Shiftwork, sleep disturbance and the metabolic syndrome among female hospital workers

Background: Shiftwork is associated with increased sleep disturbance and cardiovascular and metabolic disease risk. This thesis will focus on shiftwork-related sleep disturbance and the potential mediating role of reduced sleep duration in the relationship between a current rotational shiftwork schedule and the metabolic syndrome among female hospital employees. Objectives: 1) To describe sleep patterns in relation to different shiftwork exposure metrics (current status, cumulative exposure, number of consecutive night shifts); 2) To assess the association between shiftwork metrics and sleep duration; 3) To determine whether sleep duration on work shifts mediates the relationship between a current rotational shiftwork pattern and the metabolic syndrome; and 4) To assess whether cumulative shiftwork exposure and the number of consecutive night shifts are associated with the metabolic syndrome. Methods: 294 female hospital employees (142 rotating shiftworkers, 152 dayworkers) participated in a cross-sectional study. Shiftwork parameters were determined through self-report. Sleep was measured for one week with the ActiGraph GT3X+, a tri-axial accelerometer. The metabolic syndrome was defined according to the Joint Interim Studies Consensus Statement. Sleep was described by shiftwork exposure parameters, and multivariable linear regression was used to determine associations between shiftwork variables and sleep duration. Regression path analysis was used to assess whether sleep duration was a mediator between a current shiftwork schedule and the metabolic syndrome, and the significance of the indirect (mediating) effect was tested with bootstrap confidence intervals. Logistic regression was used to determine associations between cumulative shiftwork exposure, number of consecutive night shifts, and the metabolic syndrome. Results: Current shiftworkers slept less on work shifts, more on free days, and were more likely to nap compared to dayworkers. Sleep duration on work shifts was a strong intermediate in the relationship between a current shiftwork pattern and the metabolic syndrome. Cumulative shiftwork exposure and the number of consecutive night shifts did not affect sleep or the metabolic syndrome. Conclusions: A current shiftwork pattern disrupts sleep, and reduced sleep duration is an important intermediate between shiftwork and the metabolic syndrome among female hospital employees.

Statistically robust representation and comparison of mortality profiles in archaeozoology

Archaeozoological mortality profiles have been used to infer site-specific subsistence strategies. There is however no common agreement on the best way to present these profiles and confidence intervals around age class proportions. In order to deal with these issues, we propose the use of the Dirichlet distribution and present a new approach to perform age-at-death multivariate graphical comparisons. We demonstrate the efficiency of this approach using domestic sheep/goat dental remains from 10 Cardial sites (Early Neolithic) located in South France and the Iberian Peninsula. We show that the Dirichlet distribution in age-at-death analysis can be used: (i) to generate Bayesian credible intervals around each age class of a mortality profile, even when not all age classes are observed; and (ii) to create 95% kernel density contours around each age-at-death frequency distribution when multiple sites are compared using correspondence analysis. The statistical procedure we present is applicable to the analysis of any categorical count data and particularly well-suited to archaeological data (e.g. potsherds, arrow heads) where sample sizes are typically small.

Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis

BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity.

METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n=1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using individual participant data and multivariable logistic regression and combined using random effects meta-analysis.

RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5 cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was only statistically significant among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with decreased risk of BE. Increasing waist circumference was associated with increased risk of BE in the mutually adjusted population-based and GERD control models.

CONCLUSIONS: Although abdominal obesity is associated with increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men.

Digoxin use after diagnosis of prostate cancer and survival: a population-based cohort study

PURPOSE:
Preclinical studies have shown that digoxin exerts anticancer effects on different cancer cell lines including prostate cancer. A recent observational study has shown that digoxin use was associated with a 25% reduction in prostate cancer risk. The aim of this study was to investigate whether digoxin use after diagnosis of prostate cancer was associated with decreased prostate cancer-specific mortality.
METHODS:
A cohort of 13 134 patients with prostate cancer newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2010 prostate cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and prostate cancer-specific mortality.
RESULTS:
Overall, 701 (5%) patients with prostate cancer used digoxin after diagnosis. Digoxin use was associated with an increase in prostate cancer-specific mortality before adjustment (HR = 1.59; 95% CI 1.32-1.91), but after adjustment for confounders, the association was attenuated (adjusted HR = 1.13; 95% CI 0.93-1.37) and there was no evidence of a dose response.
CONCLUSIONS:
In this large population-based prostate cancer cohort, there was no evidence of a reduction in prostate cancer-specific mortality with digoxin use after diagnosis.

Statin use and breast cancer survival: a nationwide cohort study in Scotland

Background: Preclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality. Methods: We conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin. Results: A total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose–response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98). Conclusion: Overall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BACKGROUND: The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.

METHODS: A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.

RESULTS: In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I(2)=0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I(2)=67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04).

CONCLUSION: In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.

Calcium Channel Blocker Use and Risk of Prostate Cancer by TMPRSS2:ERG Gene Fusion Status

BACKGROUND: Calcium channel blockers (CCBs) may affect prostate cancer (PCa) growth by various mechanisms including those related to androgens. The fusion of the androgen-regulated gene TMPRSS2 and the oncogene ERG (TMPRSS2:ERG or T2E) is common in PCa, and prostate tumors that harbor the gene fusion are believed to represent a distinct disease subtype. We studied the association of CCB use with the risk of PCa, and molecular subtypes of PCa defined by T2E status.

METHODS: Participants were residents of King County, Washington, recruited for population-based case-control studies (1993-1996 or 2002-2005). Tumor T2E status was determined by fluorescence in situ hybridization using tumor tissue specimens from radical prostatectomy. Detailed information on use of CCBs and other variables was obtained through in-person interviews. Binomial and polytomous logistic regression were used to generate odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: The study included 1,747 PCa patients and 1,635 age-matched controls. A subset of 563 patients treated with radical prostatectomy had T2E status determined, of which 295 were T2E positive (52%). Use of CCBs (ever vs. never) was not associated with overall PCa risk. However, among European-American men, users had a reduced risk of higher-grade PCa (Gleason scores ≥7: adjusted OR = 0.64; 95% CI: 0.44-0.95). Further, use of CCBs was associated with a reduced risk of T2E positive PCa (adjusted OR = 0.38; 95% CI: 0.19-0.78), but was not associated with T2E negative PCa.

CONCLUSIONS: This study found suggestive evidence that use of CCBs is associated with reduced relative risks for higher Gleason score and T2E positive PCa. Future studies of PCa etiology should consider etiologic heterogeneity as PCa subtypes may develop through different causal pathways. 

Smoking during pregnancy by duration of residence among immigrants in Sweden 1991-2012 : A study on health inequalities

This study revisits the effect of duration by residence in relation to smoking during pregnancy. It contributes to the literature by incorporating a health inequity perspective, and discusses whether immigrants tend to converge with Swedish women’s smoking. The study is based on Swedish Medical Birth Register and includes 1 1864 52 pregnancies between 1991 and 2012. Logistic regression was performed to attain crude and adjusted Odds Ratios and 95 % confidence intervals. Immigrants’ are divided by categorizing countries of origin depending on levels of Human Development (IHDI). Overall immigrant women show low levels of smoking during pregnancy when they arrive to Sweden, by duration of residence levels of smoking increase and converge with smoking patterns of Swedish women. I found that there are differences in smoking patterns depending on IHDI of the country. Immigrant women of higher categories of IHDI show higher levels of smoking although the increase of smoking is higher among immigrant women from categories of lower IHDI. However, immigrant women’s smoking during pregnancy is affected by duration of residence, and the increased smoking is associated with health inequalities related to their country of origins IHDI, and by socioeconomic inequalities in Sweden. 

A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil

NORO, L. R. A. et al. A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil. Cad. Saúde Pública, v. 24, n. 7, p. 1509-1516. 2008. ISSN 0102-311X.

Evaluación del estado poblaciónal del Cangrejo violáceo Platyxanthus orbignyi (Milne Edwards y Lucas, 1843) del área de Lambayeque por medio de un modelo dinámico de Biomasa

Se hace un análisis del estado poblacional del cangrejo violáceo Platyxanthus orbignyi (Milne Edwards y Lucas, 1843) del litoral de Lambayeque – Perú para el periodo 2001-2010 por medio de: 1) El modelo dinámico de biomasa de Schaefer en su versión de error de observación; a este modelo se le introdujo la variable ambiental anomalía de la temperatura superficial del mar (ATSM) del área de San José (Lambayeque) y se obtuvo 2) el modelo dinámico con variable ambiental, ambos basados en datos de captura, esfuerzo y CPUE. Se utilizó el método de máxima verosimilitud en el proceso de ajuste y el bootstrap para determinar los intervalos de confianza de los parámetros. Los parámetros poblacionales y pesqueros estimados por el modelo dinámico de biomasa de Schaefer (MDB) fueron: K: 750 000 kg, r : 0,21 y q: 8,36 x 10-6 y por el modelo dinámico con variable ambiental (MDVA) los parámetros fueron K: 765 000 kg, r: 0,23 y q: 8,02 x 10-6. Con los valores de los parámetros estimados mediante el MDB y el MDVA se calcularon los principales puntos biológicos de referencia (PBR) los cuales fueron: MRS: 39 822 kg, BMRS: 375 000 kg, fMRS: 12 561 nasas, FMRS: 0,11, F0.1: 0,10 para el MDB; y MRS: 44 069 kg, BMRS: 382 500 kg, fMRS: 13 782 nasas, FMRS: 0,12, F0.1: 0,10 para el MDVA. Los resultados indican que el estado actual de la pesquería del cangrejo violáceo del Litoral de Lambayeque se encuentra muy cerca al nivel óptimo. En vista de que no se dispone de información de evaluaciones directas de este recurso que confirme o no los resultados del MDB y MDVA y en virtud de la calidad de datos, se sugiere que el manejo de la pesquería sea del tipo adaptativo alrededor del punto de referencia F0.1 y teniendo en cuenta las condiciones ambientales.

Méthodes de Bootstrap pour les modèles à facteurs

Cette thèse développe des méthodes bootstrap pour les modèles à facteurs qui sont couram- ment utilisés pour générer des prévisions depuis l'article pionnier de Stock et Watson (2002) sur les indices de diffusion. Ces modèles tolèrent l'inclusion d'un grand nombre de variables macroéconomiques et financières comme prédicteurs, une caractéristique utile pour inclure di- verses informations disponibles aux agents économiques. Ma thèse propose donc des outils éco- nométriques qui améliorent l'inférence dans les modèles à facteurs utilisant des facteurs latents extraits d'un large panel de prédicteurs observés. Il est subdivisé en trois chapitres complémen- taires dont les deux premiers en collaboration avec Sílvia Gonçalves et Benoit Perron. Dans le premier article, nous étudions comment les méthodes bootstrap peuvent être utilisées pour faire de l'inférence dans les modèles de prévision pour un horizon de h périodes dans le futur. Pour ce faire, il examine l'inférence bootstrap dans un contexte de régression augmentée de facteurs où les erreurs pourraient être autocorrélées. Il généralise les résultats de Gonçalves et Perron (2014) et propose puis justifie deux approches basées sur les résidus : le block wild bootstrap et le dependent wild bootstrap. Nos simulations montrent une amélioration des taux de couverture des intervalles de confiance des coefficients estimés en utilisant ces approches comparativement à la théorie asymptotique et au wild bootstrap en présence de corrélation sérielle dans les erreurs de régression. Le deuxième chapitre propose des méthodes bootstrap pour la construction des intervalles de prévision permettant de relâcher l'hypothèse de normalité des innovations. Nous y propo- sons des intervalles de prédiction bootstrap pour une observation h périodes dans le futur et sa moyenne conditionnelle. Nous supposons que ces prévisions sont faites en utilisant un ensemble de facteurs extraits d'un large panel de variables. Parce que nous traitons ces facteurs comme latents, nos prévisions dépendent à la fois des facteurs estimés et les coefficients de régres- sion estimés. Sous des conditions de régularité, Bai et Ng (2006) ont proposé la construction d'intervalles asymptotiques sous l'hypothèse de Gaussianité des innovations. Le bootstrap nous permet de relâcher cette hypothèse et de construire des intervalles de prédiction valides sous des hypothèses plus générales. En outre, même en supposant la Gaussianité, le bootstrap conduit à des intervalles plus précis dans les cas où la dimension transversale est relativement faible car il prend en considération le biais de l'estimateur des moindres carrés ordinaires comme le montre une étude récente de Gonçalves et Perron (2014). Dans le troisième chapitre, nous suggérons des procédures de sélection convergentes pour les regressions augmentées de facteurs en échantillons finis. Nous démontrons premièrement que la méthode de validation croisée usuelle est non-convergente mais que sa généralisation, la validation croisée «leave-d-out» sélectionne le plus petit ensemble de facteurs estimés pour l'espace généré par les vraies facteurs. Le deuxième critère dont nous montrons également la validité généralise l'approximation bootstrap de Shao (1996) pour les regressions augmentées de facteurs. Les simulations montrent une amélioration de la probabilité de sélectionner par- cimonieusement les facteurs estimés comparativement aux méthodes de sélection disponibles. L'application empirique revisite la relation entre les facteurs macroéconomiques et financiers, et l'excès de rendement sur le marché boursier américain. Parmi les facteurs estimés à partir d'un large panel de données macroéconomiques et financières des États Unis, les facteurs fortement correlés aux écarts de taux d'intérêt et les facteurs de Fama-French ont un bon pouvoir prédictif pour les excès de rendement.

Stepped Wedge Design for Multiple Interventions

Thesis (Master's)--University of Washington, 2016-08

Impact des techniques de fermeture utérine lors de la césarienne

Contexte: La césarienne est une procédure chirurgicale qui survient dans plus du quart des accouchements en Amérique du Nord. Les techniques chirurgicales de fermeture de l’utérus lors de la césarienne sont variées, influencent la cicatrisation et le risque de complications chez la femme à court et long terme. Il a été suggéré que la fermeture en un plan barré augmentait le risque de rupture de l’utérus et de défaut de cicatrisation de l’utérus. Cependant, en l’absence d’un haut niveau d’évidence, cette technique est toujours pratiquée au Canada et en Amérique du Nord. Objectif: Comparer l’impact des différentes techniques de fermeture de l’utérus lors de la césarienne sur les complications maternelles à court et long terme. Méthode : Trois revues systématiques et méta-analyses d’études observationnelles ou d’essais randomisés contrôlés (ECR) ont été réalisées. La prévalence des défauts de cicatrisation et les issues à court et long terme ont été comparées entre les techniques de fermeture de l’utérus. Par la suite, un essai randomisé contrôlé a évalué trois techniques de fermeture de l’utérus : un plan barré, deux plans barrés et deux plans non barrés excluant la déciduale, chez 81 femmes avec une césarienne primaire élective à ≥ 38 semaines de grossesse. L’épaisseur du myomètre résiduel a été mesurée six mois après la césarienne à l’aide d’une échographie transvaginale et comparée par un test t de Student. Résultats : Les résultats des revues systématiques et méta-analyses ont montré que 37% à 59% des femmes présentaient un défaut de cicatrisation de l’utérus après leur césarienne. Concernant les complications à court terme, les types de fermeture de l’utérus étudiés sont comparables, à l’exception de la fermeture en un plan barré qui est associée à un temps opératoire plus court que celle en deux plans (-6.1 minutes, 95% intervalle de confiance (IC) -8.7 à -3.4, p<0.001). Les fermetures de l’utérus en un plan barré sont associées à plus de risque de rupture utérine qu’une fermeture en deux plans barrés (rapport de cote 4.96; IC 95%: 2.58–9.52, P< 0.001). L’ECR a également démontré que la fermeture de l’utérus en un plan barré était associée à une épaisseur du myomètre résiduel plus mince que la fermeture en deux plans non barrés excluant la déciduale (3.8 ± 1.6 mm vs 6.1 ± 2.2 mm; p< 0.001). Finalement, aucune différence significative n’a été détectée concernant la fréquence des points d’hémostases entre les techniques (p=1.000). Conclusion : Lors d’une césarienne élective primaire à terme, une fermeture en deux plans non barrés est associée à un myomètre plus épais qu’une fermeture en un plan barré, sans augmenter le recours à des points d’hémostase. De plus, il est suggéré que la fermeture en deux plans réduirait le risque de rupture utérine lors d’une prochaine grossesse. Finalement, la fermeture chez les femmes en travail doit être plus étudiée.

Ovarian suppression using luteinizing hormonereleasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: A meta-analysis of randomized studies

Background: The role of temporary ovarian suppression with luteinizing hormone-releasing hormone agonists (LHRHa) in the prevention of chemotherapy-induced premature ovarian failure (POF) is still controversial. Our meta-analysis of randomized, controlled trials (RCTs) investigates whether the use of LHRHa during chemotherapy in premenopausal breast cancer patients reduces treatment-related POF rate, increases pregnancy rate, and impacts disease-free survival (DFS). Methods: A literature search using PubMed, Embase, and the Cochrane Library, and the proceedings of major conferences, was conducted up to 30 April 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for POF (i.e. POF by study definition, and POF defined as amenorrhea 1 year after chemotherapy completion) and for patients with pregnancy, as well hazard ratios (HRs) and 95% CI for DFS, were calculated for each trial. Pooled analysis was carried out using the fixed- and random-effects models. Results: A total of 12 RCTs were eligible including 1231 breast cancer patients. The use of LHRHa was associated with a significant reduced risk of POF (OR 0.36, 95% CI 0.23-0.57; P < 0.001), yet with significant heterogeneity (I2 = 47.1%, Pheterogeneity = 0.026). In eight studies reporting amenorrhea rates 1 year after chemotherapy completion, the addition of LHRHa reduced the risk of POF (OR 0.55, 95% CI 0.41-0.73, P < 0.001) without heterogeneity (I2 = 0.0%, Pheterogeneity = 0.936). In five studies reporting pregnancies, more patients treated with LHRHa achieved pregnancy (33 versus 19 women; OR 1.83, 95% CI 1.02-3.28, P = 0.041; I2 = 0.0%, Pheterogeneity = 0.629). In three studies reporting DFS, no difference was observed (HR 1.00, 95% CI 0.49-2.04, P = 0.939; I2 = 68.0%, Pheterogeneity = 0.044). Conclusion: Temporary ovarian suppression with LHRHa in young breast cancer patients is associated with a reduced risk of chemotherapy-induced POF and seems to increase the pregnancy rate, without an apparent negative consequence on prognosis.

A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil

NORO, L. R. A. et al. A utilização de serviços odontológicos entre crianças e fatores associados em Sobral, Ceará, Brasil. Cad. Saúde Pública, v. 24, n. 7, p. 1509-1516. 2008. ISSN 0102-311X.