Risk Difference Research Articles

Clinical risk prediction, coronary computed tomography angiography, and cardiovascular events in new-onset chest pain: the PROMISE and SCOT-HEART trials.

Whether index testing using coronary computed tomography angiography (CTA) improves outcomes in stable chest pain is debated. The risk factor weighted clinical likelihood (RF-CL) model provides likelihood estimation of obstructive coronary artery disease. This study investigated the prognostic effect of coronary CTA vs. usual care by RF-CL estimates. Large-scale studies randomized patients (N = 13 748) with stable chest pain to coronary CTA as part of the initial work-up in addition to or instead of usual care including functional testing. Patients were stratified according to RF-CL estimates [RF-CL: very-low (≤5%), low (>5%-15%), and moderate/high (>15%)]. The primary endpoint was myocardial infarction or death at 3 years. The primary endpoint occurred in 313 (2.3%) patients. Event rates were similar in patients allocated to coronary CTA vs. usual care [risk difference (RD) 0.3%, hazard ratio (HR) 0.84 (95% CI 0.67-1.05)]. Overall, 33%, 44%, and 23% patients had very-low, low, and moderate/high RF-CL. Risk was similar in patients with very low and moderate/high RF-CL allocated to coronary CTA vs. usual care [very low: RD 0.3%, HR 1.27 (0.74-2.16); moderate/high: RD 0.5%, HR 0.88 (0.63-1.23)]. Conversely, patients with low RF-CL undergoing coronary CTA had lower event rates [RD 0.7%, HR 0.67 (95% CI 0.47-0.97)]. The number needed to test using coronary CTA to prevent one event within 3 years was 143. Despite an overall good prognosis, low RF-CL patients have reduced risk of myocardial infarction or death when allocated to coronary CTA vs. usual care. Risk is similar in patients with very-low and moderate/high likelihood.

Prognostic impact of postoperative management by an intensive care unit intensivist after colonic perforation.

Postoperative management for colonic perforation is an important prognostic factor, but whether intensivists perform postoperative management varies between institutions. We investigated 291 patients with colonic perforation between 2018 and 2022. Patients were divided into those managed by an intensivists (ICU group; n = 40) and those not managed by an intensivists (non-ICU group; n = 251). We examined how management by intensivists affected prognosis using inverse probability weighting, and clarified which patients should consult an intensivists. The ICU group showed a significantly higher shock index (1.15 vs. 0.75, p < 0.01), higher APACHE II score (16.0 vs. 10.0, p < 0.001), and more severe comorbidities (Charlson Comorbidity Index 5.0 vs. 1.0, p < 0.001) and general peritonitis (85% vs. 38%, p < 0.001). Adjusted risk differences were - 24% (-34% to -13%) for 6-month mortality rate. Six-month mortality was improved by ICU intensivist management in patients with general peritonitis (risk difference - 22.8; 95% confidence interval - 34 to -11); APACHE II score ≥20 (-0.79; -1.06 to -0.52); lactate ≥1.6 (-0.38; -0.57 to -0.29); shock index ≥1.0 (-40.01; -54.87 to -25.16); and catecholamine index ≥10 (-41.16; -58.13 to -24.19). Intensivists were involved in treating patients in poor general condition, but prognosis was extremely good. Appropriate case consultation with intensivists is important.

Impact of low dose inhaled nitric oxide treatment in spontaneously breathing and intubated COVID-19 patients: a retrospective propensity-matched study

BackgroundThe benefit of Inhaled nitric oxide (iNO) therapy in the setting of COVID-19-related ARDS is obscure. We performed a multicenter retrospective study to evaluate the impact of iNO on patients with COVID-19 who require respiratory support.MethodsThis retrospective multicenter study included COVID-19 patients enrolled in the SCCM VIRUS COVID-19 registry who were admitted to different Mayo Clinic sites between March 2020 and June 2022 and required high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), or invasive mechanical ventilation (IMV). Patients were included in the ‘spontaneously breathing’ group if they remained non-intubated or were initiated on an HFNC (± NIV) before intubation. Patients who got intubated without prior use of an HFNC (± NIV) were included in the ‘intubated group.’ They were further divided into categories based on their iNO usage. Propensity score matching (PSM) and inverse propensity of treatment weighting (IPTW) were performed to examine outcomes.ResultsAmong 2767 patients included in our analysis, 1879 belonged to spontaneously breathing (153 received iNO), and 888 belonged to the intubated group (193 received iNO). There was a consistent improvement in FiO2 requirement, P/F ratio, and respiratory rate within 48 h of iNO use among both spontaneously breathing and intubated groups. However, there was no significant difference in intubation risk with iNO use among spontaneously breathing patients (PSM OR 1.08, CI 0.71–1.65; IPTW OR 1.10, CI 0.90–1.33). In a time-to-event analysis using Cox proportional hazard model, spontaneously breathing patients initiated on iNO had a lower hazard ratio of in-hospital mortality (PSM HR 0.49, CI 0.32–0.75, IPTW HR 0.40, 95% CI 0.26–0.62) but intubated patients did not (PSM HR: 0.90; CI 0.66–1.24, IPTW HR 0.98, 95% CI 0.73–1.31). iNO use was associated with longer in-hospital stays, ICU stays, ventilation duration, and a higher incidence of creatinine rise.ConclusionsThis retrospective propensity-score matched study showed that spontaneously breathing COVID-19 patients on HFNC/ NIV support had a decreased in-hospital mortality risk with iNO use in a time-to-event analysis. Both intubated and spontaneously breathing patients had improvement in oxygenation parameters with iNO therapy but were associated with longer in-hospital stays, ICU stays, ventilation duration, and higher incidence of creatinine rise.

Duration of Anticoagulation for Venous Thromboembolism in Pediatric Patients: Kids-DOTT Trial Outcomes at Two Years

The Kids-DOTT multinational randomized clinical trial (RCT) revealed non-inferiority of a six-week versus three-month duration of anticoagulation for the treatment of provoked venous thromboembolism (VTE) in patients <21 years old, in regard to net clinical benefit at one year. To evaluate non-inferiority at two years. Patients whose repeat imaging six weeks after VTE diagnosis did not show complete veno-occlusion were randomized to discontinue anticoagulation versus receive a total three-month course and followed for two years for the occurrence of symptomatic recurrent (SR-) VTE (efficacy outcome) and clinically-relevant bleeding (CRB, safety outcome). Outcomes were centrally adjudicated and net clinical benefit was compared between treatment arms via a pre-specified bivariate non-inferiority boundary, using 95% confidence intervals (CIs) in absolute risk differences (ARDs) between treatment arms. Kaplan-Meier estimates of two-year cumulative incidences in the six-week and three-months arms of the intention-to-treat (ITT) population (n=417) were 1.7% (95% CI: 0%, 3.7%) and 2.9% (95% CI: 0.3%, 5.4%) for SR-VTE and 1.1% (95% CI: 0%, 2.5%) and 3.2% (95% CI: 0.6%, 5.7%) for CRB. Bivariate analysis of the ARDs in the ITT population demonstrated that a six-week anticoagulation duration was non-inferior to a three-month course. These findings support durability of the Kids-DOTT RCT findings of net clinical benefit at two years.

Advancing Community Care and Access to Follow-Up after Acute Kidney Injury Hospitalization: A Randomized Clinical Trial.

Key Points A risk-guided intervention improved adherence to processes of care for AKI survivors.Further supports are necessary to improve uptake of processes of care for AKI survivors in primary care. Background AKI is associated with development and progression of CKD. Gaps in recommended care for CKD are common after AKI. Methods In this randomized controlled trial conducted in Alberta, Canada, we allocated adults hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or greater AKI to a risk-guided, transition of care intervention versus usual practices at the time of hospital discharge. For people in the intervention group, we used a validated risk index to predict risk of severe CKD after AKI. People at low risk (&lt;1%) received patient education alone. People at medium risk received additional clinical guidance, provided to their primary care physician. People at high risk (&gt;10%) were referred to nephrology. The primary outcome was the proportion of patients who received treatment with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), statin, and nephrology specialist follow-up within 90 days of discharge. Results One hundred fifty-five patients were recruited; the mean (SD) age was 60 (15) years, 91 (60%) were male, and 96 (62%) had eGFR &lt;60 ml/min per 1.73 m2 or urine albumin-creatinine ratio &gt;30 mg/g at discharge. The proportion of participants who received ACE-I/ARB, statin treatment, and nephrologist follow-up was 28% in the intervention group versus 3% in the usual care group (absolute risk difference [RD], 25%; 95% confidence interval [CI], 15% to 36%). The use of ACE-I or ARB in participants with urine albumin-creatinine ratio &gt;300 mg/g or diabetes was greater in the high-risk group with the intervention versus usual care (RD, 37%; 95% CI, 6% to 67%), as was statin use among those with CKD (RD, 30%; 95% CI, 5% to 56%) and nephrologist follow-up for those with sustained eGFR &lt;30 ml/min per 1.73 m2 at discharge (RD, 78%; 95% CI, 56% to 100%). Hyperkalemia was more frequent in the intervention group (RD, 10%; 95% CI, 9% to 19%). Conclusions A risk-guided intervention for patients hospitalized with AKI increased recommended processes of care for CKD for high-risk patients after hospital discharge. Clinical Trial registry name and registration number: Improving Post Discharge Care after Acute Kidney Injury (AFTER AKI), NCT02915575.

Comparison of laparoscopic-assisted flexible ureteroscopic lithotripsy with percutaneous nephrolithotripsy and flexible ureteroscopy lithotripsy: a case-control study and meta-analysis.

This study aims to compare the differences in stone clearance rate, infection rate, and bleeding risk among laparoscopic-assisted flexible ureteroscopic lithotripsy (LAFUL), percutaneous nephrolithotripsy (PCNL), and flexible ureteroscopic lithotripsy (FUL) through case-control studies and meta-analysis, to evaluate the safety and effectiveness of LAFUL. 1. Through systematic literature search, clinical studies related to LAFUL, PCNL, and FUL were screened, and data on stone clearance rate, infection rate, and bleeding events were collected and analyzed for three groups of patients, followed by meta-analysis. 2. Data of patients who met the single center inclusion criteria and received LAFUL (40 cases), PCNL (40 cases, FUL), and FUL (40 cases) treatments for kidney stones from January 2021 to December 2023 were collected. Using a case-control study method, relevant clinical data were analyzed using SPSS 26.0 software. A total of 31 studies involving 2974 patients were included. The results of case-control analysis showed the stone clearance rate in the LAFUL group (F = 225.19, P < 0.001) and the positive rate of postoperative urine bacterial culture (X2 = 4.558, P = 0.033). The results of meta-analysis showed the stone clearance rate (rate = 0.986, 95% CI 0.964-0.999) and blood transfusion rate (rate = 0, 95% CI 0-0.012) in the LAFUL group. LAFUL shows potential in improving the stone clearance rate and reducing the risk of postoperative infection and bleeding, suggesting it may have certain advantages in the treatment of renal calculi.

Comorbidities, Tobacco Exposure, and Geography: Added Risk Factors of Heat and Cold Wave Related Mortality among United States Veterans with COPD.

Understanding the health risks associated with extreme weather events is needed to inform policies to protect vulnerable populations. To address this need, we estimated heat and cold wave related mortality risks in a cohort of veteran patients with chronic obstructive pulmonary disease (COPD) and explored disparities among strata of comorbidities, tobacco exposure, and urbanicity. We designed a time stratified case-crossover study among deceased patients with COPD between 2016 to 2021 in the Veterans Health Administration system. Distributed lag models with conditional logistic regression estimated incidence rate ratios (IRR) of heat and cold wave associated mortality risk from lag days 0 to 3 for heatwaves and 0 to 7 for cold waves. Attributable risks (AR) per 100,000 patients were also calculated. Of the 377,545 deceased patients with COPD, the largest heatwave related mortality risk was in patients with COPD and asthma, AR: 14,016 (95% CI: -326, 30,706) across lag days 0 to 3. The largest cold wave related mortality burden was in patients with COPD with no other reported comorbidities, AR: 1,704 (95% CI: 759, 2,686) across lag days 0 to 7. Patients residing in urban settings had the greatest heatwave, AR: 1,062 (95% CI: (576, 1,559), and cold wave AR: 1,261 (95% CI: 440, 2,105) related mortality risk (across lag days 0 to 1 and 0 to 7 respectively). There were no differences in mortality risk by tobacco exposure. Our findings show individuals with COPD are susceptible to heat and cold waves. This information can inform clinical practice and public health policy about the mortality risk vulnerable populations experience with respect to extreme weather conditions. Furthermore, our results may be used in the development and refinement of future extreme weather warning systems designed for public health purposes.

The application value of low-risk human papillomavirus testing in cervical cancer prevention and treatment in low- and middle-resource areas

ObjectivesTo assess the application value of low-risk human papillomavirus (lrHPV) detection in the prevention and treatment of cervical cancer in low- and middle-resource areas (LMRAs). Study designA retrospective cross-sectional study. MethodsCervical HPV typing results were collected from 2019 to 2023, utilizing fluorescence PCR technology. An adjusted logistic regression model was used to assess the relative risk (OR) and 95 % confidence interval (CI) for co-infection with lrHPV and high-risk HPV (hrHPV). ResultsOut of 113,883 women included in the study, the overall lrHPV positivity rate was 1.9 %. In total, 47.7 % (1033/2167) of lrHPV positive women also had hrHPV co-infections. Multivariate analysis identified 12 hrHPV subtypes (T-hrHPV) significantly associated with co-infection risk, including HPV16, 31, 33, 39, 51, 52, 53, 56, 59, 66, 68, and 73. The risk of T-hrHPV infection was 3.77 times higher (95 % CI: 3.44-4.12) for women with a single lrHPV infection and 9.71 times higher (95 % CI: 4.72-19.99) for those with two lrHPV infections. Women screened in the gynecological outpatient clinic faced a T-hrHPV infection risk 2.64 times higher (95 % CI: 2.54-2.74) than those in the general health check department. ConclusionslrHPV positivity significantly increases the risk of T-hrHPV co-infection, particularly under multiple infections, highlighting the importance of comprehensive HPV screening in LMRAs. The notable differences in T-hrHPV infection risks across various screening settings highlight their critical role in cervical cancer prevention and offer new insights into optimizing vaccination strategies to enhance effective prevention and treatment in LMRAs.

Traumatic and Adverse Childhood Experiences and Developmental Differences in Psychiatric Risk

While adverse childhood experiences (ACEs) are known to impart significant risk for negative mental health and cognitive outcomes in youth, translation of ACE scores into clinical intervention is limited by poor specificity in predicting negative outcomes. This work expands on the ACE framework using a data-driven approach to identify 8 different forms of traumatic and adverse childhood experiences (TRACEs) and reveal their differential associations with psychiatric risk and cognition across development. Building upon the traditional ACEs model, this study aimed to characterize unique components of commonly co-occurring TRACEs and to examine moderation of longitudinal change in mental health and cognitive development during adolescence. This work draws from youth and their caregivers who completed up to 4 annual behavioral assessments from 2016 to 2021 as part of the ongoing Adolescent Brain Cognitive Development (ABCD) study. Data collection was performed at 21 regionally-distributed sites across the United States. Analyses for this work were conducted January 2023 through November 2023. Youth participants in the ABCD study's exposure to 268 different TRACEs, which were distilled into adversity components using nonlinear principal components analysis. Mixed-effects and latent change score models considered TRACEs components as moderators of longitudinal change in internalizing and externalizing mental health problems, as well as longitudinal change in cognitive ability. Data were distilled from 11 876 youth participants, who were grouped into dyads with a caregiver. ABCD study youth participants were 9 to 10 years old at baseline assessment (year 0) and 12 to 13 years old at ABCD year 3. A total of 5679 participants (47.8%) were female. Analyses revealed that TRACEs organized into 8 thematic adversity components (e.g., family conflict, interpersonal violence). At baseline assessment (year 0), exposure to nearly every adversity component was associated with poorer mental health and diminished cognitive ability. Yet across time, it was observed that different forms of adversity were variably linked to both increases and decreases in internalizing and externalizing problems. For example, while peer aggression (t = 5.31) and family conflict (t = 5.67) were associated with increases in both internalizing and externalizing problems over early adolescence, community threat (t = 2.82) and poverty (t = 2.07) were linked to decreased problems, potentially representing adaptive suppression of symptoms. Finally, adversity types related to resource deprivation (eg, poverty, caregiver maladjustment) were associated with declines in cognitive ability over early adolescence. In this cohort study, distinct forms of TRACEs differentially moderated developmental changes in psychiatric risk and cognitive ability in different ways, offering the possibility for precision-based prediction of risk for youth. Such findings could be used in targeted early prevention and intervention strategies for at-risk youth.

Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. Adult patients presenting to the emergency department with severe sepsis or septic shock. EGDT vs. usual care. A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

Mode of delivery in chorioamnionitis: impact on neonatal and maternal outcomes

BackgroundThe impact of mode of delivery in chorioamnionitis on neonatal outcomes is unclear. This retrospective cohort study compares the rate of early onset neonatal sepsis between vaginal delivery and cesarean section.MethodsSingleton pregnancies at greater than 24 + 0 weeks gestation with live birth and clinically-diagnosed chorioamnionitis from January 1, 2019 to December 31, 2021 were included. Cases with multiple gestations, terminations or histological chorioamnionitis alone were excluded. Rates of early onset neonatal sepsis, select secondary neonatal outcomes and a composite outcome of maternal infectious morbidity were compared using propensity score weighting. Subgroup analysis was done by indication for cesarean section.ResultsAfter chart review, 378 cases were included with 197 delivering vaginally and 181 delivering via cesarean section. The groups differed on age, parity, hypertension, renal disease, gestational age, corticosteroid use, magnesium sulfate use, presence of meconium and percentage meeting Gibbs criteria before propensity score weighting. Rate of early onset neonatal sepsis was greater in the cesarean section group (13.8% versus 3.1%, adjusted risk difference 8.3% [3.5–13.1], p < 0.001). Secondary neonatal outcomes were similar between groups. When compared by indication, the rate of early onset neonatal sepsis was greater in the cesarean section for abnormal fetal surveillance group compared to vaginal delivery but not in the cesarean section for other reasons group. Adjusted rates of secondary neonatal outcomes did not differ between groups. The rate of maternal infectious morbidity was greater with cesarean section. (13.8% versus 1.5% [adjusted risk difference 13.0% [7.1–18.9], p < 0.0001). No other difference in maternal secondary outcomes was identified.ConclusionsThe rate of early onset neonatal sepsis was highest in the cesarean section group, particularly in those with abnormal fetal surveillance. Fetuses affected by or vulnerable to sepsis likely have a greater need for cesarean section.

Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial.

To assess if off-label oral solution of misoprostol compared with licensed oral tablet of misoprostol approved for induction of labour (IOL) is as efficient in resulting in vaginal delivery within 24 h, using a non-inferiority design. Prospective, randomised, non-inferiority, open-label, blinded endpoint trial. Two tertiary level hospitals, Stockholm, Sweden, January 2022 to May 2023. In all, 874 women, without previous caesarean section, with an unripe cervix and a singleton, cephalic foetus at 37 + 0 to 42 + 0 gestational weeks, with a normal cardiotocography, planned for IOL were included. Women were randomised 1:1 to intervention (25 μg oral solution of misoprostol) or control (25 μg oral tablet of misoprostol) two-hourly for a maximum of eight doses. Subsequent methods of induction followed clinical practice. The primary outcome was vaginal delivery within 24 h tested using non-inferiority testing procedures at a non-inferiority margin of 5 percentage points. Secondary efficacy outcomes were tested for superiority of either treatment. Analyses were by intention-to-treat. There were 207 (47.4%) vaginal deliveries within 24 h for women receiving oral solution and 192 (43.9%) vaginal deliveries within 24 h for women receiving oral tablet, establishing non-inferiority with an absolute risk difference of 3.4% (95% CI -3.2% to 10.0%). Women receiving oral solution required fewer doses to reach active labour than women receiving oral tablet (5.7 vs. 6.1, p = 0.007). There were no significant differences for other secondary or safety outcomes. Off-label oral solution of misoprostol was non-inferior to the licensed oral tablet regarding efficacy of IOL defined as vaginal delivery within 24 h. Clinicaltrials.gov identifier: NCT05424445.

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Severe infections as risk factors for acute myocardial infarction: a nationwide, Danish cohort study from 1987 to 2018

Abstract Aims Infections have been associated with acute myocardial infarction (AMI), but differences in risk between infection types and age groups are unclear. This study aims to investigate whether infections are associated with subsequent AMI and whether the risk differs across infection sites and age groups. Methods and results Nationwide registers were used to include 702 596 adults hospitalized between 1987 and 2018 with either pneumonia (n = 344 319), urinary tract infection (UTI) (n = 270 101), soft tissue/bone infection (n = 66 718), central nervous system (CNS) infection (n = 17 025), or endocarditis (n = 4433). Patients were sex and age matched with two unexposed controls. Outcome was first-time AMI within 10 years. A time-dependent Cox proportional hazards model with cut-offs at 30 and 90 days was used for calculating adjusted hazard ratios (HRs). Pneumonia, UTI, and soft tissue/bone infection were associated with increased relative rates of AMI compared to matched, unexposed controls. Highest relative rates were found within the first 0–30 days post-exposure: pneumonia: HR 3.39 [95% confidence interval (CI) 3.15–3.65]; UTI: HR 2.44 (95% CI 2.21–2.70); soft tissue/bone infection: HR 1.84 (95% CI 1.45–2.33). Relative rates decreased over time but remained significantly elevated throughout the follow-up period and were increased in all age groups. No association was found for CNS infection and for endocarditis only at 31–90 days, HR 2.28 (95% CI 1.20–4.33). Conclusion Acute infections are associated with increased relative rates of AMI across different infection sites and age groups with higher relative rates found for pneumonia. This indicates that some infections may act as a trigger for AMI with a site and/or pathogen specific risk.

Impact of cannabis abuse on the occurrence of stroke in young people: a systematic review and meta-analysis.

The occurrence of stroke in young people has risen significantly. This can easily lead to physical disabilities, swallowing difficulties, and cognitive impairment, among other issues, having a profound impact on families and society. Risk factors for stroke in young people differ from those for traditional stroke, with cannabis abuse emerging as a significant high-risk factor. However, the extent of the impact of cannabis abuse on the occurrence of stroke and the rate of disability in young people remains unclear. To clarify this issue and provide evidence supporting the primary prevention of stroke in young people, this systematic review and meta-analysis summarizes the latest findings from previous studies. A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted until April 2023. The review included observational studies comparing stroke risk estimates between cannabis abusers and non-users. This review included six observational studies focusing on cannabis abuse, involving 119,284,152 participants. A significant association was found between cannabis abuse and an increased risk of stroke [OR = 1.14, 95% CI (1.08, 1.20)]. However, there was substantial heterogeneity among the studies (I 2 = 89%, p < 0.001). After adjusting for confounders such as smoking and alcohol abuse, we found a stronger association between cannabis abuse and stroke in young adults [OR = 1.21, 95% CI (1.12, 1.29)]. Subgroup analyses revealed no significant difference in stroke risk between ischemic and hemorrhagic strokes (p = 0.43). The results of our systematic review and meta-analysis showed that cannabis abuse has a more significant effect on the occurrence of stroke in young people; however, it was not possible to distinguish whether cannabis abuse is more likely to cause ischemic or hemorrhagic stroke. Further research is needed to explore the impact of different drug types, dosages, and behaviors on stroke risk. https://www.crd.york.ac.uk/prospero/, Identifier CRD42023443261.

Risk of Inflammatory Central Nervous System Diseases After Tumor Necrosis Factor–Inhibitor Treatment for Autoimmune Diseases

Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents. To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors. Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024. Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group. Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis. The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors. Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%). Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.

Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease.

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.

A new framework for assessing and dealing with heat risk from an urban resilience perspective

Cities are exposed to increasing environmental threats, having undergone extensive land development and rapid urbanization. Clarifying the effects of urban resilience to risk can provide effective guidance for mitigating heat risk. To our knowledge; however, quantifying these effects from an urban resilience perspective has not been considered in previous studies. Here, we proposed the adaptation-resistance-response heat-related urban resilience assessment system. The system is integrated with the minimum cumulative resistance model to construct a novel heat risk assessment framework. A case study in Shenzhen, China, showed that resilience to heat had a high degree of spatial heterogeneity. More than half of the study area was at a moderate or high level of risk. Our study provided new insights into the differences in heat risk between urban and rural areas. The heat-risk gap between urban and rural areas was lower than that indicated by surface temperatures, due to the diffusion and attenuation of high temperatures. In addition, we discussed the application of resilience to risk governance and emphasize five governance models for risk zoning. The proposed framework facilitated a better understanding of the effect of resilience on risk mitigation, and our results can be used to guide urban planning and risk management.

Using the Health Belief Model to Understand Why Making Oral HIV Self-Testing Available to Truck Drivers in Kenya Had Little Impact on Six-Month Testing.

Research has found that offering HIV self-testing (HIVST) to truckers in Kenya increased testing rates at baseline but not over 6-month follow-up. We explored possible explanations based on the Health Belief Model by assessing HIV risk perception, self-efficacy, and fatalism as possible effect modifiers of the impact of offering HIVST (intervention n = 150) versus standard of care (SOC n = 155) on 6-month testing on the multiplicative and additive scales using log binomial and linear binomial regression and stratifying on significant modifiers. We found significant interaction between the intervention and fatalism on both the multiplicative (p = 0.020) and additive (p = 0.020) scales. In the stratified models, the HIVST intervention was associated with higher HIV testing among participants with low fatalism but lower testing among those with high fatalism (risk ratio [RR] = 1.30, p = 0.065 versus RR = 0.74, p = 0.072; risk difference [RD] per 100 = 14.00, p = 0.080 versus RD=-14.69, p = 0.086). Truckers in Kenya are described as being highly fatalistic, feeling lack of control over their lives and health. We found that fatalistic views negated the potential benefit of offering HIVST to truckers. For HIVST to have an impact among truckers, psychosocial interventions may be needed that address fatalistic views.

Gender-specific associations between sleep stages and cardiovascular risk factors.

Sleep characteristics are associated with cardiovascular disease (CVD) risk and both sleep and CVD risk vary by gender. Our objective was to examine associations between polysomnographic sleep characteristics and CVD risk after excluding moderate-severe sleep apnea, and whether gender modifies these associations. This was a cross-sectional study with at-home polysomnography in adults in Brazil (n= 1,102 participants with apnea-hypopnea index (AHI)<15 events/hour). Primary exposures were N3, REM, wake after sleep onset (WASO), arousal index (AI) and AHI, and outcomes were blood pressure (BP) and lipid levels. Associations between sleep and BP varied by gender. In women, more N3 was associated with lower systolic BP (-0.40 mmHg per 10 minutes, 95%CI -0.71, -0.09), lower diastolic BP (-0.29 mmHg per 10 minutes, 95%CI -0.50, -0.07), and lower odds of hypertension (OR 0.94, 95%CI 0.89, 0.98). In men, more WASO was associated with higher systolic BP (0.41 mmHg per 10 minutes, 95%CI 0.08, 0.74) and higher odds of hypertension (OR 1.07, 95%CI 1.01, 1.14). No interactions by gender were observed for lipids. More WASO was associated with lower total cholesterol (-0.71 per 10 minutes, 95%CI -1.37, -0.05). Higher AHI was associated with higher total cholesterol (+0.97 per event/hour, 95%CI 0.24, 1.70) and higher LDL (+0.84 per event/hour, 95%CI 0.04, 1.64). N3 is more strongly associated with BP in women, which is consistent with other studies demonstrating gender differences in BP control and CVD risk and adds a novel risk factor. Longitudinal and interventional studies are required to determine whether changes in N3 result in BP changes.