Author Correction: Climate change: an enduring challenge for vector-borne disease prevention and control.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A unified framework for assessing interaction effects among environmental exposures in epidemiologic studies: A case study on temperature, air pollution, and kidney-related conditions in New York state.

BACKGROUND: There are various methods to assess interaction effects. However, current methods have limitations, and quantification of interaction effects is rarely performed. This study aimed to develop a unified quantitative framework for assessing interaction effects. METHODS: We proposed a novel framework using log-linear models with a product term(s) across the exposures that generates parametric bi-variate association and interaction effect surfaces and allows flexible functional forms for exposures in the interaction term(s). In a case study, we assessed the interaction effects between temperature and air pollution (i.e., PM2.5, NO2, and O3) on risk for kidney-related conditions in New York State (2007-2016) using a case-crossover design with conditional logistic models. Our measures of exposure were the moving averages at lag 0-5 days for air pollution (linear) and daytime mean outdoor wet-bulb globe temperature (WBGT; using a natural cubic spline). RESULTS: We derived closed-form expressions for the magnitude of multiplicative interaction effects (the joint relative risk divided by the product of the two conditional relative risks) and their uncertainties. In the case study, we found a Bonferroni-corrected significant multiplicative interaction effect (IE) between outdoor WBGT at the 99th percentile (median as the reference) and (1) PM2.5 (per 5 µg/m3 increase, IE = 1.052; 95 % confidence interval [CI]: 1.019, 1.087) for acute kidney failure and (2) O3 (per 5 ppb increase; IE = 1.022; 95 % CI: 1.008, 1.036) for urolithiasis (the latter being inconclusive based on the sensitivity analysis). CONCLUSIONS: Our framework allows different functional forms of exposure variables in the interaction term, quantifies the magnitudes of entire-exposure-range (in addition to discrete exposure level) multiplicative interaction effects and their uncertainties in a categorical or continuous (linear or non-linear) manner, and harmonizes the two-way evaluation of effect modification. The case study underscores co-consideration of heat and air pollution when estimating health burden and designing heat/pollution alert systems.

The 2020 report of The Lancet Countdown on health and climate change: responding to converging crises.

TRANSLATIONS: For the Chinese, French, German, and Spanish translations of the abstract see Supplementary Materials section.

Improving Water Quality in the Short Beach Neighborhood of Branford, Connecticut, 2019-A Citizen Science Project.

We initiated a collaboration between local government, academia, and citizen scientists to investigate high frequencies of elevated Escherichia coli bacteria levels in the coastal Short Beach neighborhood of Branford, Connecticut. Citizen scientist involvement enabled collection of short-duration postprecipitation outfall flow water samples (mean E. coli level = 4930 most probable number per 100 mL) and yielded insights into scientific collaboration with local residents. A records review and sanitary questionnaire identified aging properties with septic systems (3.3%) and holding tanks (0.6%) as potential sources of the E. coli contamination. (Am J Public Health. 2022;112(9):1261-1264. https://doi.org/10.2105/AJPH.2022.306943).

Relationships between short-term ambient temperature exposure and kidney disease hospitalizations in the warm season in Vietnam: A case-crossover study.

BACKGROUND: Under a warming climate, adverse health effects of heat are an increasing concern. We evaluated associations between short-term ambient temperature exposure and hospital admission for kidney disease in Vietnam. METHODS: We linked province-level meteorologic data with admission data from 14 province-level hospitals (2003-2015). We used a case-crossover design to evaluate associations between daily ambient temperature metrics (mean, maximum, and minimum temperature and mean heat index) and risk of hospitalization for four kidney disease subtypes: glomerular diseases, renal tubulo-interstitial diseases, chronic kidney disease, and urolithiasis, including lagged (≤lag 14 days) and cumulative (≤lag 0-6 days) associations, during the warm season. We also evaluated independent associations with extreme heat days (defined as days with daily maximum temperature >95th percentile of the provincial daily maximum temperature distribution). Akaike's information criterion and patterns of risk estimates across cumulative exposure time windows and single-day lags informed our selection of final models. RESULTS: We included 58,330 hospital admissions during the warm season. Daily mean temperature averaged over the same day and the previous six days (lag 0-6 days) was associated with risk of hospitalization for each kidney disease outcome with odds ratios (per 1 °C increase in daily mean temperature) of 1.07 (95% confidence interval [CI]: 0.99, 1.16) for glomerular diseases, 1.06 (95% CI: 0.96, 1.17) for renal tubulo-interstitial diseases, 1.12 (95% CI: 1.00, 1.24) for chronic kidney disease, and 1.09 (95% CI: 1.02, 1.16) for urolithiasis. We found no additional independent associations with extreme heat. Results for the four temperature metrics were similar. CONCLUSIONS: High ambient temperature was associated with increased risk of hospitalization for each kidney disease subtype, with the most convincing associations for chronic kidney disease and urolithiasis. Further laboratory and epidemiologic research is needed to confirm the findings and disentangle the underlying mechanisms.

Predicting spatiotemporally-resolved mean air temperature over Sweden from satellite data using an ensemble model.

Mapping of air temperature (Ta) at high spatiotemporal resolution is critical to reducing exposure assessment errors in epidemiological studies on the health effects of air temperature. In this study, we applied a three-stage ensemble model to estimate daily mean Ta from satellite-based land surface temperature (Ts) over Sweden during 2001-2019 at a high spatial resolution of 1 × 1 km2. The ensemble model incorporated four base models, including a generalized additive model (GAM), a generalized additive mixed model (GAMM), and two machine learning models (random forest [RF] and extreme gradient boosting [XGBoost]), and allowed the weights for each model to vary over space, with the best-performing model for each grid cell assigned the highest weight. Various spatial predictors were included as adjustment variables in all the base models, including land cover type, normalized difference vegetation index (NDVI), and elevation. The ensemble model showed high performance with an overall R2 of 0.98 and a root mean square error of 1.38 °C in the ten-fold cross-validation, and outperformed each of the four base models. Although each base model performed well, the two machine learning models (RF [R2 = 0.97], XGBoost [R2 = 0.98]) had better performance than the two regression models (GAM [R2 = 0.95], GAMM [R2 = 0.96]). In the machine learning models, Ts was the dominant predictor of Ta, followed by day of year, NDVI, latitude, elevation, and longitude. The highly spatiotemporally-resolved Ta can improve temperature exposure assessment in future epidemiological studies.

Timing of Antiretroviral Therapy Initiation and Risk of Cancer Among Persons Living With Human Immunodeficiency Virus.

BACKGROUND: Persons living with human immunodeficiency virus (HIV; PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). METHODS: We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µL (baseline) until incident cancer, death, lost-to-follow-up, or December 2014. Outcomes included 6 cancer groups and 5 individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. RESULTS: Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI], .37-.86), AIDS-defining cancers (HR 0.23; 95% CI, .11-.49), any virus-related cancer (HR 0.30; 95% CI, .16-.54), Kaposi sarcoma (HR 0.25; 95% CI, .10-.61), and non-Hodgkin lymphoma (HR 0.22; 95% CI, .06-.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs 2.3%; adjusted risk difference -1.6; 95% CI, -2.8, -.5). CONCLUSIONS: Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH but not non-AIDS-defining cancers (NADCs) without known or suspected viral etiology.

Relationship between flood severity and risk of hospitalisation in the Mekong River Delta of Vietnam.

OBJECTIVE: To examine the relationship between flood severity and risk of hospitalisation in the Vietnam Mekong River Delta (MRD). METHODS: We obtained data on hospitalisations and hydro-meteorological factors during 2011-2014 for seven MRD provinces. We classified each day into a flood-season exposure period: the 2011 extreme annual flood (EAF); 2012-2014 routine annual floods (RAF); dry season and non-flood wet season (reference period). We used province-specific Poisson regression models to calculate hospitalisation incidence rate ratios (IRRs). We pooled IRRs across provinces using random-effects meta-analysis. RESULTS: During the EAF, non-external cause hospitalisations increased 7.2% (95% CI 3.2% to 11.4%); infectious disease hospitalisations increased 16.4% (4.3% to 29.8%) and respiratory disease hospitalisations increased 25.5% (15.5% to 36.4%). During the RAF, respiratory disease hospitalisations increased 8.2% (3.2% to 13.5%). During the dry season, hospitalisations decreased for non-external causes and for each specific cause except injuries. CONCLUSIONS: We observed a gradient of decreasing risk of hospitalisation from EAF to RAF/non-flood wet season to dry season. Adaptation measures should be strengthened to prepare for the increased probability of more frequent extreme floods in the future, driven by climate change.

Association of Immunosuppression and Human Immunodeficiency Virus (HIV) Viremia With Anal Cancer Risk in Persons Living With HIV in the United States and Canada.

BACKGROUND: People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. METHODS: We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. RESULTS: Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6). CONCLUSIONS: Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Medical, nursing, and physician assistant student knowledge and attitudes toward climate change, pollution, and resource conservation in health care.

BACKGROUND: Climate change and pollution generated by the health care sector impose significant public health burdens. This study aimed to assess medical, nursing and physician assistant student knowledge and attitudes regarding climate change, pollution from the health care sector, and responsibility for resource conservation within professional practice. METHODS: In February-March, 2018, medical, nursing, and physician assistant students at Yale University (1011 potential respondents) were sent a 17-question online Qualtrics survey. Data analysis included descriptive statistics, as well as Fisher's exact test and logistic regression to assess associations between variables of interest and the personal characteristics of gender, age, geographic place of origin, school, and year in school (among medical students). RESULTS: The response rate was 28% (280 respondents). 90% felt that physicians, nurses, and physician assistants have a responsibility to conserve resources and prevent pollution within their professional practice. 63% agreed or strongly agreed that the relationship between pollution, climate change, and health should be covered in the classroom and should be reinforced in the clinical setting. 57% preferred or strongly preferred reusable devices. 91% felt lack of time and production pressure, and 85% believed that lack of education on disease burden stemming from health care pollution, were barriers to taking responsibility for resource conservation and pollution prevention. Women and physician assistant students exhibited a greater commitment than men and medical students, respectively, to address pollution, climate change, and resource conservation in patient care and professional practice. CONCLUSION: We found that health professional students are engaged with the concept of environmental stewardship in clinical practice and would like to see pollution, climate change, and health covered in their curriculum. In order for this education to be most impactful, more research and industry transparency regarding the environmental footprint of health care materials and specific clinician resource consumption patterns will be required.

Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study.

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses. Objective: To determine whether viral suppression is associated with decreased cancer risk. Design: Prospective cohort. Setting: Department of Veterans Affairs. Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015. Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL). Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses. Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated. Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk. Primary Funding Source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Cancer-Attributable Mortality Among People With Treated Human Immunodeficiency Virus Infection in North America.

BACKGROUND: Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. METHODS: We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. RESULTS: There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts <100 cells/mm3. PAFs for NADCs increased during 1995-2009, reaching 10.1% in 2006-2009. CONCLUSIONS: Approximately 10% of deaths in PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this fraction increased over time. A large proportion of cancer-attributable deaths were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV age.

HIV Infection, Immunosuppression, and Age at Diagnosis of Non-AIDS-Defining Cancers.

Background: It is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis. Methods: We compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count. Results: After adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count <200 cells/µL (vs ≥500) was associated with a younger age at lung cancer diagnosis (difference = 4; P = .006). Conclusions: Among PLWH, most cancers are not diagnosed at younger ages. However, this study strengthens evidence that lung cancer, anal cancer, and myeloma are diagnosed at modestly younger ages, and also shows younger ages at diagnosis of oral cavity/pharynx and kidney cancers, possibly reflecting accelerated cancer progression, etiologic heterogeneity, or risk factor exposure in PLWH.

Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.

BACKGROUND: Cancer is increasingly common among persons with HIV. OBJECTIVE: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. DESIGN: Cohort study. SETTING: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. PARTICIPANTS: 86 620 persons with HIV and 196 987 uninfected adults. MEASUREMENTS: Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. RESULTS: Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. LIMITATION: Secular trends in screening, smoking, and viral co-infections were not evaluated. CONCLUSION: Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.

Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults.

BACKGROUND: Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults. METHODS: The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively. RESULTS: A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders. CONCLUSIONS: HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV.