京都大学 / 0048 / 新制・論文博士 / 博士(社会健康医学) / 乙第13293号 / 論社医博第14号 / 新制||社医||10(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 松田 秀一, 教授 今中 雄一, 教授 古川 壽亮 / 学位規則第4条第2項該当 / Doctor of Public Health / Kyoto University / DFAM

Objective: The purpose of this study was to assess the feasibility of conducting a prospective cohort study during early pregnancy (<24 weeks gestation) examining the psychological factors associated with excessive pregnancy weight gain. Study Design: Women who had at least 1 prenatal care visit, had a live singleton gestation and were able to read English were eligible to enroll in the study. Women completed the self-administered survey at their prenatal clinics in Hamilton and Brantford, Ontario, Canada. Final pregnancy weight was obtained from women’s clinical charts. Results: All approached clinics agreed to participate in the study (100% clinic agreement). Five hundred thirty women completed the enrolment survey, which was a 90.0% uptake rate. An average of 6 women enrolled each week at less than 24 weeks gestation. Less than 10% of data were missing for all survey questions and outcome data (final pregnancy weight) was available for all but one participant (97.3%). Final pregnancy weights were obtained a median of 1.0 days (interquartile 0.0-3.5 days) prior to delivery. No psychological factors were significantly associated with the odds of gaining above the 2009 IOM/Health Canada guidelines in the exploratory univariate analysis. Conclusion: All feasibility outcomes demonstrated that conducting a full-scale study in Southwestern Ontario would be feasible. Conducting a full-scale study may identify associations between psychological factors and excessive pregnancy weight gain. / Thesis / Master of Science (MSc)

This thesis is divided in three chapters: (i) introduction to organ donation, (ii) rationale, implementation and design of a pilot observational study currently underway and (iii) justification for use of a waived consent model for observational research studies on organ donor care. Organ donation is a complex event that remains a mystery to most health care providers. The first chapter reports knowledge gaps in clinical management of deceased organ donors across Canada and summarizes ongoing trials in organ donor care. The persistent deficit in transplantable organs along with the limited scientific evidence to guide the clinical management of the organ donor justify the need for a national research program in organ donor care. There are logistical and methodological challenges unique to the design and conduct of research on deceased donors. To identify potential stakeholders involved in the process of organ donation and to provide an accurate description of usual management of deceased donor and assess its variability, we developed and initiated a prospective observational study called DONATE. The second chapter of this thesis described the pilot phase of this study. It contains the following sections: i) objectives of the study ii) the screening process, iii) data collection, iv) clinical outcomes, v) methods of measurement, vi) analysis plan and vii) strategies used to minimize the biases inherent to observational studies. The normative goal of obtaining informed consent from participants may not be appropriate for an observational study in organ donor care. The third chapter summarizes the justification for use of a waived consent model for observational studies of organ donation medicine. In this chapter, I discuss regulatory, ethical and logistical issues relevant to use of a waived consent model in organ donation research. / Thesis / Master of Science (MSc) / Organ donation saves lives and it is the most effective therapy available to treat end stage organ failure of a number of organs. Unfortunately, there is a growing gap between the number of donors and the number of patients waiting for transplantation. This thesis summarizes the foundational work of a national research program in deceased donor management. It describes the study design of a 4 centre prospective observational study in deceased donor management with outcome assessment on corresponding organ-recipients. This thesis also contains a justification for waiving the procurement of consent to research on organ donor management. Finally, it will inform investigators of future national multicentre observational studies on design and implementation issues related to donor management, in order to improve care provided to donors and outcomes of recipients while reducing the gap between transplant needs and organ supply.

<strong>Background:</strong> Stroke is a leading cause of disability and premature death in China and blood pressure is widely considered to be a major cause. Despite this, substantial uncertainty remains about the shape and strength of the association between blood pressure and stroke pathological types in China. <strong>Methods:</strong> Information from the China Kadoorie Biobank study (a prospective cohort study of 0.5 million men and women in China recruited during 2004-8) was used to relate usual blood pressure to risk of stroke, by stroke pathological type (cerebral infarction [ischaemic stroke], intracerebral haemorrhage and subarachnoid haemorrhage). Prospective analyses excluded participants with a history of vascular disease recorded at baseline; involved correction for regression dilution bias; used incident stroke events for which the diagnosis involved a head CT or MRI scan; and, assessed for confounding and effect modification by major vascular risk factors. These prospective analyses were informed by a set of prior analyses, including: a description of baseline associations between blood pressure and other vascular risk factors, to identify potential confounders; analyses of resurvey blood pressure data from ~20_000 participants, to assess regression dilution bias; and analyses of stroke follow-up data, involving an adjudication ‘sub-study’ performed specifically as part of this thesis, to evaluate the diagnostic accuracy of incident stroke events (~1000 events were adjudicated). <strong>Results:</strong> During 2.1 million person-years at risk, there were 5783 incident stroke events. At ages 40-79 years, the proportional difference in risk of both cerebral infarction and intracerebral haemorrhage associated with a given absolute difference in usual blood pressure was constant throughout the range of blood pressures examined (SBP 120-170 mm Hg, DBP 70-100 mm Hg). Overall, the strength of association was approximately 1.5-times greater for intracerebral haemorrhage than for the other stroke pathological types: 10 mm Hg higher usual SBP was associated with 82% (95% CI: 76%-89%) higher risk of intracerebral haemorrhage, 47% (44%- 50%) higher risk of cerebral infarction and 52% (35%-71%) higher risk of subarachnoid haemorrhage (the overall mean age at event for each stroke pathological type was ~60 years). For both cerebral infarction and intracerebral haemorrhage, there was strong evidence of major effect modification by age and to a lesser extent by a number of other vascular risk factors. The associations by age were around a third as extreme at age 70-79 years than at 40-49 years. The annual absolute differences in risk associated with a given absolute increase in usual blood pressure, however, were greater at older age. <strong>Conclusions:</strong> In Chinese adults, usual blood pressure was strongly and positively related to risk of all stroke pathological types. The strength of association was greater for intracerebral haemorrhage than other stroke pathological types. For both cerebral infarction and intracerebral haemorrhage, there was evidence of major effect modification by age. The overall effect of blood pressure on stroke risk was much greater than estimated by previous prospective studies in China, particularly for intracerebral haemorrhage.

Background and Objectives: Little is known about the impact of nicotine replacement therapy (NRT) use duration on smoking cessation in the general population. This study determines whether duration of NRT use is associated with smoking cessation. Methods: Data were from the Ontario Tobacco Survey longitudinal study of a population-based cohort of baseline smokers who made serious quit attempts during 18 months of follow-up. The association between NRT (any NRT, patches, or gum) use duration and smoking cessation outcomes (short-term abstinence ≥1 month and long-term abstinence ≥12 months) was estimated by Poisson regression, adjusting for all confounding variables. Results: Among the 1,590 eligible smokers, 933 (59%) did not use any NRT, 535 (34%) used NRT <8 weeks, and 112 (8%) used NRT ≥8 weeks at follow-up. The median duration of NRT use was 14 days. A consistent “J” shape of associations between quit aid use duration and smoking cessation outcomes (quit rates) was found. Using any NRT, patches, or gum <8 weeks was generally associated with a lower likelihood of quitting, but using them ≥8 weeks was generally associated with a higher likelihood of quitting, compared to not using them. Only using patches for the recommended duration (≥8 weeks) was associated with a higher likelihood of short-term (relative risk, RR 1.74, 95% confidence interval, CI 1.21-2.50) and long-term (RR 2.62, 95% CI 1.25-5.50) abstinence at the end of 18 months of follow-up, compared to not using patches. Using gum ≥8 weeks was not associated with short- or long-term abstinence at the end of 18 months of follow-up. Conclusions: Using nicotine patches for the recommended duration is associated with successful short- and long-term abstinence in the general population. More efforts are needed to encourage smokers to use nicotine patches for eight or more weeks when attempting to quit.

Background and Objectives: Little is known about the impact of nicotine replacement therapy (NRT) use duration on smoking cessation in the general population. This study determines whether duration of NRT use is associated with smoking cessation. Methods: Data were from the Ontario Tobacco Survey longitudinal study of a population-based cohort of baseline smokers who made serious quit attempts during 18 months of follow-up. The association between NRT (any NRT, patches, or gum) use duration and smoking cessation outcomes (short-term abstinence ≥1 month and long-term abstinence ≥12 months) was estimated by Poisson regression, adjusting for all confounding variables. Results: Among the 1,590 eligible smokers, 933 (59%) did not use any NRT, 535 (34%) used NRT <8 weeks, and 112 (8%) used NRT ≥8 weeks at follow-up. The median duration of NRT use was 14 days. A consistent “J” shape of associations between quit aid use duration and smoking cessation outcomes (quit rates) was found. Using any NRT, patches, or gum <8 weeks was generally associated with a lower likelihood of quitting, but using them ≥8 weeks was generally associated with a higher likelihood of quitting, compared to not using them. Only using patches for the recommended duration (≥8 weeks) was associated with a higher likelihood of short-term (relative risk, RR 1.74, 95% confidence interval, CI 1.21-2.50) and long-term (RR 2.62, 95% CI 1.25-5.50) abstinence at the end of 18 months of follow-up, compared to not using patches. Using gum ≥8 weeks was not associated with short- or long-term abstinence at the end of 18 months of follow-up. Conclusions: Using nicotine patches for the recommended duration is associated with successful short- and long-term abstinence in the general population. More efforts are needed to encourage smokers to use nicotine patches for eight or more weeks when attempting to quit.

In the US, 8.4% of children are diagnosed with asthma by age 18, making asthma one of the most common chronic conditions among children. Additionally, 25% of children experience persistent wheezing by age 6, an indicator of childhood asthma. Both childhood asthma and persistent wheezing may be linked to inflammatory and immune mechanisms, which are associated with inadequate and excessive gestational weight gain. Studies investigating the relationship between gestational weight gain and offspring asthma and wheeze phenotypes are limited by self-reported gestational weight gain, early age at asthma and wheeze assessments, limited adjustment for potential confounders and no trimester-specific evaluations. Therefore, we investigated the association between total and trimester-specific gestational weight gain, offspring asthma and wheeze phenotypes among 2128 mother-child pairs in Project Viva, a prospective cohort study in eastern Massachusetts. Gestational weight gain was abstracted from medical records and self-reported prepregnancy weight, and defined both continuously and using Institute of Medicine guidelines. Offspring asthma was obtained via maternal report at approximately 7 years, while wheeze trajectories were derived via latent class mixed models based on presence of wheeze between 1 and 9 years, inclusively, via maternal report. We investigated the relationship between gestational weight gain, offspring asthma and wheeze phenotypes using multivariable regressions and predicted probabilities, adjusting for important covariates. Most women had excessive gestational weight gain (56%), while 31% had adequate gestational weight gain and 13% had inadequate gestational weight gain. Approximately 18% of children had current mid-childhood asthma, 13% had early transient wheeze and 13% had persistent wheeze. We found a non-linear association between total gestational weight gain and offspring current mid-childhood asthma. Additionally, there was a 36% decreased odds of early transient wheeze among children of mothers with excessive third trimester gestational weight gain (aOR= 0.64; 95% CI: 0.42-0.98). This study adds to the body of literature by incorporating adequate inclusion of confounders and risk factors for adjustment, as well as being the first study to evaluate the association between trimester-specific gestational weight gain, offspring asthma and wheeze phenotypes.

Background and Aims: Prior cross-sectional research finds that electronic cigarette (e-cigarette) use clusters with higher rates of harmful alcohol consumption in the United States adult population. The current study examined prospectively the association between e-cigarette use, cigarette use and the combined use of e-cigarettes and tobacco cigarettes and alcohol use outcomes. Design: A nationally representative multi-wave cohort survey (wave 1: September 2013–December 2014, wave 2: October 2014–October 2015). Setting: United States. Participants: A representative sample of civilian, non-institutionalized adults who completed waves 1 and 2 of the Population Assessment of Tobacco and Health survey (n = 26 427). Measurements: Participants were categorized into exposure groups according to their e-cigarette and cigarette use during wave 1. Past 30-day alcohol use outcomes were (1) National Institute on Alcohol Abuse and Alcoholism (NIAAA)-defined hazardous alcohol use, (2) total alcohol drinks consumed and (3) alcohol-related consequences. Findings: After controlling for socio-demographic risk factors and alcohol use at wave 1, all exposure groups showed higher odds of hazardous alcohol use [adjusted odds ratios (aORs) = 2.05–2.12, all P < 0.001] and reported higher past-month total drinks (B = 0.46–0.70, all P < 0.001) and more alcohol consequences (B = 0.63–0.89, all P ≤ 0.10) at wave 2 compared with non-users. Cigarette users (B = 0.24, P = 0.038) and dual e-cigarette/cigarette users (B = 0.32, P = 0.038) reported higher past-month total drinks compared with e-cigarette users. There was no conclusive evidence that non-daily use of e-cigarettes or cigarettes predicted poorer alcohol use outcomes compared with daily use. Conclusions: In the United States between 2013 and 2015, after adjustment for socio-demographic characteristics, cigarette and e-cigarette use were associated with alcohol use 1 year later.

BACKGROUND: Retaining participants in multi-year prospective cohort studies presents challenges, especially in urban settings. Early identification of participants at risk for attrition may enhance retention. We examine the validity of two risk for loss-to-follow-up assessments and early retention efforts in one Primary Sampling Unit during the National Children’s Study pilot. Our goal was to identify cases requiring additional attention. Retention challenges included high poverty, frequent moves, lack of spousal support, and mistrust of research. METHODS: Recruitment ended in 2012 and research activities shifted to retention. Data collectors (DC) completed subjective risk assignments (low, medium, high) based on knowledge of participants. Descriptive statistics compared risk assessments to socio-demographic characteristics, responses regarding participation, and missed appointments 11 months after risk assessment. RESULTS: We recruited approximately 100 participants. Higher perceived risk was associated with greater likelihood for mothers to be minorities, younger, and have lower education and income (X2=15.362, p<.01; X2=12.118, p<.05; X2=9.947. p<.01; and X2= 7.720, p<.05 respectively). Participants with income below federal poverty placed higher values on receiving incentives (X2= 6.011 p<.05). African American or “other” race participants placed a higher value on feeling comfortable with the interviewers than White respondents (X2=12.539 p<.01). Risk assignment and race were associated with number of missed appointments (X2=8.698 p<.01; X2 =4.307, p<.05). CONCLUSION: Results suggest DCs’ subjective assessment of risk predicts number of missed appointments. Future research might consider strategies to improve African American and “other” race participants’ comfort with interviewers. The ethics of dollar amounts for incentives among low-income participants remain a concern.

Background: Due to a lack of prospective research in South Africa's Speech-Language Therapy (SLT) private healthcare sector, this prospective cohort study investigated associations between speech, language, and swallowing conditions (i.e. dysarthria, apraxia of speech, aphasia, dysphagia), risk factors, and outcomes post-stroke (i.e. length of hospital stay, degree of physical disability according to the Modified Rankin Scale [mRS], functional level of oral intake according to the Functional Oral Intake Scale [FOIS], dehydration, weight loss, aspiration pneumonia, mortality). Methods: Adults with a new incident of stroke without pre-existing speech, language or swallowing difficulties (N=68) were recruited. Convenience sampling was used to select participants. A prospective design was used to determine the incidence of speech, language, and swallowing conditions poststroke and association with outcomes from admission to discharge. Results: Co-occurring speech, language, and swallowing conditions frequently occurred post-stroke (88%). Participants who were referred to SLT greater than 24 hours post-admission (52.94%) stayed in hospital for a median of three days longer than those who were referred within 24 hours (p=.042). Dysphagia was significantly associated with moderate to severe physical disability. Dysphagia with aspiration was significantly associated with poor functional level of oral intake (i.e. altered consistency diets and enteral nutrition), at admission and at discharge (p<. 01). Dysphagia had a higher likelihood of mortality (OR=2.86) (p=.319). At discharge, aspiration pneumonia was significantly associated with severe physical disability (p< .01, r=0.70). Risk factors; poor oral hygiene (p=1.00), low level of consciousness (p=1.00), dependent for oral intake (p=.040), and enteral nutrition (p=.257); were not associated with aspiration pneumonia. Conclusion: In South Africa's private sector, cooccurring speech, language, and swallowing conditions commonly occurred post-stroke, and dysphagia was strongly associated with physical disability and poor functional level of oral intake. Length of hospital stay was increased by delayed SLT referrals.