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Background: Adolescent problematic social media use (PSMU) has been increasing. Digital engagement has been associated with substance use, but little is known about the potential protective role of parents. We investigated whether screen and substance-related parental rules moderated the associations between (problematic) SMU and intake of tobacco, alcohol, hashish/marijuana, and laughing gas., Methods: We used data from the Amsterdam Born Children and Development study (N = 1787; Mage = 15.86 years; SD = 0.36). Both frequent and problematic SMU in relation to tobacco, alcohol, hashish/marijuana, and laughing gas intake levels; and moderation by perceived parental rules (screen/substances), was tested with ordinal logistic regression models., Results: PSMU was associated with higher chances of higher substance use levels. Hashish/marijuana use and heavy drinking were less prevalent in adolescents reporting the presence of parental rules on alcohol/drugs, compared to adolescents reporting no rules. Although parental rules on alcohol/drugs, but not screen time, moderated the relationship between PSMU and both hashish/marijuana use and heavy drinking, the moderation effect was modest, especially in mitigating substance use at higher PSMU-scores., Conclusion: PSMU was positively associated with a wide range of substance use behaviours. The potential significant role of parental rules (alcohol/drugs) mitigating these associations are highlighted., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health.)

Social workers are uniquely positioned to support clients in crisis to reduce firearm access. However, many report needing support in navigating conversations and awareness of available options. Authors sought to understand the decision-making process social workers use, to choose which interventions (e.g., out-of-home storage) are appropriate to reduce firearm access for clients in crisis. Ten individual and group semistructured interviews were conducted with 29 social workers in Washington State; participants discussed experiences with clients at risk of harming themselves and/or others with a firearm and responded to two case examples. Grounded theory was used to develop an action plan model describing how social workers choose which interventions to pursue. Participants described two categories that influence their decision-making process for reducing firearm access for clients in crisis. The first category, sociopolitical context, included structural intersectionality, policies, professional ethics, workplace environment, and values. These influenced the second category, collaborative safety planning intervention for reducing firearm access, a process that included considering client factors, social worker actions, and options for reducing firearm access. This model can be used to develop trainings for social workers to educate them on processes to reduce firearm access for clients in crisis., (© 2024 National Association of Social Workers.)

Variable selection and large-scale hypothesis testing are techniques commonly used to analyze high-dimensional genomic data. Despite recent advances in theory and methodology, variable selection and inference with highly collinear features remain challenging. For instance, collinearity poses a great challenge in genome-wide association studies involving millions of variants, many of which may be in high linkage disequilibrium. In such settings, collinearity can significantly reduce the power of variable selection methods to identify individual variants associated with an outcome. To address such challenges, we developed a Bayesian hierarchical hypothesis testing (BHHT)-a novel multiresolution testing procedure that offers high power with adequate error control and fine-mapping resolution. We demonstrate through simulations that the proposed methodology has a power-FDR performance that is competitive with (and in many scenarios better than) state-of-the-art methods. Finally, we demonstrate the feasibility of using BHHT with large sample size (n∼ 300,000) and ultra dimensional genotypes (∼ 15 million single-nucleotide polymorphisms or SNPs) by applying it to eight complex traits using data from the UK-Biobank. Our results show that the proposed methodology leads to many more discoveries than those obtained using traditional SNP-centered inference procedures. The article is accompanied by open-source software that implements the methods described in this study using algorithms that scale to biobank-size ultra-high-dimensional data., Competing Interests: Conflicts of interest. The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Extant research shows that race adjustment in epidemiologic analyses could lead to masking of systemic racism. In this study, we compare race-adjusted and -unadjusted years of life lost (YLL), a measure of societal burden, to understand the impact of race adjustment in YLL estimation. We used North Carolina (NC) Violent Death Reporting System data from 2006-2019 linked to 2006-2019 race-adjusted and -unadjusted life tables from the Centers for Disease Control and Prevention by calendar year and age at death. We calculated total YLL and YLL per death from suicide and homicide deaths for non-Hispanic black and non-Hispanic white NC residents using both the race-adjusted and -unadjusted life tables. We found that YLL and YLL/death from suicide and homicide deaths for non-Hispanic white individuals were almost identical regardless of race adjustment. However, race-adjusted life tables vastly underestimated total YLL and YLL per death for non-Hispanic black NC residents. Overall, race adjustment resulted in an underestimation of 14,907 YLL from homicide deaths (3.1 fewer YLL/death) and 4,414 YLL from suicide deaths (2.8 YLL/death) for black NC residents. Our study shows that the baked-in underestimation of YLL for non-Hispanic Black Americans when using race-adjusted life tables hides racialized health disparity and perpetuates inequity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Even though it is preventable, cervical cancer contributes significantly to cancer-related mortality among Ethiopian women. Follow-up visits after treatment of precancerous lesions are essential to monitor lesion recurrence. In our previous study, we found a level of adherence to follow-up of 44.7%, but the reasons for low adherence have not been comprehensively explored within the Ethiopian context. This study aimed to identify these reasons by interviewing 167 women who had missed their follow-up appointments as well as 30 health professionals with experience in the field., Methods: The study employed a mixed-methods approach: Quantitative data were collected through a telephone questionnaire conducted with 167 women who had a positive visual inspection with acetic acid (VIA) and had missed their follow-up appointments. Subsequently, in-depth interviews were conducted with 30 healthcare professionals, and an inductive content analysis was carried out., Results: In the patient interviews, the reasons given most often were "lack of information about the follow-up" (35; 21.1%), "forgetting the appointment" (30; 18.1%), and "not seeing the need for follow-up" (24; 14.5%). Healthcare professionals identified various reasons such as lack of knowledge, living in a remote area/changing living area, forgetfulness, fear, poor counseling, a shortage of trained healthcare providers to give counseling and follow-up, and reminder-related barriers., Conclusion: Lack of knowledge, forgetfulness, poor health-seeking behavior, and a lack of reminders were identified as barriers contributing to the low uptake of rescreening. Further interventions should target these by creating community awareness, improving patient counseling, tracing patients in need of follow-up, and making reminder calls or using SMS., (© The Author(s) 2024. Published by Oxford University Press.)

Context: Aging increases fracture risk through bone loss and microarchitecture deterioration due to an age-related imbalance in bone resorption and formation during bone remodeling., Objective: We examined the associations between levels of phosphate, calcium (Ca), and alkaline phosphatase (ALP), and fracture risk in initially healthy older individuals., Methods: A post hoc analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial recruited 16 703 Australian participants aged 70 years and older and 2411 US participants aged 65 years and older. Analyses were conducted on ASPREE-Fracture substudy participants from Australia with serum calcium, phosphate, and ALP measurement. Fracture data were collected post randomization. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. Phosphate, Ca, and ALP were analyzed in deciles (D1-D10), with deciles 4 to 7 (31%-70%) as the reference category. Restricted cubic spline curves were used to identify nonlinear associations., Results: Of the 9915 participants, 907 (9.2%) individuals had incident fractures recorded over 3.9 (SD 1.4) years. In the fully adjusted model, men in the top decile (D10) of phosphate had a 78% higher risk of incident fracture (HR 1.78; 95% CI, 1.25-2.54). No such association was observed for women (HR 1.09; 95% CI, 0.83-1.44). The population attributable fraction in men within the D10 phosphate category is 6.9%., Conclusion: This result confirms that high-normal serum phosphate levels are associated with increased fracture risk in older men., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Type 2 diabetes mellitus is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes., Objective: To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study., Methods: The multisite MrOS study enrolled 5994 men aged ≥ 65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or type 2 diabetes, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with type 2 diabetes were also evaluated with GLM., Results: In adjusted models, hip BMD loss was greater in men with type 2 diabetes (- 2.23%; 95% CI: -2.54 to -1.91; P < .001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; P = .33) compared with NG (-1.57%; 95% CI -1.73 to -1.41). Among men with type 2 diabetes, TZD, insulin, and sulfonylurea use were associated with greater hip BMD loss., Conclusion: Men with type 2 diabetes, but not prediabetes, experienced accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH., Methods: We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW., Results: Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%-22% and <11%-120%, respectively)., Conclusions: If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines., Competing Interests: Potential conflicts of interest . E. K. discloses prior funding from ViiV Healthcare for an unrelated project. S. M. L. reports royalties from UpToDate for articles on tuberculosis infection in pregnancy. All other authors declare no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: Potential conflicts of interest. Both authors: No reported conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

The Zika virus (ZIKV) epidemic in Latin America (2015-2016) has primarily been studied in urban centers, with less understanding of its impact on smaller rural communities. To address this gap, we analyzed ZIKV seroepidemiology in 6 rural Ecuadorian communities (2018-2019) with varying access to a commercial hub. Seroprevalence ranged from 19% to 54%, measured by nonstructural protein 1 blockade of binding enzyme-linked immunosorbent assay. We observed a decline in ZIKV seroprevalence between 2018 and 2019 that was greater among younger populations, suggesting that the attack rates in the 2015-2016 epidemic were significantly higher than our 2018 observations. These data indicate that the 2015-2016 epidemic included significant transmission in rural and more remote settings. Our observations of high seroprevalence in our area of study highlights the importance of surveillance and research in rural areas lacking robust health systems to manage future Zika outbreaks and vaccine initiatives., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Vitamin D may prevent the development of hypertension through down-regulation of renin-angiotensin system. However, epidemiologic studies assessing the interrelation of vitamin D-related biomarkers with hypertension are sparse., Methods: We examined the prospective associations between vitamin D-related biomarkers and the risk of hypertension in a nested case-control study. In each of the Women's Health Study (WHS) and Physicians' Health Study (PHS) II, 500 incident hypertension cases and 500 age and race-matched controls were randomly selected. Baseline plasma 25(OH)-vitamin D [25(OH)D], parathyroid hormone (PTH), and total renin concentrations were measured., Results: Among controls, 25(OH)D and PTH were inversely correlated, but neither was correlated with total renin. In the crude model, there was a trend of association between increasing quintiles of 25(OH)D and lower risk of hypertension in women, with relative risks and 95% CIs of 1.00, 1.24 (0.84-1.83), 0.82 (0.53-1.25), 0.75 (0.48-1.16), and 0.81 (0.52-1.27) (P, trend: .07). Adjustment for body mass index and other hypertension risk factors eliminated this association (relative risk of 5th quintile: 1.03). No associations were found in men. Baseline PTH and ratio of 25(OH)D to PTH were not associated with the risk of hypertension in women or men. When men and women were included in the same model, vitamin D insufficiency (defined as 25(OH)D <20 ng/mL) also was not associated with an increased risk of hypertension. No interactions were found across subgroups., Conclusions: Our study found no association of baseline plasma 25(OH)D or PTH with the risk of hypertension or total renin concentration in middle-aged and older men and women., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

There is an increasing global burden from chikungunya virus (CHIKV). Bangladesh reported a major epidemic in 2017, but it was unclear whether there had been prior widespread transmission. We conducted a nationally representative seroprevalence survey in 70 randomly selected communities immediately before the epidemic. We found that 69 of 2938 sampled individuals (2.4%) were seropositive to CHIKV. Seropositivity to dengue virus (adjusted odds ratio, 3.13 [95% confidence interval, 1.86-5.27]), male sex (0.59 [.36-.99]), and community presence of Aedes aegypti mosquitoes (1.80 [1.05-3.0]7) were significantly associated with CHIKV seropositivity. Using a spatial prediction model, we estimated that across the country, 4.99 (95% confidence interval, 4.89-5.08) million people had been previously infected. These findings highlight high population susceptibility before the major outbreak and that previous outbreaks must have been spatially isolated., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Urinary tract infections (UTIs) occur commonly and often recur. However, recent data on the epidemiology of recurrent UTI (rUTI) are scarce., Methods: Between 1 January 2016 and 31 December 2020, index uncomplicated UTIs (uUTIs) from office, emergency department, hospital, and virtual care settings were identified from the electronic health records of women at Kaiser Permanente Southern California. We defined rUTI as ≥3 UTIs within 365 days or ≥2 UTIs within 180 days. We determined the proportion of women with cystitis index uUTI who had rUTI, and we examined factors associated with rUTIs using modified multivariable Poisson regression., Results: Among 374 171 women with cystitis index uUTI, 54 318 (14.5%) had rUTI. A higher proportion of women with rUTI vs those without rUTI were aged 18 to 27 or ≥78 years at index uUTI (19.7% vs 18.7% and 9.0% vs 6.0%, respectively), were immunocompromised, or had a positive urine culture result at index uUTI. In multivariable analyses, characteristics associated with rUTI included younger or older age (48-57 vs 18-27 years: adjusted risk ratio [aRR], 0.83 [95% CI, .80-.85]; ≥78 vs 18-27 years: aRR, 1.07 [95% CI, 1.03-1.11]), Charlson Comorbidity Index (≥3 vs 0: aRR, 1.12 [95% CI, 1.08-1.17]), and diabetes mellitus (aRR, 1.07 [95% CI, 1.04-1.10]). More frequent prior-year outpatient and emergency department encounters, oral antibiotic and oral contraceptive prescriptions, positive culture result at index uUTI, and antibiotic-resistant organisms were also associated with increased risk of rUTI., Conclusions: The high risk of rUTI among women with cystitis is concerning, especially given previous reports of increasing UTI incidence. Current assessment of the epidemiology of rUTI may guide the development of preventive interventions against UTI., Competing Interests: Potential conflicts of interest. B. K. A., S. Y. T., L. H. C., R. C., I. A. C. R., and J. H. K. are employees of KPSC, which has been contracted by GlaxoSmithKline (GSK) to conduct this study. K. J. B. is an adjunct investigator at KPSC. B. K. A. received funding from Dynavax, Genentech, Moderna, GSK, and Pfizer unrelated to this work. S. Y. T. received funding from Pfizer unrelated to this work. J. H. K. received funding from Moderna unrelated to this work. K. J. B. received funding from Dynavax, Moderna, and Pfizer unrelated to this work. M. P. is a full-time employee of the GSK group of companies and holds shares of the GSK group of companies. J. E. S. is a full-time employee of the GSK group of companies and holds shares of the GSK group of companies. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Oral human papillomavirus (HPV) infections are a leading cause of oropharyngeal cancers. In 2015 and 2016, HPV vaccines became publicly funded for gay, bisexual, and other men who have sex with men (GBM) under 27 years of age in most Canadian provinces., Methods: Between 2017 and 2019, sexually active GBM in Montreal, Toronto, and Vancouver were recruited through respondent-driven sampling. Participants aged 16-30 years were invited to self-collect oral rinse specimens for HPV testing. We estimated HPV prevalence in the oral tract overall and compared these by vaccination status., Results: Among the 838 GBM with a valid oral specimen, 36.9% reported receiving ≥1 dose of HPV vaccine. Overall, oral HPV prevalence was 2.6% (95% confidence interval [CI], 1.5%-3.7%) for at least 1 HPV type and 1.2% (95% CI, .5%-1.9%) for any high-risk type. We detected quadrivalent (HPV 6/11/16/18) vaccine-preventable types in 0.3% (95% CI, .0%-1.0%) of vaccinated individuals and 1.1% (95% CI, .1%-2.0%) of unvaccinated individuals., Conclusions: Oral HPV prevalence was low in a population of young urban GBM in Canada, of whom 37% were vaccinated. Findings serve as a benchmark for monitoring of vaccination impacts on oral HPV infection within this priority population., Competing Interests: Potential conflicts of interest. D. H. S. T.'s institution has received investigator-initiated grants from Abbvie and Gilead; and support for participation in clinical trials sponsored by Glaxo Smith Kline. F. C. reports grants from Réseau FRQS-SIDA during the conduct of the study; and grants to his institution for HPV-related work from Merck Sharp and Dome, Roche Diagnostics, and Becton Dickinson, outside of the submitted work. A. D. P. reports grants from Réseau FRQS-SIDA during the conduct of the study. C. S. is a member of the HPV working group of the National Advisory Committee on Immunization; and is an active member of the Québec Immunization Committee. J. C.’s institution has received funding from ViiV Healthcare and Gilead for research; and J. C. has received remuneration for advisory work from ViiV Healthcare and Gilead. T. A. H. has received funds as Director of the HOPE Centre from Gilead, ViiV, and DECIEM. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Pneumococcal carriage is associated with increased acquisition and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among adults. While pneumococcal conjugate vaccines (PCVs) prevent carriage of vaccine-serotype pneumococci, their potential impact on coronavirus disease 2019 (COVID-19)-related outcomes remains poorly understood in populations with prevalent immunity against SARS-CoV-2., Methods: We undertook a retrospective cohort study of adults aged ≥65 years in the Kaiser Permanente Southern California healthcare system who had received ≥2 COVID-19 vaccine doses, comparing risk of SARS-CoV-2 infection between 1 January 2021 and 31 December 2022 among recipients and nonrecipients of 13-valent PCV (PCV13) employing multiple strategies to mitigate bias from differential test-seeking behavior., Results: The ajusted hazard ratio of confirmed SARS-CoV-2 infection comparing PCV13 recipients to nonrecipients was 0.92 (95% confidence interval [CI], .90-.95), corresponding to prevention of 3.9 (95% CI, 2.6-5.3) infections per 100 person-years. Following receipt of 2, 3, and ≥4 COVID-19 vaccine doses, aHRs (95% CI) were 0.85 (.81-.89), 0.94 (.90-.97), and 0.99 (.93-1.04), respectively. The aHR (95% CI) for persons who had not received COVID-19 vaccination in the preceding 6 months was 0.90 (.86-.93), versus 0.94 (.91-.98) within 6 months after COVID-19 vaccination. Similarly, aHRs (95% CI) were 0.92 (.89-.94) for persons without history of documented SARS-CoV-2 infection, versus 1.00 (.90-1.12) for persons with documented prior infection., Conclusions: Among older adults who had received ≥2 COVID-19 vaccine doses, PCV13 was associated with modest protection against SARS-CoV-2 infection. Protective effects of PCV13 were greater among individuals expected to have weaker immune protection against SARS-CoV-2 infection., Competing Interests: Potential conflicts of interest. J. A. L. discloses receipt of research grants and consulting honoraria from Pfizer and Merck, Sharp & Dohme and consulting honoraria from Seqirus and VaxCyte, all unrelated to this research. S. Y. T. reports receipt of research grants related and unrelated to this research from Pfizer. L. R. G., A. A., A. C., L. J., and B. D. G. are employees of Pfizer and may hold stocks or stock options. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Context: X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Previous studies have found deteriorated bone microarchitecture in the XLH adults. Detailed studies on the skeletal microarchitecture of XLH adolescent and pediatric patients are still lacking., Objective: This study aimed to evaluate bone geometry, density, microarchitecture, stiffness in XLH adolescent and pediatric patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT).Method: This study utilized HR-pQCT to assess bone geometry, density, microarchitecture, and stiffness in 106 Chinese adolescent and pediatric patients with XLH., Result: Compared with the sex- and age-matched controls, XLH patients had significantly higher trabecular area (Tb.Ar), lower total volumetric bone mineral density (Tot.vBMD), lower cortical volumetric BMD (Ct.vBMD), and lower stiffness at both the distal radius and the tibia after adjusting for height and weight. Alkaline phosphatase Z score (ALP-Z), a marker to reflect the disease activity of rickets, was negatively correlated with Ct.vBMD and cortical thickness (Ct.Th) at the distal radius, and Ct.vBMD at the distal tibia, and positively correlated with cortical porosity (Ct.Po) at the distal tibia. We developed an online calculator to estimate Tb.Ar, Ct.vBMD, and stiffness of the distal tibia of XLH adolescent and pediatric patients based on clinical general characteristic and biochemical indicators., Conclusion: The bone microarchitecture of XLH adolescent and pediatric patients was deteriorated, and ALP-Z was negatively correlated with the skeletal quality of XLH adolescent and pediatric patients, especially in the cortical bone. HR-pQCT parameters can be estimated using clinical characteristics and biochemical indicators, which may assist physicians to monitor the disease progression in areas without HR-pQCT access., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth., Materials and Methods: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem to address multiple levels of influence to support All of Us data use. Statistics from the All of Us Researcher Workbench demographic survey describe trends in researchers' and institutional use of the Workbench and publication numbers., Results: From 2022 to 2024, some 13 partner organizations and their subawardees conducted outreach, built capacity, or supported researchers and institutions in using the data. Trends indicate that Workbench registrations and use have increased over time, including among researchers underrepresented in the biomedical workforce. Data Use and Registration Agreements from minority-serving institutions also increased., Discussion: All of Us built a diverse, inclusive, and growing research community via intentional engagement with researchers and via partnerships to address systemic data access issues. Future programs will provide additional support to researchers and institutions to ameliorate All of Us data use challenges., Conclusion: The approach described helps address structural inequities in the biomedical research field to advance health equity., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)

Background and Aims: Few population-based cohort studies, including both men and women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between circulating cardiometabolic-related proteins and MI risk using cohort-based and Mendelian randomization (MR) analyses and explored potential sex-specific differences., Methods: The discovery cohort included 11 751 Swedish adults (55-93 years). Data on 259 proteins assessed with Olink proximity extension assays, biochemical, and questionnaire-based information were used. Participants were followed up for incident MI and death over 8 years through linkage to Swedish registers. Replication analyses were conducted on the UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related to the proteins were used as instrumental variables. Genetic association summary statistic data for MI were obtained from the CARDIoGRAMplusC4D consortium and FinnGen., Results: Forty-five proteins were associated with incident MI in discovery and replication samples following adjustment for potential confounders and multiple testing. In the secondary analysis, 13 of the protein associations were sex-specific, with most associations identified among women. In MR analysis, genetically predicted higher levels of renin, follistatin, and retinoic acid receptor responder protein 2 were linked to an increased risk of MI. Tissue factor pathway inhibitor, tumor necrosis factor receptors 1 and 2, placenta growth factor had an inverse association with MI., Conclusions: This study identified both new and confirmed previously established associations between circulating proteins and incident MI and, for the first time, suggested sex-specific patterns in multiple protein-MI associations., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Transcriptome-wide association studies (TWAS) have been successful in identifying disease susceptibility genes by integrating cis-variants predicted gene expression with genome-wide association studies (GWAS) data. However, trans-variants for predicting gene expression remain largely unexplored. Here, we introduce transTF-TWAS, which incorporates transcription factor (TF)-linked trans-variants to enhance model building for TF downstream target genes. Using data from the Genotype-Tissue Expression project, we predict gene expression and alternative splicing and applied these prediction models to large GWAS datasets for breast, prostate, lung cancers and other diseases. We demonstrate that transTF-TWAS outperforms other existing TWAS approaches in both constructing gene expression prediction models and identifying disease-associated genes, as shown by simulations and real data analysis. Our transTF-TWAS approach significantly contributes to the discovery of disease risk genes. Findings from this study shed new light on several genetically driven key TF regulators and their associated TF-gene regulatory networks underlying disease susceptibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality., Methods: Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics., Results: We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography., Conclusions: Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population., (Published by Oxford University Press 2024.)

Introduction: Adults increasingly use e-cigarettes for cigarette cessation because of the perceived reduced risk. While e-cigarette use is associated with reduced toxicant exposure compared with smoking, it is unclear whether transitioning from cigarettes to e-cigarettes is associated with resolution of respiratory symptoms., Methods: Data were obtained from the Population Assessment of Tobacco and Health (PATH) study waves 1-5. US adult participants were separated into observations with cigarette-e-cigarette exposure intervals determined from PATH waves 1-2, 2-3, and 3-4. Observations were included if the participant reported exclusively smoking at baseline and reported a baseline cough or wheeze. Mixed-effect Poisson models measured the association between cigarette-e-cigarette transitions over the two-wave exposure interval (from smoking to nonuse, exclusive e-cigarette use, continued smoking, or dual use) and the reported resolution of the participant's cough or wheeze., Results: Among 5210 (3362 unique) observations, transitioning from cigarettes to e-cigarettes was associated with increased rates of wheeze resolution (incidence rate ratio [IRR] = 1.33; 95% confidence interval [CI] = 1.01 to 1.75) but not cough resolution (IRR = 1.18; 95% CI = 0.93 to 1.50) compared with persistent smoking. Cigarette to dual-use transitions were not associated with improvements in symptom resolution, and those who switched to dual use and maintained or increased their smoking intensity had 15% decreased rates of respiratory symptom resolution compared with persistent smoking., Discussion: E-cigarette-assisted smoking cessation may increase rates of respiratory symptoms resolution among smokers who completely transition to e-cigarettes; however, there is risk for additional harm among those who initiate e-cigarette use without decreasing their smoking intensity., Implications: Government agencies are increasingly weighing the risks and benefits of e-cigarette-assisted cigarette cessation given the reduced harm associated with e-cigarette use. This study provides novel evidence that completely transitioning from cigarettes to e-cigarettes is associated with increased rates of resolution from self-reported wheeze symptoms. However, risk exists in e-cigarette-assisted cigarette cessation, as those who transitioned from exclusive cigarette smoking to dual use and did not reduce their cigarette smoking intensity had decreased rates of respiratory symptom resolution compared with persistent smokers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Racial inequities in postpartum weight have been documented with limited studies on the influences of racism and other forms of discrimination. In a prospective longitudinal study applying ecological momentary assessment (EMA) and ambulatory assessment of weight, we measured the association between discrimination, stress and postpartum weight change. The Postpartum Mothers Mobile Study (PMOMS) is a cohort of 313 pregnant and birthing individuals who were followed during their second and third trimester through 1 year postpartum. They were recruited in clinical settings between 2017-2020 in a major city center in Pennsylvania. Measures of racism and gender-based discrimination were collected via random EMA surveys throughout pregnancy and postpartum; and weight was collected via blue-tooth enabled scales at least weekly. Among Black participants, a 10% increase in the number of days a participant experienced racial discrimination in the past month was associated with retaining 0.3 more pounds; 10% increase in EMA gender discrimination was associated with retaining 0.4 more pounds; and EMA stress reported in the past month was associated with decreased weight retention. Chronic experiences of racial and gender discrimination may contribute to weight retention immediately after pregnancy and beyond., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is a scarcity of studies regarding the obstacles in tuberculosis (TB) screening in pregnant women. This study aimed to assess the perceptions of TB as a disease and TB screening among pregnant women and healthcare workers, describe pregnant women's perceptions on specific TB screening methods and explore associations between the perceptions of TB with the intention to have TB screening by pregnant women., Methods: A cross-sectional study was conducted at six primary healthcare centres in Yogyakarta Municipality, Indonesia among 240 pregnant women and 126 healthcare workers interviewed with a structured questionnaire about their perceptions. Perceptions were analysed as percentages and associated factors were tested by multivariable logistic regression., Results: Most pregnant women and healthcare workers supported TB screening in pregnant women based on their perceptions of the susceptibility to or severity of TB and the benefits and risks of TB screening. Women who perceived the high susceptibility of TB disease and the benefits of TB screening were significantly more likely to have high intentions to accept TB screening in the future., Conclusions: Pregnant women's perceptions of TB and TB screening influenced their intention to be screened; however, appropriate testing methods for universal TB screening in pregnant women in areas with a high prevalence of TB require further studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Integrated community case management (iCCM) programs leverage lay village health workers (VHWs) to carry out the initial evaluation of children with common conditions including malaria, pneumonia and diarrhea. Therefore, it is imperative that VHWs are able to identify children who are critically ill and require referral to a health facility. Elevated venous lactate levels have been associated with severe illness and adverse health outcomes, including death. However, lactic acidosis may not be recognized in rural settings because it is not routinely measured outside of hospitals and research studies. Point-of-care lactate tests may help identify patients in need of a higher level of care and improve VHWs' ability to make timely and appropriate referrals., Methods: The study was a cross-sectional evaluation of children aged <5 y presenting to VHWs in rural southwestern Uganda with complaints of fever and cough. Demographics, clinical presentation, evaluation, management and disposition were recorded. VHWs were trained and instructed to perform lactate testing using a point-of-care assay in eligible participants., Results: During the study period, 238 children were enrolled and completed an initial assessment. Of the 204 participants included in the analysis, 113 (55.4%) were female, and the median (IQR) age was 23 (9-36) months. Most participants, 139/200 (69.5%), had negative results on the malaria rapid diagnostic test. The median lactate level was 2.1 mmol/L; 12% (24/204) had a lactate ≥3.5 mmol/L and only nine participants (4.4%) had a lactate ≥5 mmol/L. Having a lactate level above either cut-off was not associated with the presence of danger signs at presentation., Conclusions: Few children presenting with fever and cough to VHWs in western Uganda had elevated lactate levels. However, most of the children with elevated lactate levels did not otherwise satisfy established iCCM criteria based on physical examination findings for referral to a health facility. Therefore, while elevated lactate was not associated with danger signs in this small study, it is possible that there is under-recognition of severe illness using current iCCM guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objectives: To evaluate the likelihood of linking electronic health records (EHRs) to restricted individual-level American Community Survey (ACS) data based on patient health condition., Materials and Methods: Electronic health records (2019-2021) are derived from a primary care registry collected by the American Board of Family Medicine. These data were assigned anonymized person-level identifiers (Protected Identification Keys [PIKs]) at the U.S. Census Bureau. These records were then linked to restricted individual-level data from the ACS (2005-2022). We used logistic regressions to evaluate match rates for patients with health conditions across a range of severity: hypertension, diabetes, and chronic kidney disease., Results: Among more than 2.8 million patients, 99.2% were assigned person-level identifiers (PIKs). There were some differences in the odds of receiving an identifier in adjusted models for patients with hypertension (OR = 1.70, 95% CI: 1.63, 1.77) and diabetes (OR = 1.17, 95% CI: 1.13, 1.22), relative to those without. There were only small differences in the odds of matching to ACS in adjusted models for patients with hypertension (OR = 1.03, 95% CI: 1.03, 1.04), diabetes (OR = 1.02, 95% CI: 1.01, 1.03), and chronic kidney disease (OR = 1.05, 95% CI: 1.03, 1.06), relative to those without., Discussion and Conclusion: Our work supports evidence-building across government consistent with the Foundations for Evidence-Based Policymaking Act of 2018 and the goal of leveraging data as a strategic asset. Given the high PIK and ACS match rates, with small differences based on health condition, our findings suggest the feasibility of enhancing the utility of EHR data for research focused on health., (Published by Oxford University Press on behalf of the American Medical Informatics Association 2024.)

The proposal for a regulation on the European Health Data Space (EHDS) contains provisions that would significantly change health data management systems in European member states (MS). This article presents results of a country mapping exercise conducted during the Joint Action 'Towards the European Health Data Space' (TEHDAS) in 2022. It presents the state-of-play of health data management systems in 12 MS and their preparedness to comply with the EHDS provisions. The country mapping exercise consisted of virtual or face-to-face semi-structured interviews to a selection of key stakeholders of the health information systems. A semi-quantitative analysis of the reports was conducted and is presented here, focusing on key aspects related to the user journey through the EHDS. This article reveals a heterogenous picture in countries' readiness to comply with the EHDS provisions. There is a need to improve digitalization and quality of health data at source across most countries. Less than half of the countries visited have or are developing a national datasets catalogue. Although the process to access health data varies, researchers can analyse health data in secure processing environments in all countries visited. Most of the countries use a unique personal identifier for health to facilitate data linkage. The study concluded that the current landscape is heterogeneous, and no member state is fully ready yet to comply with the future regulation. However, there is general political will and ongoing efforts to align health data management systems with the provisions in the EHDS legislative proposal., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility., Objective: To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes., Design and Setting: An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study., Participants: Older black and white ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N=132; non-diabetes: N=571) were selected from the study cohort of 3075 individuals., Main Outcome Measures: Incident clinical fractures., Results: In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (HR: 1.93, 95% CI 1.26-2.95, p=0.002), but there was no evidence of an association in the non-diabetes group (HR: 0.98, 95% CI 0.81-1.18, p=0.79, p for interaction < 0.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r=-0.25, p=0.003), and with a 4-year decrease in total hip BMD (r=-0.28, p=0.008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group., Conclusions: Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Aims: Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome., Methods and Results: In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020)., Conclusion: Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Hypothesis: In the United States, women with schizophrenia face challenges in receiving gynecologic care, but little is known about how cervical cancer screening rates vary across time or states in a publicly insured population. We hypothesized that women Medicaid beneficiaries with schizophrenia would be less likely to receive cervical cancer screening across the United States compared with a control population, and that women with schizophrenia and other markers of vulnerability would be least likely to receive screening., Study Design: This retrospective cohort study used US Medicaid administrative data from across 44 states between 2002 and 2012 and examined differences in cervical cancer screening test rates among 283 950 female Medicaid beneficiaries with schizophrenia and a frequency-matched control group without serious mental illness, matched on age and race/ethnicity. Among women with schizophrenia, multivariable logistic regression estimated the odds of receiving cervical cancer screening using individual sociodemographics, comorbid conditions, and health care service utilization., Study Results: Compared to the control group, women with schizophrenia were less likely to receive cervical cancer screening (OR = 0.76; 95% CI 0.75-0.77). Among women with schizophrenia, nonwhite populations, younger women, urban dwellers, those with substance use disorders, anxiety, and depression and those connected to primary care were more likely to complete screening., Conclusions: Cervical cancer screening rates among US women Medicaid beneficiaries with schizophrenia were suboptimal. To address cervical cancer care disparities for this population, interventions are needed to prioritize women with schizophrenia who are less engaged with the health care system or who reside in rural areas., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Motivation: In the midst of an outbreak, identification of groups of individuals that represent risk for transmission of the pathogen under investigation is critical to public health efforts. Dynamic transmission patterns within these clusters, whether it be the result of changes at the level of the virus (e.g. infectivity) or host (e.g. vaccination), are critical in strategizing public health interventions, particularly when resources are limited. Phylogenetic trees are widely used not only in the detection of transmission clusters, but the topological shape of the branches within can be useful sources of information regarding the dynamics of the represented population., Results: We evaluated the limitation of existing tree shape metrics when dealing with dynamic transmission clusters and propose instead a phylogeny-based deep learning system - DeepDynaTree - for dynamic classification. Comprehensive experiments carried out on a variety of simulated epidemic growth models and HIV epidemic data indicate that this graph deep learning approach is effective, robust, and informative for cluster dynamic prediction. Our results confirm that DeepDynaTree is a promising tool for transmission cluster characterization that can be modified to address the existing limitations and deficiencies in knowledge regarding the dynamics of transmission trajectories for groups at risk of pathogen infection., Availability and Implementation: DeepDynaTree is available under an MIT Licence in https://github.com/salemilab/DeepDynaTree., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: More than 90% of children in military families attend civilian schools that may lack understanding of the unique experiences and stressors of military life. School success in children of military families has important implications on future academic achievement, health outcomes, and military groups; yet there has not been an examination of challenges of school success among children of military families in the United States using nationally representative data., Materials and Methods: Data captured in the 2021-2022 National Survey of Children's Health, limited to children aged 6 to 17 years, were used to examine the association between child's caregiver military status and challenges of school success: lack of school engagement measured through caring about school and completing schoolwork, school absenteeism, and grade repetition (n = 60,599). Weighted to be nationally representative, bivariate analyses used chi-squared tests to examine estimates between selected variables and caregiver military status. Multivariable regression analyses were used to examine the association between caregiver military status and challenges of school success measures., Results: In both unadjusted and adjusted analyses, we found that children of military families were more likely to not be engaged in school (adjusted odds ratios 1.35; 95% CI 1.19-1.53) and more likely to repeat a grade (adjusted odds ratios 1.33; 95% CI 1.09-1.64) than their civilian counterparts. There were no statistically significant differences in school absenteeism between children of military families and of civilian families., Conclusions: This study extends beyond previous research findings that have focused primarily on academic achievement by including school engagement, attendance, and grade repetition for a more holistic and complete understanding of school success of children in military families. Our findings can be informational for school systems and policymakers to create educational and connective interventions for children in military families to improve school success., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Aim: There is no consensus on the optimal time horizon for predicting cardiovascular disease (CVD) risk to inform treatment decisions. New Zealand and Australia recommend 5 years, whereas most countries recommend 10 years. We compared predicted risk and treatment-eligible groups using 5-year and 10-year equations., Methods: Individual-level linked administrative datasets identified 1,746,665 New Zealanders without CVD, aged 30-74 years in 2006, with follow-up to 2018. Participants were randomly allocated to derivation and validation cohorts. Sex-specific 5-year and 10-year risk prediction models were developed in the derivation cohort and applied in the validation cohort., Results: 28,116 (3.2%) and 62,027 (7.1%) first CVD events occurred during 5-years and 10-years follow-up respectively (cumulative risk, derivation cohort). Median predicted 10-year CVD risk (3.8%) was approximately 2.5 times 5-year risk (1.6%) and 95% of individuals in the top quintile of 5-year risk were also in the top quintile of 10-year risk, across age/gender groups (validation cohort). Using common guideline-recommended treatment thresholds (5% 5-year, 10% 10-year risk), approximately 14% and 28% of women and men respectively were identified as treatment-eligible applying 5-year equations compared to 17% and 32% of women and men applying 10-year equations. Older age was the major contributor to treatment eligibility in both sexes., Conclusions: Predicted 10-year CVD risk was approximately 2.5 times 5-year risk. Both equations identified mostly the same individuals in the highest risk quintile. Conversely, commonly used treatment thresholds identified more treatment-eligible individuals using 10-year equations and both equations identified approximately twice as many treatment-eligible men as women. The treatment threshold, rather than the risk horizon, is the main determinant of treatment eligibility., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Inherited kidney diseases (IKD) and congenital anomalies of the kidney and urinary tract (CAKUT) are causes of kidney failure requiring kidney replacement therapy (KRT) that major renal registries usually amalgamate into the primary renal disease (PRD) category 'miscellaneous' or in the glomerulonephritis or pyelonephritis categories. This makes IKDs invisible (except for polycystic kidney disease) and may negatively influence the use of genetic testing, which may identify a cause for IKDs and some CAKUT., Methods: We have re-examined the etiology of KRT by composing a separate IKD and CAKUT PRD group using data from the European Renal Association (ERA) Registry., Results: In 2019, IKD-CAKUT was the fourth most common cause of kidney failure among incident KRT patients, accounting for 8.9% of cases (IKD 7.4% [including 5.0% ADPKD], CAKUT 1.5%), behind diabetes (23.0%), hypertension (14.4%) and glomerulonephritis (10.6%). IKD-CAKUT was the most common cause of kidney failure among patients younger than 20 years (41.0% of cases), but their incidence rate was highest among those aged 45-74 years (22.5 per million age-related population). Among prevalent KRT patients, IKD-CAKUT (18.5%) and glomerulonephritis (18.7%) were the two most common causes of kidney failure overall, while IKD-CAKUT was the most common cause in women (21.6%) and in patients younger than 45 years (29.1%)., Conclusion: IKD and CAKUT are common causes of kidney failure among KRT patients. Distinct categorization of IKD and CAKUT better characterizes the epidemiology of the causes of chronic kidney disease, and highlights the importance of genetic testing in the diagnostic workup of CKD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Malnutrition is the most common acquired cause of immunodeficiency worldwide. Nutritional deficiencies can blunt both the innate and adaptive immune response to pathogens. Furthermore, malnutrition is both a cause and consequence of infectious diseases. The bidirectional relationship between infectious diseases and undernutrition, as well as the inflammatory milieu of infectious diseases, can complicate nutritional assessment. This article aims to provide clinicians and researchers with an overview of commonly used tools to assess nutritional status, with a particular emphasis on their use in the context of infectious diseases. This includes anthropometric, biochemical, clinical/physical, and dietary assessments to screen and evaluate undernutrition, diet quality, and food insecurity effectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Hypothesis: Probiotic augmentation offers a promising treatment for bipolar disorder (BD) and schizophrenia spectrum disorder (SSD). By targeting microbiome deviations, they may improve both gut and brain health., Study Design: In this double-blind, randomized, placebo-controlled trial with the multi-strain probiotic formulation Ecologic BARRIER, we aimed to improve psychiatric and cognitive symptoms, intestinal permeability, and gastrointestinal symptoms in patients with BD or SSD. A total of 131 patients were randomized 1:1 to receive either the probiotic supplement (n = 67) or a placebo (n = 64) for 3 months, in addition to treatment-as-usual. The primary outcomes were symptom severity assessed by the Brief Psychiatric Rating Scale and cognitive functioning by the Brief Assessment of Cognition in Schizophrenia., Study Results: No significant effect of probiotics was observed on psychiatric symptoms, but borderline significant improvement was observed in the cognition category of verbal memory (Linear Mixed Model (LMM) 0.33; adjusted P = .059). Probiotics beneficially affected markers of intestinal permeability and inflammation, including zonulin (LMMserum = -18.40; adjusted P = .002; LMMfecal = -10.47; adjusted P = .014) and alpha-1 antitrypsin (LMM 9.26; adjusted P = .025). Indigestion complaints significantly decreased in male participants in the probiotics group (LMM = -0.70; adjusted P = .010). Adverse events were similar between groups., Conclusions: Our study observed significant advantages of probiotics for gut health in BD and SSD, with excellent safety and tolerability. A borderline effect on verbal memory was also indicated. These results underscore the need for further research into microbiome-targeted interventions for patients with complex brain disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited., Methods: This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)., Results: Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks., Conclusions: INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: While people with HIV (PWH) start antiretroviral treatment (ART) regardless of CD4 count, CD4 measurement remains crucial for detecting advanced HIV disease and evaluating ART programmes. We explored CD4 measurement (proportion of PWH with a CD4 result available) and prevalence of CD4 <200 cells/µL at ART initiation within the International epidemiology Databases to Evaluate AIDS (IeDEA) global collaboration., Methods: We included PWH at participating ART programmes who first initiated ART at age 15-80 years during 2005-2019. We described proportions of PWH (i) with CD4 (measured within 6 months before to 2 weeks after ART initiation); and (ii) among those with a CD4, with CD4 <200; by year of ART initiation and region., Results: We included 1,355,104 PWH from 42 countries in 7 regions; 63% were female. Median (interquartile range) age at ART initiation was 37 (31-44) in men and 32 (26-39) in women. CD4 measurement initially increased, or remained stable over time until around 2013, but then declined to low levels in some regions (Southern Africa, except South Africa: from 54 to 13%; East Africa 85 to 31%; Central Africa 72 to 20%; West Africa: 91 to 53%; and Latin America: 87 to 56%). Prevalence of CD4<200 declined over time in all regions, but plateaued after 2015 at ≥30%., Conclusions: CD4 measurement has declined sharply in recent years, especially in sub-Saharan Africa. Among those with a CD4, the prevalence of CD4 <200 remains concerningly high. Scaling up CD4 testing and securing adequate funding are urgent priorities., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

While preclinical studies assessing drugs for Alzheimer's disease (AD) are conducted in animal models that usually display only one neuropathological feature of AD, patients present with a complex combination of comorbidities and neuropathologies. Importantly, it is well-established that amyloid (Aβ) plaque and tau tangle accumulation interact in a phase-dependent manner, making it difficult to predict how targeting one might influence the other, as well as downstream degeneration. We developed a transgenic mouse model, APP/PS1xTau22, with progressive cortical Aβ deposition and hippocampal tau neurofibrillary inclusions to investigate how both neuropathologies act jointly to bring about neural degeneration, synapse loss, and glial phenotypes. We then assessed whether applying murine chimeric Aducanumab, an anti-amyloid immunotherapy, could impact the synergistic relationship between amyloid and tau. Drug treatment resulted in a ∼70% reduction in Aβ deposition in hippocampal and cortical areas and produced a robust peri-plaque microglial and astrocytic response. Removing amyloid from the brain did not reverse or slow tau pathology or alter synapse loss. Our findings suggest that, once the interaction between amyloid and tau is set in motion, reducing plaque burden by Aβ immunotherapy may stimulate glial responses, but is insufficient to curb degenerative phenotypes in this model., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Prior studies have reported a decrease in the proportion of US adults with hypertension that had controlled blood pressure (BP)., Methods: We analyzed data from the National Health and Nutrition Examination Survey (n=25,128, ≥18 years of age) to determine changes in BP control from 2013-2014 to 2021-2023. Hypertension was defined as systolic BP ≥140 mmHg, diastolic BP ≥90 mmHg or antihypertensive medication use. BP control was defined as systolic BP <140 mmHg and diastolic BP <90 mmHg., Results: The age-adjusted prevalence of hypertension (95%CI) was 32.8% (31.2%-34.4%) in 2013-2014 and 32.0% (30.1%-33.9%) in 2021-2023. Among US adults with hypertension, the age-adjusted proportion (95%CI) with controlled BP was 54.1% (49.1%-59.2%), 48.6% (44.5%-52.7%), and 48.3% (45.8%-50.8%) in 2013-2014, 2015-2016 and 2017-2020, respectively (p-trend=0.058), and 51.1% (47.9%-54.3%) in 2021-2023 (p-value=0.184 comparing 2021-2023 versus 2017-2020). The proportion (95%CI) of US adults taking antihypertensive medication with controlled BP was 72.0% (68.5%-75.5%), 66.7% (62.9%-70.5%), and 67.8% (65.3%-70.3%) in 2013-2014, 2015-2016, and 2017-2020, respectively (p-trend=0.085), and 68.3% (64.8%-71.9%) in 2021-2023 (p-value=0.654 comparing 2021-2023 versus 2017-2020). Among non-Hispanic Black adults, BP control increased from 37.4% (95%CI 33.6%-41.1%) to 49.6% (95%CI 42.3%-56.9%) between 2017-2020 and 2021-2023 for those with hypertension (p-value=0.005), and from 52.6% (95%CI 47.4%-57.8%) to 62.6% (95%CI 55.6%-69.7%) for those taking antihypertensive medication (p-value=0.033). There was no difference in BP control across race/ethnicity groups in 2021-2023., Conclusions: The decline in BP control from 2013-2014 to 2017-2020 did not continue through 2021-2023. An increase in BP control occurred from 2017-2020 and 2021-2023 among non-Hispanic Black adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Individuals with mild cognitive impairment that have high dual-task gait cost (≥20% slowing in gait speed while performing a cognitive brain demanding task), are three-fold more likely to progress to dementia. However, the cortical regions that may explain this association are unknown, which may identify potentially treatable areas. The aim of the current study is to investigate whether brain grey matter volume loss and motor cortex metabolite levels explain the association between dual-task cost and incident dementia in individuals with mild cognitive impairment. We included participants with mild cognitive impairment from the Gait&Brain Study Cohort, who had a baseline MRI and were followed-up for 9 years with cognitive and gait assessments every 6 months. Gait performance was investigated under four conditions: usual gait, counting backwards by ones, naming animals and subtracting serial sevens. Dual-task cost was calculated as the percentage change in gait speed under dual-task conditions relative to usual gait speed. Data were collected from July 2007 to June 2023. From the 139 individuals with mild cognitive impairment included at baseline (mean [SD] age, 73[6] years, 62 (44%) women), and 33 (24%) progressed to dementia. Baseline high dual-task cost (≥20%) under counting backwards by ones and naming animals conditions were associated with smaller grey matter volume in several brain structures. A higher ratio of choline to creatine in the primary motor cortex was associated with higher serial sevens DTC. High dual-task cost while counting backwards by ones and naming animals was associated with a three-fold risk of incident dementia (P=0.02). Mediation analyses revealed that grey matter volume clusters localized in the right anterior and middle cingulate cortices mediated the association between counting backwards by ones dual-task cost and incident dementia (effect: 48%, P=0.045) with no mediation observed in grey matter loss in other brain regions or through motor cortex metabolite levels. Smaller grey matter volume of the right anterior and middle cingulate cortices explained the association between high dual-task cost and incident dementia in mild cognitive impairment. This result sheds light on the neural mechanisms of cognitive-motor interaction linked with cognitive decline and dementia in mild cognitive impairment and support the use of gait under dual-tasking as a motor biomarker of dementia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: This study reports rates of comorbid chronic pain and post-traumatic stress disorder (PTSD) among U.S. military veterans and rates of psychiatric comorbidities among those with both chronic pain and PTSD., Materials and Methods: This study utilized National Veterans Affairs (VA) administrative data to identify all veterans treated for chronic pain or PTSD in 2023. Multivariable logistic regression models determined the likelihood of each psychiatric comorbidity for those with chronic pain and PTSD relative to those with chronic pain only and separately to those with PTSD only, after adjusting for demographic variables and all other psychiatric comorbidities., Results: Of the 5,846,453 service users of the VA in 2023, a total of 2,091,391 (35.8%) met the criteria for chronic pain and 850,191 (14.5%) met the criteria for PTSD. Furthermore, 21.6% of those with chronic pain also had PTSD and over half (53.2%) of those with PTSD also met the criteria for chronic pain (n = 452,113). Veterans with chronic pain and PTSD were significantly more likely to be women, Black or African American, Hispanic or Latina, and urban dwelling. Veterans with chronic pain and PTSD had significantly higher rates of all selected comorbidities relative to veterans with chronic pain only., Conclusions: Patients with comorbid chronic pain and PTSD may benefit from tailored treatments to address the additive impact of these conditions., (© Oxford University Press 2024.)

Background: Analytical criteria for laboratory analysis based on biological variation are considered state-of-the-art. While biological variance should ideally be measured in patient populations for whom the tests are relevant, data are mostly only available from healthy individuals. We determined the biological variance of activated partial thromboplasmin time (APTT), prothrombin time (PT), fibrinogen, and trough dabigatran levels in patients with atrial fibrillation (AF) who were treated with dabigatran., Methods: Between 2019 and 2022, patients with AF treated >3 months with dabigatran were included. Blood was collected monthly up to 10 times for the measurement of APTT, PT, fibrinogen, and trough dabigatran levels. Between-subject variance (CVG), within-subject variance (CVI), and analytical variance (CVA) were calculated., Results: Eighteen participants (median age 65.8 years, 22.2% women) were included, with 130 samples in total. For APTT, the CVG was 11.5%, the CVI 8.8%, and the CVA 1.1%. For PT, these values were 5.2%, 4.0%, and 1.0% and for fibrinogen 13.6%, 11.8%, and 1.6%, respectively. For the dabigatran levels, the percentages were 37.9%, 33.0%, and 3.4%, respectively., Conclusions: We assessed the biological variance of APTT, PT, fibrinogen, and dabigatran in a patient population with long-term dabigatran use. The analytical performances of coagulation laboratory tests in patients with AF treated with dabigatran were comparable to those in healthy volunteers.CCMO Registration Number: NL67304.078.18., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background: Integrase strand transfer inhibitors (INSTIs) and the menopausal transition have separately been associated with body composition changes in women with HIV (WWH), but their interaction is unknown., Methods: From 2006-2019, 1131 non-pregnant WWH with viral suppression [(419 who switched to INSTI (INSTI+); 712 who did not switch (INSTI-)] and 887 women without HIV (WWOH) from the Women's Interagency HIV Study were included. Mixed effect models were used to evaluate change in waist circumference (WC) and BMI by menopausal phase defined using anti-Müllerian hormone, a biomarker of ovarian reserve., Results: During premenopause, WWH had increases in WC (INSTI+: 0.01cm per 6 month (mo); 95%CI:-0.29,0.32 and INSTI-: 0.22cm per 6mo;95%CI:-0.01,0.44) that were not statistically significantly different from WWOH; there was also little difference by INSTI status. In late perimenopause, INSTI+ had faster increases in WC (0.37cm per 6mo;95%CI:0.15,0.60) while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.06,0.34) compared to WWOH. In menopause, INSTI+ had faster increases peaking at 43mo then declining while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.02,0.30). Compared to INSTI-, in late perimenopause, INSTI+ had 0.26 cm per 6mo (95%CI:0.02,0.50) faster linear increases in WC and in menopause, INSTI+ was associated with faster increases peaking at 41mo. BMI trajectories were similar to WC in late peri- and menopausal women., Conclusions: Switching to an INSTI-based regimen during late peri- and menopause is associated with faster increases in WC and BMI when compared to women who did not switch. Menopausal status should be considered when switching to an INSTI., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)