Prospective Cohort Analysis Research Articles

Transcatheter Valve Repair for TricuspidRegurgitation: 1-Year Results from a Large European Real-World Registry.

Tricuspid valve transcatheter edge-to-edge repair has emerged as a valuable treatment option for patients with severe tricuspid regurgitation (TR). This study aims to investigate the safety and effectiveness of the PASCAL transcatheter valve repair system in treating severe TR in a real-world patient population. The PASTE (PASCAL for Tricuspid Regurgitation-a European registry) study is an investigator-initiated, multicenter, retrospective, and prospective observational cohort analysis conducted across 16 European heart valve centers including consecutive patients treated with the PASCAL transcatheter valve repair system from February 2019 to November 2023. Echocardiographic assessments were performed at baseline, discharge, and follow-up, and were subjected to centralized analysis. The study included 1,059 high-risk patients (mean age 79 ± 9 years; 53% female; TRI-SCORE risk 23% ± 18%; 87% NYHA functional class III/IV) with multiple comorbidities. Severe or higher graded TR was observed in 96% of patients. Intraprocedural success according to Tricuspid Valve Academic Research Consortium criteria was achieved in 85%, and TR reduced to ≤moderate in 87%. Independent predictors for a postprocedure residual TR of >moderate were coaptation gaps≥8mm (OR: 1.67; 95%CI: 1.03-2.72; P=0.038), tenting height≥10mm (OR: 2.18; CI: 1.30-3.65; P=0.003), the presence of a transvalvular lead (OR: 1.91; 95% CI: 1.19-3.05; P=0.007), right ventricular dilatation >42mm (OR: 3.35; 95% CI: 1.37-9.1; P=0.009) and massive/torrential TR at baseline (OR: 4.59; 95% CI:2.35-8.96; P< 0.001). At 1 year, 83% of patients showed ≤moderate TR. Significant clinical improvements included enhanced NYHA functional class (66% class I/II vs 17% at baseline; P< 0.001). Patients treated with the first-generation PASCAL system (n = 570) and with the new PASCAL Precision system (n = 489) had similar clinical profiles and TR severity at baseline. However, the Precision cohort showed greater TR reduction to trace/mild (63% vs 49%; P< 0.001), shorter procedure times (median 93minutes [Q1-Q3: 69-130 minutes] vs 120minutes [Q1-Q3: 82-165 minutes]; P< 0.001), and higher clinical success rates according to the Tricuspid Valve Academic Research Consortium at 30days and 1 year (87% vs 81% [P=0.021] and 56% vs 50% [P=0.044], respectively). Higher center experience (≥21 patients/year) resulted in higher intraprocedural and clinical success. The PASCAL system effectively treats severe TR in high-risk patients, offering sustained TR reduction and significant clinical improvements at 1-year follow-up. (PASCAL for Tricuspid Regurgitation-a European registry [PASTE]; NCT05328284).

Prolonged exposure to air pollution and risk of acute kidney injury and related mortality: a prospective cohort study based on hospitalized AKI cases and general population controls from the UK Biobank

BackgroundPrevious investigations identified a connection between air pollution and kidney diseases. Nevertheless, there is a lack of comprehensive evidence on the long-term risks posed by air pollution with respect to acute kidney injury (AKI) and AKI-related death.MethodsThis prospective cohort analysis included 414,885 UK Biobank (UKB) participants who did not exhibit AKI at the study’s outset. AKI was defined based on ICD-10 codes recorded for hospitalized patients. Cox proportional hazards models were used to assess the association between prolonged exposure to air pollutants (particulate matter with diameters of 2.5 micrometers or less (PM2.5), between 2.5 and 10 micrometers (PM2.5−10), and 10 micrometers or less (PM10), along with nitrogen dioxide (NO2) and nitrogen oxides (NOx)) and the risk of AKI and AKI-related death, adjusting for potential confounders including sex, age, ethnicity, education, income, lifestyle factors, and relevant clinical covariates. Restricted cubic splines were applied to evaluate non-linear dose-response relationships, and stratified analyses were performed to explore potential effect modification across subgroups.ResultsOver an average follow-up duration of 11.7 years, 14,983 cases of AKI and 326 cases of AKI-related death were diagnosed. Quartile analysis showed individuals exposed to higher levels of these air pollutants had a significantly higher risk of developing AKI and AKI-related death compared to those in the lowest quartile (all P < 0.05). The RCS curves depicting the relationship between PM2.5, PM2.5−10, PM10, NO2, NOx, and the risk of AKI showed a significant departure from linearity (P for non−linearity < 0.05), while the relationships between PM2.5, NO2, NOx, and the risk of AKI-related death did not exhibit a significant departure from linearity (P for non−linearity > 0.05). Sensitivity analyses confirmed the robustness of our findings.ConclusionOur study reveals a direct association between prolonged air pollution exposure and elevated risks of both AKI and AKI-related death. These findings offer scientific validation for the adoption of environmental and public health measures directed towards the reduction of air pollution. Such initiatives could potentially ease the impact associated with AKI and AKI-related death.

Comparison of short term recovery in patients with midportion Achilles tendinopathy with varying degrees of kinesiophobia treated with the Silbernagel protocol: A prospective single cohort analysis

ObjectiveTo assess short term recovery between individuals with Achilles tendinopathy with varying degrees of kinesiophobia when treated with the Silbernagel protocol. Secondarily to investigate short term change in degree of kinesiophobia. DesignProspective single cohort analysis. SettingUniversity/Clinical. Participants116 participants with midportion Achilles tendinopathy were grouped from their baseline Tampa Scale of Kinesiophobia (TSK) score: Low (≤33), Medium (34–41), and High (≥42). Main outcome measuresSymptom severity, Achilles tendon structure, and function were assessed at baseline and 8-weeks following initiation of the Silbernagel protocol. Differences in recovery between TSK groups were analyzed. ResultsNo group by time interactions were observed for symptoms, structure, or function. A significant interaction of group by time was observed for TSK score. The Medium (n = 66) and High (n = 28) TSK groups significantly decreased TSK score after 8 weeks by 2.4 and 4.4 points respectively while the Low TSK group (n = 22) did not change. ConclusionThere were no differences in short term recovery of symptoms, Achilles tendon structure, and function in individuals with midportion Achilles tendinopathy treated with the Silbernagel protocol regardless of baseline degree of kinesiophobia. Those with moderate and high levels of kinesiophobia at baseline decreased TSK score in the short term.

Assessing the role of dietary acid load in the development of hypertensive disorders during pregnancy: uncovering the association through prospective cohort analysis

BackgroundHypertensive disorders of pregnancy (HDPs) are common complications encountered in pregnancy that affect between 5% and 15% of pregnancies worldwide. Some studies have associated adherence to a diet with a high acid load with an increased risk of HDPs. This study investigates the association between Dietary Acid Load (DAL) and the incidence of preeclampsia, chronic hypertension (HTN), and gestational hypertension (GHTN).MethodsPregnant women aged 18 to 45 in the first trimester of pregnancy were selected and followed up until delivery. Diet was evaluated using a 168-question semi-quantitative food frequency questionnaire (FFQ). After calculating the DAL score, the inverse probability weight of the propensity scores, estimated from augmented generalized models, was used to obtain a causal risk ratio (RR) adjusted for potential confounders.ResultsOut of 1,856 women, 92 (4.95%) developed preeclampsia. The potential renal acid load (PRAL) score ranged from − 16.14 to 0.58, while the net endogenous acid production (NEAP) score ranged from 34.61 to 50.15. Multivariable analysis revealed a significant association between PRAL and preeclampsia in the first (aRR: 1.87, 95% CI: 1.01, 3.49, p = 0.048) and third (aRR: 2.01, 95% CI: 1.07, 3.81, p = 0.030) quartiles compared to the reference group (Q2). No significant linear association was found in continuous analyses. For chronic HTN, significant associations were observed in the first (aRR: 2.56, 95% CI: 1.21, 5.42, p = 0.014) and fourth (aRR: 4.79, 95% CI: 2.37, 9.71, p < 0.001) PRAL quartiles, with similar findings for NEAP. Continuous analysis showed a significant linear association between both PRAL and NEAP scores and chronic HTN. Regarding GHTN, significant associations were found in the first (aRR: 1.48, 95% CI: 1.02, 2.16, p = 0.041) and fourth (aRR: 1.88, 95% CI: 1.31, 2.70, p = 0.001) PRAL quartiles, and in Q4 for NEAP (aRR: 1.56, 95% CI: 1.10, 2.21, p = 0.012), with no significant linear association in continuous analysis.ConclusionExtremes in DAL, as indicated by PRAL and NEAP, are associated with an increased risk of preeclampsia, chronic HTN, and GHTN, particularly in the highest and lowest quartiles. These findings highlight the potential impact of DAL on HDPs.

Pregnancy-related hormonal changes and thyroid growth: do they have an impact on the higher incidence of differentiated thyroid cancer in women?

To analyze whether pregnancy could play a role in the higher prevalence of differentiated thyroid carcinoma (DTC) in women. Estrogens strongly modify thyroid economy by increasing iodine clearance, thyroid hormone requirement and production. Human chorionic gonadotropin (hCG) contributes to the increased thyroid hormone synthesis. Both estrogens and hCG can interfere with the regulation of thyroid volume and with thyroid nodule development and progression. The potential effect of hCG is exclusively related to its weak agonistic activity on TSH receptor. Estrogen implication on normal and nodule-derived thyrocyte growth has been demonstrated in vitro and in animal models. Furthermore, there is solid clinical evidence showing a promoting effect of pregnancy on thyroid volume and nodule development. Two metanalysis, one including retrospective and another prospective observational studies, failed to show an association between pregnancy and DTC. A large pooled prospective analysis using multivariable-adjusted Cox proportional hazard models did not demonstrate an association between DTC and parity. Similarly, no association between PTC occurrence and parity was observed in a prospective cohort analysis by linkage to the statewide Surveillance, Epidemiology, and End Results (SEER). The presently available evidence does not support an involvement of pregnancy in DTC etiology.

Prognostic Impact of HER2 Low Status in Male Breast Cancer: Prospective Cohort Analysis.

Male breast cancer (MBC) is a rare disease, and the potential influence of low expression of human epidermal growth factor receptor 2 (HER2 low) remains unexplored. In this prospective cohort study, we evaluated 870 patients treated for MBC between May 2009 and June 2023 to assess HER2 low status and its prognostic implications. With a median follow-up of 43 months (range 1-175 months), 659 eligible patients were categorized into three groups based on HER2 status: 501 (76%) HER2 low, 81 (12.3%) HER2 zero, and 77 (11.7%) HER2 positive. HER2 positivity correlated with younger age, higher proliferation index, non-specific type histology, lymphovascular invasion (LVSI), and low differentiation grade. Notably, all these parameters were equally distributed between the HER2 zero and HER2 low groups. Additionally, HER2 positivity was significantly associated with increased occurrences of regional and distant lymph nodes and pulmonary metastases. However, no statistically significant difference was observed between HER2 zero and HER2 low. Disease-free and overall survival showed no significant disparities between the groups. Our findings suggest that HER2 low status is frequently detected in MBC. Despite this, HER2 low did not correlate with clinical and pathological parameters, nor did it impact patients' survival.

Preoperative Osteoporosis Is Associated with Increased Healthcare Utilization and Compromised Pain and Function Improvement after Primary Total Hip Arthroplasty: A Prospective Cohort Analysis

Osteoporosis (OP) has been linked to complications after total hip arthroplasty (THA), but its impact on healthcare utilization and patient-reported outcomes remains unclear. This study aimed to evaluate the association between: 1) pre-THA OP and healthcare utilization as well as patient-reported pain and function outcome measures; and 2) Dual Energy X-ray Absorptiometry (DEXA) scan-based T-scores and the aforementioned outcomes. A retrospective analysis of prospectively collected data of primary THA (2015 to 2018) was performed (n = 5,321) from a validated academic institutional database of a large North American tertiary health care system; of which 4,074 (76.6%) completed one-year follow-up. Outcomes included prolonged length of stay [LOS] > 3 days, discharge disposition, 90-day readmission, and one-year reoperation, as well as Hip Disability and Osteoarthritis Outcome Score (HOOS]) Pain, HOOS-function (PS), and minimal clinically important difference thresholds (MCID), and satisfaction. The prevalence of OP pre-THA was 56.9%, of which 39.8% were not prescribed OP medications and 15.3% had a DEXA scan. Compared to those who did not have OP, those who had OP were independently associated with higher odds of prolonged LOS, non-home discharge, 90-day readmission, and 1-year reoperation (P < 0.005). Furthermore, they had significantly higher odds of failing to achieve MCID (odds ratio (OR): 1.41 (95% confidence interval (CI): 1.06 to 1.89)) for HOOS-PS and satisfaction (OR: 1.5 (95% CI: 1.16 to 1.93)) at 1-year. Higher T-scores were associated with lower odds of prolonged LOS, non-home discharge, failure to achieve MCID in HOOS-Pain, and HOOS-PS. Over half of patients had OP, however, only 15.3% of patients had a DEXA scan prior to THA. Patients who had OP were at higher risk of prolonged LOS, non-home discharge, 90-day readmission, and one-year reoperation in addition to poor pain/function improvement and dissatisfaction one year after THA.

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Rapid Electroencephalography and Artificial Intelligence in the Detection and Management of Nonconvulsive Seizures

Nonconvulsive status epilepticus is a commonly overlooked cause of altered mental status. This study assessed nonconvulsive status epilepticus prevalence in emergency department (ED) patients with acute neurologic presentations using limited electroencephalogram (EEG) coupled with artificial intelligence (AI)-enhanced seizure detection technology. We then compared the accuracy of the AI EEG interpretations to those performed by an epileptologist. In a prospective observational cohort analysis, adult patients with unexplained mental status changes identified by emergency physicians received expedited placement of a limited EEG. Data collected encompassed patient demographics, clinical history, EEG interpretations by the AI algorithm and epileptologists, treatments, and disposition determinations. There were 134 device applications on 132 patients (2 received the device twice) enrolled in the study, but 16 were missing data critical for identification or analysis and 9 did not meet the selection criteria. Of the 108 limited EEGs interpreted by an epileptologist, 69 were abnormal (diffuse slowing, highly epileptiform patterns, or spikes and sharps), 41 were normal, 5 were uninterpretable, and 3 captured episodes of seizure or status epilepticus. Limited EEG AI interpretation detected >90% seizure burden in 2 of 3 cases of seizure or status epilepticus as well as in 2 abnormal EEGs and 1 normal EEG, providing a sensitivity of 66.7% (95% confidence interval 9.4 to 99.2), a specificity of 97.0% (95% confidence interval 91.5 to 99.4), and a disease prevalence of 2.9%. Limited AI-enhanced EEG can detect nonconvulsive status epilepticus in the ED; however, the technology tended to overestimate seizure burden in our cohort. This study found a lower nonconvulsive status epilepticus prevalence compared to prior literature reports.

Recreational screen time and obesity risk in Korean children: a 3-year prospective cohort study

BackgroundStudies have shown that prolonged television watching increases obesity risk among children. However, few studies examined the associations with other types of screen time, such as computer and smartphone use, using a prospective cohort study design. Further, little is known about the specific non-screen time activity that may yield the most benefits when reallocating screen time to other activities.MethodsWe conducted a prospective cohort analysis using 3-year follow-up data from the Korean Children and Youth Panel Survey 2018 (n = 2,023; 4th grade elementary students who were not obese at baseline). Average time spent watching television, using computer and smartphone, and other after-school activities were self-reported at baseline. Weight and height were also self-reported at baseline and follow-up surveys through 2021. We performed multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between screen time and obesity incidence, adjusting for potential confounders. We also performed isotemporal substitution models to examine the associations of reallocating screen time to other non-screen time activities (physical activity, sleeping, hanging out with friends, reading, studying, and chatting with parents) in an equal time-exchange manner.ResultsLonger combined screen time (≥ 240 vs. <120 m/d) was statistically significantly associated with an increased obesity risk (OR [95% CI] = 1.68 [1.03, 2.73]). The direction of associations with television watching (≥ 180 vs. <60 m/d: OR [95% CI] = 2.86 [1.58, 5.20]), computer use (≥ 120 vs. <60 m/d: 1.38 [0.52, 3.64]), and smartphone use (≥ 180 vs. <60 m/d: 1.42 [0.76, 2.65]) were all positive, although the association was most apparent and statistically significant for television watching only. The associations did not change after additional adjustment for other lifestyle factors, including physical activity, sleep, and breakfast skipping. In the isotemporal substitution models, reallocating 1-hour of screen time to reading (OR [95% CI] = 0.67 [0.48, 0.93]) was associated with a decreased obesity risk. Reallocating 1-hour of screen time to physical activity was only marginally significantly associated with obesity risk (0.79 [0.62, 1.01]).ConclusionsOur data suggest that more efforts should focus on reducing screen time and increasing time for other non-screen time activities, particularly reading, for obesity prevention in children.

Fungibility, accessibility and clinical utility of remote electronic fetal monitoring in improving maternal emotional status compared with traditional method: A multicenter prospective cohort analysis.

Supported by remote signal processing techniques and wireless communication technology, remote electronic fetal monitoring (REFM) has emerged as a promising alternative to traditional electronic fetal monitoring (TEFM) in clinical practice. The aim of this study was to evaluate the comparability, accessibility, and clinical utility of REFM in contrast to TEFM. This was a multicenter prospective cohort study. A cohort of 2900 pregnant women were enrolled from three medical centers between June 1, 2021 and June 31, 2022. Among them, 800 utilized REFM, with 760 of them completing the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) assessments using the devices for 1 month. The control group comprised 2100 pregnant women who did not use REFM. Additionally, 80 pregnant women concurrently employed both REFM and TEFM, and their respective curve coincidence rates were determined through curve fitting. Primary outcomes encompassed pregnancy outcomes in both groups, average curve coincidence rates between REFM and TEFM, as well as SDS and SAS scores. Among the 760 pregnant women who completed SAS and SDS assessments, their average SAS scores before and after 1 month of REFM usage were 43.09 ± 8.04 and 41.58 ± 6.59, respectively. Concurrently, the average SDS scores before and after 1 month of REFM usage were 45.45 ± 9.60 and 44.80 ± 9.17, respectively. A statistically significant decrease was observed in SAS scores (P = 0.005), whereas no significant difference was noted in SDS scores (P = 0.340). Furthermore, a statistically significant difference in the rate of adverse pregnancy outcomes (neonatal asphyxia) emerged between the two groups, those who employed REFM and those who did not (P = 0.021). In the subset of 80 pregnant women employing both REFM and TEFM, all 80 results showed precise congruence between the two methods. The average coincidence rate was determined to be 79.45% ± 12.64%. REFM contributes to improved pregnancy outcomes and exhibits a high level of concordance with TEFM, thereby accurately reflecting the quality of fetal heart monitoring. Additionally, REFM effectively mitigates pregnant women's anxiety. Thus, REFM demonstrates comparability, accessibility, and clinical utility.

Serum Albumin-to-Creatinine Ratio Predicts One-Year Mortality in Elderly Patients with Non-ST-Elevation Acute Coronary Syndrome After Percutaneous Coronary Intervention: A Prospective Cohort Analysis.

BACKGROUND Recently, the albumin-to-creatinine ratio (ACR) has been suggested as a valuable biomarker for adverse events in acute myocardial infarction. However, the prognostic value of ACR in very elderly patients (≥80 years) with non-ST-elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) remains unclear. MATERIAL AND METHODS A total of 354 very elderly patients with NSTE-ACS who underwent PCI were included in this study and followed up for 1 year. Patients were divided into 3 groups according to ACR tertiles. Logistic regression analysis proportional hazard model was used to determine the prognostic value of ACR. RESULTS Sixty-two patients (17.5%) with 114 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during 1-year follow-up. Patients with lower ACR tended to be older and had a lower serum albumin level and higher uric acid and creatinine levels (P<0.05). Moreover, patients with lower ACR levels had elevated all-cause mortality and MACCEs. Kaplan-Meier analysis suggested that patients with a lower ACR had a significantly lower survival rate free of all-cause mortality and MACCEs. Multivariable logistic regression analysis demonstrated that ACR was an independent predictor of all-cause mortality in these patients. ROC analysis showed that when ACR was ≤42.8, sensitivity and specificity were 75.2% and 80.2%, respectively, and the area under the ROC curve was 0.802 (95% CI: 0.745-0.859; P<0.001). CONCLUSIONS A lower ACR was associated with a higher incidence of all-cause mortality in very elderly patients with NSTE-ACS after PCI. The ACR is a promising indicator for risk stratification and prognostic assessment in these individuals.

TBI related death has become the new epidemic in polytrauma: a 10-year prospective cohort analysis in severely injured patients.

Advances in trauma care have attributed to a decrease in mortality and change in cause of death. Consequently, exsanguination and traumatic brain injury (TBI) have become the most common causes of death. Exsanguination decreased by early hemorrhage control strategies, whereas TBI has become a global health problem. The aim of this study was to investigate trends in injury severity,physiology, treatment and mortality in the last decade. In 2014, a prospective cohort study was started including consecutive severely injured trauma patients > 15years admitted to a Level-1 Trauma Center ICU. Demographics,physiology,resuscitation, and outcome parameters were prospectively collected. Five hundred and seventy-eight severely injured patients with predominantly blunt injuries (94%) were included. Seventy-two percent were male with a median age of 46 (28-61) years, and ISS of 29 (22-38). Overall mortality rate was 18% (106/578) with TBI (66%, 70/106) being the largest cause of death. Less than 1% (5/578) died of exsanguination. Trend analysis of the 10-year period revealed similar mortality rates despite an ISS increase in the last 2years. No significant differences in demographics,and physiology in ED were noted. Resuscitation strategy changed to less crystalloids and more FFP. Risk factors for mortality were age,brain injury severity,base deficit,hypoxia,and crystalloid resuscitation. TBI was the single largest cause of death in severely injured patients in the last decade. With an aging population TBI will increase and become the next epidemic in trauma. Future research should focus on brain injury prevention and decreasing the inflammatory response in brain tissue causing secondary damage, as was previously done in other parts of the body.

Serum Erythritol and Risk of Overall and Cause-Specific Mortality in a Cohort of Men.

Erythritol occurs naturally in some fruits and fermented foods, and has also been used as an artificial sweetener since the 1990s. Although there have been questions and some studies regarding its potential adverse health effects, the association between serum erythritol and long-term mortality has not been evaluated. To examine the association between serum erythritol's biochemical status and risk of overall and cause-specific mortality, a prospective cohort analysis was conducted using participants in the ATBC Study (1985-1993) previously selected for metabolomic sub-studies. The analysis included 4468 participants, among whom 3377 deaths occurred during an average of 19.1 years of follow-up. Serum erythritol was assayed using an untargeted, global, high-resolution, accurate-mass platform of ultra-high-performance liquid and gas chromatography. Cause-specific deaths were identified through Statistics Finland and defined by the International Classification of Diseases. After adjustment for potential confounders, serum erythritol was associated with increased risk of overall mortality (HR = 1.50 [95% CI = 1.17-1.92]). We found a positive association between serum erythritol and cardiovascular disease mortality risk (HR = 1.86 [95% CI = 1.18-2.94]), which was stronger for heart disease mortality than for stroke mortality risk (HR = 3.03 [95% CI = 1.00-9.17] and HR = 2.06 [95% CI = 0.72-5.90], respectively). Cancer mortality risk was also positively associated with erythritol (HR = 1.54 [95% CI = 1.09-2.19]). The serum erythritol-overall mortality risk association was stronger in men ≥ 55 years of age and those with diastolic blood pressure ≥ 88 mm Hg (p for interactions 0.045 and 0.01, respectively). Our study suggests that elevated serum erythritol is associated with increased risk of overall, cardiovascular disease, and cancer mortality. Additional studies clarifying the role of endogenous production and dietary/beverage intake of erythritol in human health and mortality are warranted.

Community-Based Medications First for Opioid Use Disorder - Care Utilization and Mortality Outcomes.

A large treatment gap exists for people who could benefit from medications for opioid use disorder (MOUD). People OUD accessing services in harm reduction and community-based organizations often have difficulty engaging in MOUD at opioid treatment programs and traditional health care settings. We conducted a study to test the impacts of a community-based medications first model of care in six Washington (WA) State communities that provided drop-in MOUD access. Participants included people newly prescribed MOUD. Settings included harm reduction and homeless services programs. A prospective cohort analysis tested the impacts of the intervention on MOUD and care utilization. Intervention impacts on mortality were tested via a synthetic comparison group analysis matching on demographics, MOUD history, and geography using WA State agency administrative data. 825 people were enrolled in the study of whom 813 were matched to state records for care utilization and outcomes. Cohort analyses indicated significant increases for days' supply of buprenorphine, months with any MOUD, and months with any buprenorphine for people previously on buprenorphine (all results p<0.05). Months with an emergency department overdose did not change. Months with an inpatient hospital stay increased (p<0.05). The annual death rate in the first year for the intervention group was 0.45% (3 out of 664) versus 2.2% (222 out of 9893) in the comparison group in the 12 months; a relative risk of 0.323 (95% CI 0.11-0.94). Findings indicated a significant increase in MOUD for the intervention group and a lower mortality rate relative to the comparison group. The COVID-19 epidemic and rapid increase in non-pharmaceutical-fentanyl may have lessened the intervention impact as measured in the cohort analysis. Study findings support expanding access to a third model of low barrier MOUD care alongside opioid treatment programs and traditional health care settings.

Interplay between physical activity volume and intensity with modeled life expectancy in women and men: A prospective cohort analysis

BackgroundThere is a lack of research examining the interplay between objectively measured physical activity volume and intensity with life expectancy. MethodsIndividuals from UK Biobank with wrist-worn accelerometer data were included. The average acceleration and intensity gradient were extracted to describe the physical activity volume and intensity profile. Mortality data were obtained from national registries. Adjusted life expectancies were estimated using parametric flexible survival models. Results40,953 (57.1%) women (median age = 61.9 years) and 30,820 (42.9%) men (63.1 years) were included. Over a median follow-up of 6.9 years, there were 1719 (2.4%) deaths (733 in women; 986 in men). At 60 years, life expectancy was progressively longer for higher physical activity volume and intensity profiles, reaching 95.6 years in women and 94.5 years in men at the 90th centile for both volume and intensity, corresponding to 3.4 (95% confidence interval (95%CI): 2.4–4.4) additional years in women and 4.6 (95%CI: 3.6–5.6) additional years in men compared to those at the 10th centiles. An additional 10-min or 30-min daily brisk walk was associated with 0.9 (95%CI: 0.5–1.3) and 1.4 (95%CI: 0.9–1.9) years longer life expectancy, respectively, in inactive women; and 1.4 (95%CI: 1.0–1.8) and 2.5 (95%CI: 1.9–3.1) years in inactive men. ConclusionHigher physical activity volumes were associated with longer life expectancy, with a higher physical activity intensity profile further adding to a longer life. Adding as little as a 10-min brisk walk to daily activity patterns may result in a meaningful benefit to life expectancy.

ASO Visual Abstract: Associations Between Perceived Discrimination, Screening Mammography, and Breast Cancer Stage at Diagnosis: A Prospective Cohort Analysis.

ASO Visual Abstract: Associations Between Perceived Discrimination, Screening Mammography, and Breast Cancer Stage at Diagnosis: A Prospective Cohort Analysis.

Validation of candidate protein biomarkers previously identified by genetic instruments for prostate cancer risk: A prospective cohort analysis of directly measured protein levels in the ARIC study.

Multiple novel protein biomarkers have been shown to be associated with prostate cancer risk using genetic instruments. This study aimed to externally validate the associations of 30 genetically predicted candidate proteins with prostate cancer risk using aptamer-based levels in US Black and White men in the Atherosclerosis Risk in Communities (ARIC) study. Plasma protein levels were previously measured by SomaScan® using the blood collected in 1990-1992. Among 4864 eligible participants, we ascertained 667 first primary prostate cancer cases through 2015. Hazard ratios (HRs) of prostate cancer and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression for tertiles of each protein. We adjusted for age, race, and other risk factors. Of the 30 proteins and considering a nominal p trend < 0.05, two were positively associated with prostate cancer risk-RF1ML (tertile 3 vs. 1: HR = 1.23; 95% CI 1.02-1.48; p trend = 0.037) and TPST1 (1.28, 95% CI 1.06-1.55; p trend = 0.0087); two were inversely associated-ATF6A (HR = 0.80, 95% CI 0.65-0.98; p trend = 0.028) and SPINT2 (HR = 0.74, 95% CI 0.61-0.90; p trend = 0.0025). One protein, KDEL2, which was nonlinearly associated (test-for-linearity: p < 0.01) showed a statistically significant lower risk in the second tertile (HR = 0.79, 95% CI 0.65-0.95). Of these five, four proteins-ATF6A, KDEL2, RF1ML, and TPST1-were consistent in the direction of association with the discovery studies. This study validated some pre-diagnostic protein biomarkers of the risk of prostate cancer.

Impact of injury mechanism on early wound closure in patients with acute conflict-related extremity wounds: A prospective cohort analysis from two civilian hospitals in Iraq and Jordan.

Gunshots and bomb blasts are important causes of extremity injuries in conflict zones, yet little research exists on the characteristics and outcomes of these injuries in civilian populations. We performed a prospective cohort analysis utilizing data from a randomized trial conducted at two civilian hospitals in Jordan and Iraq in 2015-2019. Adults who presented ≤72h of sustaining an extremity injury were included. We used mechanism of injury (gunshot/bomb blast) as the exposure and wound closure by day 5 as the primary outcome measure. The population predominantly comprised young men (n=163, 94% male, and median age 29years) injured by gunshots (61%) or bomb blasts (39%). Compared with the gunshot group, more participants in the bomb blast group had concomitant injuries (32/63 [51%] vs. 11/100 [11%], p<0.001) and vascular injuries (9/63 [14%] vs. 4/100 [4%], p=0.02). The wounds were larger in the bomb blast group compared with the gunshot group (median area 86cm2 [IQR 24-161] vs. 21cm2 [IQR 7-57], p<0.001). Compared with the bomb blast group, significantly more participants in the gunshot group achieved wound closure by day 5 (74/100 [74%] vs. 16/63 [25%], p<0.001). This difference remained after controlling for confounding factors (odds ratio 4.7, 95% confidence interval 1.6-13.7). In civilians with conflict-related extremity injuries, bomb blast wounds had a lower likelihood of achieving closure within 5days than gunshot wounds, independent of other factors, such as wound size and vascular injuries. ClinicalTrials.gov, NCT02444598. Registered 14-05-2015, https://classic. gov/ct2/show/NCT02444598.

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.