Risk Difference Research Articles

Review: Risk Stratification of Patients With Ulcerative Colitis for Treatment With Tofacitinib

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Previously, a study of patients with rheumatoid arthritis (RA) aged ≥50 years with ≥1 additional cardiovascular risk factor (ORAL Surveillance) found increased rates of malignancies (excluding non-melanoma skin cancer), major adverse cardiovascular events (MACE), and venous thromboembolism with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to inform clinical decision-making via data review. Methods We reviewed ORAL Surveillance and tofacitinib UC clinical program data. Results In risk-enriched patients with RA in ORAL Surveillance, three differential risk factors were identified: age ≥65 years; current/past long-time smoking; atherosclerotic cardiovascular disease (ASCVD) history (MACE only). In patients with RA without differential risk factors, no risk differences in these safety outcomes with tofacitinib versus TNFi were detected. There are insufficient data on the risk with tofacitinib of safety outcomes in patients with UC with differential risk factors, but results highlighted that absolute risk of these safety outcomes with tofacitinib was low in patients with UC without differential risk factors, and similar to that for tofacitinib and TNFi in ORAL Surveillance patients without differential risk factors. Conclusions In the absence of prospective UC safety studies of sufficient size/duration, ORAL Surveillance results should be considered for UC as a precautionary approach. The differential risk factors for safety outcomes with tofacitinib versus TNFi (age ≥65 years and current/past long-time smoking or ASCVD history [MACE)]) provide a framework for an individualized risk factor-based approach to clinical decision-making on treatment with tofacitinib.

Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study

BackgroundPrevious research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.MethodsUsing 2005–2021 data from the National Alzheimer’s Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model.ResultsOf 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7).ConclusionsOur studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

Socioeconomic inequalities in adverse pregnancy outcomes in India: 2004-2019.

Although India has made substantial improvements in public health, it accounted for one-fifth of global maternal and neonatal deaths in 2015. Stillbirth, abortion, and miscarriage contribute to maternal and infant morbidity and mortality. There are known socioeconomic inequalities in adverse pregnancy outcomes. This study estimated changes in socioeconomic inequalities in rates of stillbirth, abortion, and miscarriage in India across 15 years. We combined data from three nationally representative health surveys. Absolute inequalities were estimated using the slope index of inequality and risk differences, and relative inequalities were estimated using the relative index of inequalities and risk ratios. We used household wealth, maternal education, and Scheduled Caste and Scheduled Tribe membership as socioeconomic indicators. We observed persistent socioeconomic inequalities in abortion and stillbirth from rates of 2004-2019. Women at the top of the wealth distribution reported between 2 and 5 fewer stillbirths per 1,000 pregnancies over the study time period compared to women at the bottom of the wealth distribution. Women who completed primary school, and those at the top of the household wealth distribution, had, over the study period, 5 and 20 additional abortions per 1,000 pregnancies respectively compared to women who did not complete primary school and those at the bottom of the wealth distribution. Women belonging to a Scheduled Caste or Scheduled Tribe had 5 fewer abortions per 1,000 pregnancies compared to other women, although these inequalities diminished by the end of the study period. There was less consistent evidence for socioeconomic inequalities in miscarriage, which increased for all groups over the study period. Despite targeted investments by the Government of India to improve access to health services for socioeconomically disadvantaged groups, disparities in pregnancy outcomes persist.

Effect of Perioperative Inhaled Tiotropium for patients with chronic Obstructive Pulmonary disease in Esophageal cancer surgery (EPITOPE): an open-label, randomized, parallel-group pilot study.

Chronic obstructive pulmonary disease (COPD) is a risk factor for pneumonia following esophagectomy. This study aimed to investigate the efficacy of perioperative inhaled tiotropium in patients with COPD undergoing esophagectomy. This open-label, randomized controlled trial randomly assigned 32 patients with COPD undergoing esophagectomy to conventional management or addition of tiotropium inhalation. The intervention group received tiotropium from two weeks before esophagectomy until the final evaluation one month after esophagectomy. The primary outcome was the incidence of pneumonia within 30 postoperative days. We also assessed the changes and the percentages from baseline in pulmonary function and walking distance of the incremental shuttle walking test to just before esophagectomy and final evaluation. Enrolled patients were randomly assigned to the control group (n = 18) and the intervention group (n = 14). Pneumonia was recorded in 4 (28.6%) and 5 (27.8%) patients in the intervention and control groups, respectively (risk difference: 0.8%, 95% confidence interval: - 30.6 to 32.2). The intervention group demonstrated a significant improvement in pulmonary function and walking distance preoperatively. Further, the pulmonary function test was significantly better preoperatively in the intervention group than in the control group. Postoperatively, pulmonary function deterioration was more significant in the control group than in the intervention group. Preoperative tiotropium inhalation significantly improved pulmonary function and exercise tolerance in patients with COPD undergoing esophagectomy. The perioperative tiotropium did not reduce pneumonia after esophagectomy, but it may contribute to patient recovery by reducing postoperative pulmonary function deterioration.

Prevalence, mortality and risk factors for self-reported COPD among smokers and never smokers, NHANES 1999-2018.

Cigarette smoke is the main risk factor for chronic obstructive pulmonary disease (COPD), but 25% to 50% of cases occur in non-smokers. In the US, limited recent national data compare COPD prevalence between smokers and never smokers. Furthermore, our study seeks to explore the prevalence and mortality of self-reported COPD among smokers (including current smokers and ex-smokers) and never smokers in the US from 1999 to 2018, and to identify the risk factors and differences. This cross-sectional analysis used data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Age-standardized prevalence of self-reported COPD among current smokers, ex-smokers, and never smokers was calculated using sample weights and 2010 US Census estimates. Risk factors were evaluated through weighted logistic regression models. Subsequently, participants who enrolled in the study cohort were followed until 31 December 2019, to determine all-cause mortality rates. Between 1999 and 2018, the weighted prevalence of COPD among current smokers, ex-smokers, and never smokers in the U.S. was 12.6%, 9.6%, and 4.1%, respectively. The mortality rates observed were 21.1% among current smokers with COPD, 29% among ex-smokers with COPD, and 12% among never smokers with COPD. Over this period, among the general population in the U.S., the proportion of current smokers has declined, the proportion of never smokers has increased, and the proportion of ex-smokers has remained relatively stable. From 1999 to 2018, COPD prevalence rose from 13.7% to 21.9% among current smokers, stayed at 10.1% among ex-smokers, and dropped from 4.9% to 3.3% among never smokers. Independent risk factors for COPD across all groups included being female, older, and lower income. In particular, US citizens and non-Hispanic Whites (among ex-smokers and never smokers) were at higher risk compared to their counterparts. The prevalence and all-cause mortality of COPD among current smokers and ex-smokers remain elevated. Although the prevalence of COPD among never smokers is gradually declining, it continues to be significant, thereby maintaining a substantial burden of disease. Furthermore, common independent risk factors for COPD across current smokers, ex-smokers, and never smokers include female gender, advanced age, lower income, and deviations from normal body weight whether overweight or underweight.

Novel epigenetic biomarkers for hematopoietic cancer found in twins.

This article aims to identify epigenetic markers and detect early development of hematopoietic malignancies through an epigenome wide association study of DNA methylation data. This register-based study includes 1,085 Danish twins with 31 hematopoietic malignancies and methylation levels from 450,154 5'-C-phospate-G-3' (CpG) sites. Associations between methylation levels and incidence of hematopoietic malignancy is studied through time-to-event regression. The matched case-cotwin design, where one twin has a malignancy and the cotwin does not, is applied to enhance control for unmeasured shared confounding and false discoveries. Predictive performance is validated in the independent Older Finnish Twin Cohort. We identified 67 epigenetic markers for hematopoietic malignancies of which 12 are linked to genes associated with hematologic malignancies. For some markers, we discovered a 2-3-fold relative risk difference for high versus low methylation. The identification of these 67 sites enabled the formation of a predictor demonstrating a cross-validated time-varying area under the curve (AUC) of 92% 3 years after individual blood sampling and persistent performance above 70% up to 6 years after blood sampling. This predictive performance was to a large extent recovered in the validation sample showing an overall Harrell's C of 73%. In conclusion, from a large population representative twin study on hematopoietic cancers, novel epigenetic markers were identified that may prove useful for early diagnosis.

Effects of Mediterranean diet during pregnancy on the onset of overweight or obesity in the offspring: a randomized trial.

The PREMEDI study was designed to assess the efficacy of nutritional counseling aimed at promoting Mediterranean Diet (MD) during pregnancy on the incidence of overweight or obesity at 24 months in the offspring. PREMEDI was a parallel-arm randomized-controlled trial. 104 women in their first trimester of pregnancy were randomly assigned in a 1:1 ratio to standard obstetrical and gynecological care alone (CT) or with nutritional counseling promoting MD. Women enrolled in the MD arm were provided with 3 sessions of nutritional counseling (one session per trimester). The main outcome was the proportion of overweight or obesity among the offspring at the age of 24 months. Maternal MD-adherence and weight gain during pregnancy were also evaluated. Lastly, the evaluation of epigenetic modulation of metabolic pathways in the offspring was analyzed in cord blood. Five women in the MD arm and 2 in the CT arm were lost to follow-up, so a total of 97 completed the study. At 24 months, children of MD mothers were less likely to have overweight or obesity than those of the CT mothers (6% vs. 33%, absolute risk difference = -27%, 95% CI -41% to -12%, p < 0.001; number needed to treat 3, 95% CI 2 to 8, intention to treat analysis). A significantly higher increase of MD-adherence during the trial was observed in the MD arm compared to the CT arm. A similar body weight gain at the end of pregnancy was observed in the two arms. The mean (SD) methylation rate of the leptin gene in cord blood was 30.4 (1.02) % and 16.9 (2.99) % in the CT and MD mothers, respectively (p < 0.0001). MD during pregnancy could be an effective strategy for preventing pediatric overweight or obesity at 24 months. This effect involves, at least in part, an epigenetic modification of leptin expression.

Surgery Versus Thrombolytic Therapy for the Management of Left-Sided Prosthetic Valve Thrombosis Without Hemodynamic Compromise: A Systematic Review and Meta-Analysis.

The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta-analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT. We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left-sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow-up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74-1.79; ζ2=0.89; P<0.001) versus cardiac surgery. Rates of both transient ischemic attack and non-central nervous system embolism were higher in the thrombolysis group (P=0.002 and P=0.02, respectively). Treatment success, major bleeding, and stroke were similar between groups. Sensitivity analysis including studies that used low-dose or slow-infusion thrombolysis showed that the mortality rate was lower, and treatment success was higher, in patients referred to systemic thrombolysis, with similar rates of other secondary outcomes. There is evidence to suggest that thrombolysis might be the preferred option for the management of PVT without cardiogenic shock, pending future randomized controlled trials or larger observational studies.

The impact of cancer-related diarrhea on changes in cancer therapy.

The impact of cancer-related diarrhea (CRD) on changes in cancer therapy remains poorly characterized despite its prevalence. We performed a longitudinal observational study using IQVIA PharMetrics Plus claims data. Patients included adults with CRD identified by diagnosis codes or pharmacy claims and compared their outcomes to matched (1:1) patients without CRD. Treatment parameters (discontinuation, persistence, augmentation, dose titration, adherence) were evaluated and stratified for the first cancer therapy (chemotherapy vs. targeted therapy vs. both). A multivariate Cox proportional hazards model was used to estimate the difference in risk of each treatment parameter between cohorts, adjusting for cancer type, therapy, and comorbidities. We identified 104,135 matched pairs of patients with solid (n = 94,411) or hematologic cancers (n = 9,724) receiving chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both (n = 5,313). Patients with CRD discontinued therapy more frequently than those without CRD (chemotherapy [81.5% vs. 62.3%], targeted therapy [69.2% vs. 64.3%], both [96.0% vs. 85.5%], p < 0.0001). The overall proportion of discontinuation was higher (82.4% vs. 64.6%, p < 0.0001), including a higher risk of discontinuation (HR = 1.40, p < 0.001) for patients with CRD. The mean time to discontinuation (59.6 ± 54.1 vs. 68.3 ± 76.6days), switch (72.0 ± 48.6 vs. 96.9 ± 84.0days), persistence (95.1 ± 98.1 vs. 154.3 ± 142.7days), and adherence (25.5% ± 37.2 vs. 47.9 ± 41%) were all lower (p < 0.0001) among patients with CRD. Patients who develop CRD undergo significant and clinically impactful index treatment discontinuation, treatment switching, and have lower adherence and persistence of anticancer therapy compared to patients without CRD. Strategies to control CRD to optimize cancer therapy are urgently needed.

Predator exposure early in life shapes behavioral development and individual variation in a clonal fish

Predation risk is one of the most important factors generating behavioral differences among populations. In addition, recent attention focusses on predation as a potential driver of patterns of individual behavioral variation within prey populations. Previous studies provide mixed results, reporting either increased or decreased among-individual variation in response to risk. Here, we take an explicit developmental approach to documenting how among-individual variation develops over time in response to predator exposure, controlling for both genetic and experiential differences among individuals. We reared juveniles of naturally clonal Amazon mollies, Poecilia formosa, either with or without a predator visible during feedings over 4 weeks and analyzed activity during feedings, time spent feeding and number of visits to the feeding spot. (I) Predator-exposed fish did not differ from control fish in average feeding behavior, but they were less active during feeding trials. (II) In the absence of the predator, substantial changes in among-individual variation over time were detected: among-individual differences in feeding duration increased whereas differences in activity decreased, but there were no changes in feeder visits. In contrast, in the presence of a predator, among-individual variation in all three behaviors was stable over time and often lower compared to control conditions. Our work suggests that predation risk may have an overall stabilizing effect on the development of individual variation and that differences in predation risk may well lead to population-wide differences in among-individual behavioral variation.

Short-term outcomes in infants following general anesthesia with low-dose sevoflurane/dexmedetomidine/remifentanil versus standard dose sevoflurane (The TREX trial).

The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups. There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae. These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.

Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

Risk of Venous Thromboembolism After Total Knee Arthroplasty in Patients with Obstructive Sleep Apnea: Results from a National Cohort.

Obstructive sleep apnea (OSA) is a prevalent condition associated with many comorbidities. However, establishing the independent impact of OSA on specific health outcomes can be challenging without access to a substantial patient cohort. This study aimed to investigate whether a diagnosis of OSA was independently associated with venous thromboembolism (VTE) after total knee arthroplasty (TKA). In this retrospective cohort study, we interrogated the TriNetX Analytics Research Network, a large database comprising the billing claims and electronic health record-derived data of >117 million patients. Using Current Procedural Terminology (CPT) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes, we identified US adult patients who underwent TKA between January 1, 2013 and January 1, 2023, with and without preexisting OSA (and ≥2 OSA occurrences overall). We then analyzed the 1-month postoperative incidence of VTE as a composite outcome of deep vein thrombosis (DVT) and pulmonary embolism (PE) incidence, as well as cerebrovascular accident (CVA), myocardial infarction (MI), and DVT and PE individually. Baseline demographic and comorbidity covariates were incorporated into a 1:1 propensity score-matched analysis to clarify the independent effect of OSA. During the 10-year study period, a total of 197,460 patients underwent TKA. Of these, 27,976 met the criteria for inclusion in the OSA cohort, while 150,830 had no documented history of OSA. In the initial analysis, OSA was significantly associated with the primary outcome (DVT/PE) as well as all secondary outcomes (CVA, MI, and individually with DVT and PE) at 1 month postsurgery. After generating propensity score matched cohorts, DVT/PE remained significantly associated with OSA, with an absolute risk difference of 0.7% (odds ratio [OR], 1.19, confidence interval [CI], 1.1-1.3, P < .001), as were the secondary outcomes of DVT (OR, 1.11, CI, 1.0-1.2, P = .030) and PE (OR, 1.41, CI, 1.2-1.6, P < .001). In this study encompassing a nationally representative sample of TKA patients, OSA was associated with increased incidence of VTE at 1 month postoperatively, an association that persisted after the generation of matched cohorts. While limitations related to the lack of patient-level data, disease severity, and therapy adherence should be acknowledged, our large sample size enabled us to factor many baseline characteristics into our analysis, reinforcing the association of these findings. Prospective work is needed on the impact of modulating factors such as anticoagulation regimen and positive airway pressure therapy on these outcomes.

Anticoagulation for the Prevention of Arterial Thromboembolism in Cancer Patients by Primary Tumor Site: A Systematic Review and Meta-Analysis of Randomized Trials.

Incidence of arterial thromboembolism (ATE) among ambulatory cancer patients varies by primary tumor site. However, it is unclear whether this alters the benefit-to-harm profile of prophylactic anticoagulation for ATE prevention. Therefore, we systematically evaluated the efficacy and safety of anticoagulants for ATE prevention among ambulatory cancer patients according to the primary tumor site. We conducted a systematic review using Medline, Embase, SCOPUS, and CENTRAL, and included randomized trials comparing prophylactic anticoagulation to no anticoagulation among ambulatory cancer patients who initiated tumor-directed systemic therapy. Incidence of symptomatic ATE (acute ischemic stroke, acute myocardial infarction or peripheral artery occlusion) and major bleeding, as well as risk differences (RDs) attributable to anticoagulation were meta-analyzed by primary tumor site using random-effects modeling. We included 10 randomized controlled trials with 9,875 patients with follow-up ranging from 3.3 to 68 (median 6.6) months. While prophylactic anticoagulation did not reduce ATE risks overall (RD -0.49%; 95% CI -0.49% to 0.01%; I2=0%), it conferred a protective effect among pancreatic cancer patients (RD -3.2%; 95%CI -5.7% to -0.8%; I2=0%) without a detectable increase in major bleeding (RD -1.4%; 95% CI -4.6% to 1.8%; I2=0%). Prophylactic anticoagulation was not associated with ATE risk reduction in other tumor sites. Based on available evidence, prophylactic anticoagulation did not reduce ATE risk among ambulatory cancer patients overall. However, we observed lower incidence of ATE among pancreatic cancer patients randomized to receive anticoagulation. Prophylactic anticoagulant use to reduce ATEs in pancreatic cancer should be evaluated in future research.

Canadian beach cohort study: protocol of a prospective study to assess the burden of recreational water illness

BackgroundRecreational water activities at beaches are popular among Canadians. However, these activities can increase the risk of recreational water illnesses (RWI) among beachgoers. Few studies have been conducted in Canada to determine the risk of these illnesses. This protocol describes the methodology for a study to determine the risk and burden of RWI due to exposure to fecal pollution at beaches in Canada.MethodsThis study will use a mixed-methods approach, consisting of a prospective cohort study of beachgoers with embedded qualitative research. The cohort study involves recruiting and enrolling participants at public beaches across Canada, ascertaining their water and sand contact exposure status, then following-up after seven days to determine the incidence of acute RWI outcomes. We will test beach water samples each recruitment day for culture-based E. coli, enterococci using rapid molecular methods, and microbial source tracking biomarkers. The study started in 2023 and will continue to 2025 at beaches in British Columbia, Manitoba, Ontario, and Nova Scotia. The target enrollment is 5000 beachgoers. Multilevel logistic regression models will be fitted to examine the relationships between water and sand contact and RWI among beachgoers. We will also examine differences in risks by beachgoer age, gender, and beach location and the influence of fecal indicator bacteria and other water quality parameters on these relationships. Sensitivity analyses will be conducted to examine the impact of various alternative exposure and outcome definitions on these associations. The qualitative research phase will include focus groups with beachgoers and key informant interviews to provide additional contextual insights into the study findings. The study will use an integrated knowledge translation approach.DiscussionInitial implementation of the study at two Toronto, Ontario, beaches in 2023 confirmed that recruitment is feasible and that a high completion rate (80%) can be achieved for the follow-up survey. While recall bias could be a concern for the self-reported RWI outcomes, we will examine the impact of this bias in a negative control analysis. Study findings will inform future recreational water quality guidelines, policies, and risk communication strategies in Canada.

Tailoring nonsurgical therapy for elderly patients with head and neck squamous cell carcinoma: A deep learning-based approach.

To assess deep learning models for personalized chemotherapy selection and quantify the impact of baseline characteristics on treatment efficacy for elderly head and neck squamous cell carcinoma (HNSCC) patients who are not surgery candidates. A comparison was made between patients whose treatments aligned with model recommendations and those whose did not, using overall survival as the primary metric. Bias was addressed through inverse probability treatment weighting (IPTW), and the impact of patient characteristics on treatment choice was analyzed via mixed-effects regression. Four thousand two hundred seventy-six elderly HNSCC patients in total met the inclusion criteria. Self-Normalizing Balanced individual treatment effect for survival data model performed best in treatment recommendation (IPTW-adjusted hazard ratio: 0.74, 95% confidence interval [CI], 0.63-0.87; IPTW-adjusted risk difference: 9.92%, 95% CI, 4.96-14.90; IPTW-adjusted the difference in restricted mean survival time: 16.42 months, 95% CI, 10.83-21.22), which surpassed other models and National Comprehensive Cancer Network guidelines. No survival benefit for chemoradiotherapy was seen for patients not recommended to receive this treatment. Self-Normalizing Balanced individual treatment effect for survival data model effectively identifies elderly HNSCC patients who could benefit from chemoradiotherapy, offering personalized survival predictions and treatment recommendations. The practical application will become a reality with further validation in clinical settings.

Site-based and Digital Cohort Participation Among Transgender Women in the Eastern and Southern USA: Findings from the LITE Study.

Transgender women (TW) are highly burdened by HIV. There is increasing interest in digital (i.e., through internet-based interfaces) HIV research; yet few studies have assessed potential biases of digital compared to site-based data collection. This study examined differences in characteristics between TW participating via site-based versus digital-only modes in an HIV incidence cohort. Between March 2018-Aug 2020, a multisite cohort of 1,312 adult TW in the eastern and southern USA was enrolled in site-based and exclusively digital modes. We evaluated differences in baseline demographics, socio-structural vulnerabilities, healthcare access, gender affirmation, mental health, stigma, social support, and HIV acquisition risk comparing site-based vs digital modes using chi square tests and Poisson regression modeling with robust standard errors. The overall median age was 28 (interquartile range=23-35) years and over half identified as people of color (15% Black, 13% Multiracial, 12% Another Race, 18% Latina/e/x). A higher proportion of site-based (vs. digital mode) participants resided in the Northeast, were younger, identified as people of color, experienced socio-structural vulnerabilities, had a regular healthcare provider, received medical gender affirmation, endorsed mental health symptoms and stigma, reported HIV acquisition risk but also greater experience with biomedical HIV prevention (pre-exposure and post-exposure prophylaxis), and had larger social networks (all p<0.05). Site-based and digital approaches enrolled TW with different demographics, life experiences, and HIV acquisition risks. A hybrid cohort model may achieve a more diverse and potentially representative sample of TW than either site-based or online cohorts alone for HIV research.

Unveiling the female experience through adult mortality and survivorship in Milan over the last 2000 years

This study challenges historical paradigms using a large-scale integrated bioarchaeological approach, focusing on the female experience over the last 2,000 years in Milan, Italy. Specifically, 492 skeletons from the osteological collection of Milan were used to elucidate female survivorship and mortality by integrating bioarchaeological and paleopathological data, paleoepidemiological analyses, and historical contextualization. Findings revealed changes in female longevity, with a notable increase from Roman to contemporary eras, albeit plateauing in the Middle Ages/modern period. Significant sex-specific differences in mortality risk and survivorship were observed: females had higher mortality risk and lower survivorship in the Roman (first-fifth century AD) and Modern (16th-18th century AD) eras, but this trend reversed in the contemporary period (19th-20th century AD). Cultural and social factors negatively impacted female mortality in Roman and modern Milan, while others buffered it during the Middle Ages (sixth-15th century AD). This study underscored the importance of bioarchaeological inquiries in reconstructing the past, providing answers that may challenge historical assumptions and shedding light on how the interplay of cultural, social, and biological factors shaped the female experience across millennia.

Comparative effectiveness of 6x R-CHOP21 versus 6x R-CHOP21 + 2 R for patients with advanced-stage diffuse large B-cell lymphoma

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014–2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72–1.09) and OS (HR = 0.93; 95% CI, 0.73–1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, −0.4%−34.1% and OS = 12.1%; 95% CI, −5.4–29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research.

Defining the clinical benefits of adding a neurokinin-1 receptor antagonist to control chemotherapy-induced nausea and vomiting in moderately emetogenic chemotherapy: a systematic review and meta-analysis of the clinical practice guidelines for antiemesis 2023 from the Japan society of clinical oncology.

Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC). We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT3RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model. From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events. Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy.