Adaptive COVID-19 Mitigation Strategies: Tradeoffs between Trigger Thresholds, Response Timing, and Effectiveness.

Background. To support proactive decision making during the COVID-19 pandemic, mathematical models have been leveraged to identify surveillance indicator thresholds at which strengthening nonpharmaceutical interventions (NPIs) is necessary to protect health care capacity. Understanding tradeoffs between different adaptive COVID-19 response components is important when designing strategies that balance public preference and public health goals. Methods. We considered 3 components of an adaptive COVID-19 response: 1) the threshold at which to implement the NPI, 2) the time needed to implement the NPI, and 3) the effectiveness of the NPI. Using a compartmental model of SARS-CoV-2 transmission calibrated to Minnesota state data, we evaluated different adaptive policies in terms of the peak number of hospitalizations and the time spent with the NPI in force. Scenarios were compared with a reference strategy, in which an NPI with an 80% contact reduction was triggered when new weekly hospitalizations surpassed 8 per 100,000 population, with a 7-day implementation period. Assumptions were varied in sensitivity analysis. Results. All adaptive response scenarios substantially reduced peak hospitalizations relative to no response. Among adaptive response scenarios, slower NPI implementation resulted in somewhat higher peak hospitalization and a longer time spent under the NPIs than the reference scenario. A stronger NPI response resulted in slightly less time with the NPIs in place and smaller hospitalization peak. A higher trigger threshold resulted in greater peak hospitalizations with little reduction in the length of time under the NPIs. Conclusions. An adaptive NPI response can substantially reduce infection circulation and prevent health care capacity from being exceeded. However, population preferences as well as the feasibility and timeliness of compliance with reenacting NPIs should inform response design. Highlights: This study uses a mathematical model to compare different adaptive nonpharmaceutical intervention (NPI) strategies for COVID-19 management across 3 dimensions: threshold when the NPI should be implemented, time it takes to implement the NPI, and the effectiveness of the NPI.All adaptive NPI response scenarios considered substantially reduced peak hospitalizations compared with no response.Slower NPI implementation results in a somewhat higher peak hospitalization and longer time spent with the NPI in place but may make an adaptive strategy more feasible by allowing the population sufficient time to prepare for changing restrictions.A stronger, more effective NPI response results in a modest reduction in the time spent under the NPIs and slightly lower peak hospitalizations.A higher threshold for triggering the NPI delays the time at which the NPI starts but results in a higher peak hospitalization and does not substantially reduce the time the NPI remains in force.

Evaluating the association between expanded coverage of direct-to-consumer telemedicine and downstream utilization and quality of care for urinary tract infections and sinusitis.

OBJECTIVE: To compare direct-to-consumer (DTC) telemedicine and in-person visits in rates of testing, follow-up health care use, and quality for urinary tract infections (UTIs) and sinusitis. DATA SOURCE: The Minnesota All Payer Claims Data provided 2008-2015 administrative claims data. STUDY DESIGN: Using a difference-in-differences approach, we compared episodes of care for UTIs and sinusitis among enrollees of health plans introducing coverage for DTC telemedicine relative to those without DTC telemedicine coverage. Primary outcomes included number of laboratory tests, antibiotics filled, office and outpatient visits, emergency department (ED) visits, and standardized spending, based on standardized prices of health services. DATA COLLECTION: The study sample included non-elderly enrollees of commercial health insurance plans. We constructed 30-day episodes of care initiated by a DTC telemedicine or in-person visit. PRINCIPAL FINDINGS: The UTI and sinusitis samples were comprised of 215,134 and 624,630 episodes of care, respectively. Following the introduction of coverage for DTC telemedicine, 15.7% of UTI episodes and 8.9% of sinusitis episodes were initiated with DTC telemedicine. Compared to episodes without coverage for DTC telemedicine, UTI episodes with coverage had 0.25 fewer lab tests (95% CI: -0.33, -0.18; p < 0.001), lower standardized spending for the first UTI visit (-$11.18 [95% CI: -$21.62, -$0.75]; p < 0.05), and no change in office and outpatient visits, ED visits, antibiotics filled, or standardized medical spending. Sinusitis episodes with coverage for DTC telemedicine had fewer antibiotics filled (-0.08 [95% CI: -0.14, -0.01]; p < 0.05) and a very small increase in ED visits (0.001 [95% CI: 0.001, 0.010]; p < 0.05), but no change in lab tests, office and outpatient visits, or standardized medical spending. CONCLUSIONS: Among commercially insured patients, coverage of DTC telemedicine was associated with reductions in antibiotics for sinusitis and laboratory tests for UTI without changes in downstream total office and outpatient visits or changes in ED visits.

Trends in COVID-19 Vaccine Administration and Effectiveness Through October 2021.

Importance: COVID-19 vaccines are effective, but inequities in vaccine administration and waning immunity may limit vaccine effectiveness. Objectives: To report statewide trends in vaccine administration and vaccine effectiveness in Minnesota. Design, Setting, and Participants: This cohort study used COVID-19 vaccine data from the Minnesota Immunization Information Connection from October 25, 2020, through October 30, 2021 that were linked with electronic health record (EHR) data from health systems collaborating as part of the Minnesota EHR Consortium (MNEHRC). Participants included individuals who were seen at a participating health system in Minnesota. Exposures: Individuals were considered fully vaccinated in the second week after receipt of a second dose of a BNT162b2 or mRNA-1273 vaccine or a single dose of an Ad26.COV.2.S vaccine. Main Outcomes and Measures: A completed vaccination series and vaccine breakthrough, defined as either a positive SARS-CoV-2 polymerase chain reaction (PCR) test or a hospital admission the same week or within the 3 weeks following a positive SARS-CoV-2 PCR test. A test-negative design and incident rate ratio were used to evaluate COVID-19 vaccine effectiveness separately for the BNT162b2, mRNA-1273, and Ad26.COV.2.S vaccines. Rurality and social vulnerability index were assessed at the area level. Results: This study included 4 431 190 unique individuals at participating health systems, and 3 013 704 (68%) of the individuals were fully vaccinated. Vaccination rates were lowest among Minnesotans who identified as Hispanic (116 422 of 217 019 [54%]), multiracial (30 066 of 57 412 [52%]), American Indian or Alaska Native (22 190 of 41 437 [54%]), and Black or African American (158 860 of 326 595 [49%]) compared with Minnesotans who identified as Asian or Pacific Islander (159 999 of 210 994 [76%]) or White (2 402 928 of 3 391 747 [71%]). Among individuals aged 19 to 64 years, vaccination rates were lower in rural areas (196 479 of 308 047 [64%]) compared with urban areas (151 541 of 1 951 265 [77%]) and areas with high social vulnerability (544 433 of 774 952 [70%]) compared with areas with low social vulnerability (571 613 of 724 369 [79%]). In the 9 weeks ending October 30, 2021, vaccine effectiveness as assessed by a test-negative design was 33% (95% CI, 30%-37%) for Ad26.COV.2.S; 53% (95% CI, 52%-54%) for BNT162b2; and 66% (95% CI, 65%-67%) for mRNA-1273. For SARS-CoV-2-related hospitalizations, vaccine effectiveness in the 9 weeks ending October 30, 2021, was 78% (95% CI, 75%-81%) for Ad26.COV.2.S; 81% (95% CI, 79%-82%) for BNT162b2; and 81% (95% CI, 79%-82%) for mRNA-1273. Conclusions and Relevance: This cohort study of data from a Minnesota statewide consortium suggests disparities in vaccine administration and effectiveness. Vaccine effectiveness against infection was lower for Ad26.COV.2.S and BNT162b2 but was associated with protection against SARS-CoV-2-related hospitalizations despite the increased prevalence of the Delta variant in Minnesota.

Minnesota Electronic Health Record Consortium COVID-19 Project: Informing Pandemic Response Through Statewide Collaboration Using Observational Data.

OBJECTIVE: Robust disease and syndromic surveillance tools are underdeveloped in the United States, as evidenced by limitations and heterogeneity in sociodemographic data collection throughout the COVID-19 pandemic. To monitor the COVID-19 pandemic in Minnesota, we developed a federated data network in March 2020 using electronic health record (EHR) data from 8 multispecialty health systems. MATERIALS AND METHODS: In this serial cross-sectional study, we examined patients of all ages who received a COVID-19 polymerase chain reaction test, had symptoms of a viral illness, or received an influenza test from January 3, 2016, through November 7, 2020. We evaluated COVID-19 testing rates among patients with symptoms of viral illness and percentage positivity among all patients tested, in aggregate and by zip code. We stratified results by patient and area-level characteristics. RESULTS: Cumulative COVID-19 positivity rates were similar for people aged 12-64 years (range, 15.1%-17.6%) but lower for adults aged ≥65 years (range, 9.3%-10.7%). We found notable racial and ethnic disparities in positivity rates early in the pandemic, whereas COVID-19 positivity was similarly elevated across most racial and ethnic groups by the end of 2020. Positivity rates remained substantially higher among Hispanic patients compared with other racial and ethnic groups throughout the study period. We found similar trends across area-level income and rurality, with disparities early in the pandemic converging over time. PRACTICE IMPLICATIONS: We rapidly developed a distributed data network across Minnesota to monitor the COVID-19 pandemic. Our findings highlight the utility of using EHR data to monitor the current pandemic as well as future public health priorities. Building partnerships with public health agencies can help ensure data streams are flexible and tailored to meet the changing needs of decision makers.

Comparison of Young Adult Female Cancer Survivors Recruited from a Population-Based Cancer Registry to Eligible Survivors.

BACKGROUND: Population-based cancer registries provide a resource to recruit young adult cancer survivors who may not be easily identified otherwise. METHODS: We compared demographic and cancer-related characteristics of participants in a cohort of female young adult cancer survivors to those of eligible survivors in the Georgia Cancer Registry, a population-based registry in the United States. We examined associations between survivor characteristics and nonparticipation using logistic regression and associations between survivor characteristics and different types of nonparticipation (refusal, unable to contact, or unresolved vs. interviewed) using polytomous regression. RESULTS: The Georgia Cancer Registry was able to contact 60% of eligible women (3,061/5,137). Of those, 78% agreed to study contact (n = 2,378), and of those, 56% were interviewed (n = 1,342). Participation was similar across age at contact and at diagnosis but varied across cancer type from 17% for cervical cancer to 32% for breast cancer. White women were slightly more likely to be interviewed (28%) than African American women (23%), which was mostly attributable to greater difficulty in contacting African American women (odds ratio 1.7, 95% confidence interval: 1.5-2.1). CONCLUSIONS: The greatest challenge to recruiting women was contacting them, which differed across some but not all demographic and cancer-related characteristics. When successfully contacted, most survivors agreed to participate. IMPACT: Population-based cancer registries can serve as an invaluable resource to recruit representative samples of young adult cancer survivors, who are otherwise difficult to identify.

Social Support Outside the Workplace, Coping Styles, and Burnout in a Cohort of EMS Providers From Minnesota.

Occupational burnout has been linked to the delivery of lower quality of care in some health care professions, including with turnover intentions and absenteeism in emergency medical services (EMS) workers. Thus, studies that identify factors associated with burnout may be integral to optimizing quality and workforce engagement among EMS professionals. A survey was conducted to assess social support outside the workplace, coping styles, and occupational burnout in a cohort of EMS providers from Minnesota. Surveys were returned by 217 providers (54% response), of which 167 had provided data on burnout, social support, and coping styles and were included in the analysis. The mean age was 41 years, 62% were male, and the prevalence of burnout was 17%. After adjustment for age and EMS tenure, the odds of burnout was higher among those characterized as socially isolated as compared with providers who were integrated socially or moderately integrated (odds ratio = 3.52; 95% confidence interval = [1.13, 10.98]). Common coping responses included planning, positive reframing, and active coping, while behavioral disengagement and denial were rarely used. Lack of social networks outside the workplace and frequent use of self-blame, food, or substance use as coping strategies were associated with burnout. Conversely, social integration and use of religion and instrumental support to cope with stressors were associated with reduced burnout.

Burnout and Exposure to Critical Incidents in a Cohort of Emergency Medical Services Workers from Minnesota.

INTRODUCTION: Very little quantitative data on occupational burnout and exposure to critical incidents are available from contemporary United States emergency medical services (EMS) cohorts. Given that burnout has been associated positively with turnover intentions and absenteeism in EMS workers, studies that uncover correlates of burnout may be integral to combating growing concerns around retention in the profession. METHODS: We administered a 167-item electronic survey that included the Maslach Burnout Inventory (MBI) and a modified version of the Critical Incident History Questionnaire (n=29 incident types) to paramedics, emergency medical technicians (EMTs), and dispatchers of a single ambulance service. We defined the presence of burnout as a high score on either the emotional exhaustion or depersonalization subscales of the MBI. RESULTS: Survey respondents who provided regular 911 response at the time of the survey and completed the MBI portion of the survey were included in our analysis (190 paramedics/EMTs, 19 dispatchers; 54% response). The overall prevalence of burnout was 18%, with prevalence reaching 32% among dispatchers. The seven pediatric critical incident types presented in the survey accounted for seven of the top eight rated most difficult to cope with, and severity ratings for pediatric critical incidents did not differ by parental status (all p>0.30). A significant number of respondents reported that they had been threatened with a gun/weapon (43%) or assaulted by a patient (68%) at least once while on duty. Being over the age of 50, a parent, or in a committed relationship was associated with reduced odds of burnout in unadjusted models; however, these associations did not remain statistically significant in multivariate analysis. Increasing tertile of career exposure to critical incidents was not associated with burnout. CONCLUSION: Medical dispatchers may be an EMS subgroup particularly susceptible to burnout. These data also demonstrate quantitatively that in this EMS agency, responders find pediatric critical incidents especially distressing and that violence against responders is commonplace. In this study, a simple measure of career exposure to potentially critical incidents was not associated with burnout; however, individual reactions to incidents are heterogeneous, and assessment tools that more accurately enumerate encounters that result in distress are needed.

Population-Level Estimates Of Telemedicine Service Provision Using An All-Payer Claims Database.

In recent years state and federal policies have encouraged the use of telemedicine by formalizing payments for it. Telemedicine has the potential to expand access to timely care and reduce costs, relative to in-person care. Using information from the Minnesota All Payer Claims Database, we conducted a population-level analysis of telemedicine service provision in the period 2010-15, documenting variation in provision by coverage type, provider type, and rurality of patient residence. During this period the number of telemedicine visits increased from 11,113 to 86,238, and rates of use varied extensively by coverage type and rurality. In metropolitan areas telemedicine visits were primarily direct-to-consumer services provided by nurse practitioners or physician assistants and covered by commercial insurance. In nonmetropolitan areas telemedicine use was chiefly real-time provider-initiated services delivered by physicians to publicly insured populations. Recent federal and state legislation that expanded coverage and increased provider reimbursement for telemedicine services could lead to expanded use of telemedicine, including novel approaches in new patient populations.

Retrospective cohort study of cancer incidence and mortality by HIV status in a Georgia, USA, prisoner cohort during the HAART era.

OBJECTIVE: Non-AIDS-defining cancers (NADCs) have emerged as significant contributors to cancer mortality and morbidity among persons living with HIV (PLWH). Because NADCs are also associated with many social and behavioural risk factors that underlie HIV, determining the extent to which each of these factors contributes to NADC risk is difficult. We examined cancer incidence and mortality among persons with a history of incarceration, because distributions of other cancer risk factors are likely similar between prisoners living with HIV and non-infected prisoners. DESIGN: Registry-based retrospective cohort study. PARTICIPANTS: Cohort of 22,422 persons incarcerated in Georgia, USA, prisons on 30 June 1991, and still alive in 1998. OUTCOME MEASURES: Cancer incidence and mortality were assessed between 1998 and 2009, using cancer and death registry data matched to prison administrative records. Age, race and sex-adjusted standardised mortality and incidence ratios, relative to the general population, were calculated for AIDS-defining cancers, viral-associated NADCs and non-infection-associated NADCs, stratified by HIV status. RESULTS: There were no significant differences in cancer mortality relative to the general population in the cohort, regardless of HIV status. In contrast, cancer incidence was elevated among the PLWH. Furthermore, incidence of viral-associated NADCs was significantly higher among PLWH versus those without HIV infection (standardised incidence ratio=6.1, 95% CI 3.0 to 11.7, p<0.001). CONCLUSIONS: Among PLWH with a history of incarceration, cancer incidence was elevated relative to the general population, likely related to increased prevalence of oncogenic viral co-infections. Cancer prevention and screening programmes within prisons may help to reduce the cancer burden in this high-risk population.

Implementing a Community-Driven Research Partnership: The Backyard Initiative Community Health Survey Methods and Approach.

BACKGROUND: In community-based participatory research (CBPR), issues such as creating a setting where community members drive decisions and creating culturally relevant processes remain largely underachieved. The Backyard Initiative (BYI) provided the setting for implementing a community-centered collaborative research process. The BYI is a partnership between Allina Health, the Cultural Wellness Center (CWC), and community residents to improve health. OBJECTIVES: To describe the unique community-centered method used in the 2013 BYI Community Health Survey (CHS) as a viable approach for collecting meaningful and valid health related data. With this approach, the community operates as the agent of change rather than the target. METHODS: At the core was the BYI assessment team, which brought together conventional researchers and community members to collaboratively design, implement, analyze, interpret, and disseminate the CHS results. Focusing on the CHS, this structure and process permitted and facilitated important and difficult discussions about approach, content and outcomes of the research. RESULTS: We held seven sessions (239 participants). Participants were 37% African American/African and 34% Native American, 65% female, and 72% spoke English at home. Achievement of our recruitment goals, participation of groups typically underrepresented in research, and positive community feedback were indications that the BYI approach to survey research was successful. CONCLUSIONS: The BYI CHS community-centered methods built trust among research partners and participants, engaged populations often underrepresented in research, and collected meaningful data. Our success indicates that it is possible to co-design and implement a lengthy survey to inform future research and community activities.

Piloting a computer assisted telephone interview: the FUCHSIA Women's Study.

BACKGROUND: Loss of fertility has been reported as an important concern of reproductive age women diagnosed with cancer. The Furthering Understanding of Cancer, Health, and Survivorship In Adult (FUCHSIA) Women's Study examines how cancer treatment affects the fertility of cancer survivors who were diagnosed during their reproductive years. In this paper we discuss the process of developing and pilot testing the FUCHSIA computer assisted telephone interview (CATI). METHODS: The CATI was developed in several phases and pilot tested twice to evaluate several aspects of the instrument including question sequencing, understandability of the questions, and women's comfort with certain questions. Participants were recruited from cancer and infertility support groups and study team contacts. RESULTS: Fifty-two women were recruited and participated in the first pilot. The participants had a mean age of 31.5 years, 17.3% had cancer, and 38.5% experienced a period of infertility. Twenty-four women participated in the second pilot with similar representation. CONCLUSIONS: The collection of detailed information on reproductive outcomes with the CATI may improve the understanding of how cancer treatment during the reproductive years affects female fertility. The pilot studies provided important information to improve the CATI before the full study. Our comprehensive recruitment strategy allowed us to interview a diverse group of women to ensure that questions and answer choices were easily interpreted, check complicated skip patterns and the flow of questions, and evaluate the length of the interview. This experience can be used to help inform others in what steps can be useful for developing telephone interviews for research studies.

Arsenic exposure and bladder cancer: quantitative assessment of studies in human populations to detect risks at low doses.

While exposures to high levels of arsenic in drinking water are associated with excess cancer risk (e.g., skin, bladder, and lung), exposures at lower levels (e.g., <100-200 µg/L) generally are not. Lack of significant associations may result from methodological issues (e.g., inadequate statistical power, exposure misclassification), or a different dose-response relationship at low exposures, possibly associated with a toxicological mode of action that requires a sufficient dose for increased tumor formation. The extent to which bladder cancer risk for low-level arsenic exposure can be statistically measured by epidemiological studies was examined using an updated meta-analysis of bladder cancer risk with data from two new publications. The summary relative risk estimate (SRRE) for all nine studies was elevated slightly, but not significantly (1.07; 95% confidence interval [CI]: 0.95-1.21, p-Heterogeneity [p-H]=0.543). The SRRE among never smokers was 0.85 (95% CI: 0.66-1.08, p-H=0.915), whereas the SRRE was positive and more heterogeneous among ever smokers (1.18; 95% CI: 0.97-1.44, p-H=0.034). The SRRE was statistically significantly lower than relative risks predicted for never smokers in the United States based on linear extrapolation of risks from higher doses in southwest Taiwan to arsenic water exposures >10 µg/L for more than one-third of a lifetime. By contrast, for all study subjects, relative risks predicted for one-half of lifetime exposure to 50 µg/L were just above the upper 95% CI on the SRRE. Thus, results from low-exposure studies, particularly for never smokers, were statistically inconsistent with predicted risk based on high-dose extrapolation. Additional studies that better characterize tobacco use and stratify analyses of arsenic and bladder cancer by smoking status are necessary to further examine risks of arsenic exposure for smokers.

Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.g., via questionnaire or interview) or measured pesticide or metabolite levels in biological specimens from study participants (e.g., blood, urine, etc.) or their immediate environment (e.g., personal air monitoring, home dust samples, etc.) were eligible for inclusion. Consistency, strength of association, and dose response were key elements of the framework utilized for evaluating epidemiologic studies. As a whole, the epidemiologic studies did not strongly implicate any particular pesticide as being causally related to adverse neurodevelopmental outcomes in infants and children. A few associations were unique for a health outcome and specific pesticide, and alternative hypotheses could not be ruled out. Our survey of the in vivo peer-reviewed published mammalian literature focused on effects of the specific active ingredient of pesticides on functional neurodevelopmental endpoints (i.e., behavior, neuropharmacology and neuropathology). In most cases, effects were noted at dose levels within the same order of magnitude or higher compared to the point of departure used for chronic risk assessments in the United States. Thus, although the published animal studies may have characterized potential neurodevelopmental outcomes using endpoints not required by guideline studies, the effects were generally observed at or above effect levels measured in repeated-dose toxicology studies submitted to the U.S. Environmental Protection Agency (EPA). Suggestions for improved exposure assessment in epidemiology studies and more effective and tiered approaches in animal testing are discussed.

Using pathway-specific comprehensive exposure scores in epidemiology: application to oxidative balance in a pooled case-control study of incident, sporadic colorectal adenomas.

Identifying associations of risk factors sharing the same pathway with disease risk is complicated by small individual effects and intercorrelated components; this can be addressed by creating comprehensive exposure scores. We developed and validated 3 novel weighting methods (literature review-derived, study data-based, and a Bayesian method that combines prior knowledge with study data) to incorporate components into a pathway score for oxidative balance in addition to a commonly used method that assumes all components contribute equally to the score. We illustrate our method using pooled data from 3 US case-control studies of sporadic colorectal adenoma (1991-2002). We created 4 oxidative balance scores (OBS) to reflect combined summary measures of dietary and nondietary antioxidant and prooxidant exposures. A higher score represents a predominance of antioxidant exposures over prooxidant exposures. In the pooled data, the odds ratios comparing the highest tertile of OBS with the lowest for adenoma risk ranged from 0.38 to 0.54 for the 4 measures; all were statistically significant. These findings suggest that 1) OBS are indicators of oxidative balance and may be inversely associated with colorectal adenoma risk and 2) using comprehensive exposure scores may be preferable to investigating individual component-disease associations for complex exposures, such as oxidative balance.

Epidemiologic studies of glyphosate and cancer: a review.

The United States Environmental Protection Agency and other regulatory agencies around the world have registered glyphosate as a broad-spectrum herbicide for use on multiple food and non-food use crops. Glyphosate is widely considered by regulatory authorities and scientific bodies to have no carcinogenic potential, based primarily on results of carcinogenicity studies of rats and mice. To examine potential cancer risks in humans, we reviewed the epidemiologic literature to evaluate whether exposure to glyphosate is associated causally with cancer risk in humans. We also reviewed relevant methodological and biomonitoring studies of glyphosate. Seven cohort studies and fourteen case-control studies examined the association between glyphosate and one or more cancer outcomes. Our review found no consistent pattern of positive associations indicating a causal relationship between total cancer (in adults or children) or any site-specific cancer and exposure to glyphosate. Data from biomonitoring studies underscore the importance of exposure assessment in epidemiologic studies, and indicate that studies should incorporate not only duration and frequency of pesticide use, but also type of pesticide formulation. Because generic exposure assessments likely lead to exposure misclassification, it is recommended that exposure algorithms be validated with biomonitoring data.

Potential effects of chlorpyrifos on fetal growth outcomes: implications for risk assessment.

Chlorpyrifos (CPF) is one of the most widely used organophosphate insecticides in the United States. By December 2000, nearly all residential uses were voluntarily canceled, so that today, CPF is only used to control insect pests on a variety of crops. Periodic review of the potential effects of CPF on all developmental outcomes is necessary in the United States because the Food Quality Protection Act mandates special consideration of risk assessments for infants and children. This article reviews epidemiologic studies examining the association of potential CPF exposure with growth indices, including birth weight, birth length, and head circumference, and animal studies focusing on related somatic developmental endpoints. It differs from earlier reviews by including an additional cohort study and providing in-depth systematic evaluation of the patterns of association across different studies with respect to specificity of biomarkers for CPF, consistency, dose response, strength of association, temporality, and biological plausibility (Hill 1965), as well as consideration of the potential role of effect modification and bias. The review did not identify any strong associations exhibiting consistent exposure-response patterns that were observed in more than one of the four cohort studies evaluated. In addition, the animal data indicate that developmental effects occur at doses that produce substantial maternal toxicity and red blood cell (RBC) acetylcholinesterase (AChE) inhibition. Based on consideration of both the epidemiologic and animal data, maternal RBC AChE inhibition is a more sensitive endpoint for risk assessment than somatic developmental effects reviewed in this article.

Evaluation of epidemiology and animal data for risk assessment: chlorpyrifos developmental neurobehavioral outcomes.

Developmental neurobehavioral outcomes attributed to exposure to chlorpyrifos (CPF) obtained from epidemiologic and animal studies published before June 2010 were reviewed for risk assessment purposes. For epidemiological studies, this review considered (1) overall strength of study design, (2) specificity of CPF exposure biomarkers, (3) potential for bias, and (4) Hill guidelines for causal inference. In the case of animal studies, this review focused on evaluating the consistency of outcomes for developmental neurobehavioral endpoints from in vivo mammalian studies that exposed dams and/or offspring to CPF prior to weaning. Developmental neuropharmacologic and neuropathologic outcomes were also evaluated. Experimental design and methods were examined as part of the weight of evidence. There was insufficient evidence that human developmental exposures to CPF produce adverse neurobehavioral effects in infants and children across different cohort studies that may be relevant to CPF exposure. In animals, few behavioral parameters were affected following gestational exposures to 1 mg/kg-d but were not consistently reported by different laboratories. For postnatal exposures, behavioral effects found in more than one study at 1 mg/kg-d were decreased errors on a radial arm maze in female rats and increased errors in males dosed subcutaneously from postnatal day (PND) 1 to 4. A similar finding was seen in rats exposed orally from PND 1 to 21 with incremental dose levels of 1, 2, and 4 mg/kg-d, but not in rats dosed with constant dose level of 1 mg/kg-d. Neurodevelopmental behavioral, pharmacological, and morphologic effects occurred at doses that produced significant brain or red blood cell acetylcholinesterase inhibition in dams or offspring.

A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies.

OBJECTIVE: To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent "weight-of-evidence" (WOE) methodological approach. METHODS: Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose-response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose-response trends. This WOE assessment of 153 different pesticide-outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose-response relationships (i.e., those monotonically increasing, with statistically significant trend tests). RESULTS: Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide-outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two-aldicarb and colon cancer and imazethapyr and proximal colon cancer-appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose-response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk. CONCLUSION: The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.

Quality of reviews on sugar-sweetened beverages and health outcomes: a systematic review.

BACKGROUND: Medical and public health decisions are informed by reviews, which makes the quality of reviews an important scientific concern. OBJECTIVE: We systematically assessed the quality of published reviews on sugar-sweetened beverages (SSBs) and health, which is a controversial topic that is important to public health. DESIGN: We performed a search of PubMed and Cochrane databases and a hand search of reference lists. Studies that were selected were published reviews and meta-analyses (June 2001 to June 2011) of epidemiologic studies of the relation between SSBs and obesity, type 2 diabetes, metabolic syndrome, and coronary heart disease. A standardized data-abstraction form was used. Review quality was assessed by using the validated instrument AMSTAR (assessment of multiple systematic reviews), which is a one-page tool with 11 questions. RESULTS: Seventeen reviews met our inclusion and exclusion criteria: obesity or weight (16 reviews), diabetes (3 reviews), metabolic syndrome (3 reviews), and coronary heart disease (2 reviews). Authors frequently used a strictly narrative review (7 of 17 reviews). Only 6 of 17 reviews reported quantitative data in a table format. Overall, reviews of SSBs and health outcomes received moderately low-quality scores by the AMSTAR [mean: 4.4 points; median: 4 points; range: 1-8.5 points (out of a possible score of 11 points)]. AMSTAR scores were not related to the conclusions of authors (8 reviews reported an association with a mean AMSTAR score of 4.1 points; 9 reviews with equivocal conclusions scored 4.7 points; P value = 0.84). Less than one-third of published reviews reported a comprehensive literature search, listed included and excluded studies, or used duplicate study selection and data abstraction. CONCLUSION: The comprehensive reporting of epidemiologic evidence and use of systematic methodologies to interpret evidence were underused in published reviews on SSBs and health.