Public and Patients' Perspectives Towards Data and Sample Sharing for Research: An Overview of Empirical Findings.

We aimed to review the attitudes and perspectives of the public and patients towards the sharing of data and biospecimens for research and to identify common dimensions, regardless of setting. Our review included systematic, scoping or thematic reviews of empirical studies retrieved from Medline (PubMed interface), Web of Science, Scopus, ProQuest and Cochrane Reviews. The main themes identified and synthesised across the 14 reviews were readiness and motivations; potential risks and safeguards; trust, transparency and accountability; autonomy and preferred type of consent; and factors influencing data and biospecimen sharing and consent. Sociodemographic factors and research and individual context remain relevant influencing factors in all settings, while preferences for types of consent are highly heterogeneous. Trusted environments and adapted consent options with participant engagement are relevant to improve research participation.

Restrictions on Hospital Referrals from Long-Term Care Homes in Madrid and COVID-19 Mortality from March to June 2020: A Systematic Review of Studies Conducted in Spain.

In March 2020, a ministerial directive issued by the Government of the Community of Madrid (CoM) in Spain included disability-based exclusion criteria and recommendations against hospital referral of patients with respiratory conditions living in long-term care homes (LTCHs). Our objective was to assess whether the hospitalization mortality ratio (HMR) is greater than unity, as would be expected had the more severe COVID-19 cases been hospitalized. Thirteen research publications were identified in this systematic review of mortality by place of death of COVID-19-diagnosed LTCH residents in Spain. In the two CoM studies, the HMRs were 0.9 (95%CI 0.8;1.1) and 0.7 (95%CI 0.5;0.9), respectively. Outside of the CoM, in 9 out of 11 studies, the reported HMRs were between 1.7 and 5, with lower 95% CI limits over one. Evaluation of the disability-based triage of LTCH residents during March-April 2020 in public hospitals in the CoM should be conducted.

La desconocida mortalidad de la población en las residencias de personas mayores de España / Unknown mortality of the population in long-term care homes in Spain

Es necesario conocer la mortalidad de las personas mayores que viven en residencias para evaluar sus determinantes, incluyendo las características estructurales y organizativas de estos centros y su relación con la utilización de servicios sanitarios y sociales. Al querer investigar la mortalidad de la población mayor de 65 años que vive en residencias durante la COVID-19 nos encontramos con la imposibilidad de identificar a las personas fallecidas con domicilio habitual en residencias y, en consecuencia, de conocer el número de defunciones y sus causas. En esta nota de campo describimos esta situación anómala y proponemos una solución: el cumplimiento de la ley que obliga a todos los ciudadanos al empadronamiento en el domicilio habitual, lo que debería ser exigido en el proceso de admisión a una residencia. Se aseguraría así la disponibilidad de los datos necesarios para conocer la mortalidad de la población que reside en una residencia. (AU)

It seems necessary to assess the mortality of older people living in long-term care homes to examine its determinants, including the structural and organizational characteristics of these centers and their relationship with the use of health and social services. Attempting to investigate the mortality of the population over 65 years of age living in long-term care homes during COVID-19, we were not able to identify those who died at their long-term care home and, consequently, to know their number of deaths and their causes. In this field note, we describe this anomalous situation and propose a solution: compliance with the law that obliges all citizens to register at their usual address, which should be required in the process of admission to a residence. This would ensure the availability of the necessary data to know the mortality of the population residing in a residence. (AU)

The Impact of Long-Term Care Home Ownership and Administration Type on All-Cause Mortality from March to April 2020 in Madrid, Spain.

Our aim is to assess whether long-term care home (LTCH) ownership and administration type were associated with all-cause mortality in 470 LTCHs in the Community of Madrid (Spain) during March and April 2020, the first two months of the COVID-19 pandemic. There are eight categories of LTCH type, including various combinations of ownership type (for-profit, nonprofit, and public) and administration type (completely private, private with places rented by the public sector, administrative management by procurement, and completely public). Multilevel regression was used to examine the association between mortality and LTCH type, adjusting for LTCH size, the spread of the COVID-19 infection, and the referral hospital. There were 9468 deaths, a mortality rate of 18.3%. Public and private LTCHs had lower mortality than LTCHs under public-private partnership (PPP) agreements. In the fully adjusted model, mortality was 7.4% (95% CI, 3.1-11.7%) in totally public LTCHs compared with 21.9% (95% CI, 17.4-26.4%) in LTCHs which were publicly owned with administrative management by procurement. These results are a testimony to the fatal consequences that pre-pandemic public-private partnerships in long-term residential care led to during the first months of the COVID-19 pandemic in the Community of Madrid, Spain.

[Unknown mortality of the population in long-term care homes in Spain]. / La desconocida mortalidad de la población en las residencias de personas mayores de España.

It seems necessary to assess the mortality of older people living in long-term care homes to examine its determinants, including the structural and organizational characteristics of these centers and their relationship with the use of health and social services. Attempting to investigate the mortality of the population over 65 years of age living in long-term care homes during COVID-19, we were not able to identify those who died at their long-term care home and, consequently, to know their number of deaths and their causes. In this field note, we describe this anomalous situation and propose a solution: compliance with the law that obliges all citizens to register at their usual address, which should be required in the process of admission to a residence. This would ensure the availability of the necessary data to know the mortality of the population residing in a residence.

Association of disability with mortality in the Spanish adult non-institutionalised population.

BACKGROUND: There are scant studies focused on measuring the association between disability and all-cause mortality based on large representative national samples of the community-dwelling adult population; moreover, the number of such studies which also include cause-specific mortality is yet lower. METHODS: Longitudinal cohort study that used baseline data from 162 381 adults who participated in a countrywide disability survey (2008). A nationally representative sample was selected and interviewed in their homes. We present data on people ≥18 years. Disability was considered as any substantial limitation found on a list of 44 life activities that have lasted or are expected to last more than 1 year and originate from an impairment. Cause-specific mortality data were obtained from the Spanish Statistical Office. Subjects contributed follow-up time from baseline interview until death or the censoring date (31 December 2017). We computed standardised rate ratios (SRRs), with age, sex, living with a partner and education level distribution of the total group as standard population. RESULTS: Adults with disability (11%) had an adjusted mortality rate more than twice as high as adults without disability (SRR 2.37, 95% CI 2.24 to 2.50). The increased mortality risk remained over the 10-year follow-up period. Mortality due to diseases of the nervous system (SRR 4.86, 95% CI 3.93 to 6.01), diseases of the musculoskeletal system (SRR 3.45, 95% CI 2.18 to 5.47), infectious diseases (SRR 3.38, 95% CI 2.27 to 5.01) and diabetes mellitus (SRR 3.56, 95% CI 2.71 to 4.68) was particularly high in those with disability. CONCLUSIONS: All-cause mortality rates are markedly higher among adults with disability. Preventive measures and health promotion initiatives are needed to reduce mortality risk in this population. Special attention should be paid to disabled people with certain specific diseases.

Conflicts of interest among scientific foundations and societies in the field of childhood nutrition / Conflictos de intereses de las fundaciones y sociedades científicas del ámbito de la nutrición infantil

Objective: To describe food-industry sponsorships of associations active in the field of childhood nutrition and obesity prevention in Spain in 2017-2018. Method: The associations were located at https://www.google.es/ using the words “society”, “foundation” or “federation” in combination with the terms “nutrition”, “obesity”, “childhood”, “paediatrics” and “diabetes”. Sponsorship was defined as the declaration of funding received or the appearance of a food company logo on an association's website or in the programmes of its congresses or courses. The percentage of sponsored societies and its association with the existence of ethical codes was calculated using MS Excel. Results: 64% of the associations displayed some type of sponsorship, with this being most frequent among paediatric and nutrition societies, 83% and 80% respectively, and non-existent among public health societies. No association was found between the existence of an ethical code and sponsorship (odds ratio: 0.75; 95% confidence interval: 0.14-3.94). The leading corporate sponsors were Nestlé, Coca-Cola and Danone. Whereas the initiatives of sponsored societies were targeted at changing eating individual behaviours, those of unsponsored societies sought to promote changes in the food system and eating environments. Conclusions: Food industry sponsorship of foundations and scientific societies is very widespread in Spain, except among public health associations. Unlike sponsored associations, those unsponsored propose policies opposed by the food industry, which are aimed at improving the system and food and eating environments. (AU)

Objetivo: Describir el patrocinio de compañías que comercializan alimentos y bebidas no saludables a sociedades científicas y fundaciones relacionadas con la nutrición y la prevención de la obesidad infantil en España durante 20172018. Método: Las sociedades y fundaciones fueron localizadas en www.google.es/ usando las palabras clave «sociedad», «fundación» y «federación», combinadas con «nutrición», «obesidad», «infantil», «pediatría» y «diabetes». Se consideró como patrocinio la declaración de financiación o la presencia del logo de la compañía alimentaria en la página web de la asociación o de los programas de congresos o cursos. Se calculó el porcentaje de asociaciones patrocinadas y su asociación con la existencia de código ético usando MS Excel. Resultados: El 64% de las asociaciones recibieron algún patrocinio de compañías alimentarias, más frecuente en las sociedades de pediatría (83%) y nutrición (80%) e inexistente en las de salud pública. No se encontró asociación entre la existencia de código ético y patrocinio (odds ratio: 0,75; intervalo de confianza del 95%: 0,14-3,94). Las principales compañías patrocinadoras fueron Nestlé, Coca-Cola y Danone. Las iniciativas de las asociaciones patrocinadas se dirigían exclusivamente a cambiar los hábitos individuales, mientras que las sociedades no patrocinadas promovieron cambios en el sistema y el entorno alimentarios. Conclusiones: El patrocinio de las compañías alimentarias a asociaciones relacionadas con la nutrición y la prevención de la obesidad infantil es común en España, excepto entre las sociedades de salud pública. A diferencia de las sociedades patrocinadas, las no patrocinadas promueven políticas alimentarias dirigidas a modificar el sistema y el entorno alimentarios, a las que se opone la industria alimentaria. (AU)

Human prion disease surveillance in Spain, 1993-2018: an overview.

In Spain, human transmissible spongiform encephalopathies (TSEs) have been undergoing continuous surveillance for over 25 years. In 1995, the system was launched as an EU Concerted Action, with EU surveillance network procedures being incorporated from 2002 onwards. The aim of this report was to describe performance and outcomes of this surveillance system across the period 1993-2018. Neurology and public health specialists from every region reported cases to a central hub at the Carlos III Health Institute, Madrid. In all, eight accidentally transmitted cases and five definite variant Creutzfeldt-Jakob disease (vCJD) patients were reported. All vCJD cases were diagnosed between 2005 and 2008. Two of these were family/dietary-related and spatially linked to a third. Yearly incidence of sporadic CJD per million was 1.25 across the period 1998-2018, and displayed a north-south gradient with the highest incidence in La Rioja, Navarre and the Basque Country. Genetic TSEs were observed to be clustered in the Basque Country, with a 4-fold incidence over the national rate. A total of 120 (5.6%) non-TSE sporadic, conformational, rapidly progressing neurodegenerative and vascular brain disorders were reported as suspect CJD. We conclude that TSEs in Spain displayed geographically uneven, stable medium incidences for the sporadic and genetic forms, a temporal and spatial family cluster for vCJD, and decreasing numbers for dura-mater-associated forms. The vCJD surveillance, framed within the EU network, might require continuing to cover all prion disorders. There is need for further strategic surveillance research focusing on case definition of rapid-course, conformational encephalopathies and surgical risk.

Survival Patterns of Human Prion Diseases in Spain, 1998-2018: Clinical Phenotypes and Etiological Clues.

BACKGROUND: Human transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative disorders of short duration. There are few studies on TSE survival. This study sought to analyze the survival and related factors of a TSE patient cohort, based on a nationwide surveillance system in Spain. METHODS: Survival analyses were performed on 1,530 cases diagnosed across the period 1998-2018 in Spain. We calculated median survival times and plotted survival curves using the Kaplan-Meier method for all cases and for sporadic TSE (sTSE) and genetic TSE (gTSE). Crude and adjusted Cox proportional hazard models were used to identify variables associated with shorter survival. FINDINGS: Median age at onset decreased from the sporadic forms to gTSE and, lastly, to acquired TSE. Overall median and interquartile range (IQR) survival time was 5.2 (IQR, 3.0-11.7) months and 4.9 (IQR, 2.8-10.8) months in sporadic cases and 9 (IQR, 4.9 to over 12) months in genetic cases, p < 0.001. Male sex, older age at onset, presence of 14-3-3 protein, typical MRI, and MM and VV polymorphisms at codon 129 were associated with shorter survival. gTSE showed higher survival in crude comparisons but not after adjustment. INTERPRETATION: TSE survival in Spain replicates both the magnitude of that shown and the TSE entity-specific population patterns observed in Western countries but differs from features described in Asian populations, such as the Japanese. The reduction in differences in survival between gTSE and sTSE on adjusting for covariates and international patterns might support the view that gTSE and sTSE share causal and pathophysiological features.

Conflicts of interest among scientific foundations and societies in the field of childhood nutrition.

OBJECTIVE: To describe food-industry sponsorships of associations active in the field of childhood nutrition and obesity prevention in Spain in 2017-2018. METHOD: The associations were located at https://www.google.es/ using the words "society", "foundation" or "federation" in combination with the terms "nutrition", "obesity", "childhood", "paediatrics" and "diabetes". Sponsorship was defined as the declaration of funding received or the appearance of a food company logo on an association's website or in the programmes of its congresses or courses. The percentage of sponsored societies and its association with the existence of ethical codes was calculated using MS Excel. RESULTS: 64% of the associations displayed some type of sponsorship, with this being most frequent among paediatric and nutrition societies, 83% and 80% respectively, and non-existent among public health societies. No association was found between the existence of an ethical code and sponsorship (odds ratio: 0.75; 95% confidence interval: 0.14-3.94). The leading corporate sponsors were Nestlé, Coca-Cola and Danone. Whereas the initiatives of sponsored societies were targeted at changing eating individual behaviours, those of unsponsored societies sought to promote changes in the food system and eating environments. CONCLUSIONS: Food industry sponsorship of foundations and scientific societies is very widespread in Spain, except among public health associations. Unlike sponsored associations, those unsponsored propose policies opposed by the food industry, which are aimed at improving the system and food and eating environments.

Individual interventions to improve adherence to pharmaceutical treatment, diet and physical activity among adults with primary hypertension. A systematic review protocol.

INTRODUCTION: Hypertension is a chronic disease with 31% worldwide prevalence in adults. It has been associated with non-adherence to therapeutic regime with a negative impact on the prognosis of the disease and healthcare-associated costs. So, it is necessary to identify effective interventions to improve adherence among the afflicted population. The objective of this protocol is to describe the methods for a systematic review that will evaluate the effect of individual interventions so as to improve adherence to the prescribed pharmacological treatment, as well as to prescribed diet and physical activity in adults with primary hypertension. METHODS AND ANALYSIS: A systematic search of studies will be conducted in PubMed/MEDLINE, BVS, CINAHL, Embase, Cochrane and Scopus databases. Randomised and non-randomised clinical studies conducted in human beings, published from 1 January 2009 to 13 December 2019, are to be included, in any language. Adherence to pharmacological treatment, diet and physical activity, measured by direct and indirect methods, will be the primary outcome. Two independent reviewers will select relevant studies and will extract the data following the Cochrane's Handbook for Systematic Reviews of Approach and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. Methodological quality will be evaluated using the risk-of-bias (RoB) 2 and Risk of Bias in Non-randomised Studies - of Interventions (ROBINS-I) tools. Risk of bias will also be evaluated, and if the criteria are met, a meta-analysis will be finally performed. ETHICS AND DISSEMINATION: Information to be analysed is of a grouped nature, and given that its sources are published studies, no ethics committee approval is required. Results will be published in scientific journals, and in conferences, seminars and symposiums. Copyrights will be addressed by giving due credit through bibliographic references. PROSPERO REGISTRATION NUMBER: CRD42020147655.

Social engagement within the facility increased life expectancy in nursing home residents: a follow-up study.

BACKGROUND: Social engagement (SE) has been consistently shown to improve survival among community-dwelling older people, but the evidence in nursing home residents is inconclusive and prone to short-term reverse causation and confounding by major health determinants. Our main objective was to study the potential causal effect of within-the-facility social engagement (SE) on long-term all-cause mortality in care home residents. METHODS: A representative cohort of 382 nursing home residents in Madrid without severe physical and cognitive impairments at baseline was followed up for 10-year all-cause mortality. Standardized mortality curves for residents with low/null, moderate, and high levels of SE at baseline were estimated using Kaplan-Meier methods and spline-based survival models with inverse probability of exposure weights conditional on baseline sociodemographic characteristics, facility features, comorbidity, and disability. Standardized 5-year mortality risks and median survival times were compared across levels of SE. RESULTS: The baseline prevalences of low/null, moderate, and high SE were 36, 44, and 20%, respectively. Compared with residents with low/null SE at baseline, the standardized differences (95% confidence intervals) in 5-year mortality risk were - 2.3% (- 14.6 to 10.0%) for moderately engaged residents and - 18.4% (- 33.8 to - 2.9%) for highly engaged residents. The median survival time increased by 0.4 (- 1.4 to 2.2) and 3.0 (0.8 to 5.2) years, respectively. CONCLUSION: Residents with high SE within the nursing home had an 18% lower 5-year mortality risk and a 3-year increase in their median survival, as compared with residents with similar health determinants but low/null SE. The development of adequate tailored intervention programs, addressed to increase SE in nursing home residents, could improve their long-term survival, in addition to expected gains in quality of life.

Falls and long-term survival among older adults residing in care homes.

OBJECTIVES: To assess the association between having suffered a fall in the month prior to interview and long-term overall survival in nursing-home residents. METHODS: Retrospective cohort study conducting an overall survival follow-up of 689 representative nursing-home residents from Madrid, Spain. Residents lived in three types of facilities: public, subsidized and private and its information was collected by interviewing the residents, caregivers and/or facility physicians. Residents contributed to follow-up time from their baseline interviews until death or being censored at the end of the 5-year follow-up period. The association between suffering a fall during the month prior to interview and long-term overall survival was analyzed using Cox proportional hazards models. To adjust for potential confounders we used progressive adjusted models. We then repeated the analyses with severity of the fall (no fall, non-severe, severe) as the main independent variable. RESULTS: After a 2408 person-year follow-up (median 4.5 years), 372 participants had died. In fully-adjusted models, residents who had suffered any kind of fall in the previous month showed virtually the same survival rates compared to non-fallers (hazard ratio (HR) = 1.03; 95% CI = 0.75-1.40). There was a weak graded relationship between increased fall severity and survival rates for the non-severe fall group (HR = 0.92; 95% CI = 0.58-1.45) and the severe fall group (HR = 1.36; 95% CI = 0.73-2.53) compared with residents who had not suffered any kind of fall. The hazard ratios for severe falls were higher in men, residents with less comorbidity, fewer medications, and those functionally independent. CONCLUSION: We found no associations between having suffered a fall in the month prior to interview and long-term survival; neither did we find a marked association when severity of fall was accounted for in the whole population. In some subgroups, however, the results merit further scrutiny.

Urinary incontinence and mortality among older adults residing in care homes.

AIM: To assess the association between baseline urinary incontinence and long-term, all-cause mortality. BACKGROUND: Urinary incontinence is a common disorder among older institutionalised adults, with important consequences for morbidity and quality of life. Moreover, while it is a consistent mortality marker, the extent to which this association might be causal remains controversial. DESIGN: A cohort study. METHODS: We conducted a mortality follow-up study on a cohort of 675 nursing-home residents in the city of Madrid (Spain), from their 1998-1999 baseline interviews to September 2013. Study subjects or their caregivers were asked whether the resident had experienced any involuntary leakage of urine in the preceding 14 days, with subjects being subsequently defined as continent, mildly incontinent, or severely incontinent. Hazard ratios for all-cause mortality were estimated using Cox proportional hazards models. RESULTS: After a 4061 person-year follow-up (median/maximum of 4·6/15·2 years), 576 participants had died. In fully-adjusted models, urinary incontinence was associated with a 24 per cent increased risk of all-cause mortality. There was a graded relationship across severity levels, with hazard ratios 7% higher for mild and 44% higher for severe incontinence as compared with the continent group. The adjusted mortality fraction attributable to urinary incontinence was 11 per cent. CONCLUSION: It would appear that urinary incontinence is not only a marker but also a real determinant of survival in the institutionalized population. This finding, which seems plausible in a population of frail older adults, warrants further research into mechanisms that could help to elucidate this hypothesis.

Ethical considerations surrounding the response to Ebola: the Spanish experience.

BACKGROUND: The recent Ebola virus disease (EVD) outbreak, with 28,646 reported cases and 11,323 deaths, was declared a public health emergency of international interest by the World Health Organisation. In Spain, a single reported case triggered a public health crisis of a markedly media-centred nature. The approach to the first EVD epidemic has given rise to various ethical considerations around the world. We address the most relevant ethical considerations emanating from the management of EVD in Spain. MAIN BODY: Firstly, for reasons of global justice and humanitarian assistance, rich countries have the duty to support poorer countries in building up their core public-health capacities. Secondly, quarantine for high-risk contacts might have been a disproportionate and not properly justified measure, which could have contributed to stigmatising contacts and spreading panic. Thirdly, when the first secondary case was reported in Spain, it is doubtful whether informed consent requirements were strictly complied with when disclosing information concerning the alleged accident potentially causing the contagion. Moreover, this information was used by the Regional Health Minister to blame the patient, evading his responsibility to ensure safe medical procedures for health workers. Finally, the patient received convalescent plasma for compassionate use from a colleague of the first missionary repatriated, who also participated in a research study in Spain, despite having previously been denied the chance of being transferred to Spain to receive treatment. This fact highlights the asymmetry in the relationship between rich and poor countries. SHORT CONCLUSION: The management of this crisis highlighted the technical capacity of the health system and its professionals to respond effectively to public health emergencies caused by emerging diseases. This said, the failures in the protection of the EVD patient's privacy remind us that this aspect has to be borne in mind from the outset in crisis situations. Certain coercive measures, such as quarantine, should only be applied where there is some evidence that the benefit-risk balance could be favourable. Lastly, it is essential that research and interventions targeted at combating the fragility of the health systems in poor countries respond to reasons of global justice.

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database.

BACKGROUND: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. METHODS: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. RESULTS: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. CONCLUSIONS: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely.

Melamine toxicity: one more culprit in calcium kidney lithiasis.

An outbreak of uric acid and melamine kidney stones and obstructive acute renal failure in children appeared recently in China due to the ingestion of melamine-tainted formula. Liu and colleagues show that calcium urolithiasis is also strongly associated with urine melamine in adults in Taiwan. Although its effect measure is still uncertain, such an association is likely to be causal. These findings prompt further research into the source of exposure, impact in other settings, and changes over time.