Proportional Hazards Frailty Models Research Articles

Patient and implant-related risk factors for implant failure of one-stage lateral sinus floor elevation: A 2- to 10-year retrospective study.

This retrospective study aimed to evaluate the early and late implant failure rates of one-stage lateral sinus floor elevation (LSFE)and to identify the patient and implant-related risk factors associated with these failures. All patients treated with one-stage LSFE from January 2014 to December 2021 were evaluated for inclusion. A total of 618 patients with 936 implants met the inclusion criteria. Clinical and radiographic information about patient and implants was collected. Univariate and multivariate Cox proportional hazards frailty regression models were performed to identify risk factors for early and late implant failure. The cumulative implant survival rate was 95.62% (95% CI 93.90%-97.68%), with 16 early implant failures and 25 late implant failures. The Cox analysis indicated that ≤3 mm residual bone height (RBH) was associated with a higher early failure rate. For late implant failure, smoking habit, ≤3 mm RBH, and certain implant brand were independent risk factors. Narrow sinus ostium, long infundibulum, and flat thickening of Schneiderian membrane might be non-independent risk factors for late implant failure. No significance was found in other variables, including age, periodontitis history, implant characteristics (position, diameter, length, protrusion length, marginal bone loss), surgeon experience, healing time, opposing dentition, and prosthesis. One-stage LSFE is a predictable treatment for patients with atrophic maxilla. ≤3 mm RBH increased the risk of early implant failure, while smoking habit, ≤3 mm RBH, and certain implant brand were independent risk factors for late implant failure.

Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder: a high-risk study in the Chinese population

BackgroundUnderstanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder. Nevertheless, some of the previous studies on the...

P158 Cutaneous vasculitis in systemic lupus erythematosus: trends of incidence and risk factors

Abstract Background/Aims Cutaneous vasculitis (CV) is the most common form of vasculitis observed in patients with SLE; however, the precise epidemiological trends and underlying risk factors remain uncertain. The aim of this study was to define the incidence, prevalence, and risk factors of CV in systemic lupus erythematosus (SLE) patients over a period of 20 years. Methods The Birmingham Lupus Cohort is a longitudinal observational cohort of patients with SLE. All patients fulfilled the 1997 ACR Updated Classification Criteria for SLE. Inception patients were recruited within three years of their fourth ACR criterion. Disease activity was assessed using the classic BILAG index and laboratory results recorded. The BILAG vascular domain was used to determine the incidence rate, which refers to the rate at which new cases of minor and major CV attributed to active SLE occur. Cox proportional hazards frailty models were developed to identify clinical and laboratory variables associated with development of CV. Results We analysed 392 patients, of whom 375 (92.5%) were females. There were 213 (55.0%) White, 72 (18.6%) African-Caribbean, 82 (21.1%) South Asian, 9 (2.3%) East Asian, and 11 (2.8%) other ethnicities. The median (IQR) age at enrolment was 33 (26 - 44) years and the median duration of follow up was 9.2 (5.1 - 14.7) years. The incidence rates of minor and major CV were reported in Table 1. In Cox proportional hazards models, there was a positive association between CV and discoid rash (hazard ratio [HR] 2.16 [95% CI: 1.01, 4.61]), Raynaud’s phenomenon (HR 5.67 [95% CI: 4.11, 7.81]), livedo reticularis (HR = 4.69 [95% CI: 1.83, 12.0]), arthritis (HR 3.02 [95% CI: 2.20, 4.15]), renal involvement (OR 2.40 [95% CI: 1.55, 3.71]), haematological involvement (HR = 2.46 [95% CI: 1.80, 3.36]), and Afro-Caribbean descent (HR 1.96 [95% CI: 1.03, 3.74]). In addition, CV was positively associated with anti-dsDNA (HR = 2.33 [95% CI: 1.67, 3.27]), low C3 or C4 (HR 2.29 [95% CI: 2.18, 4.10]), and history of anti-Ro or anti-La (HR = 1.92 [95% CI: 1.15, 3.21]). Conclusion The incidence rates of CV decrease over the duration of follow-up and are associated with defined clinical and serological features. Disclosure A. Saleh: Grants/research support; A.S. is a sponsored PhD student by the Egyptian ministry of higher education represented by The Egyptian Bureau for Cultural & Educational Affairs in London. C. Gordon: None. J. Reynolds: None.

Spatial Survival Model for COVID-19 in México

A spatial survival analysis was performed to identify some of the factors that influence the survival of patients with COVID-19 in the states of Guerrero, México, and Chihuahua. The data that we analyzed correspond to the period from 28 February 2020 to 24 November 2021. A Cox proportional hazards frailty model and a Cox proportional hazards model were fitted. For both models, the estimation of the parameters was carried out using the Bayesian approach. According to the DIC, WAIC, and LPML criteria, the spatial model was better. The analysis showed that the spatial effect influences the survival times of patients with COVID-19. The spatial survival analysis also revealed that age, gender, and the presence of comorbidities, which vary between states, and the development of pneumonia increase the risk of death from COVID-19.

Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study

BackgroundPrevious in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults.MethodsOur study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35–70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite.ResultsA total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses.ConclusionsOur findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose–response relationships and to refine global dietary recommendations.

Postpartum Depression in Reproductive-Age Women With and Without Rheumatic Disease: A Population-Based Matched Cohort Study.

To examine postpartum depression (PPD) among women with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), or rheumatoid arthritis (RA) in comparison with a matched population without rheumatic disease (RD). A retrospective analysis using the 2013-2018 IBM MarketScan Commercial Claims and Encounters Database was conducted. Pregnant women with axSpA, PsA, or RA were identified, and the delivery date was used as the index date. We restricted the sample to women ≤ 55 years with continuous enrollment ≥ 6 months before date of last menstrual period and throughout pregnancy. Each patient was matched with 4 individuals without RD on: (1) maternal age at delivery, (2) prior history of depression, and (3) duration of depression before delivery. Cox frailty proportional hazards models estimated the crude and adjusted hazard ratios (aHR) and 95% CI of incident postpartum depression within 1 year among women with axSpA, PsA, or RA (axSpA/PsA/RA cohort) compared to the matched non-RD comparison group. Overall, 2667 women with axSpA, PsA, or RA and 10,668 patients without any RD were included. The median follow-up time in days was 256 (IQR 93-366) and 265 (IQR 99-366) for the axSpA/PsA/RA cohort and matched non-RD comparison group, respectively. Development of PPD was more common in the axSpA/PsA/RA cohort relative to the matched non-RD comparison group (axSpA/PsA/RA cohort: 17.2%; matched non-RD comparison group: 12.8%; aHR 1.22, 95% CI 1.09-1.36). Postpartum depression is significantly higher in women of reproductive age with axSpA/PsA/RA when compared to those without RD.

Fast and accurate recurrent event analysis for genome-wide association studies.

Many diseases recur after recovery, for example, recurrences in cancer and infections. However, research is often focused on analysing only time-to-first recurrence, thereby ignoring any subsequent recurrences that may occur after the first. Statistical models for the analysis of recurrent events are available, of which the extended Cox proportional hazards frailty model is the current state-of-the-art. However, this model is too statistically complex for computationally efficient application in high-dimensional data sets, including genome-wide association studies (GWAS). Here, we develop an application for fast and accurate recurrent event analysis in GWAS, called SPARE (SaddlePoint Approximation for Recurrent Event analysis). In SPARE, every DNA variant is tested for association with recurrence risk using a modified score statistic. A saddlepoint approximation is implemented to achieve statistical accuracy. SPARE controls the Type I error, and its statistical power is similar to existing recurrent event models, yet SPARE is significantly faster. An application of SPARE in a recurrent event GWAS on bladder cancer for 6.2 million DNA variants in 1,443 individuals required less than 15 min, whereas existing recurrent event methods would require several weeks.

Associations of outdoor fine particulate air pollution and cardiovascular disease: Results from the Prospective Urban and Rural Epidemiology Study in China (PURE-China)

BackgroundEvidence on whether an excess risk of incidence and mortality of cardiovascular disease (CVD) among people exposed to a high level of ambient PM2.5 in low- and middle-income countries (LMICs) is lacking. This study aimed to investigate the associations between long-term exposure to ambient fine particulate matter<2.5 µm (PM2.5) concentrations and the risk of incidence and mortality of CVD in a large cohort study from 115 communities. MethodsIn this cohort study, we followed 42 160 adults aged 35–75 years at baseline who enrolled in the Prospective Urban and Rural Epidemiology Study conducted in China (PURE-China) between 2005 and 2009 with ambient PM2.5 estimates, and followed up until August 2021. Cox proportional hazards frailty models were used to estimate the associations between long-term mean outdoor PM2.5 concentrations and CVD events, CVD mortality, and all-cause mortality. FindingsDuring a median follow-up period of 11.8 years, we documented 2 190 deaths, including 732 CVD deaths. There were 4 559 (10.8 %) of 42 160 participants who experienced incident total CVD, among them there were 861 myocardial infarctions (MI) and 2 338 S. The 3-year median concentration of ambient PM2.5 before the cohort commencement was 52.7 µg/m3 (interquartile range [IQR] 30.3–74.6). In full adjusted model, a 10 µg/m3 increase in PM2.5 was associated with a hazard ratio (HR) of 1.12 (95 % CI 1.11–1.14) for major CVD and 1.03 (95 % CI 1.01–1.05) for all-cause mortality. Besides, long-term PM2.5 concentrations had a significantly positive gradient association with total CVD and a similar pattern of associations with other CVD outcomes was observed. InterpretationThis study demonstrated that long-term ambient PM2.5 concentrations is positively associated with increased risks of CVD in adults aged 35–70 years from China. This finding reinforces the need for policymakers to adopt more effective strategies to improve air quality.

A flexible class of generalized joint frailty models for the analysis of survival endpoints.

This article focuses on shared frailty models for correlated failure times, as well as joint frailty models for the simultaneous analysis of recurrent events (eg, appearance of new cancerous lesions or hospital readmissions) and a major terminal event (typically, death). As extensions of the Cox model, these joint models usually assume a frailty proportional hazards model for each of the recurrent and terminal event processes. In order to extend these models beyond the proportional hazards assumption, our proposal is to replace these proportional hazards models with generalized survival models, for which the survival function is modeled as a linear predictor through a link function. Depending on the link function considered, these can be reduced to proportional hazards, proportional odds, additive hazards, or probit models. We first consider a fully parametric framework for the time and covariate effects. For proportional and additive hazards models, our approach also allows the use of smooth functions for baseline hazard functions and time-varying coefficients. The dependence between recurrent and terminal event processes is modeled by conditioning on a shared frailty acting differently on the two processes. Parameter estimates are provided using the maximum (penalized) likelihood method, implemented in the R package frailtypack (function GenfrailtyPenal). We perform simulation studies to assess the method, which is also illustrated on real datasets.

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi

BackgroundWhen people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response.MethodsAdults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson’s Chi—squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR).Results411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77–86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92–97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52–7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48–231]) than participants who experienced ACPR (190 ng/ml [95% CI 101–378], p-value < 0.008).ConclusionRecurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

Combining quantitative and survival trait analyses identifies novel general and sex‐specific genes for age‐at‐onset of Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) has high genetic heritability for both disease risk and age‐at‐onset (AAO) of AD. However, our understanding of genetics of AAO of AD lags behind AD risk. Here, we utilized two statistical approaches to identify genes modifying AAO of AD globally or in a sex‐specific manner.MethodPooled data from 9,219 AD cases and 10,345 controls from 20 cohorts from the Alzheimer Disease Genetic Consortium were analyzed using a linear mixed model (LMM) for AAO from cases only, and a Cox proportional hazard frailty model (CoxFM) from all subjects with AAO observed in cases and censored at age‐at‐exam in controls. Both methods modeled outcome on SNP, sex, APOE‐e4, and 10 principal components (PCs), and incorporated random intercept by cohort. Fisher’s method was used to combine results of LMM and CoxFM. Genome‐wide significant variants were determined based on p &lt; 5×10−8 in individual or combined tests. Multiple secondary analyses were performed including sex‐specific association tests for top SNPs (p&lt; 10−6). Two gene‐expression datasets of prefrontal cortex tissues from NCBI/GEO were analyzed by sex to evaluate the sex‐specific AAO genes.ResultWe identified 34 genome‐wide significant loci. We confirmed 6 known AD risk genes (APOE, CR1, BIN1, TREM2, PICALM, and FERMT2) also regulating AAO as AD. Twenty‐eight potential novel loci were identified including ARFGEF2, MAPK9, and the MLX region harboring functional related genes for AD. Sex‐specific analyses showed the effects of PICALM, MLX, and CDH2 on AAO were solely from females, and ATP2C1 from males. Particularly, the MLX region harboring 10 genes in strong LD, including variants in COASY and HSD17B1 previously reported to associate with earlier AAO of AD in female AD patients with Down Syndrome. Gene expression further supported higher differential expression of AD over controls for HSD17B1, COASY, PLEKHH3, and MLX in females than males.ConclusionUsing two statistical methods to model AAO of AD, we identified six known AD risk genes and 28 novel loci associated with AAO of AD, and further narrowed down four loci with sex‐specific effects. Notably, HSD17B1, involved in estrogen activation, has strong functional implications warrant for further investigation.

Implant failure and associated risk factors of transcrestal sinus floor elevation: A retrospective study.

This retrospective study aimed to evaluate early and late implant loss rates after transcrestal sinus floor elevation (TSFE) and to identify the risk factors related to these failures. All patients treated with TSFE and simultaneous implant placement during October 2015 to March 2019 were evaluated for inclusion. A total of 802 patients with 976 implants met the inclusion criteria. Clinical and radiographic information was collected from medical records and image software. Univariate and multivariate Cox proportional hazards frailty regression models were performed to identify potential risk factors associated with early and late implant loss after TSFE. The 3-year cumulative implant survival rate was 96.9% (95% CI 95.8%-98.0%). Twelve implants in 12 patients were lost before or at the abutment connection, while 24 implants in 24 patients were lost after functional loading. The Cox frailty regression analyses indicated that two factors were correlated with early implant loss: TSFE with grafting materials, and operators with less clinical experience. As for late implant loss, RBH ≤6 mm, male sex, and certain implant brands were associated with a significantly increased failure rate. Transcrestal sinus floor elevation with simultaneous implant placement is a predictable treatment option in the atrophic maxilla. The presence of grafting materials and the lack of clinical experience of the surgeon were possibly associated with early implant loss, while low RBH, male sex, and certain implant brands tended to increase late implant loss.

The Impact of Preventive Dental Services on Subsequent Dental Treatment for Children in Medicaid.

The goal of this study was to use claims data linked with community-level measures to evaluate the impact of preventive services on the time to subsequent restorative, advanced restorative, and complex dental treatment among children enrolled in the Virginia Medicaid program. Four data sources were used (dental claims, eligibility files, American Community Survey, and Area Health Resource Files) for fiscal years 2011 to 2018. The outcomes of interest were time to first treatment services from birth. The treatment outcomes were basic restorative treatment, advanced restorative treatment, or complex treatment. The independent variable was a preventive service prior to a treatment service. Time-to-event curves were estimated and compared using a log-rank test. Propensity score-matched univariate and multivariate Cox proportional hazards frailty models with an inverse probability censoring weighting correction estimated hazard ratios (HRs) for treatment outcomes comparing use of preventive services while controlling for patient demographic, geospatial, and county-level socioeconomic status measures. The analysis included 430,594 children (10,204,182 claims). A log-rank test showed significant differences (P < 0.001) between the times to treatment of those who had a preventive service and those who did not have a preventive service prior to a treatment service. Both Kaplan-Meier curves and the adjusted HR (1.88; 95% confidence interval [CI], 1.46-2.15) indicated that children without preventive services were more likely to have basic restorative treatment at an earlier age along with advanced restorative treatment (HR, 1.52; 95% CI, 1.28-1.80) and complex treatment (HR, 2.13; 95% CI, 1.68-2.61). In a population of Medicaid-enrolled children, children who did not receive preventive services were significantly more likely to have treatment at an earlier age than those who did receive preventive services. This study examines the impact of the utilization of preventive dental services since birth and the subsequent dental treatment for children enrolled in a dental Medicaid program. This study also examines the influence of preventive care on dental complexity of treatment for these children. Findings can inform federal and state policy planning of dental Medicaid programs as well as interventions to improve referral systems for the early use of preventive dental services and the establishment of a dental home.

Propensity Score Modeling in Electronic Health Records with Time-to-Event Endpoints: Application to Kidney Transplantation

For large observational studies lacking a control group (unlike randomized controlled trials, RCT), propensity scores (PS) are often the method of choice to account for pre-treatment confounding in baseline characteristics, and thereby avoid substantial bias in treatment estimation. A vast majority of PS techniques focus on average treatment effect estimation, without any clear consensus on how to account for confounders, especially in a multiple treatment setting. Furthermore, for time-to event outcomes, the analytical framework is further complicated in presence of high censoring rates (sometimes, due to non-susceptibility of study units to a disease), imbalance between treatment groups, and clustered nature of the data (where, survival outcomes appear in groups). Motivated by a right-censored kidney transplantation dataset derived from the United Network of Organ Sharing (UNOS), we investigate and compare two recent promising PS procedures, (a) the generalized boosted model (GBM), and (b) the covariate-balancing propensity score (CBPS), in an attempt to decouple the causal effects of treatments (here, study subgroups, such as hepatitis C virus (HCV) positive/negative donors, and positive/negative recipients) on time to death of kidney recipients due to kidney failure, post transplantation. For estimation, we employ a 2-step procedure which addresses various complexities observed in the UNOS database within a unified paradigm. First, to adjust for the large number of confounders on the multiple sub-groups, we fit multinomial PS models via procedures (a) and (b). In the next stage, the estimated PS is incorporated into the likelihood of a semi-parametric cure rate Cox proportional hazard frailty model via inverse probability of treatment weighting, adjusted for multi-center clustering and excess censoring, Our data analysis reveals a more informative and superior performance of the full model in terms of treatment effect estimation, over sub-models that relaxes the various features of the event time dataset.

A Spatial Survival Model for Risk Factors of Under-Five Child Mortality in Kenya.

Child mortality is high in Sub-Saharan Africa compared to other regions in the world. In Kenya, the risk of mortality is assumed to vary from county to county due to diversity in socio-economic and even climatic factors. Recently, the country was split into 47 different administrative regions called counties, and health care was delegated to those county governments, further aggravating the spatial differences in health care from county to county. The goal of this study is to evaluate the effects of spatial variation in under-five mortality in Kenya. Data from the Kenya Demographic Health Survey (KDHS-2014) consisting the newly introduced counties was used to analyze this risk. Using a spatial Cox Proportional Hazard model, an Intrinsic Conditional Autoregressive Model (ICAR) was fitted to account for the spatial variation among the counties in the country while the Cox model was used to model the risk factors associated with the time to death of a child. Inference regarding the risk factors and the spatial variation was made in a Bayesian setup based on the Markov Chain Monte Carlo (MCMC) technique to provide posterior estimates. The paper indicate the spatial disparities that exist in the country regarding child mortality in Kenya. The specific counties have mortality rates that are county-specific, although neighboring counties have similar hazards for death of a child. Counties in the central Kenya region were shown to have the highest hazard of death, while those from the western region had the lowest hazard of death. Demographic factors such as the sex of the child and sex of the household head, as well as social economic factors, such as the level of education, accounted for the most variation when spatial differences were factored in. The spatial Cox proportional hazard frailty model performed better compared to the non-spatial non-frailty model. These findings can help the country to plan health care interventions at a subnational level and guide social and health policies by ensuring that counties with a higher risk of Under Five Child Mortality (U5CM) are considered differently from counties experiencing a lower risk of death.

An additive hazards frailty model with semi-varying coefficients.

Proportional hazards frailty models have been extensively investigated and used to analyze clustered and recurrent failure times data. However, the proportional hazards assumption in the models may not always hold in practice. In this paper, we propose an additive hazards frailty model with semi-varying coefficients, which allows some covariate effects to be time-invariant while other covariate effects to be time-varying. The time-varying and time-invariant regression coefficients are estimated by a set of estimating equations, whereas the frailty parameter is estimated by the moment method. The large sample properties of the proposed estimators are established. The finite sample performance of the estimators is examined by simulation studies. The proposed model and estimation are illustrated with an analysis of data from a rehospitalization study of colorectal cancer patients.

Long-term exposure to PM2.5 and cardiovascular disease incidence and mortality in an Eastern Mediterranean country: findings based on a 15-year cohort study

BackgroundEvidence concerning the impact of long-term exposure to fine Particulate Matter ≤2.5 μm (PM2.5) on Cardio-Vascular Diseases (CVDs) for those people subject to ambient air pollution in developing countries remains relatively scant. This study assessed the relationship of 15-year PM2.5 exposure with cardiovascular incidence and mortality rate in Isfahan province, Iran.MethodsThe cohort comprised 3081 participants over 35 years old who were free of CVDs. They were selected through multi-stage cluster sampling in Isfahan, Iran. PM2.5 exposure was determined separately for each individual via satellite-based spatiotemporal estimates according to their residential addresses. In this context, CVD is defined as either fatal and non-fatal Acute Myocardial Infarctions (AMI) or stroke and sudden cardiac death. The incidence risk for CVD and the ensuing mortality was calculated based on the average PM2.5 exposure within a study period of 15 years using the Cox proportional hazards frailty model upon adjusting individual risk factors. The mean annual rate of PM2.5 and the follow-up data of each residential area were combined.ResultsMean three-year PM2·5 exposure for the cohort was measured at 45.28 μg/m3, ranging from 20.01 to 69.80 μg/m3. The median time period for conducting necessary follow-ups was 12.3 years for the whole population. Notably, 105 cardiovascular and 241 all-cause deaths occurred among 393,786 person-months (27 and 61 per 100,000 person-months, respectively). In well-adjusted models, 10 μg/m3 increase in PM2.5 corresponded to a 3% increase in the incidence rate of CVDs [0.95 CI = 1.016, 1.036] (in case of p = 0.000001 per 10 μg/m3 increase in PM2.5, the Hazard Ratio (HR) for AMI and Ischemic Heart Disease (IHD) was 1.031 [0.95 CI = 1.005, 1.057] and 1.028 [0.95 CI = 1.017, 1.039]), respectively. No consistent association was observed between PM2.5 concentration and fatal CVD (fatal AMI, fatal stroke, SCD (Sudden Cardiac Death)) and all-cause mortality.ConclusionsResults from analyses suggest that the effect of PM2.5 on cardiovascular disease occurrence was stronger in the case of older people, smokers, and those with high blood pressure and diabetes. The final results revealed that long-term exposure to ambient PM2.5 with high concentrations positively correlated with IHD incidence and its major subtypes, except for mortality. The outcome accentuates the need for better air quality in many countries.

Assessing the determinants of completing OAT induction and long-term retention: A population-based study in British Columbia, Canada

BackgroundPharmacological treatments for opioid use disorder are essential, life-saving medications, yet successful induction of them and long-term retention on them is limited in many settings. Induction into opioid agonist treatment (OAT) features the highest risk of mortality throughout the treatment course, and greatest risk of discontinuation. We aimed to identify determinants of completing OAT induction and, among those completing induction, time to OAT discontinuation in British Columbia (BC), Canada. MethodsWe conducted a retrospective study using linked population-level health administrative databases to capture all individuals in BC receiving at least one OAT dispensation from January 1, 2008, to September 30, 2018. We constructed covariates capturing client demographics, clinical history, and characteristics of the treatment episode and the primary prescribing physician. We estimated a two-part model to identify determinants of the probability of completing induction using a generalized linear mixed model with logit link and the time to OAT discontinuation among those completing induction using a Cox proportional hazards frailty model. ResultsWe observed 220,474 OAT episodes (73.9% initiated with methadone, 24.7% with buprenorphine, and 1.4% with slow-release oral morphine) among 45,608 individuals over the study period. Less than 60% of all OAT episodes completed induction (59.0% for methadone episodes, 56.7% for buprenorphine/naloxone, 41.0% for slow-release oral morphine) and half of all episodes that completed induction reached the minimum effective dosage (51.0% for methadone episodes [60 mg/day], 48.2% for buprenorphine/naloxone [12 mg/day], 59.4% for slow-release oral morphine [240 mg/day]). In multiple regression analysis, the adjusted odds of completing induction with buprenorphine improved over time, exceeding that of methadone in 2018: 1.46 (1.40, 1.51). For those who completed induction, buprenorphine use was associated with shorter times to discontinuation throughout the study period, but the estimated rate of discontinuation decreased over time (adjusted hazard ratio, vs. methadone in 2008: 2.50 (2.35, 2.66); in 2018: 1.79 (1.74, 1.85)). ConclusionWe found low rates of completing OAT induction and, for those who did complete it, low rates of reaching the minimum effective dose.

Inverse probability weighted estimators of vaccine effects accommodating partial interference and censoring.

Estimating population-level effects of a vaccine is challenging because there may be interference, that is, the outcome of one individual may depend on the vaccination status of another individual. Partial interference occurs when individuals can be partitioned into groups such that interference occurs only within groups. In the absence of interference, inverse probability weighted (IPW) estimators are commonly used to draw inference about causal effects of an exposure or treatment. Tchetgen Tchetgen and VanderWeele proposed a modified IPW estimator for causal effects in the presence of partial interference. Motivated by a cholera vaccine study in Bangladesh, this paper considers an extension of the Tchetgen Tchetgen and VanderWeele IPW estimator to the setting where the outcome is subject to right censoring using inverse probability of censoring weights (IPCW). Censoring weights are estimated using proportional hazards frailty models. The large sample properties of the IPCW estimators are derived, and simulation studies are presented demonstrating the estimators' performance in finite samples. The methods are then used to analyze data from the cholera vaccine study.

The correlation between history of periodontitis according to staging and grading and the prevalence/severity of peri-implantitis in patients enrolled in maintenance therapy.

The aim of this study was to determine if a previous history of periodontitis according to the preset definitions of the 2017 World Workshop is correlated with increased implant failure, and occurrence and severity of peri-implantitis (PI). A retrospective analysis of patients with a history of periodontitis who received nonsurgical and, if indicated, surgical corrective therapy prior to implant placement was performed. Periodontitis stage and grade were determined for each included patient based on data from the time of initiation of active periodontal therapy. Cox Proportional Hazard Frailty models were built to analyze the correlation between stage and grade of periodontitis at baseline with implant failure, as well as occurrence and severity of PI. Ninety-nine patients with a history of periodontitis receiving 221 implants were followed for a mean duration of 10.6 ± 4.5 years after implant placement. Six implants (2.7%) failed and a higher rate of implant failure due to PI was found for Grade C patients (P < 0.05), whereas only an increased trend was seen for Stages III and IV compared with I and II. Grading significantly influenced the risk of marginal bone loss (MBL) >25% of the implant length (P = 0.022) in PI-affected implants. However, a direct correlation between higher-level stage and grade and PI prevalence was not recorded. No statistically significant association between periodontitis stage or grade and the prevalence of PI was found. However, when PI was diagnosed, there was a relationship between periodontitis grade and severity of PI or the occurrence of implant failure.