Estimate Risk Ratios Research Articles

Outpatient clinic attendance and outcomes among patients hospitalized with diabetic foot ulcers

BackgroundThere are limited data on post-hospital discharge clinic attendance rates and outcomes among patients with diabetic foot ulcers (DFUs). MethodsRetrospective study of patients hospitalized with a DFU from 2016 to 2019 in a large public hospital. We measured rates and predictors of clinic attendance with providers involved with DFU care within 30 days of hospital discharge (“30-day post-discharge clinic attendance”). Log-binomial regression was used to estimate risk ratios (RR) and 95 % confidence intervals (CI). ResultsAmong 888 patients, 60.0 % were between 45 and 64 years old, 80.5 % were Black, and 24.1 % were uninsured. Overall, 478 (53.8 %) attended ≥1 30-day post-discharge clinic appointment. Initial hospital outcomes were associated with clinic attendance. For example, the RR of 30-day post-discharge clinic attendance was 1.39 (95%CI 1.19–1.61) among patients who underwent a major amputation compared to patients with DFUs without osteomyelitis and did not undergo an amputation during the initial hospitalization. Among 390 patients with known 12-month outcome, 71 (18.2 %) had a major amputation or died ≤12 months of hospital discharge. ConclusionWe found a low post-discharge clinic attendance and high post-discharge amputation and death rates among patients hospitalized with DFUs. Interventions to increase access to outpatient DFU care are needed and could prevent amputations.

Wound complications after simple vulvar excisions for premalignant and malignancy lesions: A National Surgical Quality Improvement Program database study (409)

Wound complications after simple vulvar excisions for premalignant and malignancy lesions: A National Surgical Quality Improvement Program database study (409)

Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19.

BackgroundRecruitment into randomized trials of hydroxychloroquine (HCQ) for prevention of COVID-19 has been adversely affected by a widespread conviction that HCQ is not effective for prevention. In the absence of an updated systematic review, we conducted a meta-analysis of randomized trials that study the effectiveness of HCQ to prevent COVID-19.MethodsA search of PubMed, medRxiv, and clinicaltrials.gov combined with expert consultation found 11 completed randomized trials: 7 pre-exposure prophylaxis trials and 4 post-exposure prophylaxis trials. We obtained or calculated the risk ratio of COVID-19 diagnosis for assignment to HCQ versus no HCQ (either placebo or usual care) for each trial, and then pooled the risk ratio estimates.ResultsThe pooled risk ratio estimate of the pre-exposure prophylaxis trials was 0.72 (95% CI: 0.58–0.90) when using either a fixed effect or a standard random effects approach, and 0.72 (95% CI: 0.55–0.95) when using a conservative modification of the Hartung-Knapp random effects approach. The corresponding estimates for the post-exposure prophylaxis trials were 0.91 (95% CI: 0.72–1.16) and 0.91 (95% CI: 0.62–1.35). All trials found a similar rate of serious adverse effects in the HCQ and no HCQ groups.DiscussionA benefit of HCQ as prophylaxis for COVID-19 cannot be ruled out based on the available evidence from randomized trials. However, the “not statistically significant” findings from early prophylaxis trials were widely interpreted as definite evidence of lack of effectiveness of HCQ. This interpretation disrupted the timely completion of the remaining trials and thus the generation of precise estimates for pandemic management before the development of vaccines.

Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies.

STUDY QUESTIONAre children conceived by ART or born to subfertile parents more susceptible to upper or lower respiratory tract infections (URTI, LRTI)?SUMMARY ANSWERART-conceived children had a higher frequency of and risk of hospitalization for respiratory infections up to age 3, which was only partly explained by parental subfertility.WHAT IS KNOWN ALREADYSome studies report increased risks of infections in children conceived by ART. Results for URTIs and LRTIs are inconclusive, and the contribution of underlying parental subfertility remains unclear.STUDY DESIGN, SIZE, DURATIONWe included 84 102 singletons of the Norwegian Mother, Father and Child Cohort Study (MoBa) born between 1999 and 2009. Mothers reported time-to-pregnancy at recruitment and child history of, frequency of and hospitalization for, respiratory infections when the child was 6, 18 and 36 months old by questionnaires. Subfertility was defined as having taken 12 or more months to conceive. The Medical Birth Registry of Norway (MBRN) provided information on ART. URTI included throat and ear infections, while LRTI included bronchitis, bronchiolitis, respiratory syncytial virus and pneumonia.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used log-binomial regression to estimate risk ratios (RR) and 95% CI of any respiratory tract infection and hospitalization, and negative-binomial regression to calculate incidence rate ratios (IRR) and 95% CI for number of infections. We compared children conceived by ART, and naturally conceived children of subfertile parents, to children of fertile parents (<12 months to conceive) while adjusting for maternal age, education, BMI and smoking during pregnancy and previous livebirths. We accounted for dependency between children born to the same mother.MAIN RESULTS AND THE ROLE OF CHANCEA total of 7334 (8.7%) singletons were naturally conceived by subfertile parents and 1901 (2.3%) were conceived by ART. Between age 0 and 36 months, 41 609 (49.5%) of children experienced any URTI, 15 542 (18.5%) any LRTI and 4134 (4.9%) were hospitalized due to LRTI. Up to age 3, children conceived by ART had higher frequencies of URTI (adjusted IRR (aIRR) 1.16; 95% CI 1.05–1.28) and hospitalizations due to LRTI (adjusted RR (aRR) 1.25; 95% CI 1.02–1.53), which was not seen for children of subfertile parents. Children conceived by ART were not at higher risks of respiratory infections up to age 18 months; only at age 19–36 months, they had increased risk of any LRTI (aRR 1.16; 95% CI 1.01–1.33), increased frequency of LRTIs (IRR 1.22; 95% CI 1.02–1.47) and a higher risk of hospitalization for LRTI (aRR 1.35; 95% CI 1.01–1.80). They also had an increased frequency of URTIs (aIRR; 1.19; 95% CI 1.07–1.33). Children of subfertile parents only had a higher risk of LRTIs (aRR 1.09; 95% CI 1.01–1.17) at age 19–36 months.LIMITATIONS, REASONS FOR CAUTIONSelf-reported time-to-pregnancy and respiratory tract infections by parents could lead to misclassification. Both the initial participation rate and loss to follow up in the MoBa limits generalizability to the general Norwegian population.WIDER IMPLICATIONS OF THE FINDINGSART-conceived children might be more susceptible to respiratory tract infections in early childhood. This appears to be only partly explained by underlying parental subfertility. Exactly what aspects related to the ART procedure might be reflected in these associations need to be further investigated.STUDY FUNDING/COMPETING INTEREST(S)Funding was received from the Swiss National Science Foundation (P2BEP3_191798), the Research Council of Norway (no. 262700), and the European Research Council (no. 947684). All authors declare no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

The association between time-to-pregnancy and postpartum depressive symptoms in a North American prospective cohort study

To prospectively examine the association between time-to-pregnancy (TTP) and postpartum depression (PPD) and determine whether perceived stress during early pregnancy mediated this association. In Pregnancy Study Online, an internet-based preconception cohort study of pregnancy planners, participants completed questionnaires every 8 weeks for up to 12 months or conception, during pregnancy, and at postpartum. A total of 2643 women provided information on sociodemographic factors, reproductive history, and stress (i.e., Perceived Stress Scale [PSS]) during preconception and early pregnancy (completed at ∼4-12 weeks' gestation) and on postpartum depressive symptoms (i.e., Edinburgh Postnatal Depression Scale [EPDS]) at ∼6 months postpartum. We used multivariable modified Poisson regression models to estimate risk ratios and 95% confidence intervals (CIs) for the association between TTP (&lt;3, 3-5, 6-11, ≥12 menstrual cycles) and PPD (EPDS score ≥13). Causal mediation analyses assessed the mediating role of early pregnancy PSS scores. 10.6% of women had EPDS scores indicating possible PPD (≥13). Compared with women who took less than 3 cycles to conceive, risk ratios for those who took 3-5, 6-11, and greater than or equal to 12 were 1.06 (95% CI: 0.77, 1.45), 1.24 (95% CI: 0.90, 1.70), and 1.31 (95% CI: 0.87, 1.99), respectively. Approximately 30% of the association between infertility (TTP ≥ 12) and PPD was mediated by early pregnancy PSS. There was a modest positive dose-response association between delayed conception and PPD. Perceived stress in early pregnancy explained a small proportion of this association. However, given the width of the CIs, chance cannot be ruled out as an explanation for the observed association.

Effectiveness of Casirivimab-Imdevimab and Sotrovimab During a SARS-CoV-2 Delta Variant Surge

The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant. To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab. This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria. For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy. For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound. A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence. In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant. ClinicalTrials.gov Identifier: NCT04790786.

Intimate Partner Violence and Contraception among Adolescent Girls and Young Women: A Longitudinal Analysis of the Girl Power-Malawi Cohort

PurposeIn sub-Saharan Africa, sexually active adolescent girls and young women (AGYW) experience high rates of intimate partner violence (IPV) and low levels of contraceptive use, but the effect of IPV on contraceptive use is not well understood. MethodsIn the Girl Power-Malawi study, AGYW aged 15-24 were recruited from 4 health centers in Lilongwe, Malawi, and followed for 1 year. At baseline, AGYW were assessed for IPV using the modified Conflict Tactics Scale. AGYW reported contraceptive method use at 6 and 12 months, characterized as barrier, non-barrier, or any modern method. Modified Poisson regression was implemented to estimate risk ratios (RRs) and 95% confidence intervals (CIs) to examine the effect of IPV on contraceptive use. ResultsOne thousand AGYW were enrolled, and 954 non-pregnant participants were included. Baseline prevalence of IPV with the most recent partner was 35.5% (physical), 46.2% (sexual), and 76.9% (emotional). Baseline IPV did not affect contraceptive use at 6 months (aRR [95% CI]: physical 0.98 [0.91-1.05]; sexual 1.00 [0.94-1.07]; emotional 1.03 [0.94-1.12]) or 12 months (physical 0.95 [0.89-1.02]; sexual 0.96 [0.90-1.02]; emotional 0.98 [0.91-1.05]). None of the 3 IPV categories affected contraceptive use when the outcome was restricted to either barrier or non-barrier methods. ConclusionsIn this cohort, IPV was not a key driver of contraceptive use in longitudinal analyses. Interventions are needed to address the alarming rates of IPV in this population, but addressing IPV alone might be insufficient to address low contraceptive use, and multifaceted youth-friendly health services might be necessary.

Adverse childhood experiences and disordered eating among middle-aged adults: Findings from the coronary artery risk development in young adults study

Adverse childhood experiences (ACEs) include childhood abuse, neglect, and household substance abuse. Childhood abuse is a risk factor for disordered eating (DEB). Less well established are associations of childhood neglect and household substance abuse with DEB, and little research has examined ACE associations with DEB in middle adulthood. The objective of this study was to examine associations between ACEs and DEBs among middle-aged adults and examine sex differences. ACEs prior to age 18 were retrospectively assessed in the Coronary Artery Risk Development in Young Adults study in 2000–2001 (N = 3340, ages 32 to 46). DEB outcomes (i.e., concerns about weight and shape, anxiety about eating or food, unhealthy weight control behaviors, chronic dieting, overeating, and binge eating) were assessed in 1995–1996 (ages 27 to 41). Modified Poisson regressions estimated risk ratios (RRs) for associations of a history of any ACE, each ACE, and cumulative ACEs with DEB outcomes. Among women, emotional abuse, physical neglect, and emotional neglect were each modestly associated with most DEBs (RRs = 1.21–1.35, 1.21–1.45, and 1.23–1.41 across DEBs, respectively) after adjustment for sociodemographic variables, BMI, and depressive symptoms. A cumulative ACE score was associated with all DEBs in a stepwise manner (p for trend ≤0.05) except concerns about weight and shape and overeating. Among men, emotional abuse was most consistently related to the majority of DEBs (RRs = 1.23–1.92); household substance abuse was modestly associated with overeating (RR = 1.26, 95% CI = 1.04–1.53). ACEs were cumulatively associated with unhealthy weight control behaviors, overeating, and binge eating (p for trend <0.01).

A Longitudinal Study on the Impact of Indoor Temperature on Heat-Related Symptoms in Older Adults Living in Non-Air-Conditioned Households.

Background:Both chronic and acute heat result in a substantial health burden globally, causing particular concern for at-risk populations, such as older adults. Outdoor temperatures are often assessed as the exposure and are used for heat warning systems despite individuals spending most of their time indoors. Many studies use ecological designs, with death or hospitalizations rates. Individual-level outcomes that are directly related to heat-symptoms should also be considered to refine prevention efforts.Objectives:In this longitudinal study, we assessed the association between indoor temperature and proximal symptoms in individuals of age living in non–air-conditioned households in Montérégie, Quebec, during the 2017–2018 summer months.Methods:We gathered continuously measured indoor temperature and humidity from HOBO sensors and repeated health-related questionnaires about health-related symptoms administered across three periods of increasing outdoor temperatures, where the reference measurement (T1) occurred during a cool period with a target temperature of 18–22°C and two measurements (T2 and T3) occurred during warmer periods with target temperatures of 28–30°C and 30–33°C, respectively. We used generalized estimating equations with Poisson regression models and estimated risk ratios (RRs) between temperature, humidity, and each heat-related symptom.Results:Participants () had an average age of . Higher indoor temperatures were associated with increased risk of dry mouth (T3 ; 95% CI: 1.8, 3.5), fatigue (; 95% CI: 1.8, 3.0), thirst (; 95% CI: 2.5, 4.5), less frequent urination (; 95% CI: 1.8, 7.3), and trouble sleeping (; 95% CI: 1.6, 3.2) compared with T1. We identified a nonlinear relationship with indoor temperatures across most symptoms of interest.Discussion:This study identified that increasing indoor temperatures were associated with various health symptoms. By considering the prevalence of these early stage outcomes and indoor temperature exposures, adaptation strategies may be improved to minimize the burden of heat among vulnerable communities. https://doi.org/10.1289/EHP10291

P-789 Early childhood respiratory tract infections according to parental subfertility and conception by assisted reproductive technologies

Abstract Study question Are children conceived by assisted reproductive technologies (ART) or born to subfertile parents more susceptible for upper- or lower respiratory infections (URTI, LRTI)? Summary answer ART-conceived children had higher frequency and risk of hospitalization for respiratory infections up to age 3, which can only partly be explained by parental subfertility. What is known already Some studies report higher health care use, health care costs and increased risks of infections in children conceived by ART. Results for URTIs and LRTIs are inconclusive, and the contribution of underlying parental subfertility remains unclear. Study design, size, duration We included 84 102 singletons of the prospective Norwegian Mother, Father and Child Cohort Study (MoBa) born between 1999-2008. Mothers reported time-to-pregnancy at recruitment and respiratory infections, frequency, and hospitalisation by questionnaires when the child was 6, 18 and 36 months old. The birth registry provided information on ART and subfertility was defined ≥ 12 months to conception. URTI included throat and ear infections, while LRTI included bronchitis, bronchiolitis, respiratory syncytial virus, and pneumonia. Participants/materials, setting, methods We used log-binomial regression to estimate risk ratios (RR) and 95% confidence intervals (CI) of any infection and hospitalisation. We used negative-binomial regression receiving incidence rate ratios (IRR) and 95% CI for number of infections. We compared children conceived by ART and naturally conceived by subfertile parents to children of fertile parents (reference) while adjusting for maternal age, education, body-mass-index and smoking during pregnancy and previous livebirths. We clustered children born to the same mother. Main results and the role of chance A total of 7334 (8.7%) singletons were naturally conceived by subfertile parents and 1901 (2.3%) by ART. Between age 0-36 months, 41 639 (49.5%) of children experienced any URTI, 15 542 (18.5%) any LRTI, and 4134 (4.9%) were hospitalized due to LRTI. Over the first three years of life, the risk for higher frequency of URTI (aIRR 1.16; 95% CI 1.05-1.28) and any hospitalisation due to LRTI (aRR 1.25; 95% CI 1.02-1.53) was increased for children conceived by ART but not for children of subfertile parents. Risks of respiratory infections were not increased at age 0-6 or 7-18 months. Only at age 19-36 months, children of subfertile parents had higher risk of LRTIs (adjusted relative risk (aRR) 1.09, 95%CI 1.01-1.17). Children conceived by ART had an increased risk of any LRTI (aRR 1.16, 95% CI 1.01-1.33), increased frequency of LRTI’s (IRR 1.26; 95%CI 1.04- 1.51) and higher risk of hospitalisation for LRTI (aRR 1.38; 95% CI 1.03-1.84) at 19-36 months as well as an increased frequency of URTI’s (aIRR 1.20; 95% CI 1.08-1.34). Limitations, reasons for caution Use of self-reported time-to-pregnancy and respiratory tract infections by parents could lead to misclassification. Selection bias makes the MoBa Cohort somewhat different from the general Norwegian population and lost to follow-up is not at random. Wider implications of the findings ART-conceived children might be more susceptible to respiratory tract infections in early childhood. This appears to be only partly explained by factors related to underlying parental subfertility. The immune response in children might be affected by parental subfertility or through ART technology and this should be further investigated. Trial registration number not applicable

Efficacy and safety of urate-lowering agents in asymptomatic hyperuricemia: systematic review and network meta-analysis of randomized controlled trials

BackgroundAsymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.MethodsMEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.ResultsNMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m2, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m2, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.ConclusionsEvidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.Trial registration.This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12th November 2019.

Temporal variation in individual social risk factors associated with testing positive for SARS-CoV-2 among veterans in the veterans health administration

PurposeMarginalized communities have been disproportionally impacted by SARS-CoV-2. How the associations between social determinants of health and the risk of SARS-CoV-2 infection shifted across time is unknown. In this evaluation, we examine individual-level social determinants of health as social risk factors for SARS-CoV-2 infection across the first 12 months of the pandemic among US Veterans.MethodsWe conducted a retrospective cohort analysis of 946,358 Veterans who sought testing or treatment for SARS-CoV-2 infection in U.S. Department of Veterans Affairs medical facilities. We estimated risk ratios for testing positive by social risk factors, adjusting for demographics, comorbidities, and time. Adjusted models were stratified by pandemic phase to assess temporal fluctuations in social risks.ResultsApproximately 19% of Veterans tested positive for SARS-CoV-2. Larger household size was a persistent risk factor and this association increased over time. Early in the pandemic, lower county-level population density was associated with lower SARS-CoV-2 infection risk, but between June 1 and August 31, 2020, this trend reversed.ConclusionsTemporal fluctuations in social risks associated with Veterans’ SARS-CoV-2 infection suggest the need for ongoing, real-time tracking as the social and medical environment continues to evolve.

Serious arrhythmia in initiators of citalopram, escitalopram, and other selective serotonin reuptake inhibitors: A population-based cohort study in older adults.

The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued. We conducted a series of nationwide cohort studies emulating a target trial using Danish healthcare register data from January 1, 2002, to December 31, 2016. We included patients (aged ≥65 years) who filled an SSRI prescription with a 1‐year washout period before the index date. The outcome was an event of serious arrhythmia. Individuals were followed for a maximum of 6 months using an intention‐to‐treat approach. Log‐binomial regression analyses were performed, estimating risk ratios (RRs) and 95% confidence intervals (CIs) adjusting for age and sex, comorbidities, and comedications with propensity scores. Dose–response effects were not investigated because dosage instructions were not available. We included 167,366 (146,014 individuals), 40,113 (37,069 individuals), and 50,281 (44,754 individuals) person‐trials of citalopram, escitalopram, and other SSRIs, respectively. In total, there were 228 events of serious arrhythmia. No difference in risk was observed in the entire study period for either citalopram (0.87 [0.62–1.22]) or escitalopram (0.85 [0.53–1.40]). We identified lower point estimates after the safety warning, RR 0.54 (95% CI 0.31–0.93) for citalopram and 0.58 (0.20–1.63) for escitalopram. Initiation of citalopram and escitalopram was not associated with an increased risk of serious arrhythmia. However, lower point estimates were observed after the safety warning.

Factors associated with testing for HIV and other sexually transmitted infections in men who have sex with men and transgender women in Bangkok, Thailand

BackgroundRoutine screening for HIV and other sexually transmitted infections (STIs) facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We estimated the prevalence of prior HIV/STI testing among men who have sex with men (MSM) and transgender women (TGW) in Bangkok, Thailand, and identified factors associated with prior testing.MethodsCross-sectional analyses were performed using data collected at enrollment into an HIV incidence cohort. From April to October 2017, MSM and TGW were enrolled if they were aged 18–35 years, reported anal intercourse with a male or TGW partner, and reported behavioral vulnerability to HIV. Participants answered questions about demographics, sexual behaviors, and lifetime HIV/STI testing history. Multivariable robust Poisson regression was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for factors potentially associated with prior testing.ResultsAmong 1,014 participants, 348 (34.3%) were TGW and the median age was 21.6 (interquartile range 20.0-24.8) years. Prior testing for HIV was reported by 421 (41.5%) and for other STIs by 268 (26.4%). HIV testing was more common among participants aged ≥ 22 years (RR 1.37 [95% CI 1.13–1.67]), with college education as compared to secondary or less (RR 1.37 [95% CI 1.08–1.72]), and who met male sexual partners online (RR 1.52 [95% CI 1.24–1.85]), but lower among participants attracted to both men and women as compared to men only (RR 0.64 [95% CI 0.51–0.81]) and who met male sexual partners in bars (RR 0.83 [95% CI 0.72–0.97]). Similar associations were observed with prior testing for other STIs, including increased testing among participants with college education (RR 1.52 [95% CI 1.11–2.09]) and who met male sexual partners online (RR 1.73 [95% CI 1.30–2.31]), but lower among participants attracted to both men and women (RR 0.70 [95% CI 0.51–0.96]) and who met male sexual partners in bars (RR 0.67 [95% CI 0.54–0.83]).ConclusionsDespite behavioral vulnerability, prior testing for HIV and other STIs was uncommon. Online engagement strategies may be effectively reaching Thai MSM and TGW who meet sexual partners online, but new interventions are needed to encourage testing among younger, less educated, and bisexual MSM and TGW.

Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium.

The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time.

What is the association between secondhand smoke (SHS) and possible obstructive sleep apnea: a meta-analysis

BackgroundAssociation between smoking and sleep apnea is well-known from previous studies. However, the influence of secondhand smoke (SHS), which is a potential risk factor of obstructive sleep apnea (OSA), remains unclear. Our aim was to investigate the relationship between SHS and OSA using a meta-analysis.Materials and methodsFor the meta-analysis, searches were performed in MEDLINE, EMBASE, and Web of Science databases on January 10, 2022, by combining various keywords including “SHS exposure” and “OSA”. Data were extracted using defined inclusion and exclusion criteria. Fixed-effects model meta-analyses were used to pool risk ratio (RR) estimates with their 95% confidence intervals (CI). I2 was used to assess heterogeneity. Moreover, we performed subgroup meta-analyses of children-adults, and smoker fathers and mothers.ResultsIn total, 267 articles were obtained through an electronic search. Twenty-six articles were included in our analysis according to the inclusion and exclusion criteria. We found evidence of an association between SHS exposure and possible OSA (RR 1.64, 95% CI 1.44–1.88). The results of the subgroup analyses showed that children passive smokers (RR 1.84, 95% CI 1.60–2.13) were at greater risks of possible OSA than adult passive smokers (RR 1.35, 95% CI 1.21–1.50). Also, significant differences were observed in mothers with smoking exposure (RR 2.61, 95% CI 1.62–4.21, p < 0.0001), as well as in fathers with smoking exposure (RR 2.15, 95% CI 0.98–4.72, p = 0.06).Short conclusion.Our meta-analysis confirmed that SHS exposure is significantly associated with OSA. In the subgroup analyses, the association of SHS and possible OSA was significant in both children and adults, as well as in smoker mothers and fathers.

Abstract CT551: Randomized phase III study comparing the efficacy and safety of CT-P16, a new biosimilar, to reference bevacizumab (Avastin®) in patients with metastatic or recurrent non-small cell lung cancer (NSCLC)

Abstract Background: CT-P16 is a proposed biosimilar to FDA approved reference bevacizumab (BV), namely Avastin®. This trial (NCT03676192) compared the efficacy and safety of CT-P16 and BV in patients with metastatic or recurrent non-squamous NSCLC. Methods: This double blind, randomized, multicenter study randomly assigned patients to CT-P16 or BV with carboplatin and paclitaxel, up to 6 cycles (Induction Period), followed by maintenance CT-P16 or BV monotherapy until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) during the Induction Period. ORR includes complete or partial responses based on RECIST v1.1 assessed by an independent reviewer. Secondary endpoints were Quality of life (QoL), PK, safety, and immunogenicity. Results: A total of 689 patients were randomized (CT-P16: 342, BV: 347). The baseline characteristics were well balanced. ORRs were similar between the two treatment arms and the 90% confidence intervals (CIs) for the risk ratio estimate (0.7368, 1.3572) and 95% CIs for risk difference estimate (±12.5%) were within the equivalence margin in both ITT (intent-to-treat) and PP (per-protocol) sets. QoL results (QLQ-C30 and QLQ-LC13) and PK parameter (Ctrough) were comparable between the two treatment arms. The overall incidence of treatment-emergent adverse events (TEAEs), serious AEs (TESAEs), AEs leading to discontinuation, and AEs leading to death was similar between the two treatment arms (96.2% vs. 92.4%, 19.4% vs. 20.1%, 15.1% vs. 14.5%, and 6.4% vs. 6.4% for the CT-P16 and BV treatment arm, respectively). The incidence of treatment-emergent anti-drug antibodies was comparable (14.2% vs. 16.0%). Conclusions: This study demonstrated that CT-P16 is equivalent to BV as measured by ORR in patients with metastatic or recurrent adenocarcinoma of the lung. Other endpoints including PK, QoL, safety and immunogenicity were comparable. Primary endpoint ITT PP CT-P16 (N=342) BV (N=347) CT-P16 (N=318) BV (N=303) Independent reviewer ORR (%) 95% CI 42.40 (37.16 - 47.64) 42.07 (36.88 - 47.27) 45.28 (39.81 - 50.75) 47.19 (41.57 - 52.82) Risk ratio estimate (90% CI) 1.0136 (0.8767, 1.1719) 0.9662 (0.8387, 1.1132) Risk difference estimate (%) (95% CI) 0.40 (-7.02, 7.83) -1.90 (-9.80, 6.00) Investigator ORR (%) 95% CI 43.86 (38.60 - 49.12) 39.19 (34.06 - 44.33) 46.54 (41.06 - 52.02) 43.89 (38.31 - 49.48) Risk ratio estimate (90% CI) 1.1234 (0.9683, 1.3032) 1.0648 (0.9209, 1.2313) Risk difference estimate (%) (95% CI) 4.87 (-2.53, 12.26) 2.90 (-4.99, 10.79) Citation Format: Yuichiro Ohe, Igor Bondarenko, Zoran Andric, Yuriy Ostapenko, Tudor Ciuleanu, Fedor Moiseenko, Tamta Makharadze, Sergii Shevnya, Alona Oleksiienko, Eduardo Yañez Ruiz, SungHyun Kim, KeumYoung Ahn, TaeHong Park, Sijin Park, JiEun Lee, MinJi Kim, Claire Verschraegen. Randomized phase III study comparing the efficacy and safety of CT-P16, a new biosimilar, to reference bevacizumab (Avastin®) in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT551.

Abstract 1239: Prognostic and predictive value of PIK3CA mutations in metastatic CRC (mCRC)

Abstract Background: Molecular aberrations including MSI, RAS, RAF, and HER2 have been used to guide the management of mCRC. However, the role of PIK3CA mutations is unclear in mCRC. In this study, we aimed to determine the prognostic value of PIK3CA mutations and their predictive value of response to anti-EGFR therapy in mCRC patients (pts). Methods: Pts with mCRC and clinical next generation sequencing were identified from the Clinical Genomics Action Committee database at Moffitt Cancer Center. Clinical and molecular aberration data were retrospectively collected. Progression-free survival (PFS) was the time from treatment initiation to clinical or radiographic disease progression. Overall survival (OS) was the time from diagnosis of metastatic disease to death. Kaplan Meier method and log-rank test were used for survival analysis. A parametric exponential model was implemented for PIK3CA exon analysis to account for small sample size. Pearson correlation coefficient was determined for correlation between PIK3CA and co-mutations. An additional meta-analysis was performed including prior studies of pts with KRAS wild-type (wt) PIK3CA mutant (mut) mCRC receiving anti-EGFR therapy using random effects model. Results: Among 639 pts with mCRC, PIK3CA mutation was positively correlated with KRAS mutation (r=0.11, p=0.006) and negatively correlated with TP53 mutation (r=-0.18, p=&amp;lt;0.001). It was not correlated with BRAF or APC mutations. Among 335 pts with KRAS wt mCRC, 174 were PIK3CA wt without anti-EGFR therapy; 111 were PIK3CA wt with anti-EGFR therapy; 33 were PIK3CA mut without anti-EGFR therapy; and 16 were PIK3CA mut with anti-EGFR therapy. Median OS of PIK3CA mut pts was 35.5 months, significantly shorter (HR 2.0, 95%CI 1.2-3.1) that median OS of 55.3 months in PIK3CA wt mCRC pts. The same was observed in pts (n=10) with PIK3CA exon 20 mutation (mOS: 18.5 months, HR 2.6, 95%CI 1.1-6.0) and pts (n=18) with PIK3CA exon 9 mutation (mOS: 38 months, HR 2.15, 95%CI 1.1-4.3). Among 166 pts evaluable for response rate, 44% PIK3CA wt pts responded to anti-EGFR therapy compared to 56% PIK3CA mut pts (p=0.51). Median PFS between PIK3CA mut and PIK3CA wt pts receiving anti-EGFR therapy was 10.3 versus 7.2 months (p=0.6), respectively. Our study and previously published 12 studies from 2005 to 2015 were examined in a meta-analysis where the included studies lacked significant heterogeneity (I2=0%, p=0.6). Among 1047 pts with KRAS wt mCRC who received anti-EGFR therapy, 104 of them were PIK3CA mut. The estimated risk ratio for response to anti-EGFR therapy was 0.77 (95%CI 0.5-1.1) with prediction interval between 0.4 and 1.6. Conclusion: PIK3CA mutation has positive correlation with KRAS mutation and negative correlation with TP53 mutation in mCRC. PIK3CA mutation confers a worse prognosis but is not predictive for response to anti-EGFR therapy in pts with KRAS wt mCRC. The latter finding was confirmed in an updated meta-analysis of 13 studies including ours. Citation Format: Elaine Tan, Wenyi Fan, Michael Schell, Ibrahim Sahin, Jason Fleming, Todd Knepper, Hao Xie. Prognostic and predictive value of PIK3CA mutations in metastatic CRC (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1239.

Comparison of robot-assisted sleeve gastrectomy outcomes in multiple staple line treatment modalities from 2015 to 2019: a 5-year propensity score-adjusted MBSAQIP® analysis.

Robot-assisted sleeve gastrectomy (RSG) is an increasingly common approach to sleeve gastrectomy (SG). Staple line reinforcement (SLR) is well-discussed in laparoscopic SG literature, but not RSG- likely due to the absence of dedicatedrobotic SLR devices. However, most RSG cases report SLR. This retrospective analysis compares outcomes in RSG cases reporting (1) any staple line treatment (SLT) vs none and (2) SLR vs oversewing. MBSAQIP was queried for adults who underwent RSG from 2015 to 2019. Open procedures, Natural Orifice Transluminal Endoscopic Surgery, hand-assisted, single-incision, concurrent procedures, and illogical BMIs were excluded (n = 3444). Final sample included 52,354 patients. Two comparisons were made: SLT (n = 34,886) vs none (n = 17,468) and SLR (n = 22,217) vs oversew (n = 5620). We fitted multivariable regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) and performed propensity score analysis with inverse probability of treatment weight based on patient factors. Most RSG cases utilized SLT (66.6%). Cases with SLT had a reduced risk of organ space SSI (RR 0.68 [0.49, 0.94]), 30-day reoperation (RR 0.77 [0.64, 0.93]), 30-day re-intervention (RR 0.80 [0.67, 0.96]), sepsis (RR 0.58 [0.35, 0.96]), unplanned intubation (RR 0.59 [0.37, 0.93]), extended ventilator use (RR 0.46 [0.23, 0.91]), and renal failure (RR 0.40 [0.19, 0.82]) compared to no-treatment cases. In single-treatment cases (n = 27,837), most utilized SLR (79.8%). Cases with oversew had a higher risk of any SSI (RR 1.70 [1.19, 2.42]), superficial incisional SSI (RR 1.71 [1.06, 2.76]), septic shock (RR 6.47 [2.11, 19.87]), unplanned intubation (RR 2.18 [1.06, 4.47]), and extended ventilator use (> 48h) (RR 4.55 [1.63, 12.71]) than SLR. Our data suggest SLT in RSG is associated with reduced risk of some adverse outcomes vs no-treatment. Among SLT, SLR demonstrated lower risk than oversewing. However, risk of all-cause mortality, cardiac arrest, and unplanned ICU admission were not significant.

Area-level socioeconomic deprivation, non-national residency, and Covid-19 incidence: A longitudinal spatiotemporal analysis in Germany.

SummaryBackgroundSocioeconomic conditions affect the dynamics of the Covid-19 pandemic. We analysed the association between area-level socioeconomic deprivation, proportion of non-nationals, and incidence of Covid-19 infections in Germany.MethodsUsing linked nationally representative data at the level of 401 German districts from three waves of infection (January-2020 to May-2021), we fitted Bayesian spatiotemporal models to assess the association between socioeconomic deprivation, and proportion of non-nationals with Covid-19 incidence, controlling for age, sex, vaccination coverage, settlement structure, and spatial and temporal effects. We estimated risk ratios (RR) and corresponding 95% credible intervals (95% CrI). We further examined the deprivation domains (education, income, occupation), interactions between deprivation, sex and the proportion of non-nationals, and explored potential pathways from deprivation to Covid-19 incidence.FindingsCovid-19 incidence risk was 15% higher (RR=1·15, 95%-CrI=1·06–1·24) in areas classified with the highest deprivation quintile (Q5) compared to the least deprived areas (Q1). Medium-low (Q2), medium (Q3), and medium-high (Q4) deprived districts showed 6% (1·06, 1·00–1·12), 8% (1·08, 1·01–1·15), and 5% (1·05, 0·98–1·13) higher risk, respectively, compared to the least deprived. Districts with higher proportion of non-nationals showed higher incidence risk compared to districts with lowest proportion, but the association weakened across the three waves. During the first wave, an inverse association was observed with highest incidence risk in least deprived areas (Q1). Deprivation interacted with sex, but not with the proportion of non-nationals.InterpretationSocioeconomic deprivation, and proportion of non-nationals are independently associated with the incidence of Covid-19. Regional planning of non-pharmaceutical interventions and vaccination strategies would benefit from consideration of area-level deprivation and non-national residency.FundingThe study was funded by the German Ministry of Health (ZMV I 1 - 25 20 COR 410).