Relative Risk Estimates Research Articles

Differential Effectiveness of Water, Sanitation, and Handwashing Interventions to Reduce Child Diarrhea in Dry and Rainy Seasons: A Systematic Review and Meta-Analysis of Intervention Trials.

Studies evaluating how water, sanitation, and/or handwashing (WASH) interventions in low- and middle-income countries impact diarrheal diseases have shown inconsistent results. The prevalence of enteric pathogen infections and diarrhea are highly seasonal and climate-sensitive, which could explain heterogeneous findings. Understanding how season influences the effectiveness of WASH interventions is critical for informing intervention approaches that will be resistant under the varying weather conditions that climate change will bring. We conducted a systematic review of the literature and meta-analysis to test whether and to what extent the impact of WASH interventions on diarrhea differs by season. We searched the literature for randomized and nonrandomized controlled WASH intervention trials and identified the season in which data were collected-rainy, dry, or both-for each study using proximate land station weather datasets. We compared the relative risk (RR) estimates for the impact of interventions on diarrhea for each study, stratified by season, and analyzed estimates using meta-analysis and meta-regression. This study is registered with PROSPERO, CRD42021231137. A total of 50 studies met the inclusion criteria, resulting in 34 drinking water intervention estimates, 8 sanitation intervention estimates, and 14 handwashing intervention estimates. Of the total studies, 60% () spanned more than one season, with most single-season studies (75%, ) occurring exclusively in the dry season. The effect of WASH interventions was stronger in dry seasons than in rainy seasons, with a 33% [95% confidence interval (CI): 24%, 41%] and 18% reduction (95% CI: 5%, 29%) in diarrhea risk, respectively. When stratified by type of intervention, the stronger effect size in dry seasons was consistent for water and handwashing interventions but not for sanitation interventions. Estimates of the seasonal impact of WASH interventions revealed larger effects in the dry season than in the rainy season overall and for water and handwashing interventions in particular. These patterns likely affected previous estimates of intervention effectiveness, which included more dry season estimates. These findings suggest the need to collect data across seasons and report seasonally stratified results to allow for more accurate estimates of the burden of disease impacted by WASH investments and to improve projections of potential impacts of these interventions under future climate conditions. These findings also underscore the need for robust WASH interventions designed to be resistant to seasonal variations in temperature and rainfall now and under future climate change scenarios. https://doi.org/10.1289/EHP14502.

Calculation of lifetime relative risks from summary cohort data and application to calculation of attributable fractions.

In cohort studies, relative risks are estimated by comparing eventual disease risk in individuals exposed to the risk factor at baseline with similar unexposed individuals. However, such relative risk estimates intrinsically depend on how many of the unexposed individuals develop exposure after baseline and on the ages at which the exposed individuals developed exposure prior to baseline. These factors pertain to the distribution of risk factor incidence in the population, rather than to the causal effect the risk factor has on disease. As such, these cohort relative risk estimates have no straightforward causal interpretation, even after adjustment for confounding. Here, we instead consider initial exposure to the risk factor at differing ages as differing treatments, with corresponding potential outcomes. Subsequently, we define lifetime relative risk as the relative probability of eventual disease comparing initial exposure to the risk factor at differing ages to lifetime non-exposure. We describe a procedure to approximate lifetime relative risks using summary data from published cohort studies, and detail conditions under which such estimation is valid. In addition to being of independent interest, lifetime relative risks are useful in estimating population attributable fractions (PAF)s. In our applied example, we illustrate this connection via application of estimated lifetime relative risks to assess the PAF for incident vascular dementia due to hypertension in the United Kingdom.

Severe Maternal Morbidity Associated With Chronic Hypertension, Preeclampsia, and Gestational Hypertension

Chronic hypertension and preeclampsia are leading risk enhancers for maternal-neonatal morbidity and mortality. Severe maternal morbidity (SMM) indicators include heart, kidney, and liver disease, but studies have not excluded patients with preexisting diseases that define SMM. Thus, SMM risks for uncomplicated chronic hypertension specific to preeclampsia remain unclear. To determine SMM rates and estimate relative risks associated with hypertensive disorders of pregnancy among patients with and without chronic hypertension unencumbered by preexisting vascular or end organ diseases. This retrospective cohort study used longitudinal health data from electronic health records from patients within a community-based, integrated health care system in northern California. The study cohort selected 263 518 pregnant patients without pregestational heart, kidney, or liver disease entering prenatal care at 14 weeks' gestation or earlier and delivering a singleton stillbirth or live birth in 2009 to 2019. The data were analyzed between February 2022 and March 2024. Five joint subgroups combining chronic hypertension status and the hypertensive disorders developing during pregnancy, defined as follows: (1) chronic hypertension with superimposed preeclampsia, (2) chronic hypertension and no preeclampsia, (3) no chronic hypertension with preeclampsia, (4) gestational hypertension, and (5) no chronic hypertension and no preeclampsia or gestational hypertension (reference group). The main outcome was SMM rates at delivery hospitalization (cases per 10 000 births) using the Centers for Disease Control and Prevention criteria (≥1 of 21 indicators to define SMM) obtained from electronic health records. Modified Poisson regression models estimated crude and adjusted relative risks (aRRs) and 95% CIs of SMM associated with the chronic hypertension and developing hypertensive disorders of pregnancy groups vs the reference group (no chronic hypertension and no preeclampsia or gestational hypertension) adjusted for clinical, sociodemographic, social, and behavioral covariates. The analysis included a total of 263 518 pregnant patients (mean [SD] age at delivery, 31.0 [5.3] years), including 249 892 patients without chronic hypertension (4.7% developed preeclampsia) and 13 626 patients with chronic hypertension (31.5% developed superimposed preeclampsia). The highest SMM rates occurred in the no chronic hypertension with preeclampsia (934.3 [95% CI, 882.3-988.3] cases per 10 000 births) and the chronic hypertension with superimposed preeclampsia (898.3 [95% CI, 814.5-987.8] cases per 10,000 births) groups. Lower SMM rates occurred in the chronic hypertension and no preeclampsia (195.1 [95% CI, 168.0-225.2] cases per 10,000 births), gestational hypertension (312.7 [95% CI, 281.6-346.1] cases per 10,000 births), and no chronic hypertension and no preeclampsia or gestational hypertension (165.8 [95% CI, 160.6-171.2] cases per 10,000 births) groups (P < .001). Compared with the no chronic hypertension and no preeclampsia or gestational hypertension group, risks of SMM were significantly higher for the chronic hypertension with superimposed preeclampsia group (aRR, 4.97 [95% CI, 4.46-5.54]), no chronic hypertension with preeclampsia group (aRR, 5.12 [95% CI, 4.79-5.48]), chronic hypertension and no preeclampsia group (aRR, 1.17 [95% CI, 1.003-1.36]; P = .046), and the gestational hypertension group (aRR, 1.78 [95% CI 1.60-1.99]). This cohort study found that the highest SMM rates at delivery hospitalization occurred for preeclampsia superimposed on chronic hypertension and preeclampsia without chronic hypertension, while gestational hypertension had intermediate rates of SMM. The patients with chronic hypertension who did not develop preeclampsia had SMM rates that were nearly the same as the lowest-risk patients without chronic hypertension who did not develop preeclampsia or gestational hypertension. These findings provide evidence that prevention of preeclampsia among patients with uncomplicated chronic hypertension is paramount to mitigating maternal morbidity.

Cancer Incidence Among People With a Prior Hospital Record of Depression in Scotland, 1991-2019: A Cohort Study.

Current evidence on the association between depression and cancer risk is conflicting, with little understanding of how associations vary by time period or sociodemographic factors. We aimed to compare cancer incidence in people with versus without a previous hospital admission record for depression, by sociodemographic factors and over time. We conducted a cohort study using national linked data in Scotland from 1991 to 2019. We calculated sex-stratified age standardised incidence rates for all cancers, lung, female breast, colorectal and prostate cancer, and used quasi-Poisson regression models to obtain sex-specific estimates of cancer incidence and relative risks of cancer in those with versus without a prior hospital admission record of depression. There were 128,654 people with a hospital record of depression with 12,802 incident cancers and 847,656 cancers among those without depression. Age-standardised cancer incidence rates were higher in both males and females with versus without depression. Depression was associated with a 20%-30% increased risk of all cancers combined, a difference that did not vary by sex, age or deprivation and persisted over three decades. Depression was associated with higher risks of lung (RR 1.79, 95% CI 1.70-1.88) and colorectal cancer (RR 1.12, 95% CI 1.05-1.19), but not breast or prostate cancer. We identified an entrenched disparity in cancer incidence by depression status. Further research should identify underlying mechanisms and inform cancer prevention strategies in this vulnerable group. Meanwhile, health care professionals have a key role to play in optimising physical health care for people with depression.

Cerclage in singleton pregnancies with no prior spontaneous PTB and short cervix: a randomized controlled trial.

PTB (PTB) remains a leading cause of neonatal morbidity and mortality. Cerclage for short cervical length (CL) ≤25mm in singletons with a history of spontaneous PTB is associated with decreased neonatal morbidity/mortality. Both vaginal progesterone and cerclage individually have level 1 evidence supporting benefit in prevention of PTB in pregnancies complicated by short CL, however there is a paucity of level 1 evidence regarding the potential benefit of cerclage with progesterone compared to progesterone alone for short CL ≤25mm in singletons without a history of spontaneous PTB. We aimed to conduct a pragmatic randomized controlled trial to evaluate the additional benefit of cerclage with vaginal progesterone compared to vaginal progesterone alone in singletons without prior spontaneous PTB and with a current mid-trimester transvaginal ultrasound (TVU) CL ≤25mm STUDY DESIGN: This is a multicenter international randomized controlled trial from 09/2017-09/2023 with four sites in the United States and Italy. Singleton pregnancies without prior spontaneous PTB received TVUCL (universal) screening during mid-trimester anatomy ultrasound as part of routine care. Inclusion criteria was TVUCL≤25mm at 18 0/7 - 23 6/7 weeks. Exclusion criteria included current or planned cerclage, cervical dilation, symptoms of labor, infection, bleeding, rupture of membranes at screening. Participants were randomized 1:1 to cerclage with vaginal progesterone (200mg vaginal progesterone daily) or vaginal progesterone alone; randomization was stratified by study site and TVUCL≤15mm. Primary outcome was PTB<35 weeks by intention to treat analysis. Secondary outcomes included PTB <37,32,28,24 weeks, gestational age at delivery, latency to delivery, and neonatal outcomes. Categorical variables were compared with Pearson Chi-Square and relative risk (RR) estimate and 95% confidence interval (CI). Continuous variables compared with Mann Whitney U test. Latency to delivery and gestational age at delivery were also compared with Kaplan Meier Survival Curve. Planned enrollment was N=206 based on an estimated 0.54 relative risk with cerclage and a 34% incidence of PTB with standard care. The trial was registered on clinicaltrials.gov (NCT03251729) on June 22, 2017. Enrollment ran from September 22nd, 2017- October 31st, 2023, and it was halted early due to lagging enrollment. Ninety-three participants were randomized, three were excluded due to withdrawal (n=1) and loss to follow up (n=2). Of the 90 included in the intention to treat analysis, 43 to cerclage and progesterone, and 47 to progesterone alone. Overall, 40 (40.4%) had a TVUCL≤15mm. There was no significant difference in primary outcome PTB<35 weeks in those randomized to cerclage with progesterone vs progesterone alone: 16.3% vs 23.4%, RR 0.70 (0.30-1.63). Those randomized to cerclage with progesterone had significantly increased latency from randomization to delivery, median difference 13 (5-20) days (p=0.01), and a significantly later gestational age at delivery, median difference 1.0 (0.2-1.7) weeks (p=0.035). Kaplan Meier Survival curve also demonstrated increased latency to delivery and gestational age at delivery for cerclage with progesterone compared to progesterone alone, Mantel Cox Log Rank p<0.001 and p=0.003 respectively. These findings persisted within both subgroups of ≤15mm and at 16-25mm. In singleton gestations without a prior spontaneous PTB, and a TVU CL ≤25mm before 24 weeks, cerclage with progesterone was not found to significantly reduce PTB rate, but did result in a significantly longer latency from randomization to delivery, and a significantly later gestational age at delivery, compared to progesterone alone. These results suggest the potential for benefit with cerclage and progesterone compared to progesterone alone in singletons without a prior spontaneous PTB and a short cervical length ≤25mm before 24 weeks. This trial was halted early and these findings should be confirmed in larger trial or meta-analysis. In singletons with short cervix and no prior spontaneous PTB cerclage with progesterone compared to progesterone alone did not reduce incidence of PTB; but those with cerclage and progesterone had increased latency to delivery and gestational age of delivery. This trial was halted early, and larger clinical trials or meta-analyses are necessary.

Cardiovascular disease risk in cancer survivors: a population-based cohort study from the UK Biobank, and meta-analysis of cohort studies

IntroductionIn addition to the well-recognised cardiotoxicity of cancer treatment, possible aetiological links between cancer diagnosis and cardiovascular disease (CVD) have gained growing research interests. We aimed to estimate the CVD...

Positive clinical tests for medial epicondylalgia are more common than tests for lateral epicondylalgia in recreational pickleball players: A cross-sectional study.

Epicondylalgia is a common overuse injury in tennis. However, little is known regarding epicondylalgia in pickleball. This study examined the prevalence of positive epicondylalgia tests in recreational pickleball players and the relationship between positive tests and player characteristics. Cross-sectional study. Clinical tests for epicondylalgia were performed courtside on the dominant arm of 129 recreational pickleball players.Participants completed a survey with questions related to demographics and play characteristics. Descriptive data were reported for epicondylalgia testing and survey performance. Chi-squared analysis and Fisher's exact test were used to determine associations between testing and survey responses. Relative risk estimates for positive tests for epicondylalgia were calculated based on pickleball playing characteristics. The prevalence of positive tests was 7% for medial epicondylalgia, 5.4% for lateral epicondylalgia, and 2.3% for both medial epicondylalgia and lateral epicondylalgia. Ninety-two participants (71.3%) completed the survey. Those who participated in tournaments were less likely to have a positive test for medial epicondylalgia (Fisher's exact test, p=0.017). The relative risk of having a positive epicondylalgia test was lower for those who have played for at least 4 years (medial=0.875 [CI 0.81-0.95] and lateral 0.913 [CI 0.866-0.979]). Epicondylalgia testing was not associated with age, sex, hand dominance, level of play, location of play, warm-up performance, frequency of play, or length of play. Among pickleball players, there was a lower prevalence of positive tests for lateral epicondylalgia than for medial epicondylalgia. Compared to tennis, lateral epicondylalgia may be less common due to a lower elbow torque, while medial epicondylalgia may be more common due to methods to impart spin. Given the differences among sports, clinicians may need to utilize different prevention and intervention strategies when working with pickleball players.

Excess Relative Risk of Mortality from Diseases of the Circulation System after Irradiation. Report 2. Combined Data Analysis for Nuclear Workers

In the second part of the review on estimates of excess relative risks (ERR) per 1 Gy/Sv for mortality from diseases of the circulatory system (ICD-9: 390–459; ICD-10: I00–I99) after irradiation, a combined analysis and meta-analysis was carried out for nuclear industry workers of various countries. The completeness of the sample at the end of 2021 appeared to be exhaustive. The combined analysis of the data consisted in assessing the average for the sample after eliminating outliers from it; ERR per 1 Gy/Sv was 0.20 (95% CI: 0.11; 0.30). The meta-analysis was performed on the full sample, without removing outliers. Some heterogeneity was identified, so a Random effect model was used for the meta-analysis, and the ERR per 1 Gy/Sv was 0.11 (95% CI: 0.01; 0.22). The mean value of ERR per 1 Gy/Sv obtained here only for nuclear industry workers, as well as the result of the meta-analysis, did not differ much from the data of M.P. Little and co-workers (2010–2016) for heterogeneous samples from different populations. At the same time, the data for ‘Mayak’ PA on mortality from circulatory pathologies in general, and not for their individual types, indicate lower risks for external exposure (Azizova TV et al., 2018): ERR per 1 Gy/Sv was 0.04 (95% CI: –0.00; 0.09). All listed risks from the point of view of classical epidemiology, when using the common Monson scale for relative risks (RR), should be considered either ignorable (RR = = 1.0–1.2) or weak (RR = 1.2–1.5). An estimation of the absolute risk of mortality from circulatory pathologies for a hypothetical group of 100,000 nuclear workers who each accumulated a dose of 1 Gy, based on data on the baseline mortality of men from these pathologies for the United States, showed an increase of 1400 deaths over 20 years of employment. However, recalculation for the real average dose accumulated by workers in different countries (31.1 mSv; Koterov A.N. et al., 2021) revealed an insignificant increase in mortality at 0.6% of the baseline level, which risk cannot be taken into account for such multifactorial pathologies. The results obtained in the second part of the presented study: a) reinforce the conclusion made in Report 1 about the advisability of adhering to the dose threshold of 0.5 Gy for circulatory pathologies mortality established by UNSCEAR, ICRP, NCRP, BEIR, etc.; b) they indicate very low, negligible risks of mortality from circulatory pathologies attributed to the radiation factor for nuclear industry workers in recent decades and for most of those even in the previous period; c) they show that for the real activity and health protection of the majority of workers in the nuclear industry, the determination/calculation of the radiation risks of mortality from circulatory pathologies is of an exclusively theoretical nature. These conclusions are important, among other things, for expert advices on establishing the causality of occupational pathologies in nuclear industry workers.

Evaluation of a mobile application to decrease opioid misuse in patients undergoing cesarean section: a randomized controlled trial

BackgroundOpioid misuse and addiction are at epidemic levels in the United States. Postoperative opioid prescription is inconsistent and often excessive, including for cesarean section patients. Technology, such as mobile applications and clinical decision support tools, can be used to decrease opioid use and misuse among patients, and to determine more appropriate prescribing practices for specific procedures. The objective of this study was to examine the preliminary impact of the Continuing Precision Medicine (CPM) mobile application to reduce the use of opioid pain medication among women who underwent cesarean section. The primary outcome is morphine milligram equivalents (MME), while the secondary outcomes will be delay to dosages, decrease of usage, and pain scores.MethodsPatients undergoing cesarean section were randomized to either a control group or an experimental group, which used the CPMRx mobile app to help manage postoperative pain. Logistic regression analyses were run to predict opioid misuse by group (control [electronic monitoring blister pack only] versus CPMRx [electronic monitoring blister pack plus mobile application]) and odds ratios (ORs) were calculated. Relative risk (RR) was also estimated by log-binomial regression.ResultsIn phase I, 105 patients were assessed for eligibility, however, 66 were excluded (not meeting criteria or declined to participate). In phase 2, 98 patients were assessed for eligibility, however, 48 were excluded for the aforementioned. Results of the logistic regression showed that opioid misuse differed significantly by group (χ2 = 7.27, p = 0.007) with participants in the CPMRx group experiencing a 92% reduction in odds of opioid misuse compared to blister packs only (OR = 0.08, p = 0.03). Relative risk estimation by log-binomial regression also revealed that patients in the control group were at 7 times higher risk of opioid misuse than those using the CPMRx app (Wald χ2 = 3.82, RR = 7.00, p = 0.05). Among the 21 participants in Phase I who did not misuse their prescription opioids, the average number of pills used was 2.7 (SD = 3.5); 95% of patients used 8 or fewer pills, 90% used 6 or fewer, 75% used 4 or fewer, and half of participants used 1 or fewer opioids.ConclusionsWomen using the CPMRx mobile application were less likely to misuse their prescription opioids during the postoperative period following cesarean section. A prescription of 7 tablets of 5 mg oxycodone may be a more appropriate prescription size among this group. Systematically right-sizing prescriptions, including for subgroups, may decrease both patient- and community-level risk of opioid misuse and reduce public health burden.Trial registrationThe study was registered at ClinicalTrials.gov (NCT05461196, 18/07/2022).

Using Double Negative Controls to Adjust for Healthy User Bias in a Recombinant Zoster Vaccine Safety Study.

Unmeasured confounding is a major concern in many epidemiologic studies that are not randomized. Negative control methods can detect and reduce confounding by leveraging the proxies of the unmeasured confounders, including negative control outcomes (NCO) and exposures (NCE). An NCO is presumably unaffected by the exposure of interest but would be associated with unmeasured confounders; an NCE presumably does not affect the outcome of interest but would be associated with unmeasured confounders. A recently proposed double negative control method leverages both NCO and NCE for unmeasured confounding bias. To demonstrate this relatively new methodology in pharmacoepidemiologic studies, we re-analyzed data from a prior safety study of Recombinant Zoster Vaccine (RZV). The prior study compared risk of safety outcomes of RZV versus unvaccinated comparators, using logistic regression with propensity score adjustment. We identified NCOs and NCEs that could be used to adjust for unmeasured confounding bias that could arise if RZV recipients are incomparable to the comparators due to unmeasured factors. The double negative control analysis yielded relative risk estimates slightly closer to 1.0 than those reported previously, providing additional evidence of RZV safety that is less vulnerable to unmeasured confounding.

Alcoholic beverage consumption and female breast cancer risk:A systematic review and meta-analysis of prospective cohort studies.

Alcohol consumption is an established cause of female breast cancer. This systematic review examines in detail the association between alcohol and female breast cancer overall and among the described subgroups, using all of the evidence to date. A systematic review of PubMed and Embase was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included articles published up to November 15, 2023. Meta-analyses and regressions were performed for alcohol consumption of less than 1 standard drink (10 g of ethanol) per day and for a range of alcohol consumption categories in relation to breast cancer. Analyses by menopausal status, hormone receptor status, human epidermal growth factor receptor 2 status, and molecular subtype were performed. The search yielded 5645 publications, of which 23 publications of individual and pooled studies examined the association between overall alcohol consumption and breast cancer incidence. The meta-regression showed a positive association; relative risks (RR) of breast cancer were 1.05 (95% CI: 1.04, 1.06), 1.10 (95% CI: 1.08, 1.12), 1.18 (95% CI: 1.15, 1.21), and 1.22 (95% CI: 1.19, 1.25) for 0.5, 1, 2, and 3 standard drinks per day compared with nondrinking, respectively. A meta-analysis of nine studies indicated that for consumption of less than one standard drink per day, the RR estimate of breast cancer was 1.04 (95% CI: 1.01, 1.07) compared with nondrinking. Consumption of an additional 1 standard drink per day was associated with a higher risk of premenopausal (RR: 1.03 (95% CI: 1.01, 1.06)) and postmenopausal (RR: 1.10 (95% CI: 1.08, 1.12)) breast cancer. Alcohol consumption increases female breast cancer risk, even for women who consume one drink per day. Furthermore, alcohol consumption is associated with both pre- and postmenopausal breast cancer risk. These findings support evidence-based cancer prevention guidelines to reduce alcohol-related risks.

Assessing the contribution of smoking to the disease burden in Belgium, 2013-2020

Abstract Tobacco use remains a challenge given its substantial role in contributing to disability and premature death globally. Understanding its impact on population health, as an attributable burden, can help monitor progress on the effectiveness of tobacco policies. In this study, we used the Comparative Risk Assessment (CRA) method to estimate the share of the disease burden due to smoking in Belgium from 2013 to 2020. Population attributable fractions (PAF) were computed for risk-outcome pairs by age, sex, and region in Belgium for 2013-2020. Exposure estimates were extracted from a time series of the Belgian Health Interview Survey. Dose-response curves or relative risk estimates were drawn from the Global Burden of Disease Study 2019. In Belgium, smoking-related deaths decreased from 12,851 deaths (PAF=11%) in 2013 to 9,413 deaths (PAF=7%) in 2020. Deaths among men (2013: PAF=18%, n = 9859; 2020: PAF=11%, n = 7041) were three times higher than among women (2013: PAF=5%, n = 2991; 2020: PAF=3%, n = 2341). Over time, larynx cancer (2013: PAF=72%, n = 185; 2020: PAF=63%, n = 125), trachea, bronchus, and lung cancer (2013: PAF=60%, n = 4,899; 2020: PAF=60%, n = 3,682), other pharyngeal and oropharyngeal cancers (2013: PAF=47%, n = 118; 2020: PAF=40%, n = 100), mouth cancer (2013: PAF=37%, n = 172; 2020: PAF=30%, n = 122), and aortic aneurysm (2013: PAF=40%, n = 268; 2020: PAF=33%, n = 209) emerged as the primary contributors to smoking-related deaths in Belgium. While the ranking of contributing causes stayed mostly consistent in both genders over the years, cervical cancer (2013: PAF=23%, n = 53; 2020: PAF=21%, n = 64) ranked fourth instead of mouth cancer (2013: PAF=22%, n = 28; 2020: PAF=14%, n = 15) among women. Despite decreasing trends over time, smoking remains a significant contributor to cancer deaths in Belgium, particularly among men. Results from this study can help inform the development of strategies for smoking prevention and reinforce the need for continued efforts in prevention initiatives. Key messages • Cancers are the primary cause of smoking-related deaths in Belgium, with a decline in the death toll over time. • Understanding the role of smoking on population health as an attributable burden can improve health monitoring.

Africa Health Research Institute (AHRI) Household Contact study: a study protocol, statistical analysis and modelling plan

Household case-contact studies are an established method to estimate the relative infectiousness of people with pulmonary tuberculosis. Testing of child household contacts with a QuantiFERON TB Gold plus (QFT) assay provides a proxy measure of M. tuberculosis infection in exposed household members. This study aims to generate data about the effect of antiretroviral treatment (ART) and of tuberculosis symptoms on risk of intra-household M. tuberculosis transmission to children and investigate the conditions under which symptom-agnostic screening should be considered, which could provide evidence to support a paradigm shift in tuberculosis screening strategy. Index people diagnosed with bacteriologically-confirmed pulmonary tuberculosis who have been identified by routine health services and starting tuberculosis treatment at one of the 12 health facilities serving the population of the Africa Health Research Institute health and demographic surveillance area will be eligible for recruitment. For each consenting index participant, we will enroll all household members aged 2-14 years who will undergo a symptom screen and provide a blood sample for a QFT and HIV test. We will compare the proportion of child contacts who are QFT-positive in households of (i) index adults who are living with HIV and taking ART vs not taking ART and (ii) index adults engaged in ART care who report no symptoms vs those who report symptoms. We will use a novel mathematical model, incorporating new insights into TB natural history and transmission, to determine the circumstances under which screening for TB, regardless of reported symptoms, would have most impact on tuberculosis incidence and mortality, and explore comparative cost-effectiveness of interventions along the diagnostic pathway at different levels of the health system. Estimates of relative risk of intra-household M. tuberculosis transmission, combined with healthcare utilisation and cost data, will allow us to generate mathematical model estimates of the potential epidemiological impact and relative cost-effectiveness of different approaches to tuberculosis case-finding including symptom-agnostic tuberculosis screening at different levels of the health system.

Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study

ObjectiveTo evaluate the association between paternal metformin use and risk of congenital malformations in offspring.DesignPopulation based, cross national cohort study.SettingNorway and Taiwan.Participants619 389 offspring with paternal data during the period...

Polymorbidity and Health Outcomes Among Middle-Aged and Older Adults: Evidence from the Longitudinal Ageing Study in India

Polymorbidity is the leading cause of morbidity and mortality, particularly in the aging population. The present study analyses the prevalence and explores the determinants of polymorbidity among middle-aged and older adults. The study utilizes the 2017–2018 Longitudinal Ageing Study in India (LASI 2017–2018), a national representative dataset on health conditions of people aged 45 years and above, to study the relative risk estimates. The analysis uses the multinomial logit model (MNL) with their relative risk ratios (RRR). The findings of RRR suggest that the risk of polymorbidity significantly depends on parents’ medical history, residing in a front-runner state, and consultation at healthcare centers in both middle-aged and older adults. The prevalence of severe polymorbidity is higher among well-educated individuals and rural residents. The richer household carries a lower risk of polymorbidity, and the older adults from the general caste category are at higher risk of severe polymorbidity. The findings aim to redress the problems attached to the old age population in India. The paper recommends promoting preventive and precautionary attitudes over curative attitudes through health policies by introducing a patient-oriented and disease-centered approach to healthcare provision in India.

Assessing subgroup differences and underlying causes of ozone-associated mortality burden in China using multi-source data

Long-term ozone exposure is a significant public health concern. To mitigate its impact, it is crucial to identify diseases, populations, and regions that are particularly sensitive to ozone. In this study, we used high-quality data and updated relative risk estimates to investigate subgroup differences in mortality burden due to ozone exposure in China. In 2020, nationwide ozone-associated deaths totaled 276,800 (95 % CI: 106,700–451,900), representing 3.2 % of all deaths, with respiratory and cardiovascular diseases accounting for 16.8 % and 83.2 %, respectively. The per capita ozone-associated mortality in China was 20 per 100,000 person-years, with a significantly higher rate observed in elderly individuals aged ≥75 years (189 deaths per 100,000) compared to young individuals aged 30–44 years (1 death per 100,000). There were notable spatial patterns of ozone-associated deaths among the regions, indicating a critical response to ozone levels and population density. Interestingly, urban areas exhibited a 22.4 % lower mortality rate related to ozone compared to rural areas. This difference was attributed to the combined influence of ozone exposure (+19.9 %), population size (+17.7 %), age structure (−39.2 %), and baseline mortality (−20.8 %). By emphasizing subgroup differences and driving factors, these findings significantly enhance the understanding of the ozone-associated mortality burden, providing valuable insights for policymakers.

Unbiased temperature-related mortality estimates using weekly and monthly health data: a new method for environmental epidemiology and climate impact studies

Exposure to environmental factors has a high burden on human health, with millions of premature annual deaths associated with the short-term health effects of ambient temperatures and air pollution. However, direct estimations of exposure-related mortality from real data are still not available in most parts of the world, especially in low-resource settings, due to the unavailability of daily health records to calibrate epidemiological models. In this study, we have filled the crucial gap in available direct estimations by developing a method to make valid inference for the relationship between exposure and response data that uses only exposure and temporally aggregated response data. We provided the mathematical derivation of the method, and compared the results by using simulations applied to daily temperature and daily, weekly, and monthly mortality data. The method was then applied to the newly created database of the EARLY-ADAPT project. The daily and weekly models produced similar and unbiased estimates of the temperature-related relative risks and attributable mortality, with only slightly more imprecision in the weekly model. Even the estimates of the monthly model were unbiased when using enough data, although at the expense of a substantial increase in variability. The real data analysis showed that the similarity between the regional values of two aggregation models increased with the number of years and regions of the dataset, and decreased with the difference in their degree of temporal aggregation. Our method opens the door to conducting epidemiological studies in low-resource settings, where access to daily health data is not possible. Moreover, it allows accurate estimation of the short-term health effects of environmental exposures in near-real time, when daily health data are still not available, such as in the estimation of the mortality burden of recent record-breaking heat episodes. Overall, our method represents an important new approach to how the public health community can use data to create new evidence for research, translation and policy making. European Research Council (ERC).

Health care contact days in older adults enrolled in SWOG cancer clinical trials.

64 Background: Health care contact days—days with health care contact outside the home—are a measure of how much of a patient’s life is consumed by health care. This number of contact days are especially relevant for older adults with advanced cancer facing limited survival. One concern is that patients with different sociodemographic and clinical backgrounds may be at particular risk of increased contact days. Thus, there is a critical need to understand factors associated with contact days. Methods: We linked data from 6 SWOG trials in advanced cancer to Medicare claims data. These trials encompassed a variety of primary cancer types [prostate (S9916, S0421), lung (S0003, S0124, S0819), and pancreas (S0205)]. Health care contact days (days with ambulatory, emergency department, inpatient, or facility-based care) in the first 12 months were calculated using Medicare database files. A day with &gt;1 source of contact counted as 1. We examined sociodemographic (age, race, ethnicity, sex, insurance status, rurality, area deprivation index) and clinical (prognostic risk, cancer type, performance status) predictors of contact days, using negative binomial regression, with a log link and clustering by study ID, including an offset variable for duration of observation. We examined predictors in univariate and multivariable analysis. We report relative risk (RRs) estimates and 95% CI. Results: We included 1,429 patients (median age, 71 years, 7.6% Black, 2.7% Hispanic, 21.4% female, and 23.5% rural residence). Of these, 741 (51.9%) patients died in the first year. The median number of contact days was 48, out of a median of 350 days of observation. At a trial level, median percentage of contact days ranged from 14% (prostate) to 27% (lung). The most common sources of contact days were ambulatory clinician visits (median=17), tests (median=12), and treatments (median=11). In multivariable regression, factors associated with increased contact days included increasing age (per year, RR=1.02 [1.01-1.02], p&lt;.001), insurance status (Medicare alone or with Private or Medicaid insurance, vs Military/VA, none, or other insurance, RR=2.47 [2.16-2.83], p&lt;.001), higher prognostic risk score (RR=1.14 [1.04-1.25], p=.004), and type of cancer (pancreas, RR=1.69 [1.51-1.89] and lung, RR=1.69 [1.54-1.85] vs prostate, p&lt;.001 for both). Conclusions: This novel linkage of trial and claims data to evaluate contact days and associated factors found that older trial participants spent up to one in four days with health care contact. Ambulatory appointments were the most common source of contact days. Encouragingly, rural residence and neighborhood deprivation were not associated with contact days, increasing confidence that participants from diverse geographic areas may receive equitable care in trials. These data highlight the frequency of contact days for trial participants, while identifying factors to consider when benchmarking contact days.

Abstract IA004: Risk of therapy-related subsequent cancers in individuals with germline TP53 variants

Abstract Background. Based primarily on in vitro and animal studies, germline TP53 variants are considered to confer sensitivity to ionizing radiation-induced DNA damage, but data in humans are sparse. We sought to quantify risk of developing radiotherapy and chemotherapy-related subsequent neoplasms by pooling individual-level data from nine cohorts of individuals with confirmed pathogenic/likely pathogenic germline TP53 variants. Methods. 891 individuals were followed from six months after first cancer until diagnosis of a subsequent neoplasm, death or date of last follow-up. Radiotherapy and chemotherapy for each cancer were considered as time-dependent covariates in Cox regression models with age as the time-scale, adjusted for sex and occurrence of prior malignant or benign tumors. Subsequent cancers were classified as in- or out-of-field based on the body region of previous cancers. Results. Among 891 individuals, 643 (72.2%) were female and 297 (33.3%) were diagnosed with a first cancer before age 20 years. Breast cancer was the most commonly diagnosed first cancer (N=371), followed by soft tissue sarcoma (N=131) and central nervous system cancers (N=84). First cancer treatment included radiotherapy for 237 (26.6%) and/or chemotherapy for 421 (47.3%) individuals. Analyses are underway to define the characteristics of subsequent neoplasms (including age at diagnosis, latency, and distribution of diagnosis type) and to calculate relative and absolute risk estimates for radiotherapy and chemotherapy overall and by subsequent neoplasm type. Conclusions. This study will quantify the contribution of radiotherapy and chemotherapy to the risk of subsequent cancers among individuals with Li-Fraumeni syndrome. Understanding the magnitude of this risk will support health care providers and patients in making informed decisions about cancer management. Citation Format: Anita Villani, Payal Khincha, Jessica Hatton, Sara Schonfeld, Catherine Goudie, Leatrisse Oba, Kishan Pithadia, Birte Sänger, Christian Kratz, Anh N. Le, Caitlin Orr, Kara N. Maxwell, Anne Naumer, Jennie Vagher, Wendy Kohlmann, Joshua Schiffman, Elizabeth Santana dos Santos, Orli Michaeli, Jacob J. Carson, Derek S. Tsang, Raymond Kim, Jamie L. Maciaszek, Kim E. Nichols, Victoria E. Goodman, Suzanne P. MacFarland, Lara Reichman, Maria Isabel Achatz, Sharon Savage, David Malkin, Lindsay M. Morton. Risk of therapy-related subsequent cancers in individuals with germline TP53 variants [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr IA004.

Cancer incidence in a cohort of Danish firefighters: An extended long-term follow-up 1968-2021.

To update and extend the examination of cancer incidence in a cohort of Danish firefighters, now adding 7 years of follow-up and 2766 additional firefighters. The primary focus was directed toward cancer sites that recently contributed to the hazard evaluation conducted by the International Agency for Research on Cancer (IARC). The updated cohort consisted of 11,827 male Danish firefighters who were followed up for cancer from 1968 to 2021. Cohort cancer morbidity was compared with a working population reference group, and standardized incidence ratios (SIR) were used for estimation of relative risks, along with 95% confidence intervals (95% CI). Among full-time firefighters, SIR of skin melanoma was 1.30 (95% CI: 1.02-1.66), and SIR = 1.37 (95% CI: 1.02-1.85) for over 5 years of employment. Slightly positive associations were also observed for cancer of the urinary bladder (SIR = 1.16; 95% CI: 0.93-1.45), prostate (SIR = 1.11; 95% CI: 0.97-1.28), and testis (SIR = 1.11; 95% CI: 0.75-1.63). This updated study provides evidence indicating an elevated risk of skin melanoma in firefighters. Consistent with IARC's evaluation, we also identified positive associations for urinary bladder, prostate, and testis cancer. In contrast, our findings did not suggest an increased risk of colon cancer, non-Hodgkin lymphoma, and mesothelioma. The latter may be due to small numbers in our still relatively young cohort. Continuous follow-up for cancer in firefighters is warranted, including assessment of influence from surveillance bias.