Development of spatial statistical methods for modelling point-referenced spatial data in malaria epidemiology

Plasmodium falciparum malaria is the world’s most important parasitic disease and a major cause of morbidity and mortality in Africa. However figures for the burden of malaria morbidity and mortality are very uncertain, since reliable maps of the distribution of malaria transmission and the numbers of affected individuals are not available for most of the African continent. Accurate statistics on the geographical distribution of different endemicities of malaria, on the populations at risk, and on the implications of given levels of endemicity for morbidity and mortality are important for effective malaria control programs. These estimates can be obtained using appropriate statistical models which relate infection, morbidity, and mortality rates to risk factors, measured at individual level, but also to factors that vary gradually over geographical locations. Statistical models which incorporate geographical or individual heterogeneity are complex and highly parameterized. Limitations in statistical computation have until recently made the implementation of these models impractical for non-normal response data, sampled at large numbers of geographical locations. Modern developments in Markov chain Monte Carlo (MCMC) inference have greatly advanced spatial modelling, however many methodological and theoretical problems still remain. For data collected over a fixed number of locations (point-referenced or geostatistical data) such as malaria morbidity and mortality data used in this study, spatial correlation is best specified by parameterizing the variance-covariance matrix of the outcome of interest in relation to the spatial configuration of the locations (variogram modelling). This has been considered infeasible for a large number of locations because of the repeated inversion of the variance-covariance matrix involved in the likelihood. In addition the spatial correlation in malariological data could be dependent not only on the distance between locations but on the locations themselves. Variogram models need to be further developed to take into account the above property which is known as non-stationarity. This thesis reports research with the objectives of: a) developing Bayesian hierarchical models for the analysis of point-referenced malaria prevalence, malaria transmission and mortality data via variogram modelling for a large number of locations taking into account non-stationarity and misalignment, while present in the data; b) producing country specific and continent-wide maps of malaria transmission and malaria prevalence in Africa, augmented by the use of climatic and environmental data; c) assessing the magnitude of the effects of malaria endemicity on infant and child mortality after adjusting of socio-economic factors and geographical patterns. A comparison of the MCMC and the Sampling-Importance-Resampling approach for Bayesian fitting of variogram models showed that the latter was no easier to implement, did not improve estimation accuracy and did not lead to computationally more efficient estimation. Different approaches were proposed to overcome the inversion of large covariance matrices. Numerical algorithms especially suited within the MCMC framework were implemented to convert large covariance matrices to sparse ones and to accelerate inversion. A tesselation-based model was developed which partition the space into random Voronoi tiles. The model assumes a separate spatial process in each tile and independence between tiles. Model fit was implemented via reversible jump MCMC which takes into account the varying number of parameters arised due to random number of tiles. This approach facilitates inversion by converting the covariance matrix to block diagonal form. In addition, this model is well suited for non-stationary data. An accelerated failure time model was developed for spatially misaligned data to assess malaria endemicity in relation to child mortality. The misalignment arised because the data were extracted from databases which were collected at a different set of locations. The newly developed statistical methodology was implemented to produce smooth maps of malaria transmission in Mali and West- and Central Africa, using malaria survey data from the Mapping Malaria Risk in Africa (MARA) database. The surveys were carried out at arbitrary locations and include non-standardized and overlapping age groups. To achieve comparability between different surveys, the Garki transmission model was applied to convert the heterogeneous age prevalence data to a common scale of a transmission intensity measure. A Bayesian variogram model was fitted to the transmission intensity estimates. The model adjusted for environmental predictors which were extracted from remote sensing. Bayesian kriging was used to obtain smooth maps of the transmission intensity, which were converted to age-specific maps of malaria risk. TheWest- and Central African map was based on a seasonality model we developed for the whole of Africa. Expert opinion suggests that the resulting maps improve previous mapping efforts. Additional surveys are needed to increase the precision of the predictions in zones were there are large disagreement with previous maps and data are sparse. The survival model for misaligned data was implemented to produce a smooth mortality map in Mali and assess the relation between malaria endemicity and child and infant mortality by linking the MARA database with the Demographic and Health Survey (DHS) database. The model was adjusted for socio-economic factors and spatial dependence. The analysis confirmed that mothers education, birth order and preceding birth interval, sex of infant, residence and mothers age at birth have a strong impact on infant and child mortality risk, but no statistically significant effect of P. falciparum prevalence could be demonstrated. This may reflect unmeasured local factors, for instance variations in health provisions or availability of water supply in the dry Sahel region, which could have a stronger influence than malaria risk on mortality patterns

Fitting Generalized Linear Mixed Models For Point-Referenced Spatial Data

Non-Gaussian point-referenced spatial data are frequently modeled using generalized linear mixed models (GLMM) with location-specific random effects. Spatial dependence can be introduced in the covariance matrix of the random effects. Maximum likelihood-based or Bayesian estimation implemented via Markov chain Monte Carlo (MCMC) for such models is computationally demanding especially for large sample sizes because of the large number of random effects and the inversion of the covariance matrix involved in the likelihood. We review three fitting procedures, the Penalized Quasi Likelihood method, the MCMC, and the Sampling-Importance-Resampling method. They are assessed in terms of estimation accuracy, ease of implementation, and computational efficiency using a spatially structured dataset on infant mortality from Mali

"The experiences and needs of persons with disabilities in using paratransit services".

BACKGROUND Persons with disabilities do not yet experience equality with the rest of the population when using transportation. Paratransit services take over transportation for persons with disabilities when public transportation cannot be used or can only be used to a limited extent. The usefulness of these services remains limited due to financial and structural reasons. OBJECTIVE This study aims to identify the experiences of persons with disabilities with paratransit in Switzerland, explores their needs and verifies facilitators and barriers to the use of paratransit services. Furthermore, perceived experiences of how barriers and facilitators of transportation influence the participation in different areas of life of these persons are examined. METHODS In this study, we adopted a qualitative approach with four online focus group discussions and one physically present discussion group, including 31 participants overall. We collected data between July and October 2021 and analyzed the data using content analysis according to Mayring (2015). RESULTS Overall, persons with disabilities experience paratransit as important and appreciated this alternative to public transportation. Specifically, the services' need is individual for each person and depends on different facilitating factors (e.g., habits, health condition, activities, safety, accessibility, service) and barriers (e.g., costs, weather conditions). CONCLUSIONS The need for paratransit services is highly individual and impacts participation in different life areas. On one hand, the federalist system in Switzerland supports a local and cultural embedment, but on the other hand leads to difficulties concerning transportation beyond the close local environment and for longer distances

Examining the representativeness of home outdoor PM2.5, EC, and OC estimates for daily personal exposures in Southern California

Recent studies have linked acute respiratory and cardiovascular outcomes to measurements or estimates of traffic-related air pollutants at homes or schools. However, few studies have evaluated these outdoor measurements and estimates against personal exposure measurements. We compared measured and modeled home outdoor concentrations with personal measurements of traffic-related air pollutants in the Los Angeles air basin (Whittier and Riverside). Personal exposure of 63 children with asthma and 15 homes were assessed for particulate matter with an aerodynamic diameter less than 2.5μm (PM2.5), elemental carbon (EC), and organic carbon (OC) during sixteen 10-day monitoring runs. Regression models to predict daily home outdoor PM2.5, EC, and OC were constructed using home outdoor measurements, geographical and meteorological parameters, as well as CALINE4 estimates at outdoor home sites, which represent the concentrations from local traffic sources. These home outdoor models showed the variance explained (R 2) was 0.97 and 0.94 for PM2.5, 0.91 and 0.83 for OC, and 0.76 and 0.87 for EC in Riverside and Whittier, respectively. The PM2.5 outdoor estimates correlated well with the personal measurements (Riverside R 2 = 0.65 and Whittier R 2 = 0.69). However, excluding potentially inaccurate samples from Riverside, the correlation between personal exposure to carbonaceous species and home outdoor estimates in Whittier was moderate for EC (R 2 = 0.37) and poor for OC (R 2 = 0.08). The CALINE4 estimates alone were not correlated with personal measurements of EC or other pollutants. While home outdoor estimates provide good approximations for daily personal PM2.5 exposure, they may not be adequate for estimating daily personal exposure to EC and O

Use of professional home care in persons with spinal cord injury in Switzerland: a cross-sectional study

BACKGROUND Persons with spinal cord injury (SCI) living in the community often require care. The boundaries between professional home care and informal care are blurred, and it is unclear who the typical user of home care is. The objective of this study was to describe the characteristics of persons with SCI using professional home care in Switzerland, determine the frequency of home care visits, and investigate the association of sociodemographic factors, SCI-specific characteristics, secondary health conditions, and functional independence with the use of home care. METHODS We used cross-sectional data from the 2017 community survey of the Swiss Spinal Cord Injury Cohort Study (SwiSCI). Out of 3,959 eligible individuals 1294 completed the questionnaire and were included in the analysis (response rate 33%). Using descriptive statistics, differences between home care users and non-users as well as the frequency of home care visits were investigated. The association between sociodemographic factors, SCI-specific characteristics, secondary health conditions, functional independence and the use of home care was analyzed using multivariable logistic regression. Multiple imputation was used to account for missing data. RESULTS Of 1,294 participants, 280 (22%) used professional home care. The median weekly professional home care duration was 6 h (Q1 = 2, Q3 = 12). More home care was used in persons with lower functional independence (Odds ratio (OR) 0.30 per 10 unit decrease in the Spinal Cord Independence Measure, 95%-Confidence interval (CI) 0.24-0.37), fewer secondary health conditions (OR 0.96 per unit Spinal Cord Injury Secondary Conditions Scale, 95%-CI 0.94-0.99), tetraplegia (OR 2.77, 95%-CI 1.92-4.00), women (OR 2.42, 95%-CI 1.70-3.43), higher age (OR 1.22 per 10 years increase, 95%-CI 1.06-1.39), living alone (OR 2.48, 95%-CI 1.53-4.03), and those receiving support from an informal caregiver (OR 1.88, 95%-CI 1.27-2.77). CONCLUSIONS This is the first study to examine the use of professional home care from the perspective of persons with SCI in Switzerland. Lower functional independence strongly predicts increased home care use. The findings showed that professional home care complements informal care and is more likely to be used by individuals with SCI who live alone, have tetraplegia, and are female

Gleichberechtigte Mobilität dank ÖV-ergänzender Fahrdienste? : eine Mixed-Method Studie über die Mobilität von Menschen mit Behinderung in der Schweiz

Zusammenfassung in leichter Sprache (Übersetzung in Leichte Sprache, Stufe A2: Pro Infirmis, Büro für Leichte Sprache): Bessere Mobilität für Menschen mit Behinderung in der Schweiz Viele Menschen mit Behinderung können den öffentlichen Verkehr nicht nutzen. Fahr-Dienste sind des-halb für viele Menschen mit Behinderung wichtig. Die ZHAW hat ein Forschungs-Projekt zum Thema Fahr-Dienste gemacht. Die Resultate zeigen: Das Angebot der Fahr-Dienste kann verbessert werden. Dazu braucht es andere Regeln für die Fahr-Dienste im Gesetz. Wie ist es im Moment? Viele Menschen in der Schweiz können den öffentlichen Verkehr (ÖV) nicht nutzen. Oder sie können den ÖV nicht immer nutzen. Zum Beispiel: Sie haben eine Gehbehinderung oder Sehbehinderung. Damit diese Menschen trotzdem am öffentlichen Leben teilhaben können, brauchen sie zusätzliche Fahr-Dienste. Diese Fahr-Dienste sind aber nicht in der ganzen Schweiz gleich organisiert. Sie werden auch nicht in der ganzen Schweiz gleich finanziert. Es gibt unterschiedliche Regeln in der Schweiz, wer diese Fahr-Dienste nutzen darf. Was war das Ziel des Forschungs-Projekts? Die Forschenden wollten mit dem Projekt diese Fragen untersuchen: - Wie nutzen Menschen mit Behinderung Fahr-Dienste? - Welche Auswirkungen haben die Transport Möglichkeiten auf den Alltag von Menschen mit Behinderung? Wie waren die Methoden des Forschungs-Projekts? Die Forschenden haben diese Methoden genutzt: - Sie haben die Themen in fünf Gruppen diskutiert. - Sie haben einen Online-Fragebogen erstellt. - 536 Personen aus der ganzen Schweiz haben diesen Fragebogen ausgefüllt. - Sie haben die Gesetze für die Fahr-Dienste genau angeschaut. Die Forschenden haben die Resultate ausgewertet. Dann haben sie Empfehlungen dazu geschrieben, was man machen sollte. Sie haben mit verschiedenen Personen über diese Empfehlungen diskutiert. Sie haben zwei Arbeitsgruppen für diese Diskussionen gemacht. Nach den Arbeitsgruppen haben sie die Empfehlungen überarbeitet. Was sind die Resultate des Forschungs-Projekts? Die Forschenden konnten Antworten auf die folgenden Fragen finden. Wozu nutzen Menschen die Fahr-Dienste? Für: - Arzt-Besuche - Therapie-Besuche - Freizeit-Aktivitäten - Einkäufe - Arbeits-Wege Sie nutzen Fahr-Dienste vor allem für kurze Strecken. Was schätzen Menschen an den Fahr-Diensten? Menschen schätzen an den Fahr-Diensten vor allem: - die persönliche Betreuung durch die Fahrerinnen und Fahrer - die Zuverlässigkeit der Fahr-Dienste - die Sicherheit der Fahr-Dienste Wie oft nutzen Menschen Fahr-Dienste? Menschen nutzen die Fahr-Dienste unterschiedlich oft. Manche Menschen haben andere Transport-Möglichkeiten. Sie haben zum Beispiel Angehörige, die sie irgendwohin fahren können. Andere Menschen haben keine anderen Transport-Möglichkeiten. Für sie sind Fahr-Dienste die einzige Transport-Möglichkeit. Diese Menschen erleben Einschränkungen in ihrem Alltag, weil das Fahr-Dienst-Angebot nicht optimal ist. Das heisst zum Beispiel: - weil die Fahr-Dienste zu viel kosten - weil nicht klar ist, wer die Fahr-Dienste finanziert - weil die Fahr-Dienste nicht immer verfügbar sind - weil die Fahr-Dienste nicht schweizweit organisiert sind Was hat die Untersuchung der Gesetze gezeigt? Die Untersuchung der Gesetze hat gezeigt: - Es ist nicht klar, mit welchen Gesetzen die Fahr-Dienste geregelt werden. - Es ist deshalb auch nicht klar, wer für die Fahr-Dienste zuständig ist: der Bund oder die Kanto-ne? - Die Fahr-Dienste werden nicht im Behinderten-Gleichstellungs-Gesetz erwähnt. - Die Grundrechte von Menschen mit Behinderung werden verletzt, weil sie nicht genug Trans-port- Möglichkeiten haben. - Die Ziele der Behinderten-Rechts-Konvention im Bereich Mobilität sind im Moment nicht erfüllt. Empfehlungen: Was sollte man tun? Die Forschenden haben Empfehlungen gemacht. Diese Empfehlungen beruhen auf den Resultaten des Forschungs-Projekts. 3. Empfehlung: Fahr-Dienste für Menschen mit Behinderung sollten Teil des Behinderten-Gleichstellungs-Gesetzes sein. Dieses Gesetz ist ein Bundes-Gesetz. Damit die Fahr-Dienste Teil dieses Gesetzes sein können, muss man das Gesetz überarbeiten. 2. Empfehlung: Die Fahr-Dienste sollten Teil des öffentlichen Verkehrs sein. Damit sie Teil des öffentlichen Verkehrs sein können, muss man sie in das Personen-Beförderungs-Gesetz aufnehmen. Dieses Gesetz ist ebenfalls ein Bundes-Gesetz. 3. Empfehlung: Die Fahr-Dienste sollten in der ganzen Schweiz gleich organisiert sein. Das heisst, diese Dinge sollten überall gleich organisiert sein: - Angebot: Es braucht überall genug Fahr-Dienste. - Nutzung: Man sollte die Fahr-Dienste überall auf die gleiche Art nutzen können. - Die Bestellung: Man sollte die Fahr-Dienste überall auf die gleiche Art bestellen können. - Bezahlung: Die Fahr-Dienste sollten überall gleich viel kosten. - Es sollte überall klar sein, wer die Fahr-Dienste finanziert. Das Ziel davon ist: Menschen mit Behinderung können Transport-Möglichkeiten so nutzen wie Menschen ohne Behinderung.Hintergrund: Viele Menschen in der Schweiz können den öffentlichen Verkehr (ÖV) nicht oder nur beschränkt nutzen, zum Beispiel weil sie eine Geh- oder Sehbehinderung haben. Um dennoch am öffentlichen Leben teilzuhaben, sind die Betroffenen auf ÖV-ergänzende Fahrdienste angewiesen. Diese sind schweizweit äusserst heterogen organisiert. Ziel: Beschreibung von Angebot, Nutzung und Bedarf ÖV-ergänzender Fahrdienste aus Sicht der Menschen mit Behinderung, sowie aus rechtlicher Sicht. Methoden: Das Forschungsteam wandte im Projekt gemischte Methoden (qualitativ, quantitative und Rechtsanalyse) an. Das Forschungsteam sammelte die Daten in fünf Fokusgruppendiskussionen und einer nationalen Querschnittstudie anhand eines Online-Fragebogens und rechtlichen Dokumenten. Die qualitativen Daten wurden anhand der Methode der Inhaltsanalyse, die quantitativen Daten anhand deskriptiver und inferenzstatistischer Methoden und die rechtliche Situation «de lege lata» analysiert. Aufgrund der Studienresultate wurden Handlungsempfehlungen entworfen, mit Vertreter:innen aus der Politik, aus Behinderten- und Altersorganisationen, aus dem öffentlichen Transportwesen und von ÖV-ergänzenden Fahrdiensten an zwei Workshops diskutiert und anschliessend überarbeitet. Ergebnisse: Insgesamt nahmen 594 Menschen mit und ohne Behinderung an den Studien des Projektes teil. Davon waren 336 (57%) Frauen, 256 (43%) Männer und zwei anderen Geschlechts. Die Teilnehmer:innen waren zwischen 18 und 103 Jahren alt (m=62,4, SD=19,6). Die Ergebnisse zeigen, dass ÖV-ergänzende Fahrdienste zu unterschiedlichen Zwecken genutzt werden: für Therapie- und Arztbesuche, Freizeitaktivitäten, Einkäufe oder Arbeitswege. Hauptsächlich werden Fahrdienste für kurze Strecken eingesetzt. Der Service der Fahrdienste wird besonders wegen der persönlichen Betreuung von Fahrer:innen, der Verlässlichkeit und Sicherheit geschätzt. Die Nutzung der Fahrdienste variiert je nach Person. Während einige auf alternative Fahrdienste zurückgreifen können, sind für andere diese die einzige Option. Folglich wirken sich gerade für diese Personen die hohen Preise, unklare Finanzierungszuständigkeit, begrenzte Verfügbarkeiten und ungenügende überkantonale Koordination einschränkend aus. Die rechtliche Verortung von ÖV-ergänzenden Fahrdiensten ist unklar, und die Zuständigkeit von Bund und Kanton nicht eindeutig. Schlussfolgerungen: Zusammenfassend schätzen Menschen mit Behinderung das Angebot der ÖV-ergänzenden Fahrdienste als eine wichtige Unterstützung für die Ausführung ihrer täglichen Aktivitäten und die gesellschaftliche Partizipation. Dennoch sind Grundrechte von Menschen mit Behinderung tangiert und die Ziele der Behindertenrechtskonvention im Bereich der Mobilität nicht erfüllt. Daraus resultieren folgende Handlungsempfehlungen: 1) Ausweitung des Geltungsbereichs des Bundesgesetzes über die Beseitigung von Benachteiligungen von Menschen mit Behinderung auf Fahrdienste. 2) Einbindung der Fahrdienste in den ÖV, indem sie dem Personenbeförderungsgesetz unterstellt werden. 3) Sicherstellung einer schweizweiten Koordination von Fahrdiensten in den Bereichen Angebot, Nutzung, Bestellung und Bezahlung

Methods to convert continuous outcomes into odds ratios of treatment response and numbers needed to treat: meta-epidemiological study

Background Clinicians find standardized mean differences (SMDs) calculated from continuous outcomes difficult to interpret. Our objective was to determine the performance of methods in converting SMDs or means to odds ratios of treatment response and numbers needed to treat (NNTs) as more intuitive measures of treatment effect. Methods Meta-epidemiological study of large-scale trials (≥100 patients per group) comparing active treatment with placebo, sham or non-intervention control. Trials had to use pain or global symptoms as continuous outcomes and report both the percentage of patients with treatment response and mean pain or symptom scores per group. For each trial, we calculated odds ratios of observed treatment response and NNTs and approximated these estimates from SMDs or means using all five currently available conversion methods by Hasselblad and Hedges (HH), Cox and Snell (CS), Furukawa (FU), Suissa (SU) and Kraemer and Kupfer (KK). We compared observed and approximated values within trials by deriving pooled ratios of odds ratios (RORs) and differences in NNTs. ROR <1 and positive differences in NNTs imply that approximations are more conservative than estimates calculated from observed treatment response. As measures of agreement, we calculated intraclass correlation coefficients. Results A total of 29 trials in 13 654 patients were included. Four out of five methods were suitable (HH, CS, FU, SU), with RORs between 0.92 for SU [95% confidence interval (95% CI), 0.86-0.99] and 0.97 for HH (95% CI, 0.91-1.04) and differences in NNTs between 0.5 (95% CI, −0.1 to −1.6) and 1.3 (95% CI, 0.4-2.1). Intraclass correlation coefficients were ≥0.90 for these four methods, but ≤0.76 for the fifth method by KK (P for differences ≤0.027). Conclusions The methods by HH, CS, FU and SU are suitable to convert summary treatment effects calculated from continuous outcomes into odds ratios of treatment response and NNTs, whereas the method by KK is unsuitabl

Swiss national community survey on functioning after spinal cord injury:Protocol, characteristics of participants and determinants of non-response

Objective: To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. Design: The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. Participants: Community-dwelling persons with chronic spinal cord injury in Switzerland. Methods: Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. Results: Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. Conclusions: The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community

A 7-Step Guideline for Qualitative Synthesis and Meta-Analysis of Observational Studies in Health Sciences

Objectives: To provide a step-by-step, easy-to-understand, practical guide for systematic review and meta-analysis of observational studies. Methods: A multidisciplinary team of researchers with extensive experience in observational studies and systematic review and meta-analysis was established. Previous guidelines in evidence synthesis were considered. Results: There is inherent variability in observational study design, population, and analysis, making evidence synthesis challenging. We provided a framework and discussed basic meta-analysis concepts to assist reviewers in making informed decisions. We also explained several statistical tools for dealing with heterogeneity, probing for bias, and interpreting findings. Finally, we briefly discussed issues and caveats for translating results into clinical and public health recommendations. Our guideline complements "A 24-step guide on how to design, conduct, and successfully publish a systematic review and meta-analysis in medical research" and addresses peculiarities for observational studies previously unexplored. Conclusion: We provided 7 steps to synthesize evidence from observational studies. We encourage medical and public health practitioners who answer important questions to systematically integrate evidence from observational studies and contribute evidence-based decision-making in health sciences

Differences in Heart Rate Variability Associated with Long-Term Exposure to NO2

BACKGROUND: Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV. OBJECTIVE: Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). METHODS: We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants >or= 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO2 at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO2 and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects. RESULTS: For women, but not for men, each 10-microg/m3 increment in 1-year averaged NO2 level was associated with a decrement of 3% (95% CI, -4 to -1) for the standard deviation of all normal-to-normal RR intervals (SDNN), -6% (95% CI, -11 to -1) for nighttime low frequency (LF), and -5% (95% CI, -9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, -8 to -1) per 10-microg/m3 increase in NO2. CONCLUSIONS: There is some evidence that long-term exposure to NO2 is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease