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Objectives: Inflammatory disorders including periodontitis have been investigated for their impact on systemic inflammation and bone health. The present study was conducted with an aim to evaluate impact of control of periodontal inflammation through subgingival instrumentation on serum interleukin 6 and serum C-terminal telopeptide of type I collagen (CTX) in premenopausal females with stage II and III periodontitis. Method and materials: In this single-arm prospective study, periodontal parameters, serum interleukin 6, serum CTX, and hematologic parameters (total leukocyte count, differential leukocyte count, platelet count, mean platelet volume, and platelet distribution width) were assessed at baseline. Subgingival instrumentation was done, and oral hygiene instructions were given. At week 4, professional plaque control was performed, and oral hygiene instructions were reinforced. Serum and hematologic parameters were reassessed at 8 weeks after subgingival instrumentation, in individuals meeting the clinical endpoints (ie, bleeding on probing < 10%). Results: There was significant reduction in serum interleukin 6 of 0.168 ± 0.164 pg/mL (P = .000), and serum CTX of 17.459 ± 4.363 pg/mL (P = .000) at 8 weeks after subgingival instrumentation. There was significant decrease in eosinophil count (P = .018) and mean platelet volume (P = .016) at 8 weeks after subgingival instrumentation; however, no significant change was found in other hematologic parameters. Conclusion: Following subgingival instrumentation, biomarkers of both systemic inflammation (interleukin 6) and bone turnover (CTX) were observed to reduce significantly. This finding hints towards a positive impact of periodontal intervention on bone health. [ABSTRACT FROM AUTHOR]

Purpose: Recent evidence suggests that plant-based diets may reduce the risk of breast cancer (BC). However, the macronutrient composition of plant-based diets and its potential impact on BC risk has not been well explored. This analysis investigated the association of macronutrient composition with BC risk across a spectrum of plant-based diet indexes using a multidimensional approach. Design: This study followed 64,655 participants from the Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort from 1993 to 2014. Diets were evaluated using validated 208-item diet history questionnaires at baseline (1993) and follow-up (2005), to calculate adherence to the overall plant-based diet (PDI), healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI). The association of macronutrient composition with BC risk was assessed via generalized additive time-dependent Cox models across different levels of these indexes. Response surfaces were generated to visualize compositional associations at the 25th, 50th, and 75th percentile of each index (low, moderate, and high). Results: A total of 3,932 incident BC cases were identified during the 21-year follow-up. There was a significant association between macronutrient composition and BC risk for hPDI, uPDI, and PDI (all P < 0.001). Akaike information criterion favored the hPDI model for characterizing the association between macronutrients and BC. BC risk was highest for individuals with a lower hPDI score who also consumed a diet containing lower protein (10%), lower carbohydrate (35%), and higher fat (55%). The lowest risk of BC was observed in those with higher hPDI scores with the lowest intake of protein (10%). At higher PDI and uPDI, diets containing higher protein (30%) and fat (45%) had the highest BC risk. Conclusion: These results demonstrate a complex relationship between macronutrient composition, plant-based diet quality, and BC risk. Further research is needed to examine specific foods that may be driving these associations. Registry: The protocol is registered at clinicaltrials.gov as NCT03285230. [ABSTRACT FROM AUTHOR]

Introduction: We examine the heterogeneity and distribution of the cohort populations in two publicly used radiological image cohorts, the Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCIA TCGA KIRC) collection and 2019 MICCAI Kidney Tumor Segmentation Challenge (KiTS19), and deviations in real-world population renal cancer data from the National Cancer Database (NCDB) Participant User Data File (PUF) and tertiary center data. PUF data are used as an anchor for prevalence rate bias assessment. Specific gene expression and, therefore, biology of RCC differ by self-reported race, especially between the African American and Caucasian populations. AI algorithms learn from datasets, but if the dataset misrepresents the population, reinforcing bias may occur. Ignoring these demographic features may lead to inaccurate downstream effects, thereby limiting the translation of these analyses to clinical practice. Consciousness of model training biases is vital to patient care decisions when using models in clinical settings. Methods: Data elements evaluated included gender, demographics, reported pathologic grading, and cancer staging. American Urological Association risk levels were used. Poisson regression was performed to estimate the population-based and sample-specific estimation for prevalence rate and corresponding 95% confidence interval. SAS 9.4 was used for data analysis. Results: Compared to PUF, KiTS19 and TCGA KIRC oversampled Caucasian by 9.5% (95% CI, −3.7 to 22.7%) and 15.1% (95% CI, 1.5 to 28.8%), undersampled African American by −6.7% (95% CI, −10% to −3.3%), and −5.5% (95% CI, −9.3% to −1.8%). Tertiary also undersampled African American by −6.6% (95% CI, −8.7% to −4.6%). The tertiary cohort largely undersampled aggressive cancers by −14.7% (95% CI, −20.9% to −8.4%). No statistically significant difference was found among PUF, TCGA, and KiTS19 in aggressive rate; however, heterogeneities in risk are notable. Conclusion: Heterogeneities between cohorts need to be considered in future AI training and cross-validation for renal masses. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Intensive rehabilitation aims to improve and maintain functioning in young people who experience disability due to illness or injury. Day rehabilitation may have advantages for families and healthcare systems over inpatient models of rehabilitation. METHODS: This study evaluated the goals and outcomes of a cohort of young people in Western Australia who attended a specialist intensive day rehabilitation programme ("iRehab") at Perth Children's Hospital. Analysis of the iRehab service database was performed. Rehabilitation goals and outcomes were recorded as per the Canadian Occupational Performance Measure (COPM), Children's Functional Independence Measure (WeeFIM), and Goal Attainment Scale (GAS). RESULTS: There were 586 iRehab admissions between August 11, 2011, and December 31, 2018. Admissions were divided by diagnosis: Cerebral Palsy (228, 38.5%), Acquired Brain Injury (125, 21.3%), Spinal Cord Disorders (91, 15.5%), and Other (141, 24.2%). Mean COPM Performance increased by 2.78 points from admission to discharge (95% CI 2.58 to 2.98, p < 0.001). Mean COPM Satisfaction was 3.29 points higher at discharge than admission (95% CI 3.07 to 3.51, p < 0.001). Mean total WeeFIM score improved by 6.51 points between admission and discharge (95% CI 5.56 to 7.45, p < 0.001), and by 3.33 additional points by six months post discharge (95% CI 2.14 to 4.53, p < 0.001). Mean GAS T-scores increased by 27.85 (95% CI 26.73 to 28.97, p < 0.001) from admission to discharge, and by 29.64 (95% CI 28.26 to 31.02, p < 0.001) from admission to six months post discharge, representing improvement consistent with team expectations. CONCLUSION: This study describes a model by which intensive rehabilitation can be delivered in a day rehabilitation setting. A diverse population of young people who experienced disability achieved significant improvements in occupational performance, independence, and goal attainment after accessing intensive day rehabilitation. Improvements were measured in all diagnostic subgroups and were maintained six months after discharge. [ABSTRACT FROM AUTHOR]

Research over many years indicates that individuals with problematic alcohol or drug use or gambling disorders can cause considerable burden on family members. And yet, affected family members (AFMs) are largely neglected in research, health and social care policy and provision. To address the needs of AFMs of people struggling with a substance use or gambling disorder, the 5-Step Method was developed. The goal of this study is to evaluate the routinely delivered 5-Step Method in the Netherlands using measures at baseline (N = 145), and end-of-treatment (N = 102). In addition, a subsample at three-month post intervention (N = 70) was included. The intervention was delivered via video-conferencing to half (47.6%) of the participants. Participants reported significantly lower rates of Total Family Burden after completing the 5-Step Method, when comparing measurements at baseline and end-of-treatment (d = 0.56), and measurements at baseline and three-month post intervention (d = 0.85). In addition, participants following the intervention via video-conferencing (N = 69) performed equally well or better compared to participants following the intervention face-to-face (N = 76). Following the 5-Step Method for AFMs results in lower Total Family Burden. In accordance with the Stress-Strain-Information-Coping-Support (SSICS) model, the effectiveness of the intervention could be improved by finding new ways of increasing support for AFMs. [ABSTRACT FROM AUTHOR]

Objective: Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross‐sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. Methods: We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of "pseudogout" or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. Results: We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person‐years) versus comparators (5.5 per 1,000 person‐years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3–2.3]); results were similar in sensitivity analyses. Conclusion: In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin‐related protein (SMRP) and cancer antigen 125 (CA‐125) are established blood‐based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD). Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post‐operation, and (3) recurrence. Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow‐up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA‐125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease‐free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA‐125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA‐125 across the study timepoints (p = 0.47). Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA‐125 could be helpful in recognizing abdominal recurrences. [ABSTRACT FROM AUTHOR]

There is a growing evidence base that identifying positive experiences in providing care can have a beneficial influence on carer wellbeing. However, there is a need to better understand what carers identify as the positive aspects of care-giving. The aim of this study is to explore the satisfying aspects of providing care to people with dementia. This study utilised Time 1 data from 1,277 carers of people in the mild-to-moderate stages of dementia taking part in the IDEAL (Improving the experience of Dementia and Enhancing Active Life) cohort study. Responses from 900 carers who answered the open-ended question 'What is your greatest satisfaction in caring for your relative/friend?' were analysed using thematic analysis. From the responses, 839 carers detailed satisfactions. Eight themes were identified, pertaining to three groups of beneficiaries: carers, people with dementia and the dyad. Perceived benefits for carers included identifying aspects of personal growth, seeing glimpses of the person, feeling they were making a difference and doing their duty. For the person with dementia, these included retaining independence, receiving good quality care and being happy. Dyadic benefits concerned the continuation of the relationship between carer and person with dementia. The findings highlight the need to take a dyadic approach when conceptualising positive experiences in providing care. Further research is needed to understand the role these positive experiences play and to develop interventions. Professionals working with carers should identify and validate these experiences. [ABSTRACT FROM AUTHOR]

Background: The risk of incident dementia after surgery in older adults is unclear. The study objective was to examine the rate of incident dementia among older adults after elective surgery compared with a matched nonsurgical control group. Methods: We conducted a population‐based, propensity‐matched retrospective cohort study using data from linked administrative databases in Ontario, Canada. All community‐dwelling individuals aged 66 years and older who underwent one of five major elective surgeries between April 1, 2007 and March 31, 2011 were included. Each surgical patient was matched 1:1 on surgical specialty of the surgeon at consultation, age, sex, fiscal year of entry, and propensity score with a patient who attended an outpatient visit with a surgeon of the same surgical specialty but did not undergo surgery. Patients were followed for up to 5 years after cohort entry for the occurrence of a new dementia diagnosis, defined from administrative data. Cause‐specific hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between surgery and the hazard of incident dementia. Subgroup and sensitivity analyses were performed. Results: A total of 27,878 individuals (13,939 matched pairs) were included in the analysis. A total of 640 (4.6%) individuals in the surgical group and 965 (6.9%) individuals in the control group developed dementia over the 5‐year follow‐up period. Individuals who underwent surgery had a reduced rate of incident dementia compared with their matched nonsurgical controls (HR 0.88; 95% CI 0.80–0.97; p = 0.01). This association was persistent in most subgroups and after sensitivity analyses. Conclusions: Elective surgery did not increase the rate of incident dementia when compared with matched nonsurgical controls. This could be an important consideration for patients and surgeons when elective surgery is considered. See related editorial by Tammy Hshieh and article by Tang et al. in this issue. [ABSTRACT FROM AUTHOR]

The UK Biobank study contains several sources of diagnostic data, including hospital inpatient data and data on self-reported conditions for approximately 500,000 participants and primary-care data for approximately 177,000 participants (35%). Epidemiologic investigations require a primary disease definition, but whether to combine data sources to maximize statistical power or focus on only 1 source to ensure a consistent outcome is not clear. The consistency of disease definitions was investigated for venous thromboembolism (VTE) by evaluating overlap when defining cases from 3 sources: hospital inpatient data, primary-care reports, and self-reported questionnaires. VTE cases showed little overlap between data sources, with only 6% of reported events for persons with primary-care data being identified by all 3 sources (hospital, primary-care, and self-reports), while 71% appeared in only 1 source. Deep vein thrombosis–only events represented 68% of self-reported VTE cases and 36% of hospital-reported VTE cases, while pulmonary embolism–only events represented 20% of self-reported VTE cases and 50% of hospital-reported VTE cases. Additionally, different distributions of sociodemographic characteristics were observed; for example, patients in 46% of hospital-reported VTE cases were female, compared with 58% of self-reported VTE cases. These results illustrate how seemingly neutral decisions taken to improve data quality can affect the representativeness of a data set. [ABSTRACT FROM AUTHOR]

Sexual assault is a form of violence disproportionately perpetrated against women by men; however, men also experience high rates of sexual victimization. While recent research exploring victimization of sexual assault among men does exist, little is known about situational characteristics and consequences surrounding men's assault experiences. Therefore, the current study examines narratives of men's sexual assault to further understand the unique experiences of men receiving a sexual assault medical forensic examination. To accomplish this, we conducted a retrospective medical chart review of sexual assault narratives from N = 45 men receiving a sexual assault medical forensic examination at a large academic medical institution in the southeastern United States. Three general constructs were identified within the records: a) Perpetrator use of coercive tactics, b) Memory loss, and c) Contextual factors. Nested within these constructs, five specific themes emerged, including: a1) Use of weapons and physical force; a2) Tactical administration of alcohol and drugs; b1) Difficulties remembering assault; c1) Consensual sexual activity turned non-consensual; c2) Incarceration. Findings from the present study common identified characteristics of sexual assaults among men receiving a sexual assault medical forensic examination, including coercive tactics used by perpetrators, consequences of sexual assault, and high-risk settings for male victimization. [ABSTRACT FROM AUTHOR]

Background: Carpal Tunnel Syndrome (CTS) is associated with a significant personal and societal burden. Evaluating access to care can identify barriers, limitations, and disparities in the delivery of healthcare services in this population. The purpose of this study was to evaluate access to overall healthcare and healthcare utilization among patients with CTS. Methods: This is a retrospective cohort study conducted with the All of Us database. Patients diagnosed with CTS that completed the access to care survey were included and matched to a control group. The primary outcomes were access to care across 4 domains: (1) delayed care, (2) could not afford care, (3) skipped medications, and (4) over 1 year since seeing provider. Secondary analysis was then performed to identify patient-specific factors associated with reduced access to care. Results: In total, 7649 patients with CTS were included and control matched to 7649 patients without CTS. In the CTS group, 33.7% (n = 2577) had delayed care, 30.4% (n = 2323) could not afford care, 15.4% (n = 1180) skipped medications, and 1.6% (n = 123) had not seen a provider in more than 1 year. Within the CTS cohort, low-income, worse physical health, and worse mental health were associated with poor access to care. Conclusion: Patients experience notable challenges with delayed care, affordability of care, and medication adherence regardless of having a diagnosis of CTS. Targeted interventions on modifiable risk factors such as low income, poor mental health, and poor physical health are important opportunities to improve access to care in this population. [ABSTRACT FROM AUTHOR]

We evaluated first-pass endotracheal intubation (ETI) success within the critical care transport (CCT) environment using a natural experiment created by the COVID-19 pandemic. Our primary objective was to evaluate if the use of personal protective equipment (PPE) or the COVID-19 time period was associated with differences in first-pass success rates of ETI within a large CCT system with a high baseline ETI first-pass success rate. We hypothesized that pandemic-related challenges would be associated with decreased first-pass success rates. We performed a retrospective before-after cohort study of airway management by CCT personnel relative to the COVID-19 pandemic. We used a mixed effects logistic regression to evaluate the association between enhanced PPE (N95 mask, eye protection) use and the pandemic time period on first-pass intubation success, while controlling for other factors potentially associated with intubation success. Variables in the final model included patient demographics (age, sex, and race), body mass index, medical category (trauma versus non-trauma), interfacility or scene response, blade size (Macintosh 3 versus 4), use of face mask, use of eye protection, and crew member length of service. We identified 1279 cases involving intubation attempts on adult patients during the study period. A total of 1133 cases were included in the final analysis, with an overall first-pass success rate of 95.7% (96.4% pre-COVID-19 and 94.8% during COVID-19). In our final mixed effects logistic regression model, enhanced PPE use and the COVID-19 time period were not associated with first-pass intubation success rate. In a large regional CCT system with a high ETI first-pass success rate, neither PPE use nor the COVID-19 time period were associated with differences in ETI first-pass success while controlling for relevant patient and operational factors. Other emergency medical services (EMS) systems may have encountered different effects of pandemic-related PPE use on intubation success rates. Further studies are needed to evaluate the influence of sustained use of enhanced PPE or changes in training or procedural experience on post-pandemic ETI first-pass success rates for non-CCT EMS clinicians. [ABSTRACT FROM AUTHOR]

Background: Concurrent administration of vancomycin and piperacillin/tazobactam (VAN+PTZ) may increase the risk of acute kidney injury (AKI) in hospitalized patients. Comprehensive characterization of VAN+PTZ associated AKI and recovery patterns remains lacking in previous reports. Objective: To compare the incidence of AKI associated with VAN+PTZ compared to either cefepime (CEF) or meropenem (MER) with VAN in adult general ward patients. Methods: A multicenter, retrospective, propensity score cohort study was conducted in non-critically ill adult patients. Included patients were concurrently administered VAN+PTZ or VAN+CEF/MER. Patients developing AKI ≤48 hours following combination therapy were excluded. The primary endpoint was to compare the incidence of AKI between study groups. Multivariable Cox regression modeling in predicting AKI was also conducted. Results: A total of 3199 patients met inclusion criteria and were evaluated. The incidence of AKI in VAN+PTZ and VAN+CEF/MER groups were 16.4% and 8.7%, respectively (P <.001). The onset to AKI was 1.8 days earlier with VAN+PTZ compared to VAN+CEF/MER (P <.001). Multivariable prediction model showed concomitant VAN+PTZ was identified as an independent risk factor of developing AKI (HR 2.34, 1.82-3.01, P <.001). The VAN+PTZ group experienced significantly higher rates of severe AKI (stage II or III) compared to the VAN+CEF/MER group (P =.002). No differences in the AKI recovery patterns were found between study groups. Conclusions: Concomitant VAN+PTZ in adult general ward patients was independently associated with an increased risk of AKI overall. More severe AKI was also associated with VAN+PTZ. [ABSTRACT FROM AUTHOR]

We integrated safer conception care into a Ugandan HIV clinic. People with HIV (PWH), or partnered with a PWH, and desiring children were eligible for the Healthy Families Clinic Program. Clients completed quarterly safer conception counselling visits and questionnaires to provide information around method preferences and outcomes (partner pregnancy, partner seroconversion). We used clinic level data to evaluate longitudinal viral suppression among PWH. Between November 2016 and January 2020, 361 clients (53% men) accessed services. 75% were PWH (51% women, 96% men): 99% were on antiretroviral therapy (ART) and most reported HIV-sero-different partnerships (97%). Frequently selected safer conception methods included ART (86%), timed condomless sex (74%), and PrEP (40%) with important differences by HIV-serostatus and gender. 22.5% reported pregnancy. Most (97%) PWH were virally suppressed at enrolment and 81% of non-virally suppressed PWH were virally suppressed at 15 months. Two HIV-negative clients (2%) had HIV seroconversion. There is demand for safer conception care in a public sector HIV-clinic in Uganda. Men and women have unique safer conception care preferences. The majority of clients engaged in safer conception care had viral suppression at follow up. [ABSTRACT FROM AUTHOR]

Background: There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. Patients and Methods: A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. Results: In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). Conclusion: Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control. Uncertainty remains regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer. This article reports patterns of disease recurrence and outcomes of reoperative surgery in a cohort of consecutively treated patients. [ABSTRACT FROM AUTHOR]

Background: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). Methods: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. Results: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. Conclusions: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are at higher risk for the development of coronary artery disease (CAD) later in life. We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM, and risk of premature CAD (PCAD). Methods: This research project involved a data linkage approach merging three databases of South Australian cohorts by using a retrospective, age-matched case–control study design. Cases (n = 721) were ascertained from the Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to ascertain their prior pregnancy outcomes. Controls (n = 194) were selected from North West Adelaide Health Study (NWAHS) and comprised women who were healthy or had other health conditions unrelated to CAD, age-matched to CADOSA (±5 years), and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as >50% stenosis in one or more coronary arteries at coronary angiography. Results: Compared with women without a history of PCAD, women who were diagnosed with PCAD were more likely to have experienced the placenta-mediated pregnancy complications of preterm birth (adjusted odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.21–5.00) or low-birth weight (adjusted OR = 2.44, 95% CI: 1.22–4.88), or have been diagnosed with active asthma during pregnancy (adjusted OR = 3.52, 95% CI: 1.05–11.76). Conclusion: Placenta-mediated pregnancy complications should be recognized as clear risk markers for future PCAD. [ABSTRACT FROM AUTHOR]

Vascular access devices play vital roles within neonatal care. We aimed to identify neonatal vascular access device insertion and management practices, and describe the incidence and risk factors for complication development. This is a prospective cohort study of neonates requiring vascular access devices over 3 months in an Australian quaternary-referral neonatal intensive care unit. In addition to describing current practices, primary outcomes were device failure, complications, and skin complications. Results are reported using descriptive statistics and with risk factors calculated via Cox proportional hazards regression. A total of 104 neonates required 302 vascular access devices, over 1375 catheter days. Peripheral intravenous catheters (PIVCs) were most used (n = 186; 62%), followed by umbilical venous catheters (n = 52; 17%). Insertion attempts were often undocumented; but for those recorded, 5% of devices (n = 15) required 4 attempts or more. Device failure occurred in 28% (n = 82), at an incidence rate of 62.5 per 1000 catheter days (95% confidence interval [CI] 49.775.9). Failure was most frequent in PIVCs (37%; n = 68), peripheral arterial catheters (33%; n = 2), and peripherally inserted central catheters (20%; n = 6). Infiltration and extravasation were the most frequent cause of PIVC failure (12%; n = 35). A birth weight less than 1500 g was associated with a significant decrease in PIVC failure (hazard ratio 0.58; 95% CI 0.34-0.99). [ABSTRACT FROM AUTHOR]

Objective: The study aim was to investigate associations of 11 anthropometric measures with incident type 2 diabetes and compare their predictive performance. Methods: This prospective cohort study included 161,127 White European UK Biobank participants who were free of diabetes at baseline. Anthropometric measures included height, weight, BMI, A Body Shape Index, waist circumference, waist to hip ratio, waist to height ratio (WHtR), hip circumference, visceral adiposity index, hip index, and anthropometric risk index. The associations were examined using Cox proportional hazard models. The differences in C‐index were used to compare predictive performance between BMI and other anthropometric measures. Results: The median follow‐up was 10.0 (interquartile range: 9.3–10.8) years, during which 6315 participants developed type 2 diabetes. All markers except height and hip index were positively associated with incident type 2 diabetes. The strongest associations were found for WHtR (hazard ratio per 1‐SD increment: 2.27 [95% CI 2.19–2.35] in women; 1.96 [95% CI 1.90–2.01] in men). Compared with BMI, WHtR and anthropometric risk index had significantly better type 2 diabetes risk discrimination. Conclusions: Although most adiposity markers were associated with type 2 diabetes, the magnitude of the associations differed. WHtR had the strongest associations and predictive ability for type 2 diabetes and thus could be a more suitable marker for clinical use. [ABSTRACT FROM AUTHOR]

The link between memory and comorbid depression in persons with HIV (PWH) is unclear based on evidence from published cohorts. We compared verbal memory in the HVLT-R in a well-characterized HIV cohort (n = 354) with (n = 102) or without (n = 252) comorbid depressive symptoms, and examined memory correlates in both scenarios. Memory fell within unimpaired ranges, but was lower in depressed than non-depressed PWH. Memory was related to quality of life, sociodemographic, and mental health factors, but not to assessed HIV-related or antiretroviral factors. However, longitudinally (n = 52) memory declined with presence and severity of depressive symptoms. In this treated cohort, verbal memory was unrelated to HIV-related variables but to quality of life and depressive symptoms. Greater performance decline over time also related to acute or ongoing depressive symptoms. These findings highlight the importance of addressing comorbid depressive symptoms to improve quality of life in persons with treated HIV. [ABSTRACT FROM AUTHOR]

Background: Relatively little is known about how distressing symptoms change among older persons in the setting of major surgery. Our objective was to evaluate changes in distressing symptoms after major surgery and determine whether these changes differ according to the timing of surgery (nonelective vs. elective), sex, multimorbidity, and socioeconomic disadvantage. Methods: From a prospective longitudinal study of 754 nondisabled community‐living persons, 70 years of age or older, 368 admissions for major surgery were identified from 274 participants who were discharged from the hospital from March 1998 to December 2017. The occurrence of 15 distressing symptoms was ascertained in the month before and 6 months after major surgery. Multimorbidity was defined as more than two chronic conditions. Socioeconomic disadvantage was assessed at the individual level, based on Medicaid eligibility, and neighborhood level, based on an area deprivation index (ADI) score above the 80th state percentile. Results: In the month before major surgery, the occurrence and mean number of distressing symptoms were 19.6% and 0.75, respectively. In multivariable analyses, the rate ratios, denoting proportional increases in the 6 months after major surgery relative to presurgery values, were 2.56 (95% confidence interval [CI], 1.91–3.44) and 2.90 (95% CI, 2.01–4.18) for the occurrence and number of distressing symptoms, respectively. The corresponding values were 3.54 (95% CI, 2.06–6.08) and 4.51 for nonelective surgery (95% CI, 2.32–8.76) and 2.12 (95% CI, 1.53–2.92) and 2.20 (95% CI, 1.48–3.29) for elective surgery; p‐values for interaction were 0.030 and 0.009. None of the other subgroup differences were statistically significant, although men had a greater proportional increase in the occurrence and number of distressing symptoms than women. Conclusions: Among community‐living older persons, the burden of distressing symptoms increases substantially after major surgery, especially in those having nonelective procedures. Reducing symptom burden has the potential to improve quality of life and enhance functional outcomes after major surgery. [ABSTRACT FROM AUTHOR]

Objectives: Investigate the characteristics of wrist, hand and finger (WHF) injuries in Australian footballers presenting to EDs and determine if injury profiles differed between females and males, and between children and adults. Methods: In this prospective observational study that took place during an entire football season, patients attended 1 of 10 EDs in Victoria, Australia with a WHF injury sustained while playing Australian football. Data were extracted from patient medical records by trained researchers. Data included injury type (e.g. fracture), body part (e.g. metacarpal) and mechanism of injury. Males versus females, and children versus adults were compared using chi‐squared tests or Fisher's exact tests. Results: In total, 528 patients had a WHF injury, of which 105 (19.9%) were female and 308 (59.2%) were children. Fractures and sprains were the most common injury types (45.3% and 38.6%, respectively). Fingers were more often injured than wrists or hands (62.5%, 23.5% and 15.0%, respectively). Ball contact was the most common mechanism of injury (38.1% of injuries). Females were more likely than males to (i) have a sprain/strain injury, (ii) injure a finger (rather than wrist or hand) and (iii) injure themselves through ball contact. Children were more likely to injure their wrists, have a sprain/strain injury, or be injured falling to the ground. Adults were more likely to dislocate a joint or injure their hands. Conclusions: Differences in injury type, location and mechanism between females and males, and children and adults, suggest an opportunity for customised injury prevention and management strategies by sex and age. [ABSTRACT FROM AUTHOR]

Background: Despite significant morbidity, there remains a critical need for prospective analyses to investigate the impact of comorbid chronic rhinosinusitis (CRS) with asthma (CRSwA) on patient centered outcomes. The objective of this study was to ascertain critical stakeholder feedback from patients that could inform future study design based on patient preferences, in an effort to optimize patient enrollment. Methods: A prospective, descriptive study was performed in order to determine the importance of various factors on CRSwA treatment among critical stakeholders. A Likert-scale survey highlighting various aspects of treatment of CRSwA and elucidating patient enthusiasm for clinical enrollment was constructed and prospectively administered to patients with CRSwA. A univariate analysis was instituted to understand the significance of the different trial design preferences. Results: Survey responses were collected from a total of 17 patients with CRSwA. With Likert scores >4/5, responses indicated significant stakeholder interest in research focused on understanding symptom triggers, including the impact of air quality and allergens. Importantly, the highest mean scores noted were for studies focused on improving (1) overall quality of life (4.8/5) and (2) lung function (4.8/5). Patients appeared least interested in participation in a randomized trial, whereas the greatest support was communicated for a purely observational trial (P =.08). Conclusion: Patients with CRSwA demonstrate enthusiasm for participation in research that focuses on improving patient centered outcomes—specifically quality of life and lung function. Stakeholder feedback also indicates a preference for observational study design over randomized control trials. [ABSTRACT FROM AUTHOR]

Aims: To investigate the combined association of adiposity and walking pace with incident type 2 diabetes. Methods: We undertook a prospective cohort study in 194 304 White‐European participants (mean age 56.5 years, 55.9% women). Participants' walking pace was self‐reported as brisk, average or slow. Adiposity measures included body mass index (BMI), waist circumference (WC) and body fat percentage (BF%). Associations were investigated using Cox proportional hazard models, with a 2‐year landmark analysis. A four‐way decomposition analysis was used for mediation and additive interaction. Results: The median (interquartile range) follow‐up was 5.4 (4.8‐6.3) years. During the follow‐up period, 4564 participants developed type 2 diabetes. Compared to brisk‐walking participants with normal BMI, those with obesity who walked briskly were at an approximately 10‐ to 12‐fold higher risk of type 2 diabetes (hazard ratio [HR] 9.64, 95% confidence interval [CI] 7.24‐12.84, in women; HR 11.91, 95% CI 8.80‐16.12, in men), whereas those with obesity and walked slowly had an approximately 12‐ to 15‐fold higher risk (HR 12.68, 95% CI 9.62‐16.71, in women; HR 15.41, 95% CI 11.27‐21.06, in men). There was evidence of an additive interaction between WC and BF% and walking pace among women, explaining 17.8% and 47.9% excess risk respectively. Obesity mediated the association in women and men, accounting for 60.1% and 44.9%, respectively. Conclusions: Slow walking pace is a risk factor for type 2 diabetes independent of adiposity. Promoting brisk walking as well as weight management might be an effective type 2 diabetes prevention strategy given their synergistic effects. [ABSTRACT FROM AUTHOR]

Introduction: Although stroke is an emerging cause of disability and mortality globally, associations between physical capability markers and mortality in stroke survivors are elusive. This study investigated the individual and combined associations of walking pace and grip strength with all‐cause and stroke mortality in stroke survivors. Methods: Individual and combined associations of walking pace and grip strength with stroke deaths and all‐cause mortality were investigated using Cox proportional‐hazard models adjusted for sociodemographic, lifestyle, and health‐related variables. Results: Seven thousand four hundred eighty‐six stroke survivors from the UK Biobank study (aged 40–70 years; 42.4% women) were included in this prospective study. Over a median follow‐up of 12.6 (IQR: 11.9–13.3) years, 1490 (19.9%) participants died, of whom 222 (3.0%) died from stroke. After adjusting for confounding factors, and compared to individuals in the average/brisk walking pace category, those who reported a slow walking pace had 2.00 (95% CI: 1.50–2.68) and 1.99 (95% CI: 1.78–2.23) times higher risk of stroke mortality and all‐cause mortality, respectively. Similar associations were identified for participants with low grip strength compared with those with normal levels. For combined associations, those with both slow walking pace and low grip strength showed the highest risk of stroke mortality (hazard ratio: 2.86 [95% CI: 1.93–4.22]). Similar results were found for all‐cause mortality. Conclusions: Low grip strength and slow walking pace were associated with a higher risk of stroke and all‐cause mortality in stroke survivors. If these associations are causal, improving physical capability among stroke survivors might potentially prolong survival. [ABSTRACT FROM AUTHOR]

Background: There is a wide range of literature on patellar tendon injury, making it increasingly difficult to stay informed on the most influential studies in this field. It is essential to be familiar with the foundational articles of patellar tendon injury research to understand the current state of the literature and deliver high quality care. Purpose: To objectively identify the 50 most influential articles relating to patellar tendon injury and conduct a bibliometric analysis to identify key features of these articles. Study Design: Cross-sectional study. Methods: The Clarivate Analytics Web of Knowledge database was utilized to gather metrics on the 50 most cited articles on patellar tendon injury on June 27, 2022. The information extracted from each article included publication year, number of citations, author information, article type, level of evidence, country of origin, journal name, study focus, and industry influence. Results: The top 50 studies were cited a total of 8543 times and published between 1977 and 2015. The majority of articles were published after 2003, and the majority of citations were accrued after 2011. The most prevalent article types were cohort studies (n = 23), and the majority of studies were of evidence level 2 (n = 14) or 4 (n = 13). Australia and the United States (US) each published the most studies (n = 11). Only 4 (8%) studies focused on patellar tendon rupture, and 12 (24%) of the top 50 studies were associated with industry. Conclusion: The majority of the top 50 most influential articles in patellar tendon injury were published and accumulated citations in the past 10 to 20 years. Non-US countries, institutions, and journals published many of the top 50 studies, reflecting a global interest and commitment to research in this field. Patellar tendon rupture and surgical repair represents a minority of research in the top 50 studies and could be a point of growth in the future. [ABSTRACT FROM AUTHOR]

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer's Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated via the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLDtau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10-15.83, p < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05-72.40, p < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02-0.74, p < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]

Background Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally. Methods In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities. Results Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine. Conclusions Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment. [ABSTRACT FROM AUTHOR]

Objective: Investigate the economic consequences of injuries to female Australian footballers from a health sector and societal perspective. Methods: This prospective observational study invited 242 females to complete an online questionnaire 3–6 months following an Australian football injury which involved presentation to an ED in Victoria, Australia. The questionnaire inquired regarding healthcare use, time off work, return to playing football and extent of recovery following injury. Relevant information was also extracted from respondents' medical records regarding injury‐type, body part injured, investigations and treatments. Healthcare costs were determined for each respondent's ED presentation, hospital admission/s (when relevant), and subsequent healthcare use. Societal costs were determined as lost income to the respondent and/or carer. Results: A total of 108 people responded to the questionnaire. Sprains/strains and fractures accounted for 84.2% of respondents' injuries. Sixteen respondents (14.8%) required admission to hospital at the time of injury and 81 (75.0%) required subsequent healthcare appointments following discharge from the ED or hospital. Time off work or school following the injury was common (64.8% of respondents) and 27.8% of respondents had a carer take time off work. More than 80% of respondents missed training and matches following the injury. The median healthcare cost per respondent was AUD$753 and the median cost due to work absence was AUD$1393. One‐quarter of respondents reported a full recovery. Conclusions: Injuries to female Australian footballers can produce substantial healthcare and societal costs, which has important implications for healthcare provision and prioritising and implementing injury prevention programmes and post‐injury rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown. Methods: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine‐learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within the past 12 months, body mass index, physiologic frailty (VACS Index 2.0), illicit substance and alcohol use disorders, and measures of multimorbidity and polypharmacy. We separately fit multivariable logistic models to each outcome using generalized estimating equations. From these models, the longitudinal extensions of average attributable fraction (LE‐AAF) for modifiable risk factors were estimated. Results: Key risk factors for both outcomes included physiologic frailty (VACS Index 2.0) (serious falls [15%; 95% CI 14%–15%]; fractures [13%; 95% CI 12%–14%]), a serious fall in the past year (serious falls [7%; 95% CI 7%–7%]; fractures [5%; 95% CI 4%–5%]), polypharmacy (serious falls [5%; 95% CI 4%–5%]; fractures [5%; 95% CI 4%–5%]), an opioid prescription in the past month (serious falls [7%; 95% CI 6%–7%]; fractures [9%; 95% CI 8%–9%]), and diagnosis of alcohol use disorder (serious falls [4%; 95% CI 4%–5%]; fractures [8%; 95% CI 7%–8%]). Conclusions: This study confirms the contributions of risk factors important in the general population to both serious falls and fragility fractures among older PWH. Successful prevention programs for these outcomes should build on existing prevention efforts while including risk factors specific to PWH. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL‐23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL‐23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non‐responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL‐23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL‐17A and IL‐17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL‐23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy. [ABSTRACT FROM AUTHOR]

Background: Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose–response relationship between device-measured PA and incident type 2 diabetes. Methods: This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework. Results: The median follow-up period was 6.3 years (IQR: 5.7–6.8), with 591 participants developing type 2 diabetes. Compared to those achieving < 150 min/week of moderate PA, people achieving 150–300, 300–600 and > 600 min/week were at 49% (95% CI 62–32%), 62% (95% CI 71–50%) and 71% (95% CI 80–59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving < 25 min/week, individuals achieving 25–50, 50–75 and > 75 min/week were at 38% (95% CI 48–33%), 48% (95% CI 64–23%) and 64% (95% CI 78–42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively. Conclusions: PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction. Trial registration: The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011). [ABSTRACT FROM AUTHOR]

Purpose: We explored the accuracy of a urine-based epigenetic test for detecting upper tract urothelial carcinoma. Materials and Methods: Under an Institutional Review Board–approved protocol, urine samples were prospectively collected from primary upper tract urothelial carcinoma patients before radical nephroureterectomy, ureterectomy, or ureteroscopy between December 2019 and March 2022. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and 2 internal control loci using methylation-sensitive restriction enzymes coupled with quantitative polymerase chain reaction. Results were reported as the Bladder CARE Index score and quantitatively categorized as positive (>5), high risk (2.5-5), or negative (<2.5). The findings were compared with those of 1:1 sex/age-matched cancer-free healthy individuals. Results: Fifty patients (40 radical nephroureterectomy, 7 ureterectomy, and 3 ureteroscopy) with a median (IQR) age of 72 (64-79) years were included. Bladder CARE Index results were positive in 47, high risk in 1, and negative in 2 patients. A significant correlation was found between Bladder CARE Index values and tumor size. Urine cytology was available for 35 patients, of whom 22 (63%) results were false-negative. Upper tract urothelial carcinoma patients had significantly higher Bladder CARE Index values compared to the controls (mean 189.3 vs 1.6, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the Bladder CARE test for detecting upper tract urothelial carcinoma were 96%, 88%, 89%, and 96%, respectively. Conclusions: Bladder CARE is an accurate urine-based epigenetic test for the diagnosis of upper tract urothelial carcinoma, with much higher sensitivity than standard urine cytology. [ABSTRACT FROM AUTHOR]

Introduction: Hearing loss (HL) is considered a potentially modifiable risk factor for dementia. We aimed to examine the relationship between HL and incident dementia diagnosis in a province-wide population-based cohort study with matched controls. Methods: Administrative healthcare databases were linked to generate a cohort of patients who were aged ≥40 years at their first claimed hearing amplification devices (HAD) between April 2007 and March 2016 through the Assistive Devices Program (ADP) (257,285 with claims and 1,005,010 controls). The main outcome was incident dementia diagnosis, ascertained using validated algorithms. Dementia incidence was compared between cases and controls using Cox regression. Patient, disease, and other risk factors were examined. Results: Dementia incidence rates (per 1,000 person-years) were 19.51 (95% confidence interval [CI]: 19.26–19.77) and 14.15 (95% CI: 14.04–14.26) for the ADP claimants and matched controls, respectively. In adjusted analyses, risk of dementia was higher in ADP claimants compared with controls (hazard ratio [HR]: 1.10 [95% CI: 1.09–1.12, p < 0.001]). Subgroup analyses showed a dose-response gradient, with risk of dementia higher among patients with bilateral HADs (HR: 1.12 [95% CI: 1.10–1.14, p < 0.001]), and an exposure-response gradient, with increasing risk over time from April 2007-March 2010 (HR: 1.03 [95% CI: 1.01–1.06, p = 0.014]), April 2010-March 2013 (HR: 1.12 [95% CI: 1.09–1.15, p < 0.001]), and April 2013-March 2016 (HR: 1.19 [95% CI: 1.16–1.23, p < 0.001]). Conclusion: In this population-based study, adults with HL had an increased risk of being diagnosed with dementia. Given the implications of HL on dementia risk, understanding the effect of hearing interventions merits further investigation. [ABSTRACT FROM AUTHOR]

Background: Most older adults hospitalized with COVID-19 survive their acute illness. The impact of COVID-19 hospitalization on patient-centered outcomes, including physical function, cognition, and symptoms, is not well understood. To address this knowledge gap, we collected longitudinal data about these issues from a cohort of older survivors of COVID-19 hospitalization. Methods: We undertook a prospective study of community-living persons age ≥ 60 years who were hospitalized with COVID-19 from June 2020–June 2021. A baseline interview was conducted during or up to 2 weeks after hospitalization. Follow-up interviews occurred at one, three, and six months postdischarge. Participants completed comprehensive assessments of physical and cognitive function, symptoms, and psychosocial factors. An abbreviated assessment could be performed with a proxy. Additional information was collected from the electronic health record. Results: Among 341 participants, the mean age was 71.4 (SD 8.4) years, 51% were women, and 37% were of Black race or Hispanic ethnicity. Median length of hospitalization was 8 (IQR 6–12) days. All but 4% of participants required supplemental oxygen, and 20% required care in an intensive care unit or stepdown unit. At enrollment, nearly half (47%) reported at least one preexisting disability in physical function, 45% demonstrated cognitive impairment, and 67% were pre-frail or frail. Participants reported a mean of 9 of 14 (SD 3) COVID-19-related symptoms. At the six-month follow-up interview, more than a third of participants experienced a decline from their pre-hospitalization function, nearly 20% had cognitive impairment, and burdensome symptoms remained highly prevalent. Conclusions: We enrolled a diverse cohort of older adults hospitalized with COVID-19 and followed them after discharge. Functional decline was common, and there were high rates of persistent cognitive impairment and symptoms. Future analyses of these data will advance our understanding of patient-centered outcomes among older COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Background Acute undifferentiated fever (AUF) ranges from self-limiting illness to life-threatening infections, such as sepsis, malaria, dengue, leptospirosis and rickettsioses. Similar clinical presentation challenges the clinical management. This study describes risk factors for death in patients hospitalized with AUF in India. Methods Patients aged ≥5 y admitted with fever for 2–14 d without localizing signs were included in a prospective observational study at seven hospitals in India during 2011–2012. Predictors identified by univariate analysis were analyzed by multivariate logistic regression for survival analysis. Results Mortality was 2.4% (37/1521) and 46.9% (15/32) died within 2 d. History of heart disease (p=0.013), steroid use (p=0.011), altered consciousness (p<0.0001), bleeding (p<0.0001), oliguria (p=0.020) and breathlessness (p=0.015) were predictors of death, as were reduced Glasgow coma score (p=0.005), low urinary output (p=0.004), abnormal breathing (p=0.006), abdominal tenderness (p=0.023), leucocytosis (p<0.0001) and thrombocytopenia (p=0.001) at admission. Etiology was identified in 48.6% (18/37) of fatal cases. Conclusions Bleeding, cerebral dysfunction, respiratory failure and oliguria at admission, suggestive of severe organ failure secondary to systemic infection, were predictors of death. Almost half of the patients who died, died shortly after admission, which, together with organ failure, suggests that delay in hospitalization and, consequently, delayed treatment, contribute to death from AUF. [ABSTRACT FROM AUTHOR]

Background Depression is common in people with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), with biological and psychosocial mechanisms at play. Direct acting antivirals (DAA) result in high rates of sustained virologic response (SVR), with minimal side-effects. We assessed the impact of SVR on presence of depressive symptoms in the HIV-HCV coinfected population in Canada during the second-generation DAA era (2013–2020). Methods We used data from the Canadian CoInfection Cohort (CCC), a multicenter prospective cohort of people with a HIV and HCV coinfection, and its associated sub-study on food security. Because depression screening was performed only in the sub-study, we predicted Center for Epidemiologic Studies Depression Scale-10 classes in the CCC using a random forest classifier and corrected for misclassification. We included participants who achieved SVR and fit a segmented modified Poisson model using an interrupted time series design, adjusting for time-varying confounders. Results We included 470 participants; 58% had predicted depressive symptoms at baseline. The median follow-up was 2.4 years (interquartile range [IQR]: 1.0–4.5.) pre-SVR and 1.4 years (IQR: 0.6–2.5) post-SVR. The pre-SVR trend suggested depressive symptoms changed little over time, with no immediate level change at SVR. However, post-SVR trends showed a reduction of 5% per year (risk ratio: 0.95 (95% confidence interval [CI]:.94–.96)) in the prevalence of depressive symptoms. Conclusions In the DAA era, predicted depressive symptoms declined over time following SVR. These improvements reflect possible changes in biological pathways and/or better general health. If such improvements in depression symptoms are durable, this provides an additional reason for treatment and early cure of HCV. [ABSTRACT FROM AUTHOR]

Background: Critical illness often leads to persistent functional impairment among older Intensive Care Unit (ICU) survivors. Identification of high‐risk survivors prior to discharge from their ICU hospitalization can facilitate targeting for restorative interventions after discharge, potentially improving the likelihood of functional recovery. Our objective was to develop and validate a prediction model for persistent functional impairment among older adults in the year after an ICU hospitalization. Methods: The analytic sample included community‐living participants enrolled in the National Health and Aging Trends Study 2011 cohort who survived an ICU hospitalization through December 2017 and had a follow‐up interview within 1 year. Persistent functional impairment was defined as failure to recover to the pre‐ICU level of function within 12 months of discharge from an ICU hospitalization. We used Bayesian model averaging to identify the final predictors from a comprehensive set of 17 factors. Discrimination and calibration were assessed using area‐under‐the‐curve (AUC) and calibration plots. Results: The development cohort included 456 ICU admissions (2,654,685 survey‐weighted admissions) and the validation cohort included 227 ICU admissions (1,350,082 survey‐weighted admissions). In the development cohort, the median age was 81.0 years (interquartile range [IQR] 76.0, 86.0) and 231 (50.7%) participants were women; demographic characteristics were comparable in the validation cohort. The rates of persistent functional impairment were 49.3% (development) and 50.2% (validation). The final model included age, pre‐ICU disability, probable dementia, frailty, prior hospitalizations, vision impairment, depressive symptoms, and hospital length of stay. The model demonstrated good discrimination (AUC 71%, 95% confidence interval [CI] 0.66–0.76) and good calibration. When applied to the validation cohort, the model demonstrated comparable discrimination (AUC 72%, 95% CI 0.66–0.78) and good calibration. Conclusions: Application of the model prior to discharge from an ICU hospitalization may identify older adults at the highest risk of persistent functional impairment in the subsequent year, thereby facilitating targeted interventions and follow‐up. [ABSTRACT FROM AUTHOR]

Background Post-COVID conditions are characterised by persistent symptoms that negatively impact quality of life after SARS-CoV-2 diagnosis. While post-COVID risk factors and symptoms have been extensively described in localised regions, especially in the global north, post-COVID conditions remain poorly understood globally. The global, observational cohort study HVTN 405/HPTN 1901 characterises the convalescent course of SARS-CoV-2 infection among adults in North and South America and Africa. Methods We categorised the cohort by infection severity (asymptomatic, symptomatic, no oxygen requirement (NOR), non-invasive oxygen requirement (NIOR), invasive oxygen requirement (IOR)). We applied a regression model to assess correlations of demographics, co-morbidities, disease severity, and concomitant medications with COVID-19 symptom persistence and duration across global regions. Results We enrolled 759 participants from Botswana, Malawi, South Africa, Zambia, Zimbabwe, Peru, and the USA a median of 51 (interquartile range (IQR)=35-66) days post-diagnosis, from May 2020 to March 2021. 53.8% were female, 69.8% were 18-55 years old (median (md)=44 years old, IQR=33-58). Comorbidities included obesity (42.8%), hypertension (24%), diabetes (14%), human immunodeficiency virus (HIV) infection (11.6%) and lung disease (7.5%). 76.2% were symptomatic (NOR=47.4%; NIOR=22.9%; IOR=5.8%). Median COVID-19 duration among symptomatic participants was 20 days (IQR=11-35); 43.4% reported symptoms after COVID-19 resolution, 33.6% reported symptoms ≥30 days, 9.9% reported symptoms ≥60 days. Symptom duration correlated with disease severity (P<0.001, NIOR vs NOR; P=0.003, IOR vs NOR), lung disease (P=0.001), race (P<0.05, non-Hispanic Black vs White), and global region (P<0.001). Prolonged viral shedding correlated with persistent abdominal pain (odds ratio (OR) = 5.51, P < 0.05) and persistent diarrhoea (OR=6.64, P<0.01). Conclusions Post-COVID duration varied with infection severity, race, lung disease, and region. Better understanding post-COVID conditions, including regionally-diverse symptom profiles, may improve clinical assessment and management globally. [ABSTRACT FROM AUTHOR]

Background: The study objectives were: provide longitudinal data on upper aerodigestive tract function and late complications following IMRT for nasopharyngeal carcinoma, and elucidate factors that might predict a worse outcome. The hypotheses were: (1) Despite advances such as IMRT, radiation will cause significant functional decline and late complications that often progress or arise years after treatment. (2) Larger radiation volume will be associated with poorer outcomes. Methods: Longitudinal, observational cohort study of nasopharyngeal carcinoma patients with retrospective analysis of prospectively collected, population-based data. Late sequelae and validated measures of overall performance, speech, and swallowing were documented pre-treatment and 3,6,12, 24, 36 and ≥ 60-months post-treatment. Results: Forty-two patients treated curatively with radiation (N = 9) or chemoradiation (N = 33) were followed for a median 74 months. Functional outcomes showed an initial nadir at 3 months associated with acute effects of treatment, followed by initial recovery. There was subsequent functional decline years post-treatment with advancing dysphagia/aspiration, trismus, muscle spasm, and hypoglossal nerve palsy. Univariable regression analysis revealed that increasing high-dose radiation volumes (PTV 70 Gy) were associated with increased likelihood of less than solid diet (Performance Status Scale (PSS)—Normalcy of Diet score < 50; p = 0.04), and reduced PSS—Understandability of Speech (p = 0.005). The probability of poor outcome increased with time. Eleven percent of patients were tube feed dependent at ≥ 5 years. Conclusions: Despite improvements in radiation delivery, late effects of radiation remain common. Higher radiation volumes are associated with poorer outcomes that worsen over time. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is an effective treatment for depression, mania, and refractory schizophrenia. Its tolerability profile is established for acute treatment, but less is known regarding the effects of longer treatment courses, particularly on cognitive performance.Objectives: To assess the effect of the long-term ECT on cognition.Methods: We searched CINAHL, EMBASE, PsychInfo and Pubmed, for the period between January 1, 2010, and June 30, 2022, in English or French, for randomized controlled trials, prospective or retrospective studies of ECT continued for at least 2 months for the treatment of mood or schizophrenic disorders and which measured cognition before and at the end of treatment. Non-peer reviewed records were excluded. The Cochrane Risk of Bias tool was used to assess study quality. Classical meta-analyses, with heterogeneity statistics (tau2, I2) were complemented with three level-meta-analysis and Bayesian Meta-analyses.Results: Nine studies were included in the narrative and quantitative review. Controlled comparison at 6 months (k = 6, n = 334) and at 12 months (k = 3, n = 56), within-subject comparisons at 6 (k = 6, n = 218) and 12 months (k = 4, n = 147) showed no detrimental effect of maintenance or continuation ECT on cognition, with little to no heterogeneity. Bayesian analysis further confirmed that data better supported the no effects hypothesis.Limitations: Insufficient data resulted in imprecision in estimates.Conclusions: Continuation and maintenance ECT do not appear detrimental for cognitive performance. However, the low number of studies limit the interpretation of the results. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic led to measures that reduced social contact and support. We explored whether UK residents with more frequent or supportive social contact had fewer depressive symptoms during March−August 2020, and potential factors moderating the relationship. Methods: A convenience sample of UK dwelling participants aged ⩾18 in the internet-based longitudinal COVID-19 Social Study completed up to 22 weekly questionnaires about face-to-face and phone/video social contact frequency, perceived social support, and depressive symptoms using the PHQ-9. Mixed linear models examined associations between social contact and support, and depressive symptoms. We examined for interaction by empathic concern, perspective taking and pre-COVID social contact frequency. Results: In 71 117 people with mean age 49 years (standard deviation 15), those with high perceived social support scored 1.836 (1.801–1.871) points lower on PHQ-9 than those with low support. Daily face-to-face or phone/video contact was associated with lower depressive symptoms (0.258 (95% confidence interval 0.225–0.290) and 0.117 (0.080–0.154), respectively) compared to no contact. The negative association between social relationships and depressive symptoms was stronger for those with high empathic concern, perspective taking and usual sociability. Conclusions: We found during lockdown that those with higher quality or more face-to-face or phone/video contact had fewer depressive symptoms. Contact quality was more strongly associated than quantity. People who were usually more sociable or had higher empathy had more depressive symptoms during enforced reduced contact. The results have implications for COVID-19 and potential future pandemic management, and for understanding the relationship between social factors and mental health. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study analyzed 138,151 radical cystectomy patient encounters to determine which patient and facility characteristics are associated with discharge home and discharge to continued rehabilitation facilities. We used multivariate logistic regression to statistically analyze these datapoints while controlling for other variables. We found that older age, single/widowed marital status, female gender, increased Charlson Comorbidity Index, Medicaid, and Medicare insurance and open surgery are associated with Continued Rehabilitation Facility (CRF) discharge. Objective: To assess predictors of discharge disposition—either home or to a CRF—after undergoing RC for bladder cancer in the United States. Methods: In this retrospective, cohort study, patients were divided into two cohorts: those discharged home and those discharged to CRF. We examined patient, surgical, and hospital characteristics. Multivariable logistic regression models were used to control for selected variables. All statistical tests were two-sided. Patients were derived from the Premier Healthcare Database. International classification of disease (ICD)-9 (<2014), ICD-10 (≥2015), and Current Procedural Terminology (CPT) codes were used to identify patient diagnoses and encounters. The population consisted of 138,151 patients who underwent RC for bladder cancer between 1 January 2000 and 31 December 2019. Results: Of 138,151 patients, 24,922 (18.0%) were admitted to CRFs. Multivariate analysis revealed that older age, single/widowed marital status, female gender, increased Charlson Comorbidity Index, Medicaid, and Medicare insurance are associated with CRF discharge. Rural hospital location, self-pay status, increased annual surgeon case, and robotic surgical approach are associated with home discharge. Conclusions: Several specific patient, surgical, and facility characteristics were identified that may significantly impact discharge disposition after RC for bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research typically requires participants to enroll with a "study partner" (SP). Little is known about what predicts who steps into the SP role or whether the SP's relationship to the participant affects their reports of disease severity. Methods: Health and Retirement Study data (HRS), collected prior to the Aging, Demographics and Memory Study (ADAMS), was used to identify sociocultural factors that predict who serves as a SP in ADAMS. SP-reported outcomes were compared between three types of participant-SP relationships: spousal, adult child, and other. Results: Spouses (35%) and adult children (39%) were similarly likely to serve as SPs. Factors predicting who served differed. In multivariable analyses, adult children rated participants less impaired than spouses on measures of memory, judgment, and organizational abilities (p <.05). Conclusions: The participant-SP relationship has independent effects on the SP's reports of the severity of cognitive impairments. [ABSTRACT FROM AUTHOR]

Background: Studies on physical activity (PA) and mental health are largely limited to self-reported PA. This study aims to use prospective cohort data to investigate the association between device-measured PA and affective disorders.Methods: A total of 37,327 participants from UK Biobank who had not had any prior affective disorder diagnoses were included in this prospective cohort study. Wrist-worn accelerometers were used to measure total, light (LPA), moderate (MPA), and vigorous (VPA) PA. Associations between PA domains and affective disorders were analysed using penalised splines in Cox proportional hazard models. Analyses were adjusted for other intensity-specific PA and sociodemographic and lifestyle factors. Sensitivity analyses were conducted adjusting for body mass index and longstanding illnesses as well as excluding events in the first 2 years of follow-up. Preventable fractions for the population were estimated for MPA and VPA.Results: Over a median follow-up of 6.8 years, 1262 (3.4%) individuals were diagnosed with affective disorders. Replacing 30 min of sedentary behaviour in a week with MPA (HR 0.95, 95% CI 0.94-0.97) or VPA (HR 0.91, 95% CI 0.85-0.98) was associated with lower risk of affective behaviours, up to 500 and 120 min of MPA and VPA. Assuming causality, 5.14% and 18.88% of affective disorders could have been prevented if MPA ≥150 min/week and VPA ≥75 min/week were achieved, respectively, across the study population.Conclusions: Device-measured MPA and VPA were associated with lower risk of affective disorders. The potential mental health benefits of MPA continue to accrue above the current World Health Organization recommendation. [ABSTRACT FROM AUTHOR]

Objective: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks or very preterm birth at 28-32 weeks gestation).Design: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age.Setting: Infants born at a single Scottish hospital.Participants: 45 term-born, 42 very preterm and 16 extremely preterm infants.Outcomes: Cortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol.Results: Compared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/L, difference in means: -7.3 nmol/L, 95% CI -14.0 to -0.6) and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI -7.4 to 2.0) and diurnal slope at 4 months (difference in geometric means: -33.6%, 95% CI -62.0 to 16.0) did not differ significantly in infants born very preterm compared with infants born at term.Conclusions: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity and could contribute to later metabolic and neurodevelopmental phenotypes observed in this population. [ABSTRACT FROM AUTHOR]