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Abstract Female development includes significant morphological changes across the breast. Yet, whether differences in breast surface area (BrSA) modify breast skin stiffness and tactile sensitivity at rest and after exercise in the heat remain unclear. We investigated the relationship between BrSA and skin stiffness and tactile sensitivity in 20 young to middle‐aged women (27 ± 8 years of age) of varying breast sizes (BrSA range: 147–502 cm2) at rest and after a submaximal run in a warm climatic chamber (32C ± 0.6C; 53% ± 1.7% relative humidity). Skin stiffness above and below the nipple and tactile sensitivity from the nipple down were measured. Associations between BrSA and both skin stiffness and tactile sensitivity at rest were determined via correlation analyses. Effects of exercise and test site were assessed by a two‐way ANOVA. Skin stiffness was positively correlated with BrSA 3 cm above the areola edge (r = 0.61, P = 0.005) and at the superior areola border (r = 0.54, P = 0.016), but not below the nipple (P > 0.05). The area 3 cm below the areola was also significantly stiffer than all other test sites (P 0.09), but it varied across the breast (i.e., the area 3 cm below the areola was more sensitive than the inferior areola edge; P = 0.018). Skin stiffness and tactile sensitivity across the breast decreased after exercise by ∼37% (P

Abstract Background Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely.

Abstract Female development includes significant morphological changes across the breast. Yet, whether differences in breast surface area (BrSA) modify sweat gland density and output remains unclear. The present study investigated the relationship between BrSA and sweat gland density and output in 22 young to middle‐aged women (28±10 years) of varying breast sizes (BrSA range: 147–561 cm2) during a submaximal run in a warm environment (32 ±0.6°C; 53 ±1.7% relative humidity). Local sweat gland density and local sweat rate (LSR) above and below the nipple and at the bra triangle were measured. Expired gases were monitored for the estimation of evaporative requirements for heat balance (Ereq, in W/m2). Associations between BrSA and (i) sweat gland density; (ii) LSR; and (iii) sweat output per gland for the breast sites were determined via correlation and regression analyses. Our results indicated that breast sweat gland density decreased linearly as BrSA increased (r = −0.76, P

Abstract Sperm whales spatially segregate by sex and social behavior as they mature. In the North Atlantic, male whales move to higher latitudes as far as Svalbard at 80° N, while females and young whales typically remain around lower latitudes below 40–45° N. The Azores, Madeira, and the Canary Islands constitute important nursery grounds for female and young sperm whales. Irish waters represent a midpoint for this species’ spatial segregation in the Northeast Atlantic, where the species occurs along the submarine canyon systems to the west of the country. Historically, just male whales were thought to be found in this region between 51 and 55° N, but one adult female was caught by commercial whalers in 1910, and a 5.49 m calf was found stranded in 1916. Between 1995 and 2023, 10 female sperm whales have been stranded around the coast of Ireland. Eight of these whales have been stranded since 2013, and there has been at least one stranding per year between 2019 and 2023. Four of these strandings have occurred in Donegal in the northwest of Ireland, indicating the presence of female whales along the continental shelf off this region. Two females were stranded within a day of each other and were found in similar states of decomposition in February 2022, indicating that they may have been part of the same group rather than being lone vagrant individuals. Sperm whale calves and juveniles were also sighted in Irish waters in 2001, 2004, and 2010 in the Rockall Trough, along the Porcupine Bank and Goban Spur, where between 1 and 3 individuals were observed on four occasions while one calf live stranded in 2004. These records indicate a historical presence of female and young sperm whales in this region but that an apparent increase in occurrence has taken place over the past decade.

Background African American women bear a disproportionate burden of cardiovascular diseases, potentially due to altered central hemodynamics. Racism and sexism often lead to African American women taking on numerous caretaking roles and overall increases their use of the Strong Black Woman (ie, Superwoman) mindset, which may have negative health consequences. We hypothesized that endorsing the Superwoman role and its Obligation to Help Others dimension would be associated with a deleterious central hemodynamics profile in African American women. Methods and Results Using cross‐sectional data, we examined central systolic blood pressure (mm Hg; n=408), augmentation index (percentage, adjusted for height and heart rate; n=408), and pulse wave velocity (m/s; n=368) in African American women aged 30 to 46 years. The Giscombe Superwoman Schema (SWS) questionnaire assessed endorsement of Overall SWS (range, 0–105) and SWS–Obligation to Help Others (range, 0–3). Multiple linear regression modeled associations between Overall SWS (10‐unit increments) and SWS–Obligation to Help Others (1‐unit increments) and central hemodynamics while adjusting for pertinent sociodemographic, clinical, and psychosocial factors. In fully adjusted models, central systolic blood pressure was significantly associated with Overall SWS (β=0.83 [95% CI, 0.19–1.47]) and SWS–Obligation to Help Others (β=2.03 [95% CI, 0.39–3.67]). Augmentation index was associated with Overall SWS (β=0.66 [95% CI, 0.02–1.30]) and SWS–Obligation to Help Others (β=2.21 [95% CI, 0.58–3.84]). Significant associations were not observed between pulse wave velocity and SWS. Conclusions Greater endorsement of the Superwoman role and prioritizing caregiving over self‐care were associated with higher central systolic blood pressure and augmentation index, which may contribute to adverse cardiovascular health among African American women.

Background Although myocardial infarction with nonobstructive coronary arteries (MINOCA) is more common in women, it is unknown whether sex is a risk factor for adverse outcomes in patients with MINOCA. We aimed to investigate the relationship between sex differences and outcomes of patients with MINOCA. Methods and Results A systematic literature search was performed in PubMed, Embase, and Cochrane databases from their inception until August 2023 for relevant studies. End points were pooled using the Hartung–Knapp–Sidik–Jonkman random‐effects model as odds ratio (OR) with 95% CIs. Nine studies, involving 30 281 patients with MINOCA (comprising 18 079 women and 12 202 men), were included in the study. Women were older and had a higher prevalence of hypertension, diabetes, and stroke compared with men. The median duration of follow‐up was 3.5 years, with an interquartile range of 2.2 to 4.2 years. Pooled analysis revealed no statistically significant difference in the risk of all‐cause mortality (OR, 1.03 [95% CI, 0.87–1.22]), major adverse cardiovascular events (OR, 1.18 [95% CI, 0.89–1.58]), heart failure (OR, 1.32 [95% CI, 0.57–3.03]), stroke (OR, 1.13 [95% CI, 0.56–2.26]), and myocardial infarction (OR, 1.04 [95% CI, 0.29–3.76]) between the 2 groups. Regarding short‐term outcomes, women had a significantly higher risk of in‐hospital major adverse cardiovascular events compared with men (OR, 1.33 [95% CI, 1.16–1.53]) whereas there was no significant difference in the risk of in‐hospital mortality (OR, 0.90 [95% CI, 0.64–1.28]) between the 2 patient groups. Conclusions Despite the differences in demographics and comorbidity profiles, there was no significant difference in the long‐term outcomes for patients with MINOCA between sexes. However, it is noteworthy that women experienced a higher risk of in‐hospital major adverse cardiovascular events compared with men.

Abstract Background Little is known about factors that influence footwear selection by field hockey players. Methods An online survey was used to collect data on participant demographics and physical characteristics, factors influencing footwear selection, perceptions regarding footwear design features on injury and performance, and experiences regarding usability. Nominal and ordinal data were described as absolute frequencies and relative frequencies. Free text responses were analysed using content analysis. Sex‐related differences in quantitative and qualitative data were explored. Results A total of 401 hockey players completed the survey. Participants reported that fit, comfort, support, and cushioning were the most important factors when selecting hockey footwear. Most hockey players believed that stud design could influence athletic performance (65%) and injury risk (63%) but reported having no preference on outsole design or stud shape. Most participants (63%) used hockey‐specific footwear, but 46% of female hockey players did not, with 40% using trail running footwear instead. Qualitative analysis revealed that hockey players, particularly female participants, encounter difficulties finding properly fitting footwear. They desire more options for wide or narrow feet and face challenges in accessing suitable hockey shoes due to limited choices and availability. Conclusions With over a third of field hockey players not using hockey‐specific footwear, future research should attempt to understand the reasons and assess the impact of different footwear features on comfort, performance, injury risk, and usability.

Background Among those with heart failure (HF), women are more likely to develop depression than men. Few studies have focused on the outcomes of female patients with HF with depressive symptoms. Methods and Results A total of 506 female patients with HF with preserved ejection fraction were included in this secondary analysis from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) cohort, and 439 female patients with HF with reduced ejection fraction were included from the HF‐ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) cohort. Depressive symptoms were measured using the Patient Health Questionnaire‐9 and Beck Depression Inventory‐II. The depression class was categorized by severity, and the change in clinical depression class was defined as aggravated (1‐grade increase) or improved (1‐grade decrease). The prognostic value of depressive symptoms was determined by using multivariable Cox proportional hazards models. Female patients with improved depressive symptoms had worse depressive status at baseline and lower baseline Kansas City Cardiomyopathy Questionnaire scores. Depression class at the 12‐month visit and depression class change were the dominant prognostic factors for cardiovascular death in female patients with HF with preserved ejection fraction (hazard ratio [HR], 1.43 [95% CI, 1.02–2.01], P=0.036; HR, 1.71 [95% CI, 1.14–2.55], P=0.009). Among the patients with HF with reduced ejection fraction, both the depression class at baseline and depression class change had significant prognostic effects on cardiovascular death (HR, 3.30 [95% CI, 1.70–6.39], P

Abstract Aim To recognize, appraise and summarize the research evidence that has explored the results of pelvic floor muscle training on female sexual function. Design Systematic review and possible meta‐analysis. Methodology Between September and October 2022, the Cochrane Library, CINAHL, MEDLINE, EMBASE, PsycINFO and Scopus electronic databases will be searched. We will include RCT's in English, Spanish and Portuguese that investigate the results of pelvic floor muscle training on female sexual function. The data will be extracted by two researchers independently. Risk of bias will be measured from the Cochrane Risk of Bias Tool. The meta‐analysis of the results will be performed using Comprehensive Meta‐Analysis Version 2. Results This systematic review and possible meta‐analysis will contribute significantly to the promotion of pelvic floor health and women's sexual function and to strengthen clinical practice and define other areas of study.

Abstract To explore the moderating effect of mindfulness on the relationship between anxiety and somatization symptoms in middle‐aged and elderly female patients with hypertension and provide a foundation for the development of more effective mindfulness intervention strategies. A total of 109 middle‐aged and elderly female patients with hypertension participated in this cross‐sectional study from April to July 2022 and provided valid responses to the Five Facet Mindfulness Questionnaire (FFMQ), the Hospital Anxiety and Depression Scale (HADS), and the Somatization Symptom Self‐rating Scale (SSS). The moderating effect of mindfulness was determined using multiple linear regression. The participants’ average scores were as follows: mindfulness: 123.86 ± 10.49; anxiety: 7.41 ± 3.62; and somatization symptoms: 41.2 ± 9.44. The anxiety (P = .000) and somatization symptoms (P = .001) of participants with high mindfulness were significantly reduced. Anxiety was positively correlated with somatization symptoms (r = 0.606, P = .000), while mindfulness was negatively correlated with both anxiety (r = ‐0.468, P = .000) and somatization symptoms (r = ‐0.439, P = .000). Moreover, mindfulness had a significant moderating effect on the relationship between anxiety and somatization symptoms (n = 109) (B = ‐0.166, t = ‐2.125, P = .036). The effect of mindfulness on anxiety and somatization symptoms was more significant in participants with low mindfulness levels (n = 56) (B = 0.144, t = 2.805, P = .008) than in participants with high mindfulness levels (n = 53) (B = ‐0.037, t = ‐0.864, P = .393). The moderating effect analysis based on regression analysis showed that mindfulness had a significant moderating effect on anxiety and somatization symptoms, especially in participants with low mindfulness levels.

Introduction Urethral recurrence after radical cystectomy in female patients with bladder cancer is relatively uncommon. Recurrent bladder tumors with neuroendocrine differentiation are extremely rare. Case presentation A 71‐year‐old female patient who underwent radical cystectomy for bladder cancer presented with vaginal bleeding 19 months postoperatively. She was diagnosed with bladder cancer urethral recurrence. Urethral tumor en‐bloc resection with the anterior vaginal wall was performed by combining abdominal and vaginal approaches. Pathological examination revealed a recurrent tumor of urothelial bladder cancer containing small‐cell carcinoma components. Conclusion This case is the first report of a recurrent tumor with small‐cell carcinoma in the female urethra after radical cystectomy for pure urothelial carcinoma.

Abstract Aim To clarify the content of nursing care provided to sexually assaulted females when they present at a medical institution immediately after the assault. Design Qualitative descriptive study. Methods Individual semi‐structured interviews were conducted with 20 female nurses and midwives affiliated with medical institutions collaborating with the one‐stop Support Center for sexual violence victims. Data were analysed using content analysis. Results The study identified five forms of nursing care: providing safety and reassurance, supporting smooth physical exams, building trusting relationships, supporting the recovery of emotional/physical health and dignity, and ensuring continuity of support. There were three types of institutional systems in victim care: (a) male doctors are sometimes involved in care, (b) female doctors provide care with nursing supervisors, and (c) female doctors take the lead to provide care. Nursing care content extracted in this study was influenced by the structure of the medical institution with which the nurses were affiliated.

Abstract Objective To determine the distribution of female physicians throughout the rank from resident to leadership positions in German Otolaryngology‐Head and Neck Surgery (OHNS) departments. Methods This cross‐sectional study collected data about the physician workforce in the German OHNS. The primary outcome was the proportion of female physicians. Data were collected from 165 departments from January 2022 to February 2022. The physician workforce was stratified based on gender and leadership. Results We included 2089 physicians from 165 departments of OHNS in German hospitals. Female residents and specialists outnumbered male peers (484/872 [55.5%] vs. 388/872 [44.5%] and 224/363 [61.71%] vs. 139/363 [38.29%], respectively). However, the women proportion decreased gradually with elevated hierarchical rank starting at the attending physician level to reaching its lowest extreme (14/165 [7.23%]) at the head of the department level. Holding a leadership position was associated with being male (n = 282 [85.2%] vs. n = 49 [14.8%], p

Abstract Aim To identify, describe and analyse the gender perspective in the use of the diagnoses contained in the NANDA‐I taxonomy in observational studies published in the scientific literature. Design and methods A systematic review has been conducted spanning from 2002 to 2020. The most frequent NANDA‐I nursing diagnoses in care plans reported in observational studies, and the defining characteristics and related factors identified for men and women have been described. The Preferred Reporting Items for Systematic Reviews (PRISMA‐P) have guided our research. The main findings have been summarized using a descriptive narrative synthesis approach. Results Forty‐one articles were included in our study. With regard to gender analysis, the percentage of men and women that make up the sample were not specified in all articles, and half of the studies did not identify gender either in the diagnosis label or in their defining characteristics or related factors. Based on the reviewed articles, gender perspectives are not systematically incorporated in the use of the NANDA‐I diagnosis. Therefore, gender biases in its use in the scientific literature may exist. This situation poses barriers to determine the health responses that are different and unequal between women and men.

Abstract Introduction Effective use of pre‐exposure prophylaxis (PrEP) has been low among adolescent girls and young women (AGYW) in sub‐Saharan Africa. The MTN‐034/REACH trial offered AGYW a menu of adherence support strategies and achieved high adherence to both daily oral PrEP and the monthly dapivirine vaginal ring. Understanding how these strategies promoted product use could inform the design of adherence support systems in programmatic settings. Methods REACH was a randomized crossover trial evaluating the safety of and adherence to the ring and oral PrEP among 247 HIV‐negative AGYW (ages 16–21) in South Africa, Uganda and Zimbabwe from January 2019 to September 2021 (NCT03593655). Adherence support included monthly counselling sessions with drug‐level feedback (DLF) plus optional daily short message service (SMS) reminders, weekly phone or SMS check‐ins, peer support clubs, “peer buddies” and additional counselling. Counsellors documented adherence support choices and counselling content on standardized forms. Through focus groups, serial in‐depth interviews (IDIs) and single IDIs (n = 119 total), we explored participants’ experiences with adherence support and how it encouraged product use. Results Participants received counselling at nearly all visits. DLF was provided at 54.3% of sessions and, across sites, 49%–68% received results showing high adherence for oral PrEP, and 73%–89% for the ring. The most popular support strategies were in‐person clubs and weekly calls, followed by online clubs, additional counselling and SMS. Preferences differed across sites but were similar for both products. Qualitative results demonstrated that the REACH strategies supported adherence by providing information about HIV and PrEP, continually motivating participants, and supporting the development of behavioural skills and self‐efficacy, aligning with the Information, Motivation, and Behavioural Skills (IMB) model. Effectiveness was supported by three foundational pillars: strong interpersonal relationships with counsellors; ongoing, easily accessible support and resources; and establishing trust in the counsellors and study products through counsellor relationships, peer‐to‐peer exchange and DLF. Conclusions Implementation programmes could support effective PrEP use by offering a small menu of counsellor‐ and peer‐based support options that are youth‐friendly and developmentally appropriate. The same menu options can support both ring and oral PrEP users, though content should be tailored to the individual products.

Abstract Background Worldwide, breast cancer (BC) is the most frequently discovered tumor in women. Breast self‐examination (BSE) is a helpful screening method that gives women more control over their bodies by educating them about the structures of their breasts and assisting in the early detection of any developing breast abnormalities. The purpose of this research was to assess Palestinian girls' degree of BSE awareness and practice. Method A self‐administered questionnaire was used to gauge participants' knowledge about BC and associated topics. Through an online survey, all girls above the age of 20 are encouraged to take part in the study. Female university students at academic levels I, II, III, and IV in Palestine were also invited to participate in the study by way of an online survey. Results The study included 467 female participants, with 69% of the individuals being single. The majority of females (68.7%) scored poorly on knowledge of BC disease (possible risk, methods of detection, methods of diagnosis, methods of treatment, signs and symptoms, information about mammography, and other knowledge questions), whereas only 31.7% scored well. Conclusion BC, which is thought to be the most common malignant development among them and the second leading cause of cancer mortality, is one of the issues that women in the West Bank face. Screening methods are crucial for the early detection of BC and for lowering disease‐related morbidity and mortality. It has been advised that starting at age 20, every woman should take the BSE.

Abstract This study examines whether internet usage among micro and small enterprises (MSEs) could influence household membersʼ use of the internet in terms of intensity as well as usage for productive activities. Using longitudinal data from MSEs in Yogyakarta, Indonesia, covering the period before and during the COVID‐19 pandemic, the study finds that more intensive use of the internet by female entrepreneurs is positively associated with at least an 8 percentage‐point higher probability of internet use for school‐related purposes by household members. Findings from qualitative analysis indicate that female entrepreneurs who are intensive users of the internet are more effective in persuading their household members to accept use of the internet especially for purposes related to their domain of responsibilities, such as childrenʼs education. We argue that policymakers should focus on improving digital literacy among female entrepreneurs as an affirmative action policy to ensure they can enjoy the maximum benefits that digitalisation has to offer.

Abstract Aims Chronic stress and glucocorticoid exposure are risk factors for depression. Oxytocin (OT) has been shown to have antistress and antidepressant‐like effects in male rodents. However, depression is twice as common in women than in men, and it remains unclear whether OT exerts antidepressant‐like effects in women with depression. Therefore, in this study, we investigated the therapeutic effect of chronic OT administration in a female mouse model of dexamethasone (DEX)‐induced depression. Methods Female C57BL/6J mice were administered saline (vehicle, s.c.), DEX (s.c.), or OT (i.p.) + DEX (s.c.) daily for 8 weeks, and then assessed for anxiety‐ and depression‐like behaviors. We also examined the hippocampal levels of phosphorylated cAMP response element‐binding protein (p‐CREB) and brain‐derived neurotrophic factor (BDNF), which are important mediators of the response to antidepressants. Results Simultaneous OT treatment blocked the adverse effects of DEX on emotional behaviors. Furthermore, it upregulated p‐CREB and BDNF in the hippocampus. Conclusion OT may exert antidepressant‐like effects by activating hippocampal CREB‐BDNF signaling in a female mouse model of depression.

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug‐eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG‐DES (Platelet Function and Genotype‐Related Long‐Term Prognosis in Drug‐Eluting Stent–Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all‐cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity‐adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20–2.12]; women with HPR: HR, 0.99 [95% CI, 0.69–1.42]) and all‐cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07–2.44]; women with HPR: HR, 0.92 [95% CI, 0.57–1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (Pinteraction=0.013) or all‐cause mortality (Pinteraction=0.025). Conclusions In this study, HPR was a differential risk factor for 1‐year MACCEs and all‐cause mortality in women and men. And it was an independent predictor of 1‐year MACCEs and all‐cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028

Abstract Background In response to chronic injury, the muscles of the rotator cuff (RC) experience a unique degeneration characterized by extensive fatty infiltration and loss of contractile function. Human studies suggest this degeneration is also a feature of RC sarcopenia and may precede RC injury. In this study, we investigated whether RC muscles exhibit a similar unique sarcopenia in the mouse. Methods Male and female mice were subdivided into four age groups: 3, 9, 18, and 24 months. The supraspinatus (SS) and infraspinatus muscles of the RC and the tibialis anterior (TA) muscle of the hindlimb were assessed. Muscle mass, contractile function, fibre cross‐sectional areas and numbers, fatty infiltration, and fibrosis were assessed at each time point. Targeted transcriptional analyses were performed to assess the role of metabolic and inflammatory derangement in the pathology. Results The 24‐month‐aged female mice exhibited decreased mass (25% lower than at 9 and 18 months, P

Abstract Background Population‐based estimates of the impact of gender throughout the whole course of brain metastases (BMs) at the time of diagnosis of systemic malignancies are insufficient. We aimed to discover the influence of gender on the presence of BMs in newly diagnosed malignancies and the survival of those patients on a population‐based level. Methods Midlife patients (40 years ≤ age ≤60 years) with newly diagnosed malignancies and BMs at the time of diagnosis were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. Clinical variables adjusted patient data. The LASSO regression was performed to exclude the possibility of collinearity. Univariable and multivariable logistic regression analyses were applied to find independent predictors for the presence of BMs, while univariable and multivariable Cox proportional hazard regression analyses were used to determine prognosticators of survival. K‐M curves were used to perform the survival analysis. Result 276,327 population‐based samples met inclusion criteria between 2014 and 2016, and 5747 (2.08%) patients were diagnosed with BMs at the time of diagnosis of systematic malignancies. Among all midlife patients with cancer, 44.02% (121,634) were male, while 51.68% (2970) were male among patients with BMs at the time of diagnosis. The most frequent tumor type was breast cancer (23.11%), and lung cancer had the highest incidence proportion of BMs among the entire cohort (19.34%). The multivariable logistic regression model suggested that female (vs. male, odds ratio [OR] 1.07, 95% CI: 1.01–1.14, p

Abstract Background Some meta‐analyses have proved the superiority of non‐pharmacological interventions in overactive bladder (OAB), but the best choice is still controversial. Aim To assess the most effective interventions in female with OAB. Methods Studies for relevant randomized controlled trials which compare different kinds of non‐pharmacological interventions in females with OAB will be retrieved from 8 databases including PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database and China Biology Medicine disc, from inception to 1 January 2021. After screening titles and abstracts, detailed data including participates, interventions and outcomes will be extracted according to the eligible criteria. Then, Cochrane risk‐of‐bias tool will be used to assess the quality of the literature. The pairwise meta‐analysis will be conducted by STATA. Network meta‐analysis will be performed to compare and rank the effects of different non‐pharmacological interventions, in terms of alleviation of symptoms, by OpenBUGS, R and STATA. Results This network meta‐analysis will present the best available evidence about non‐pharmacological interventions for OAB to both relieve symptoms and improve life quality.

Trivariate joint modeling for longitudinal count data, recurrent events, and a terminal event for family data has increased interest in medical studies. For example, families with Lynch syndrome (LS) are at high risk of developing colorectal cancer (CRC), where the number of polyps and the frequency of colonoscopy screening visits are highly associated with the risk of CRC among individuals and families. To assess how screening visits influence polyp detection, which in turn influences time to CRC, we propose a clustered trivariate joint model. The proposed model facilitates longitudinal count data that are zero-inflated and over-dispersed and invokes individual-specific and family-specific random effects to account for dependence among individuals and families. We formulate our proposed model as a latent Gaussian model to use the Bayesian estimation approach with the integrated nested Laplace approximation algorithm and evaluate its performance using simulation studies. Our trivariate joint model is applied to a series of 18 families from Newfoundland, with the occurrence of CRC taken as the terminal event, the colonoscopy screening visits as recurrent events, and the number of polyps detected at each visit as zero-inflated count data with overdispersion. We showed that our trivariate model fits better than alternative bivariate models and that the cluster effects should not be ignored when analyzing family data. Finally, the proposed model enables us to quantify heterogeneity across families and individuals in polyp detection and CRC risk, thus helping to identify individuals and families who would benefit from more intensive screening visits., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: Maternal nutrition during pregnancy is known to have an effect on fetal growth and development. It is recommended that women increase their calcium intake during pregnancy and lactation, although the recommended dosage varies among professionals. Currently, there is no consensus on the role of routine calcium supplementation for pregnant women other than for preventing or treating hypertension., Objectives: To determine the effect of calcium supplementation on maternal, fetal and neonatal outcomes, excluding women with multiple gestation (other than for preventing or treating hypertension), including the occurrence of adverse effects., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (which includes results of comprehensive searches of CENTRAL, MEDLINE, Embase, CINAHL, two trials registers and relevant conference proceedings) on 3 December 2022. We also searched the reference lists of retrieved studies., Selection Criteria: We considered all published, unpublished and ongoing randomised controlled trials (RCTs) comparing maternal, fetal and neonatal outcomes in pregnant women who received calcium supplementation versus placebo or no treatment. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and cross-over studies were not eligible for inclusion., Data Collection and Analysis: Two review authors independently assessed trials for inclusion. At least one review author assessed trials meeting the inclusion criteria for trustworthiness, consulting another review author in cases that were not immediately clear. Two review authors independently assessed the studies for risk of bias, extracted data, and checked trials for accuracy. We assessed the certainty of the evidence using GRADE., Main Results: Twenty-one studies met the inclusion criteria, but only 19 studies contributed data to the review. These 19 trials recruited 17,370 women, with 16,625 women included in the final analyses. The trials were generally at low risk of bias for randomisation and allocation concealment. We chose three outcomes for GRADE assessment: preterm birth less than 37 weeks, preterm birth less than 34 weeks and low birthweight (less than 2500 g). All trials compared calcium supplementation with placebo or no treatment with 17 trials comparing high-dose calcium (greater than 1000 mg/day). Calcium supplementation probably slightly reduces the risk of preterm birth less than 37 weeks (average risk ratio (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; 11 trials, 15,379 women; moderate-certainty evidence), but probably has little effect on the risk of preterm birth less than 34 weeks (average RR 1.03, 95% CI 0.79 to 1.35; 3 trials, 5569 women; moderate-certainty evidence), and may have little or no effect on low birthweight (less than 2500 g) (average RR 0.93, 95% CI 0.81 to 1.07; 6 trials, 14,162 women; low-certainty evidence; 1 study reported low birthweight (less than 2500 g) but recorded 0 events in both groups. Thus, the RR and CIs were calculated from 5 studies rather than 6). We downgraded the evidence for imprecision (wide CIs crossing the line of no effect) and inconsistency (high levels of heterogeneity between the studies). There was no evidence that calcium supplementation had any effect on maternal weight gain during pregnancy; increasing bone mineral density in pregnant women; rate of intrauterine growth restriction; perinatal mortality; stillbirth or fetal death rate; increase birth length or fetal head circumference; and adverse effects such as postpartum haemorrhage, gall stones, gastrointestinal symptoms, headache, urinary stones, urinary tract infection or impaired renal function., Authors' Conclusions: This review indicates that calcium supplementation probably reduces preterm birth before 37 weeks. There are no clear additional benefits to calcium supplementation in preterm birth before 34 weeks or prevention of low birthweight. Large multicentre trials to detect the effect of calcium supplementation on fetal birthweight and preterm birth before 34 weeks as the primary outcomes are needed. Further research into the short- and long-term effects of calcium supplementation would also be beneficial., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Trust is an essential component of the relationship between veterinarians and horse owners. To what extent do horse owners consider their vets to be trustworthy, what aspects are important to horse owners when evaluating their vet's trustworthiness and how can equine vets become more trusted?, Methods: Using an anonymous online survey, we asked horse owners whether they consider their veterinarians to be credible, reliable, empathetic and self-orientated, and therefore trustworthy compared with other professionals. Which of their equine vet's characteristics and behaviours influence how credible, reliable, empathetic and self-orientated, and therefore trustworthy, they appear? Credibility, reliability, empathy and self-orientation scores for equine veterinarians, human medical general practitioners (GPs), hairdressers/barbers and dentists were compared using a Kruskal‒Wallis H-test and post hoc Dunn's test and then combined to create a trustworthiness rating. The importance of various characteristics and behaviours displayed by equine vets when horse owners assess how credible, reliable, empathetic and self-orientated they appear was investigated using quantitative scoring and thematic analysis., Results: A total of 415 horse owners completed the survey. Overall, respondents considered equine veterinarians to be significantly more credible, reliable and empathetic than GPs, hairdressers/barbers and dentists. Using the trust equation, equine veterinarians had the highest trustworthiness rating (8.33), followed by hairdressers/barbers and dentists (5.5) and then GPs (4.75)., Limitations: Only the views of a small subset of horse owners are represented. As such, the findings may not be representative of horse owners more generally., Conclusions: Veterinarians' communication skills influence clients' perceptions of their credibility, reliability, empathy and self-orientation. Additionally, equine veterinarians should develop their clinical skills and knowledge to increase credibility. Meanwhile, perceptions of reliability, empathy and self-orientation can be improved by continuity of care, demonstrating a clear interest in the patient and avoiding rushed consultations, respectively., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Antimicrobial stewardship (AMS) initiatives are imperative to safeguard antimicrobials and reduce resistance. Across the UK, AMS relies in part on the self-regulation of the veterinary profession, particularly in farm animal practice, alongside voluntary schemes and quality assurance systems. In Europe, AMS initiatives are often statutory and require responsibility from several sectors. Consideration of broader AMS initiatives, potentially unfamiliar to the Welsh veterinary profession, could optimise future policy and align it with the requirements of Welsh veterinarians., Methods: AMS initiatives were collated from nations with long-standing low antimicrobial use. A survey was constructed permitting veterinarians' evaluation of initiative feasibility and effectiveness (collectively, 'acceptability') within Welsh farm animal practice., Results: Veterinarian-directed AMS initiatives, particularly those implemented within individual practices, were considered most acceptable. Initiatives that demanded cooperation from entities outside practices, or those regarded as punitive, were less acceptable., Limitations: The findings of this voluntary survey may be biased towards particularly motivated respondents in the veterinary sector. Additionally, the cause or effect of the recorded professional behaviour is not known in this study., Conclusion: Future antimicrobial policy should consider AMS acceptability by veterinarians, alongside farmers and other stakeholders, to promote compliance and attainment. The study data suggest that veterinarians may perceive continuous professional development/knowledge exchange as being most acceptable, alongside activities allied to a strong veterinarian‒client prescribing relationship. Continued support should focus on expanding these areas. Decoupling (ie, abolishing the professional licence for veterinarians to both prescribe and dispense medicines) was viewed as least acceptable by veterinarians in this study., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease., Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions., Results: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 10 9 /L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05)., Conclusions: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients., Plain Language Summary: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients., (© 2024 American Cancer Society.)

Introduction: Family planning among female physicians is harmed by high risks of infertility, workload burden, poor family leave policies, and gender discrimination. Many women report feeling unsupported in the workplace, despite national policies to protect against unfair treatment., Methods: This secondary analysis applied a modified version of the rigorous and accelerated data reduction technique to conduct a thematic analysis of comments to an open-ended prompt. Comments were coded by multiple trained researchers then grouped and merged into illustrative themes via qualitative techniques., Results: Of 1004 responses to the quantitative survey, 162 physicians completed the open-ended prompt. Initial codes (n = 16) were combined into eight groups including, from which three overarching themes were identified. Institutional barriers were highlighted with comments discussing the increased need for parental leave, part-time options and the concern for academic or professional punishment for being pregnant and/or having children. Departmental barriers were explored with comments grouped around codes of discrimination/negative culture and challenges with breastfeeding/pumping and childcare. Personal barriers were discussed in themes highlighting the difficulties that female physicians faced around the timing of family planning, challenges with reproductive health and assistance, and alternative circumstances and/or decisions against family planning., Conclusion: Barriers to family planning in oncology exist across career domains from dysfunctional maternity leave to poor education on infertility risk. Solutions include improving institutional support, expanding parental leave, and general cultural change to improve awareness and promotion of family and career balance., (© 2024 American Cancer Society.)

Background: Accurate variant classification and relaying reclassified results to patients is critical for hereditary cancer care delivery. Over a 5- to 10-year period, 6%-15% of variants undergo reclassification. As the frequency of reclassifications increases, the issue of whether, how, when, and which providers should recontact patients becomes important but remains contentious., Methods: The authors used inductive thematic analysis to analyze open-ended comments offered by oncologists and genetic counselors (GCs) from a large national survey., Results: Of the 634 oncologists and cancer GCs, 126 (20%) offered substantive free-text comments. Four thematic areas emerged: 1) ambiguity over professional responsibility to recontact, 2) logistical challenges with recontact, 3) importance of inter-institutional communication, and 4) suggested solutions. Some oncologists felt that laboratories, not them, are responsible for recontact; others believed that ordering providers/GCs were responsible; GCs readily acknowledged their own responsibility in recontact but added important caveats. Besides the lack of up-to-date patient contact information, providers raised unique challenges with recontact: financial instability of laboratories, lack of clinical resources, contacting family members, and accumulating burden of reclassifications. There were numerous calls for developing practice guidelines on prioritizing variants for recontact and discussion on whether duty for recontact may be fulfilled via unidirectional, low touch modalities. Potential solutions to recontact including national databases and patient facing databases were discussed., Conclusions: The authors confirm previous themes of stakeholder opinions and add previously unreported contextual details to qualify those themes. Clarifying provider responsibilities through professional guidelines for reclassification and recontact addressing the subthemes identified here will better serve all constituencies., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: This was a single-arm, phase 2 clinical trial of Bavarian Nordic (BN)-Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression-free survival (PFS), and safety of the combination in chordoma., Methods: A total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury and one vaccine dose of fowlpox virus (FPV)-Brachyury before RT. After RT, booster vaccinations were given with FPV-Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients., Results: Two of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6-20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4-90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7-25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study., Conclusions: This trial confirms the safety of BN-Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine-based study in chordoma, an ultra-rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity., (© 2024 American Cancer Society.)

Background: Older head and neck cancer (HNC) survivors have concerning rates of potentially unsafe opioid prescribing. Identifying the specialties of opioid prescribers for HNC survivors is critical for targeting the settings for opioid safety interventions. This study hypothesized that oncology and surgery providers are primarily responsible for opioid prescriptions in the year after treatment but that primary care providers (PCPs) are increasingly involved in prescribing over time., Methods: Using linked Surveillance, Epidemiology, and End Results-Medicare data, a retrospective analysis was conducted of adults aged >65 years diagnosed between 2014 and 2017 with stage I-III HNC and who had ≥6 months of treatment-free follow-up through 2019. Starting at treatment completion, opioid fills were assigned to a prescriber specialty: oncology, surgery, primary care, pain management, or other. Prescriber patterns were summarized for each year of follow-up. Multinomial logistic regression models captured the likelihood of opioids being prescribed by each specialty., Results: Among 5135 HNC survivors, 2547 (50%) had ≥1 opioid fill (median, 2.1-year follow-up). PCPs prescribed 47% of all fills (42%-55% each year). PCPs prescribed opioids to 45% of survivors with ≥1 opioid fill, which was a greater share than other specialties. PCPs prescribed longer supplies of opioids (median, 20 days/fill; median, 30 days/year) than oncologists or surgeons. The likelihood of an opioid being prescribed by an oncology provider was four times lower than that of it being prescribed by a PCP., Conclusions: PCP involvement in opioid prescribing remains high throughout HNC survivorship. Interventions to improve the safety of opioid prescribing should target primary care, as is typical for opioid reduction efforts in the noncancer population., (© 2024 American Cancer Society.)

Background: Understanding the impact of clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) on solid tumor risk and mortality can shed light on novel cancer pathways., Methods: The authors analyzed whole genome sequencing data from the Trans-Omics for Precision Medicine Women's Health Initiative study (n = 10,866). They investigated the presence of CHIP and mCA and their association with the development and mortality of breast, lung, and colorectal cancers., Results: CHIP was associated with higher risk of breast (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.03-1.64; p = .02) but not colorectal (p = .77) or lung cancer (p = .32). CHIP carriers who developed colorectal cancer also had a greater risk for advanced-stage (p = .01), but this was not seen in breast or lung cancer. CHIP was associated with increased colorectal cancer mortality both with (HR, 3.99; 95% CI, 2.41-6.62; p < .001) and without adjustment (HR, 2.50; 95% CI, 1.32-4.72; p = .004) for advanced-stage and a borderline higher breast cancer mortality (HR, 1.53; 95% CI, 0.98-2.41; p = .06). Conversely, mCA (cell fraction [CF] >3%) did not correlate with cancer risk. With higher CFs (mCA >5%), autosomal mCA was associated with increased breast cancer risk (HR, 1.39; 95% CI, 1.06-1.83; p = .01). There was no association of mCA (>3%) with breast, colorectal, or lung mortality except higher colon cancer mortality (HR, 2.19; 95% CI, 1.11-4.3; p = .02) with mCA >5%., Conclusions: CHIP and mCA (CF >5%) were associated with higher breast cancer risk and colorectal cancer mortality individually. These data could inform on novel pathways that impact cancer risk and lead to better risk stratification., (© 2024 American Cancer Society.)

Background: Despite the rise in gender-affirming care, our understanding of prostate cancer (PCa) in transgender women (TGW) remains in its infancy. Health disparities and lack of PCa awareness and screening are possible barriers to providing quality care for this population. In addition, the implication of hormonal manipulation for the aggressiveness of PCa in TGW is yet to be determined. Here, this study sought to compare oncological characteristics and survival outcomes between transgender and cisgender (CG) patients with PCa via two national data sets., Methods: The Veterans Affairs Informatics and Computing Infrastructure database (1999-2020) and the Surveillance, Epidemiology, and End Results-Medicare database (2010-2017) were reviewed. Demographic and clinical details were analyzed. Logistic regression analysis was performed on propensity score-matched groups to identify predictors of high-risk disease and metastasis in patients with PCa. Groups were matched 5:1 (CG:TGW) on the basis of age, race, year of diagnosis, and Charlson Comorbidity Index score. Primary outcomes included metastatic presentation, high-risk localized disease, overall survival (OS), and prostate cancer-specific mortality (PCSM)., Results: A total of 1194 patients were included (199 TGW; 995 CG). Associations between transgender identity and metastatic presentation (odds ratio [OR], 0.38; p = .2), high-risk localized disease (OR, 1.19; p = .50), or PCSM (hazard ratio [HR], 0.65; p = .3) were not detected. Transgender identity was associated with improved OS (HR, 0.67; p = .014)., Conclusions: PCa-specific outcomes seem comparable between TGW and CG men, although the study was underpowered to detect modest differences. Further investigation into the incidence and outcomes of PCa in TGW is warranted., (© 2024 American Cancer Society.)

Background: Clear cell sarcoma (CCS) and alveolar soft part sarcoma (ASPS) are rare, and standard systemic therapy is not established except for sunitinib in ASPS. It is known that CCS and ASPS have a common biological feature of melanoma and Xp11.2/TFE3 translocation renal cell carcinoma, and immune-checkpoint inhibitors (ICIs) are effective in these tumors. The authors conducted a phase 2 trial to evaluate the efficacy and safety of nivolumab for CCS and ASPS., Methods: The number of patients expected to be enrolled was 15-25 and was determined based on the Bayesian design. The primary end point was the confirmed objective response rate (ORR) according to the central review and the secondary end points included ORR, progression-free survival (PFS), overall survival (OS), and safety., Results: A total of 26 patients (CCS, 12; ASPS, 14) were enrolled. Efficacy and safety were analyzed on 25 and 26 patients, respectively. The minimum number of responses required for a positive conclusion regarding the efficacy was four. However, only one patient (4.0%) with ASPS had a partial response. Complete response, stable disease, progression disease, and not evaluable were 0%, 60%, 32%, and 4.0%, respectively. Adverse events of grade 3 or 4 occurred in 57.7% (15 of 26). The median PFS was 4.9 months (95% confidence interval [CI], 3.7-8.6 months) and the median OS was 15.8 months (95% CI, 8.2-not reached)., Conclusions: The primary end point of the ORR was not met for CCS and ASPS on the central review. Further studies are needed to evaluate ICIs in patients with ASPS., (© 2024 American Cancer Society.)

Background: Particulate matter consisting of fine particles measuring 2.5 microns or less in diameter (PM 2.5 ), a component of air pollution, has been linked to adverse health outcomes. The objective of this study was to assess the association between ambient PM 2.5 exposure and survival in children with cancer in the United States., Methods: Individuals aged birth to 19 years who were diagnosed with cancer between January 1, 2004, and December 31, 2019, were selected from the National Cancer Database. The association between the annual PM 2.5 level at the patient's zip code of residence at the time of diagnosis and overall survival was evaluated using time-varying Cox proportional hazards models (crude and adjusted for diagnosis year and age). To address concerns that exposure to air pollution is correlated with other social determinants of health, the authors tested the association between PM 2.5 levels and survival among sociodemographic subgroups., Results: Of the 172,550 patients included, 27,456 (15.9%) resided in areas with annual PM 2.5 concentrations above the US Environmental Protection Agency (EPA) annual PM 2.5 standard of 12 μg/m 3 . Residing in these high-pollution areas was associated with worse overall survival (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.012-1.10). Similarly, when PM 2.5 was evaluated as a linear measure, each unit increase in PM 2.5 exposure was associated with worse survival (aHR, 1.011; CI, 1.005-1.017). Exposure to PM 2.5 at levels above the EPA standards was also significantly associated with worse overall survival among sociodemographic subgroups., Conclusions: Exposure to PM 2.5 was significantly associated with worse overall survival among children with cancer, even at levels below EPA air quality standards. These results underscore the importance of setting appropriate air quality standards to protect the health of this sensitive population., Plain Language Summary: The authors investigated how living in areas with high air pollution (defined as particulate matter consisting of fine particles measuring 2.5 microns or less in diameter; PM 2.5 ) affects the overall survival of children with cancer in the United States. The results indicated that children living in areas with higher PM 2.5 levels, and even at levels below prior and current US Environmental Protection Agency standards, had lower survival rates than children living in areas with lower levels of PM 2.5 . This finding emphasizes the need for stricter air quality standards to better protect children, particularly those with serious health conditions like childhood cancer., (© 2024 American Cancer Society.)

Background: In 2017, the Food and Drug Administration approved pembrolizumab for treatment of any mismatch repair-deficient (dMMR) tumor making MMR immunohistochemistry (IHC) testing beneficial for all tumor types. For the first time, MMR IHC was not performed exclusively to screen for Lynch syndrome (LS)., Methods: In this study, all MMR IHC reports issued between 2017 and 2021 at an academic hospital were reviewed and completion of genetic testing was determined through chart review. Colorectal cancers (CRCs), endometrial cancers (ECs), and noncancerous lesions were excluded., Results: Between 2017 and 2021, MMR IHC was completed in 1939 patients with a malignancy other than CRC or EC. Absent or weak staining for at least one MMR protein was detected in 115 (5.9%) patients and 59 (51%) of those completed germline genetic testing. Overall, the identification rate of LS in this cohort was 0.72%, which is similar to the rate in our previously reported CRC and EC universal screening cohort. A diagnosis of LS was most commonly made in patients with dMMR brain (18.75%) and small intestinal cancers (10.20%). Five additional patients were found to carry a pathogenic variant in a non-LS gene., Conclusions: Pan-cancer MMR testing for pembrolizumab consideration can identify LS cases at a rate similar to universal CRC and EC screening programs. A persistent challenge is subsequent uptake of genetic testing. MMR testing should be prioritized in brain and small intestinal tumors, and multigene panel testing is recommended in patients with dMMR, as unexpected pathogenic variants in non-LS genes were found as frequently as LS gene variants., (© 2024 American Cancer Society.)

Background: Depression and anxiety are prevalent in older adults with cancer but are often undertreated. Older adults are also at increased risk of chemotherapy toxicity (CT). This study evaluated the impact of depression and anxiety symptoms on severe CT risk in older adults with cancer., Methods: This is a secondary analysis of a randomized trial (2:1) evaluating geriatric assessment-driven intervention (GAIN) versus standard of care (SOC) to reduce grade 3+ CT in older adults with cancer. Mental health was assessed via the Mental Health Inventory 13. CT was graded by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0., Results: A total of 605 patients enrolled (402 GAIN; 203 SOC). Overall, 35% were depressed and 47% were anxious. Patients with depression had increased CT in the SOC arm (70.7% vs. 54.3%; p = .02) but not in the GAIN arm (54.3% vs. 48.5%; p = .27). CT was more likely in SOC patients with depression (odds ratio [OR], 2.03; 95% CI, 1.10-3.72). This association persisted after adjusting for Cancer and Aging Research Group toxicity score (OR, 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85). Depression and CT were not associated in the GAIN arm (OR, 1.26; 95% CI, 0.84-1.91). Anxiety and CT were not associated in either arm., Conclusions: Elevated depression symptoms are associated with increased risk of severe CT in older adults with cancer, which was mitigated with GAIN. This suggests that treating depression symptoms may lower toxicity risk. Future studies are needed to confirm and investigate the impact of depression-specific interventions on outcomes., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Perineal trauma after vaginal birth is common and can be associated with short- and long-term health problems. Perineal hyaluronidase (HAase) injection has been widely used to reduce perineal trauma, perineal pain and the need for episiotomy since the 1950s. The administration of HAase is considered to be a simple, low risk, low cost and effective way to decrease perineal trauma without causing adverse effects., Objectives: To assess the effectiveness and safety of perineal HAase injection for reducing perineal trauma, episiotomy and perineal pain during vaginal delivery., Search Methods: To identify studies for inclusion in this review, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, CINAHL (EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) in November 2023., Selection Criteria: Randomised and quasi-randomised controlled trials comparing women giving birth to their first baby receiving perineal HAase injection compared to placebo injection or no intervention during vaginal delivery of a single foetus with vertex foetal presentation (foetus with head engaging the maternal pelvis)., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Two review authors independently assessed trials for inclusion, extracted and checked data, and evaluated the risk of bias in the studies. Our primary outcomes were perineal trauma (tears or episiotomy, or both), episiotomy and perineal pain. Our secondary outcomes were first and second degree perineal lacerations, third and fourth degree perineal lacerations, perineal oedema 1 hour after vaginal delivery, perineal oedema 24 hours after vaginal delivery and neonatal Apgar scores of less than 7 at five minutes after birth (Apgar score is a measure of the health status of a newborn). We assessed the certainty of the evidence using the GRADE approach., Main Results: We included five randomised controlled trials involving a total of 747 women (data were available for 743 women). The dosage of HAase used in the perineal injection varied from 750 turbidity-reducing units to 5000 international units. The certainty of the evidence was largely low (ranging from very low to moderate). Perineal HAase injection versus placebo injection Data from three trials involving 426 women provided low-certainty evidence that there may be no difference between the HAase and placebo groups in the incidence of perineal trauma (tears or episiotomy, or both) (RR 0.94, 95% CI 0.87 to 1.03; 426 participants, 3 studies), episiotomy (RR 0.91, 95% CI 0.71 to 1.15; 427 participants, 3 studies), first and second degree perineal lacerations (RR 1.02, 95% CI 0.87 to 1.18; 341 participants, 3 studies), third and fourth degree perineal lacerations (RR 0.46, 95% CI 0.11 to 2.05; 426 participants, 3 studies), and perineal oedema one hour after vaginal delivery (RR 0.99, 95% CI 0.78 to 1.25; 303 participants, 2 studies). Moreover, perineal HAase injection during the second stage of labour likely resulted in a reduction in incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection (RR 0.42, 95% CI 0.26 to 0.70; 303 participants, 2 studies; moderate-certainty evidence). There may be no difference between groups in Apgar scores less than 7 at five minutes (RR 5.00, 95% CI 0.24 to 105.95; 148 participants, 1 study; low-certainty evidence). Perineal HAase injection versus no intervention Data from three trials involving 373 women suggested that perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) (RR 0.61, 95% CI 0.42 to 0.88; 373 participants, 3 studies; low-certainty evidence) compared with no intervention. The evidence is very uncertain for episiotomy (RR 0.79, 95% CI 0.44 to 1.42; 373 participants, 3 studies), first and second degree perineal lacerations (RR 0.59, 95% CI 0.30 to 1.18; 373 participants, 3 studies) and perineal oedema one hour after vaginal delivery (RR 0.32, 95% CI 0.01 to 7.71; 139 participants, 1 study), all very low certainty evidence. No third and fourth degree perineal lacerations, perineal oedema 24 hours after vaginal delivery or Apgar scores less than 7 at five minutes were reported in these three trials. No side effects were reported in the included trials., Authors' Conclusions: Perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) compared with no intervention, but not compared with placebo injection, in women having a vaginal delivery. Meanwhile, perineal HAase injection likely reduces the incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection. The potential use of perineal HAase injection as a method to reduce perineal trauma and perineal oedema remains to be determined as the number of high-quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries, including evaluating whether there is any differential effect based on the dose, frequency and positioning of HAase injection., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: The role of sex in choosing between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease has gained interest., Methods: Randomized controlled trials and adjusted observational studies comparing PCI versus CABG in ULMCA patients with outcomes by sex were included. The primary endpoint was major adverse cardiovascular events (MACE), with secondary endpoints being all-cause mortality and repeated revascularization., Results: Ten studies (3 randomized, 7 observational) involving 22,141 ULMCA disease patients (13,411 PCI, 8730 CABG) with a median 5-year follow-up were included. Among males, PCI was associated with a higher risk of MACE (HR 1.18, 95% CI 1.01-1.38), while no significant difference was seen in females. However, moderator analysis showed no significant interaction between sex and revascularization strategy for MACE (p for interaction .422). No differences in all-cause mortality were observed between PCI and CABG for either sex. Repeated revascularization risk was significantly higher with PCI for both sexes (HR 3.51, 95% CI 2.21-5.59 in males and HR 4.20, 95% CI 2.57-6.87 in females)., Conclusions: In males with ULMCA disease, CABG was associated with a lower risk of MACE compared to PCI, while no significant differences were seen in females. The lack of a significant interaction between sex and revascularization strategy suggests that these findings may not reflect true sex-based effect modification. PCI was linked to a higher risk of repeated revascularization in both sexes compared to CABG., Trial Registration: The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42024537726)., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To identify and assess the effect of support interventions focused on psychological, social, and emotional outcomes for bereaved parents (including birth and non-birthing mothers, fathers, partners) and family members of parents (e.g. grandparents; siblings) who have experienced stillbirth or neonatal death., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rationale: Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is recommended for treating PPH; it reduces the risk of death from haemorrhage by one-third when given soon after bleeding onset, but not overall risk of death. Interest in whether TXA may be effective in preventing PPH is growing. Evidence indicates that TXA given more than three hours after injury to bleeding trauma patients increases mortality. Potential harm becomes critical in prophylactic use of TXA. Reliable evidence of the effect and safety profile of TXA is required before widespread prophylactic use can be considered., Objectives: To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women during caesarean birth., Search Methods: We searched CENTRAL, MEDLINE, Embase, and WHO ICTRP to 20 February 2024 and searched reference lists of retrieved studies., Eligibility Criteria: We included randomised controlled trials (RCTs) evaluating the use of TXA alone or plus uterotonics during caesarean birth for preventing PPH. Trials needed to be prospectively registered (i.e. before starting recruitment). We applied a trustworthiness checklist., Outcomes: The critical outcome was blood loss ≥ 1000 mL, measured using estimated or calculated methods. Important outcomes included maternal death, severe morbidity, blood transfusion, the use of additional surgical interventions to control PPH, thromboembolic events, use of additional uterotonics, hysterectomy, maternal satisfaction, and breastfeeding at discharge., Risk of Bias: We assessed risk of bias in the included studies using Cochrane's RoB 1 tool., Synthesis Methods: Two review authors independently selected trials, extracted data, and assessed risk of bias and trial trustworthiness. We pooled data using random-effects meta-analysis. We assessed the certainty of the evidence using GRADE., Included Studies: We included six RCTs with 15,981 participants. All 12 trials in the previous version of this review were not included after review of trial registrations and trustworthiness checklists. Most included studies involved women at low risk of PPH and were conducted in high-resource settings., Synthesis of Results: Prophylactic TXA in addition to standard care compared to placebo in addition to standard care or standard care alone TXA results in little to no difference in estimated blood loss ≥ 1000 mL (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.79 to 1.11; 4 RCTs; n = 13,042; high certainty evidence), resulting in 8 fewer per 1000 women having estimated blood loss ≥ 1000 mL (from 30 fewer to 16 more). TXA likely results in a slight reduction in calculated blood loss ≥ 1000 mL (RR 0.83, 95% CI 0.76 to 0.92; 2 RCTs; n = 4327; moderate certainty evidence), resulting in 53 fewer per 1000 having calculated blood loss ≥ 1000 mL (from 75 fewer to 25 fewer). The evidence is very uncertain about the effect of TXA on maternal death (one event in placebo group, none in TXA group). No trials measured severe morbidity. TXA likely results in little to no difference in blood transfusion (RR 0.88, 95% CI 0.72 to 1.08; 5 RCTs; n = 15,740; moderate certainty evidence), resulting in 4 fewer per 1000 women requiring a blood transfusion (from 10 fewer to 3 more). TXA results in little to no difference in additional surgical interventions to control PPH (RR 1.02, 95% CI 0.86 to 1.22; 4 RCTs; n = 15,631; high certainty evidence), resulting in 1 more per 1000 women requiring additional surgical intervention (from 4 fewer to 7 more). The evidence is very uncertain about the effect of TXA on thromboembolic events (RR 1.40, 95% CI 0.22 to 8.90; 4 RCTs; n = 14,480; very low certainty evidence), resulting in 1 more per 1000 women having a thromboembolic event (from 2 fewer to 17 more). TXA results in little to no difference in the need for additional uterotonics (RR 0.88, 95% CI 0.78 to 1.00; 4 RCTs; n = 15,728; high certainty evidence), resulting in 15 fewer per 1000 women requiring additional uterotonics (from 27 fewer to 0 fewer). The evidence is very uncertain about the effect of TXA on hysterectomy (RR 0.80, 95% CI 0.20 to 3.29; 2 RCTs; n = 4546; very low certainty evidence), resulting in 3 fewer per 10,000 women requiring a hysterectomy (from 11 fewer to 31 more). One trial measuring maternal satisfaction reported no difference between groups at day two postpartum. No data were available on breastfeeding. Overall, studies had low risk of bias. We downgraded the certainty of evidence mainly for imprecision., Authors' Conclusions: Prophylactic TXA in addition to standard care during caesarean birth results in little to no difference in estimated blood loss ≥ 1000 mL and likely results in a slight reduction in calculated blood loss ≥ 1000 mL compared to placebo. There were no data for severe morbidity due to PPH. Event rates for further interventions to control PPH were low and similar across groups. Prophylactic TXA thus results in little to no difference between groups for additional surgical interventions (32 versus 31 per 1000), and likely results in little to no difference between groups for blood transfusions (31 versus 36 per 1000) and use of additional uterotonics (107 versus 121 per 1000). There were very few events for the outcomes maternal death (1 in placebo group), thromboembolic events (2 versus 3 per 1000), and hysterectomy (1 per 1000 in each group). Evidence for these serious adverse events is therefore very uncertain. Decisions about implementing routine prophylactic TXA during caesarean birth should not only consider outcomes related to blood loss, but also the relatively low rates of PPH morbidity and uncertainty of serious adverse events. Most studies included women at low risk of PPH, thereby precluding any conclusions about women at high risk of PPH. Cost associated with routine use of an additional drug for all caesarean births needs to be considered., Funding: This Cochrane review was funded in part by the World Health Organization., Registration: The published protocol and updates to the review can be accessed: Protocol (2009) DOI: 10.1002/14651858.CD007872 Original Review (2010) DOI: 10.1002/14651858.CD007872.pub2 Review Update (2015) DOI: 10.1002/14651858.CD007872.pub3., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Research into vaccine hesitancy is a critical component of the public health enterprise, as rates of communicable diseases preventable by routine childhood immunization have been increasing in recent years. It is therefore important to estimate proportions of "never-vaccinators" in various subgroups of the population in order to successfully target interventions to improve childhood vaccination rates. However, due to privacy issues, it may be difficult to obtain individual patient data (IPD) needed to perform the appropriate time-to-event analyses: state-level immunization information services may only be willing to share aggregated data with researchers. We propose statistical methodology for the analysis of aggregated survival data that can accommodate a cured fraction based on a polynomial approximation of the mixture cure model log-likelihood function relying only on summary statistics. We study the performance of the method through simulation studies and apply it to a real-world data set from a study examining reminder/recall approaches to improve human papillomavirus (HPV) vaccination uptake. The proposed methods may be generalized for use when there is interest in fitting complex likelihood-based models but IPD is unavailable due to data privacy or other concerns., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

Sensor devices, such as accelerometers, are widely used for measuring physical activity (PA). These devices provide outputs at fine granularity (e.g., 10-100 Hz or minute-level), which while providing rich data on activity patterns, also pose computational challenges with multilevel densely sampled data, resulting in PA records that are measured continuously across multiple days and visits. On the other hand, a scalar health outcome (e.g., BMI) is usually observed only at the individual or visit level. This leads to a discrepancy in numbers of nested levels between the predictors (PA) and outcomes, raising analytic challenges. To address this issue, we proposed a multilevel longitudinal functional principal component analysis (mLFPCA) model to directly model multilevel functional PA inputs in a longitudinal study, and then implemented a longitudinal functional principal component regression (FPCR) to explore the association between PA and obesity-related health outcomes. Additionally, we conducted a comprehensive simulation study to examine the impact of imbalanced multilevel data on both mLFPCA and FPCR performance and offer guidelines for selecting optimal methods., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: Allergy immunotherapy (AIT), a treatment approach for allergic rhinitis (AR), is recognized for its potential to modify the disease course beyond mere symptom relief. Interleukin-36 γ (IL-36 γ ), a key player in immune responses, has been implicated in promoting eosinophilic inflammation in AR by activating eosinophils. We aimed to investigate the effect of IL-36 γ on group II lymphoid cell (ILC2) in AR patients who underwent sublingual immunotherapy (SLIT). Methods: Twenty-four AR patients were enrolled and administered with SLIT. Serum proteins of IL-36 γ , interleukin-5 (IL-5), and interleukin-13 (IL-13) during SLIT were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). The proportion of ILC2 was determined by flow cytometry. Sorted ILC2s were stimulated by IL-36 γ and ILC2 cell differentiation, and type II cytokines expression were examined. Results: SLIT treatment decreased the serum protein levels of IL-36 γ , IL-5, IL-13, and the proportion of ILC2 significantly. IL-36 γ suppressed the proliferation of ILC2 by inhibiting the levels of ILC2 transcription factor. IL-36 γ also inhibited IL-5 and IL-13 expression from ILC2. Conclusion: The changes of IL-36 γ during SLIT were related to the inhibited function of ILC2, implying that IL-36 γ may be used as a new biomarker for monitoring the efficacy of SLIT in AR., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Xiaowei Qin et al.)

Background: Appendicectomy is a well-established surgical procedure to manage acute appendicitis. The operation was historically performed as an open procedure and is currently performed using minimally invasive surgical techniques. A recent development in appendicectomy technique is the introduction of single-incision laparoscopic surgery. This incorporates all working ports (either one multi-luminal port or multiple mono-luminal ports) through a single skin incision; the procedure is known as single-incision laparoscopic appendicectomy or SILA. Unanswered questions remain regarding the efficacy of this novel technique, including its effects on patient benefit and satisfaction, complications, and long-term outcomes, when compared to multi-incision conventional laparoscopy (CLA). This is an update of a review published in 2011., Objectives: To assess the effects of single-incision laparoscopic appendicectomy compared with multi-incision laparoscopic appendicectomy, on benefits, complications, and short-term outcomes, in patients with acute appendicitis., Search Methods: We searched the Cochrane Central Register of Controlled trials (CENTRAL, the Cochrane Library 2018 Issue 2), Ovid MEDLINE (1983 to January 2024), Ovid Embase (1983 to January 2024), the WHO International Clinical Trial Register (January 2024), and Clinicaltrials.gov (January 2024). We also searched reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases. The searches were carried out on 20 January 2024., Selection Criteria: We included randomised controlled trials (RCTs) that compared the single-incision procedure SILA against CLA for patients (male and female) over the age of 10 years, diagnosed with appendicitis, or symptoms of appendicitis, and undergoing laparoscopic appendicectomy., Data Collection and Analysis: Two review authors independently selected studies for inclusion, extracted data into a standardised form, and assessed the risk of bias in the studies. We extracted data relevant to the predetermined outcome measures. Where appropriate, we calculated a summary statistic: odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous data and mean difference (MD) with 95% CI for continuous data. We used Review Manager Web for our statistical analysis., Main Results: This review was first published in 2011, when there was no RCT evidence available. For this update, we identified 11 RCTs involving 1373 participants (689 in the SILA groups and 684 in the CLA groups). The participants were similar at baseline in terms of age (mean 31.7 (SILA) versus 30.9 years (CLA)) and sex (female: 53.0% (SILA) versus 50.3% (CLA)). Diagnosis of appendicitis was based on clinical assessment; none of the studies used a diagnosis confirmed by imaging as part of their inclusion criteria. The certainty of the evidence was low to moderate, and the outcomes were predominately reported in the short term. Pain scores at 24 hours after surgery may be similar between the SILA and CLA groups (mean score SILA 2.53 versus CLA 2.65; mean difference (MD) in pain score -0.12, 95% CI -0.52 to 0.28; 294 participants, 4 RCTs; low-certainty evidence). SILA probably had superior cosmetic results as indicated by patients using the Body Image questionnaire (5 to 20) (mean score SILA 14.9 versus CLA 12.4; cosmesis score MD 1.97, 95% CI 1.60 to 2.33; 266 participants, 3 RCTs; moderate-certainty evidence). The rate of visceral and vascular injury was probably similar with both techniques (SILA 0/168 versus 4/169; OR 0.20, 95% CI 0.02 to 1.79; 337 participants, 3 RCTs; moderate-certainty evidence). The conversion rate to CLA or open surgery may be higher for SILA procedures than the conversion rate from CLA to open surgery (SILA 32/574 versus CLA 7/569; OR 2.95, 95% CI 1.36 to 6.42; 1143 participants, 9 RCTs; low-certainty evidence). Use of an additional port site was probably more likely with SILA compared to CLA (SILA 28/328 versus CLA 4/336; OR 3.80, 95% CI 1.13 to 12.72; 664 participants, 5 RCTs; moderate-certainty evidence). The recovery time was probably similar for both interventions for hospital stay (mean length of stay in hospital for SILA 2.25 days versus 2.29 days for CLA patients; MD -0.13, 95% CI -0.23 to 0.03; 1241 participants, 10 RCTs; moderate-certainty evidence) and time to return to normal activities (SILA 9.28 days versus CLA 10.0 days; MD -0.59, 95% CI -1.99 to 0.81; 451 participants, 4 RCTs; moderate-certainty evidence). We have low-to-moderate confidence in our findings due to differences in the measurement of certain outcomes, and lack of blinding in the studies, which makes them prone to performance bias., Authors' Conclusions: There is low-to-moderate certainty evidence that single-incision laparoscopic appendicectomy is comparable to conventional laparoscopic appendicectomy in terms of complications, length of hospital stay, return to normal activities, and postoperative pain in the first 24 hours. The disadvantage of SILA may be a higher conversion rate, but SILA is probably associated with better patient cosmetic satisfaction., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Venous thromboembolism (VTE) involves the formation of a blood clot in a vein, and includes deep venous thrombosis (DVT) or pulmonary embolism (PE). The annual incidence for VTE varies from 0.75 to 2.69 per 1000 individuals, with about 40 million people worldwide impacted by VTE. Statins, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors, inhibit cholesterol biosynthesis and display several vascular-protective effects, including antithrombotic properties. However, the potential role of statins in the primary prevention of VTE is still not clear., Objectives: To evaluate the benefits and risks of statins in preventing venous thromboembolism (VTE) in individuals with no prior history of VTE., Search Methods: We used standard Cochrane search methods. The search was last updated on 13 March 2023., Selection Criteria: We included randomized controlled trials (RCTs) comparing statins with any control intervention (including placebo and usual care) in healthy individuals or participants with conditions other than VTE. There were no restrictions on the dose, duration, route, or timing of statins., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were VTE, DVT, and PE. Our secondary outcomes were serious adverse events, adverse events, and mortality. We used the trial sequential analysis (TSA) method to judge whether the evidence was sufficient, and we used the GRADE approach to assess the certainty of the evidence for each outcome., Main Results: We included 27 RCTs involving 122,601 adults (aged 18 years and above) who were healthy, had various medical conditions (e.g. hypercholesterolemia), or were at risk for cardiovascular disease. Both males and females were included in all studies. Two studies focused solely on participants over 60 years of age. We deemed four studies to have a low risk of bias overall, while 19 were at high risk of bias, and four were unclear. The 27 studies compared use of statins versus placebo or usual care in individuals who had never experienced VTE. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. Twenty-three studies followed up participants for over a year, with six of those extending follow-ups for over five years. Twenty-five studies were based in hospitals, and 24 studies were funded by industry. Only one study used VTE as a primary endpoint. The median incidence of VTE in the statins group was 0.72% (ranging from 0% to 10.53%), and in the control group it was 0.89% (ranging from 0% to 6.83%). Our pooled analysis of the 27 studies showed that, relative to control groups, statins may slightly reduce the overall incidence of VTE (odds ratio (OR) 0.86, 95% confidence intervals (CI) 0.76 to 0.98; 27 studies, 122,601 participants; low-certainty evidence). Of the statins we evaluated, only rosuvastatin seemed to be associated with a reduced incidence of VTE, albeit the reduction in incidence was very small. The evidence did not clearly indicate a difference between groups in the incidence of DVT (OR 0.70, 95% CI 0.41 to 1.18; six studies, 40,305 participants; low-certainty evidence), PE (OR 0.83, 95% CI 0.46 to 1.52; five studies, 28,427 participants; low-certainty evidence), or myopathy (OR 1.10, 95% CI 0.83 to 1.45; 10 studies, 75,551 participants; low-certainty evidence). Nonetheless, statin use might slightly decrease the incidence of any serious adverse event (OR 0.95, 95% CI 0.91 to 0.99; 13 studies, 67,020 participants; low-certainty evidence) and any death (OR 0.90, 95% CI 0.86 to 0.95; 24 studies, 116,761 participants; low-certainty evidence), compared to control., Authors' Conclusions: Using statins for the primary prevention of VTE may slightly reduce the incidence of VTE and all-cause mortality. However, this effect is likely too weak to be considered significant. Statin use may not decrease the occurrence of DVT and PE. The current evidence is insufficient to draw strong conclusions because of the risk of bias in the studies, imprecision in the effect estimates, and potential publication bias. More evidence from well conducted and fully reported RCTs is needed to assess the preventive effects of different types of statins, as well as the effects of different dosages and treatment durations in various populations., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Dementia leads to progressive cognitive decline, and represents a significant health and societal burden. Its prevalence is growing, with Alzheimer's disease as the leading cause. There is no cure for Alzheimer's disease, but there are regulatory-approved pharmacological interventions, such as galantamine, for symptomatic relief. This review updates the 2006 version., Objectives: To assess the clinical effects, including adverse effects, of galantamine in people with probable or possible Alzheimer's disease or mild cognitive impairment, and to investigate potential moderators of effect., Search Methods: We systematically searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register on 14 December 2022 using the term 'galantamine'. The Register contains records of clinical trials identified from major electronic databases (including CENTRAL, MEDLINE, and Embase), trial registries, grey literature sources, and conference proceedings. We manually searched reference lists and collected information from US Food and Drug Administration documents and unpublished trial reports. We imposed no language restrictions., Selection Criteria: We included double-blind, parallel-group, randomised controlled trials comparing oral galantamine with placebo for a treatment duration exceeding four weeks in people with dementia due to Alzheimer's disease or with mild cognitive impairment., Data Collection and Analysis: Working independently, two review authors selected studies for inclusion, assessed their quality, and extracted data. Outcomes of interest included cognitive function, change in global function, activities of daily living, functional disability, behavioural function, and adverse events. We used a fixed-effect model for meta-analytic synthesis, and presented results as Peto odds ratios (OR) or weighted mean differences (MD) with 95% confidence intervals. We used Cochrane's original risk of bias tool (RoB 1) to assess the risk of bias in the included studies., Main Results: We included 21 studies with a total of 10,990 participants. The average age of participants was 74 years, and 37% were male. The studies' durations ranged from eight weeks to two years, with 24 weeks being the most common duration. One newly included study assessed the effects of galantamine at two years, and another newly included study involved participants with severe Alzheimer's disease. Nineteen studies with 10,497 participants contributed data to the meta-analysis. All studies had low to unclear risk of bias for randomisation, allocation concealment, and blinding. We judged four studies to be at high risk of bias due to attrition and two due to selective outcome reporting. Galantamine for dementia due to Alzheimer's disease We summarise only the results for galantamine given at 8 to 12 mg twice daily (total galantamine 16 mg to 24 mg/day), assessed at six months. See the full review for results of other dosing regimens and assessment time points. There is high-certainty evidence that, compared to placebo, galantamine improves: cognitive function, as assessed with the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) (MD-2.86, 95% CI -3.29 to -2.43; 6 studies, 3049 participants; minimum clinically important effect (MCID) = 2.6- to 4-point change); functional disability, as assessed with the Disability Assessment for Dementia (DAD) scale (MD 2.12, 95% CI 0.75 to 3.49; 3 studies, 1275 participants); and behavioural function, as assessed with the Neuropsychiatric Inventory (NPI) (MD -1.63, 95% CI -3.07 to -0.20; 2 studies, 1043 participants) at six months. Galantamine may improve global function at six months, as assessed with the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus) (OR 1.58, 95% CI 1.36 to 1.84; 6 studies, 3002 participants; low-certainty evidence). Participants who received galantamine were more likely than placebo-treated participants to discontinue prematurely (22.7% versus 17.2%) (OR 1.41, 95% CI 1.19 to 1.68; 6 studies, 3336 participants; high-certainty evidence), and experience nausea (20.9% versus 8.4%) (OR 2.89, 95% CI 2.40 to 3.49; 7 studies, 3616 participants; high-certainty evidence) during the studies. Galantamine reduced death rates at six months: 1.3% of participants in the galantamine groups had died compared to 2.3% in the placebo groups (OR 0.56, 95% CI 0.33 to 0.96; 6 studies, 3493 participants; high-certainty evidence). Galantamine for mild cognitive impairment We summarise results, assessed at two years, from two studies that gave participants galantamine at 8 to 12 mg twice daily (total galantamine 16 mg to 24 mg/day). Compared to placebo, galantamine may not improve cognitive function, as assessed with the expanded ADAS-cog for mild cognitive impairment (MD -0.21, 95% CI -0.78 to 0.37; 2 studies, 1901 participants; low-certainty evidence) or activities of daily living, assessed with the Alzheimer's Disease Cooperative Study - Activities of Daily Living scale for mild cognitive impairment (MD 0.30, 95% CI -0.26 to 0.86; 2 studies, 1901 participants; low-certainty evidence). Participants who received galantamine were probably more likely to discontinue prematurely than placebo-treated participants (40.7% versus 28.6%) (OR 1.71, 95% CI 1.42 to 2.05; 2 studies, 2057 participants) and to experience nausea (29.4% versus 10.7%) (OR 3.49, 95% CI 2.75 to 4.44; 2 studies, 2057 participants), both with moderate-certainty evidence. Galantamine may not reduce death rates at 24 months compared to placebo (0.5% versus 0.1%) (OR 5.03, 95% CI 0.87 to 29.10; 2 studies, 2057 participants; low-certainty evidence). Results from subgroup analysis and meta-regression suggest that an imbalance in discontinuation rates between galantamine and placebo groups, together with the use of the 'last observation carried forward' approach to outcome assessment, may potentially bias cognitive outcomes in favour of galantamine., Authors' Conclusions: Compared to placebo, galantamine (when given at a total dose of 16 mg to 24 mg/day) slows the decline in cognitive function, functional ability, and behaviour at six months in people with dementia due to Alzheimer's disease. Galantamine probably also slows declines in global function at six months. The changes observed in cognition, assessed with the ADAS-cog scale, were clinically meaningful. Gastrointestinal-related adverse events are the primary concerns associated with galantamine use in people with dementia, which may limit its tolerability. Although death rates were generally low, participants in the galantamine groups had a reduced risk of death compared to those in the placebo groups. There is no evidence to support the use of galantamine in people with mild cognitive impairment., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Bovine tuberculosis (bTB) is the most important animal health concern in Wales. Annual testing across all cattle herds in Wales commenced in 2010. In 2017, a new geographic division of Wales was conceived, with bespoke cattle controls and eradication milestones reflecting the geographical heterogeneity of bTB distribution., Methods: This observational study uses descriptive analysis and Poisson regression modelling to analyse bTB surveillance data from all herds in Wales., Results: Since 2010, there has been a significant decrease (p < 0.0001) in bTB incidence (8.6%‒6.3%) and plateauing prevalence across Wales. Conversely, there has been an increase in bTB incidence and prevalence in discrete areas. Recurrence and persistence remain important drivers of bTB infection. One of the sharpest declines in bTB incidence was observed in an intensive action area where enhanced cattle control and wildlife vaccination were implemented in an area of high bTB prevalence. Increased herd size, dairy herd type and herd location are important risk factors affecting the rate of bTB incidents in Wales., Limitations: This study includes data from Wales only., Conclusions: Improvements in trends of bTB occurred from 2010 to 2021, but the spatial variations described in this paper support the continued need for regionally adapted surveillance and control measures., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Background: Syrian hamsters are a relatively common pet species in the UK. However, we know very little about how they are kept. The aim of this study was to identify areas of good and poor practices among Syrian hamster owners using owner surveys., Method: A survey of pet hamster owners was conducted with questions on husbandry, behaviour and health., Results: There were 548 survey responses. Over 95% of the owners provided a wheel, hideaway or chew toy, and over 90% housed their hamster alone. However, 18.4% of the owners used hamster balls, hamsters may have been fed a diet that was not entirely appropriate, and over 45% of respondents reported that their hamsters were housed in close proximity to predator species. Most (65.9%) hamsters had never been taken to a veterinarian. Hamster ball use, shallower substrate depth and more frequent handling were significantly associated with greater owner observations of bar biting., Limitations: A key limitation is that the respondents may not be representative of the average pet hamster owner, so this research does not provide a complete picture of the current state of hamster welfare., Conclusion: There are some welfare concerns regarding the way Syrian hamsters are currently kept in the UK. Therefore, attempts to better distribute information about hamster care to owners should be made., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)