registry - Chinese Clinical Trials Registry number: ChiCTR2100045939; registered on 2021/04/29 ( https://www.chictr.org.cn/showproj.html?proj=125878 )., (© 2023. The Author(s).)

Social protection can buffer the negative impacts of unemployment on health. Have stimulus packages introduced during the COVID-19 pandemic mitigated potential harms to health from unemployment? We performed a systematic review of the health effects of job loss during the first year of the pandemic. We searched three electronic databases and identified 49 studies for inclusion. Three United States-based studies found that stimulus programs mitigated the impact of job loss on food security and mental health. Furloughs additionally appeared to reduce negative impacts when they were paid. However, despite the implementation of large-scale stimulus packages to reduce economic harms, we observed a clear pattern that job losses were nevertheless significantly associated with negative impacts, particularly on mental health, quality of life, and food security. We also observe suggestive evidence that COVID-related job loss was associated with child maltreatment, worsening dental health, and poor chronic disease outcomes. Overall, although we did find evidence that income-support policies appeared to help protect people from the negative health consequences of pandemic-related job loss, they were not sufficient to fully offset the threats to health. Future research should ascertain how to ensure adequate access to and generosity of social protection programs during epidemics and economic downturns.

Chronic liver disease (CLD) and its associated complications (cirrhosis and liver cancer) cause significant mortality, morbidity, and economic burden. Published data from the World Health Organization and/or the Global Burden of Disease show that the burden of CLD is large and increasing, primarily owing to the increasing burden of nonalcoholic fatty liver disease and alcohol-related liver disease (ALD). Middle Eastern, Northern African, and Asian regions of the globe are most affected by hepatitis B and hepatitis C virus. Furthermore, Middle Eastern and North African regions also are affected by nonalcoholic fatty liver disease, and Eastern European, West African, and Central Asian regions are affected by ALD. In this context, the rate of increase for cirrhosis is highest in the Middle East, as well as in middle high and high sociodemographic index (SDI) regions. On the other hand, the highest SDI countries are experiencing increasing rates of hepatocellular carcinoma (HCC). Assessing HCC burden based on country and etiology shows that China, Korea, India, Japan, and Thailand have the highest hepatitis B virus-related HCC cases, while China, Japan, and the United States have the highest hepatitis C virus-related HCC cases. Additionally, the United States has the highest ALD-related HCC cases, while India, the United States, and Thailand have the highest nonalcoholic steatohepatitis-related HCC cases. Although the burden of CLD is increasing globally, regions of the world are impacted differently as a result of a number of sociodemographic factors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Internationally, colorectal cancer screening participation remains low despite the availability of home-based testing and numerous interventions to increase uptake. To be effective, interventions should be based on an understanding of what influences individuals' decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)-based colorectal cancer screening uptake., Methods: Regression modeling of data from a cross-sectional survey within a population-based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake., Results: Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of "deny immediacy to be tested" (OR, 0.53; 95% confidence interval [CI], 0.43-0.65; p < .001) and "self-exemption" (OR, 0.80; 95% CI, 0.68-0.96; p < .001) independently predicted nonuse of FIT-based screening., Conclusions: This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT-based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self-exempting oneself from screening, may be promising targets for future interventions to improve uptake., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: To investigate the prospective associations between oral health and progression of physical frailty in older adults., Design: Prospective analysis., Setting and Participants: Data are from the British Regional Heart Study (BRHS) comprising 2137 men aged 71 to 92 years from 24 British towns and the Health, Aging, and Body Composition (HABC) Study of 3075 men and women aged 70 to 79 years., Methods: Oral health markers included denture use, tooth count, periodontal disease, self-rated oral health, dry mouth, and perceived difficulty eating. Physical frailty progression after ∼8 years follow-up was determined based on 2 scoring tools: the Fried frailty phenotype (for physical frailty) and the Gill index (for severe frailty). Logistic regression models were conducted to examine the associations between oral health markers and progression to frailty and severe frailty, adjusted for sociodemographic, behavioral, and health-related factors., Results: After full adjustment, progression to frailty was associated with dentition [per each additional tooth, odds ratio (OR) 0.97; 95% CI: 0.95-1.00], <21 teeth with (OR 1.74; 95% CI: 1.02-2.96) or without denture use (OR 2.45; 95% CI 1.15-5.21), and symptoms of dry mouth (OR ≥1.8; 95% CI ≥ 1.06-3.10) in the BRHS cohort. In the HABC Study, progression to frailty was associated with dry mouth (OR 2.62; 95% CI 1.05-6.55), self-reported difficulty eating (OR 2.12; 95% CI 1.28-3.50) and ≥2 cumulative oral health problems (OR 2.29; 95% CI 1.17-4.50). Progression to severe frailty was associated with edentulism (OR 4.44; 95% CI 1.39-14.15) and <21 teeth without dentures after full adjustment., Conclusions and Implications: These findings indicate that oral health problems, particularly tooth loss and dry mouth, in older adults are associated with progression to frailty in later life. Additional research is needed to determine if interventions aimed at maintaining (or improving) oral health can contribute to reducing the risk, and worsening, of physical frailty in older adults., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens. Yet, COVID-19 vaccine and booster uptake remain sluggish due to the mistaken beliefs that children have low rates of severe COVID-19 illness as well as rare but severe complications from COVID-19 vaccine are common. In this study we examined composite sAEFI reported in association with COVID-19 vaccines in the United States (US) amongst 5-17-year-old children, to ascertain the composite reported risk associated with vaccination. Between December 13, 2020, and April 13, 2022, a total of 467,890,599 COVID-19 vaccine doses were administered to individuals aged 5-65 years in the US, of which 180 million people received at least 2 doses. In association with these, a total of 177,679 AEFI were reported to the Vaccine Adverse Event reporting System (VAERS) of which 31,797 (17.9%) were serious. The rates of ED visits per 100,000 recipients were 2.56 (95% CI: 2.70-3.47) amongst 5-11-year-olds, 18.25 (17.57-18.95) amongst 12-17-year-olds and 33.74 (33.36-34.13) amongst 18-65-year olds; hospitalizations were 1.07 (95% CI 0.87-1.32) per 100,000 in 5-11-year-olds, 6.83 (6.42-7.26) in 12-17-year olds and 8.15 (7.96-8.35) in 18-65 years; life-threatening events were 0.14 (95% CI: 0.08-0.25) per 100,000 in 5-11-year olds, 1.22 (1.05-1.41) in 12-17-year-olds and 2.96 (2.85-3.08) in 18-65 year olds; and death 0.03 (95% CI 0.01-0.10) per 100,000 in 5-11 year olds, 0.08 (0.05-0.14) amongst 12-17-year olds and 0.76 (0.71-0.82) in 18-65 years age group. The results of our study from national population surveillance data demonstrate rates of reported serious AEFIs amongst 5-17-year-olds which appear to be significantly lower than in 18-65-year-olds. These low risks must be taken into account in overall recommendation of COVID-19 vaccination amongst children., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mangat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The use of real-world evidence (RWE) studies, including pragmatic randomised controlled trials (RCTs; randomised RWE studies), to aid the development of treatment guidelines, is gradually becoming a mainstay within clinical practice. RWE is an integral part of patient-driven decision-making and offers important value to add complimentary evidence to traditional RCTs; these provide a more well-rounded view of the benefits to patient-reported outcomes and improve the external validity of a given treatment versus findings from traditional RCTs alone. Discussions in recent scientific workshops explored the importance of pragmatic RCTs in optimising guideline development and patient care in chronic obstructive pulmonary disease (COPD) and asthma. The Salford Lung Study in patients with COPD (NCT01551758) and asthma (NCT01706198) were the world's first prelicence pragmatic RCTs that compared novel investigational treatments with existing COPD and asthma treatments and, more recently (2021), RWE studies have been used by the American Thoracic Society and the US Food and Drug Administration to support the approval of an immunosuppressant drug in patients receiving lung transplants. This highlights the importance of RWE data in supporting clinical guideline development and emphasises the advantages for the use of pragmatic RCTs in guiding clinical practice., Competing Interests: Competing interests: NDB reports grants and personal fees from GSK, Novartis and Almirall/AstraZeneca, and congress attendance fees from Boehringer-Ingelheim. KN and GC are employees of and shareholders in GSK. NGS is a former employee of GSK. RS reports previous honoraria/sponsorship for consultancy work, lecturing and educational events unrelated to this workshop from GSK, Cogora, Pharman, Chiesi, Boehringer Ingelheim, Teva, AstraZeneca and the Centre for Pharmacy Postgraduate Education, and is a member of the National Institute for Health and Care Excellence COPD guidelines committee and the British Thoracic Society specialist advisory group. ADS reports grants, personal fees and other financial activities from AstraZeneca, Bayer, GSK, Gilead, Novartis, Pfizer, Teva and Chiesi., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In January 2019, the United States National Academy of Medicine initiated a comprehensive study of the status of current knowledge and clinical practices associated with temporomandibular disorders (TMDs). The National Academy of Sciences, which includes the National Academy of Medicine, was chartered by the US Government in the late 1800s as a non-profit institution working outside of government in order to provide unbiased, objective opinions on matters including healthcare. In this brief paper, we will discuss the open access 2020 report Temporomandibular disorders: priorities for research and care, available online. While the main focus of this report was the situation of TMDs in the US, the evidence base, authorship, expertise and literature scope was international and the findings therefore are at least in part generalisable to and important for the UK.The authors of this commentary were directly involved in the National Academy process, with RO a panel member, JD a consultant and CG one of 15 reviewers of the draft report. There was a wide variety of clinical and research fields involved in gathering the evidence and constructing the report. In addition, there was extensive involvement from affected patients with TMDs and their families, which is critical because their perspective is typically omitted in textbooks and professional consensus meetings., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Background: Preventing oral health problems can be crucial for maintaining physical independence in older adults. We aimed to examine the associations of a range of oral health problems with incidence of disability in older adults., Methods: We used prospective data from the British Regional Health Study (BRHS) (N = 2147, 71-92 years), and the Health, Aging and Body Composition (HABC) study (USA) (N = 3075, 71-80 years). Oral health measures included tooth loss, periodontal disease, self-rated oral health, and self-reported dry mouth. Participants were followed for onset of disability over a follow-up period of 3 years. Onset of disability was assessed through new cases of mobility limitations, activities of daily living (ADL), and instrumental activities of daily living (IADL). Logistic regression was performed to calculate the odds of incident disability., Results: In the BRHS, tooth loss was associated with greater odds of mobility limitations and ADL difficulties. Periodontal disease was associated with greater incidence of mobility limitations. Self-report of ≥3 dry mouth symptoms was associated with increased odds of incident mobility limitations and ADL difficulties (OR = 2.08, 95% CI 1.27-3.42; OR = 1.73, 95% CI 1.03-2.90). Fair/poor self-rated oral health was associated with greater incidence of IADL difficulties. In the HABC study, complete tooth loss was associated with greater incidence of mobility limitations (OR = 1.86, 95% CI 1.13-3.06), and fair/poor self-rated oral health was associated with increased odds of incident ADL difficulties (OR = 1.42, 95% CI 1.04-1.94)., Conclusions: Oral health problems in older adults, particularly tooth loss, self-reported dry mouth and self-rated oral health were associated with greater incidence of disability. Poor oral health plays a potentially important role in the development of disability in older populations, which in turn is an essential part of quality of life and healthy aging., (© 2022 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Research on religiosity and health has generally focussed on the United States, and outcomes of health or mortality but not both. Using the European Values Survey 2008, we examined cross-sectional associations between four dimensions of religiosity/spirituality: attendance, private prayer, importance of religion, belief in God; and healthy life expectancy (HLE) based on self-reported health across 47 European countries (n = 65,303 individuals). Greater levels of private prayer, importance of religion and belief in God, at a country level, were associated with lower HLE at age 20, after adjustment for confounders, but only in women. The findings may explain HLE inequalities between European countries., (© 2021. The Author(s).)

Policy Points The number of social prescribing practices, which aim to link patients with nonmedical services and supports to address patients' social needs, is increasing in both England and the United States. Traditional health care financing mechanisms were not designed to support social prescribing practices, and flexible payment approaches may not support their widespread adoption. Policymakers in both countries are shifting toward developing explicit financing streams for social prescribing programs. Consequently, we need an evaluation of them to assess their success in supporting both the acceptance of these programs and their impacts. Investment in community-based organizations and wider public services will likely be crucial to both the long-term effectiveness and the sustainability of social prescribing., (© 2022 The Authors. The Milbank Quarterly published by Wiley Periodicals LLC on behalf of The Milbank Memorial Fund.)

Agent-based model should inform the action plan to curb algal blooms in Lake Erie.

The current study addresses the need to empirically develop effective mental health interventions for youth from ethnic/racial minority and low-income neighborhoods. Using Stage Model evaluation methods supported by the National Institutes of Health in the US to address underutilization of mental healthcare among racial/ethnic minority youth, this feasibility study demonstrates empirical adaptation of an innovative sport-specific psychological intervention for use in youth from ethnic/racial minority and low-income neighborhoods. An international group of professionals familiar with sport performance and mental health intervention serving the target population experientially examined the adapted intervention protocols in workshops and provided feedback. Survey results indicated the professionals found the intervention components were easy to administer and likely to be safe, enjoyable, engaging and efficacious for youth mental health and sport performance. The protocols were revised based on feedback from these professionals and the intervention was examined in a case trial involving an Asian American youth who evidenced Social Anxiety Disorder. Case study results indicated the intervention could be implemented with integrity, and severity of psychiatric symptoms and factors interfering with sport performance decreased after intervention implementation. The participant's relationships with family, coaches and teammates were also improved.

Background: Robotic esophagogastric cancer surgery is gaining widespread adoption. This population-based cohort study aimed to compare rates of textbook outcomes (TOs) and survival from robotic minimally invasive techniques for esophagogastric cancer., Methods: Data from the United States National Cancer Database (NCDB) (2010-2017) were used to identify patients with non-metastatic esophageal or gastric cancer receiving open surgery (to the esophagus, n = 11,442; stomach, n = 22,183), laparoscopic surgery (to the esophagus [LAMIE], n = 4827; stomach [LAMIG], n = 6359), or robotic surgery (to the esophagus [RAMIE], n = 1657; stomach [RAMIG], n = 1718). The study defined TOs as 15 or more lymph nodes examined, margin-negative resections, hospital stay less than 21 days, no 30-day readmissions, and no 90-day mortalities. Multivariable logistic regression and Cox analyses were used to account for treatment selection bias., Results: Patients receiving robotic surgery were more commonly treated in high-volume academic centers with advanced clinical T and N stage disease. From 2010 to 2017, TO rates increased for esophageal and gastric cancer treated via all surgical techniques. Compared with open surgery, significantly higher TO rates were associated with RAMIE (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.27-1.58) and RAMIG (OR 1.30; 95% CI 1.17-1.45). For esophagectomy, long-term survival was associated with both TO (hazard ratio [HR 0.64, 95% CI 0.60-0.67) and RAMIE (HR 0.92; 95% CI 0.84-1.00). For gastrectomy, long-term survival was associated with TO (HR 0.58; 95% CI 0.56-0.60) and both LAMIG (HR 0.89; 95% CI 0.85-0.94) and RAMIG (HR 0.88; 95% CI 0.81-0.96). Subset analysis in high-volume centers confirmed similar findings., Conclusion: Despite potentially adverse learning curve effects and more advanced tumor stages captured during the study period, both RAMIE and RAMIG performed in mostly high-volume centers were associated with improved TO and long-term survival. Therefore, consideration for wider adoption but a well-designed phase 3 randomized controlled trial (RCT) is required for a full evaluation of the benefits conferred by robotic techniques for esophageal and gastric cancers., (© 2021. The Author(s).)

Few reports have examined whether prophylactic allogeneic hematopoietic cell transplantation (HCT) for X-linked lymphoproliferative syndrome type 1 (XLP1) improves the prognosis. We compared the prognosis of symptomatic probands and affected siblings in the same family. Twenty-two cases (10 probands and 12 affected siblings) in Japan, the United Kingdom, and the United States were analyzed. The overall survival (OS) rate at 5 years after diagnosis was 70.0% in probands and 91.7% in affected siblings (p = 0.0789). The prognosis of patients who developed symptoms of XLP1 before HCT and those who did not was also compared. The 5-year probability of OS from the time of diagnosis in asymptomatic patients (100%) was significantly better than that in symptomatic patients (66.7%). These results suggested that early HCT as soon as the diagnosis is made improves the prognosis in asymptomatic XLP1 patients., (Copyright © 2022. Published by Elsevier Inc.)

Aim: Ongoing randomized controlled trials seek to evaluate the potential organ-preservation strategy of definitive chemoradiotherapy as a primary treatment for esophageal cancer. This population-based cohort study aimed to assess survival following definitive chemoradiotherapy (DCR) with or without salvage esophagectomy (SALV) in the treatment of esophageal cancer., Patients and Methods: Data from the National Cancer Database (NCDB) from 2004 to 2015, was used to identify patients with nonmetastatic esophageal cancer receiving either DCR (n = 5977) or neoadjuvant chemoradiotherapy with planned esophagectomy (NCRS) (n = 13,555). Propensity score matching and multivariable analyses were used to account for treatment selection bias. Subset analyses compared patients receiving SALV after DCR with NCRS., Results: Comparison of baseline demographics of the unmatched cohort revealed that patients receiving NCRS were younger, had a lower burden of medical comorbidities, lower proportion of squamous cell carcinoma (SCC), and more positive lymph nodes. Following matching, NCRS was associated with significantly improved survival compared with DCR [hazard ratio (HR): 0.60, 95% confidence Interval (CI): 0.57-0.63, P < 0.001], which persisted in subset analyses of patients with adenocarcinoma (HR: 0.60, 95% CI: 0.56-0.63, P < 0.001) and SCC (HR: 0.58, 95% CI: 0.53-0.63, P < 0.001). Of 829 receiving SALV after DCR, 823 patients were matched to 1643 NCRS. There was no difference in overall survival between SALV and NCRS (HR: 1.00, 95% CI: 0.90-1.11, P = 1.0)., Conclusions: Surgery remains an integral component of the management of patients with esophageal cancer. Neoadjuvant therapy followed by planned esophagectomy appears to remain the optimum curative treatment regime in patients with locoregional esophageal cancer., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Research conducted in the United States suggests that two primes (citrus smells and pictures of a person's eyes) can increase hand gel dispenser use on the day they are introduced in hospital. The current study, conducted at a hospital in the United Kingdom, evaluated the effectiveness of these primes, both in isolation and in combination, at the entry way to four separate wards, over a longer duration than the previous work., Methods: A crossover randomized controlled trial was conducted. Four wards were allocated for 6 weeks of observation to each of four conditions, including "control," "olfactory," "visual," or "both" (i.e., "olfactory" and "visual" combined). It was hypothesized that hand hygiene compliance would be greater in all priming conditions relative to the control condition. The primary outcome was whether people used the gel dispenser when they entered the wards. After the trial, a follow up survey of staff at the same hospital assessed the barriers to, and facilitators of, hand hygiene compliance. The trial data were analyzed using regression techniques and the survey data were analyzed using descriptive statistics., Results: The total number of individuals observed in the trial was 9,811 (female = 61%), with similar numbers across conditions, including "control" N = 2,582, "olfactory" N = 2,700, "visual" N = 2,488, and "both" N = 2,141. None of the priming conditions consistently increased hand hygiene. The lowest percentage compliance was observed in the "both" condition (7.8%), and the highest was observed in the "visual" condition (12.7%). The survey was completed by 97 staff (female = 81%). "Environmental resources" and "social influences" were the greatest barriers to staff cleaning their hands., Conclusions: Taken together, the current findings suggest that the olfactory and visual priming interventions investigated do not influence hand hygiene consistently. To increase the likelihood of such interventions succeeding, future research should focus on prospectively determined mechanisms of action., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Schmidtke, Aujla, Marshall, Hussain, Hodgkinson, Arheart, Birnbach, Kudrna and Vlaev.)

Pluronic (PEO-PPO-PEO) block copolymers can form nano-sized micelles with a structure composed of a hydrophobic PPO core and hydrophilic PEO shell layer. Pluronics are U.S. Food and Drug Administration approved polymers, which are widely used for solubilization of drugs and their delivery, gene/therapeutic delivery, diagnostics, and tissue engineering applications due to their non-ionic properties, non-toxicity, micelle forming ability, excellent biocompatibility and biodegradability. Although Pluronics have been employed as drug carrier systems for several decades, numerous issues such as rapid dissolution, shorter residence time in biological media, fast clearance and weak mechanical strength have hindered their efficacy. Pluronics have been functionalized with pH-sensitive, biological-responsive moieties, antibodies, aptamers, folic acid, drugs, different nanoparticles, and photo/thermo-responsive hydrogels. These functionalization strategies enable Pluronics to act as stimuli responsive and targeted drug delivery vehicles. Moreover, Pluronics have emerged in nano-emulsion formulations and have been utilized to improve the properties of cubosomes, dendrimers and nano-sheets, including their biocompatibility and aqueous solubility. Functionalization of Pluronics results in the significant improvement of target specificity, loading capacity, biocompatibility of nanoparticles and stimuli responsive hydrogels for the promising delivery of a range of drugs. Therefore, this review presents an overview of all advancements (from the last 15 years) in functionalized Pluronics, providing a valuable tool for industry and academia in order to optimize their use in drug or therapeutic delivery, in addition to several other biomedical applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The impact of palliative gastrectomy for metastatic gastric adenocarcinoma, especially by site of metastasis remains unclear., Methods: The National Cancer Database, 2010-2015, was used to identify patients with clinical metastatic (cM1) gastric adenocarcinoma (n = 19,411) at diagnosis. The main variable was index management for cM1 gastric adenocarcinoma (ie, no treatment, palliative chemotherapy, or palliative gastrectomy). Cox multivariable analyses were used to account for treatment selection bias and reported as hazard ratio (HR) and 95% confidence interval., Results: Of 19,411 patients, 10,893 (56%) received palliative chemotherapy, and only 1,101 (6%) received palliative gastrectomy only. The median survival was 6.1 months, and 5-year survival was 4% in the entire cohort. Patients receiving palliative gastrectomy had a significantly longer survival than patients without any treatment or palliative chemotherapy (median: 12.8 vs 1.8 vs 9.5 months, P < .001), which remained after multivariable adjustment (HR: 0.76, 95% confidence interval: 0.71-0.81, P < .001) compared with palliative chemotherapy. Stratified analyses by clinical nodal stage (cN) demonstrated survival benefit with palliative gastrectomy: cN0 (HR: 0.71, 95% confidence interval: 0.62-0.82), cN1 (HR: 0.68, 95% confidence interval: 0.59-0.79), cN2 (HR: 0.86, 95% confidence interval: 0.70-0.94), and cN3 (HR: 0.82, 95% confidence interval: 0.70-0.92) over palliative chemotherapy. Stratified analyses by metastasis site demonstrated that palliative gastrectomy remained superior compared with palliative chemotherapy for metastatic disease limited to liver, bone, and peritoneum, but equivalent to lung metastasis and inferior to brain metastasis., Conclusion: Palliative gastrectomy appears to have a modest survival benefit over palliative chemotherapy alone. Differences in outcomes by site of metastasis warrant further research to understand tumor biology and identify specific subgroups which may benefit from palliative gastrectomy., (Copyright © 2021. Published by Elsevier Inc.)

Background: In the context of substantial financial disinvestment from alcohol and drug treatment services in England, our aim was to review the existing evidence of how such disinvestments have impacted service delivery, uptake, outcomes and broader health and social implications., Methods: We conducted a systematic review of quantitative and qualitative evidence (PROSPERO CRD42020187295), searching bibliographic databases and grey literature. Given that an initial scoping search highlighted a scarcity of evidence specific to substance use treatment, evidence of disinvestment from publicly funded sexual health and smoking cessation services was also included. Data on disinvestment, political contexts and impacts were extracted, analysed, and synthesized thematically., Results: We found 20 eligible papers varying in design and quality including 10 related to alcohol and drugs services, and 10 to broader public health services. The literature provides evidence of sustained disinvestment from alcohol and drug treatment in several countries and a concurrent decline in the quantity and quality of treatment provision, but there was a lack of methodologically rigorous studies investigating the impact of disinvestment., Conclusions: This review identified a paucity of scientific evidence quantifying the impacts of disinvestment on alcohol and drug treatment service delivery and outcomes. As the global economy faces new challenges, a stronger evidence base would enable informed policy decisions that consider the likely public health impacts of continued disinvestment., (© 2021. The Author(s).)

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome., Competing Interests: Declaration of interests P.-A.K. and F.I.S. are cofounders and shareholders of Dioscure Therapeutics SE. F.I.S. is a consultant and shareholder of IFM Therapeutics. J.R.H. is founder and board member of Isoplexis and PACT Pharma. J.D.G. declares contracted research with Gilead, Lilly, and Regeneron. K.H., J.M.J., and A.J.B. work at Quanterix Corporation. All other authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Race is an important prognostic factor affecting receipt of surgical intervention and survival from cancer in the USA. The findings of this study highlight the importance of implementing changes aimed at narrowing the disparities in outcomes between race in patients with cancers., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)