AMPREDICT PROsthetics-Predicting Prosthesis Mobility to Aid in Prosthetic Prescription and Rehabilitation Planning.

OBJECTIVE: To develop and validate a patient-specific multivariable prediction model that uses variables readily available in the electronic medical record to predict 12-month mobility at the time of initial post-amputation prosthetic prescription. The prediction model is designed for patients who have undergone their initial transtibial (TT) or transfemoral (TF) amputation because of complications of diabetes and/or peripheral artery disease. DESIGN: Multi-methodology cohort study that identified patients retrospectively through a large Veteran's Affairs (VA) dataset then prospectively collected their patient-reported mobility. SETTING: The VA Corporate Data Warehouse, the National Prosthetics Patient Database, participant mailings, and phone calls. PARTICIPANTS: Three-hundred fifty-seven veterans who underwent an incident dysvascular TT or TF amputation and received a qualifying lower limb prosthesis between March 1, 2018, and November 30, 2020 (N=357). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Amputee Single Item Mobility Measure (AMPSIMM) was divided into a 4-category outcome to predict wheelchair mobility (0-2), and household (3), basic community (4), or advanced community ambulation (5-6). RESULTS: Multinomial logistic lasso regression, a machine learning methodology designed to select variables that most contribute to prediction while controlling for overfitting, led to a final model including 23 predictors of the 4-category AMPSIMM outcome that effectively discriminates household ambulation from basic community ambulation and from advanced community ambulation-levels of key clinical importance when estimating future prosthetic demands. The overall model performance was modest as it did not discriminate wheelchair from household mobility as effectively. CONCLUSIONS: The AMPREDICT PROsthetics model can assist providers in estimating individual patients' future mobility at the time of prosthetic prescription, thereby aiding in the formulation of appropriate mobility goals, as well as facilitating the prescription of a prosthetic device that is most appropriate for anticipated functional goals.

Association Between Testosterone Treatment and Risk of Incident Cardiovascular Events Among US Male Veterans With Low Testosterone Levels and Multiple Medical Comorbidities.

Background Testosterone treatment is common in men, although risks for major cardiovascular events are unclear. Methods and Results A study was conducted in US male veterans, aged ≥40 years, with low serum testosterone and multiple medical comorbidities and without history of myocardial infarction, stroke, venous thromboembolism, prostate cancer, or testosterone treatment in the prior year. For the primary outcome, we examined if testosterone treatment was associated with a composite cardiovascular outcome (incident myocardial infarction, ischemic stroke, or venous thromboembolism). Testosterone use was modeled as intramuscular or transdermal and as current use, former use, and no use. Current testosterone users were compared with former users to reduce confounding by indication. The cohort consisted of 204 857 men with a mean (SD) age of 60.9 (9.9) years and 4.7 (3.5) chronic medical conditions. During follow-up of 4.3 (2.8) years, 12 645 composite cardiovascular events occurred. In adjusted Cox regression analyses, current use of transdermal testosterone was not associated with risk for the composite cardiovascular outcome (hazard ratio [HR], 0.89; 95% CI, 0.76-1.05) in those without prevalent cardiovascular disease, and in those with prevalent cardiovascular disease was associated with lower risk (HR, 0.80; 95% CI, 0.70-0.91). In similar analyses, current use of intramuscular testosterone was not associated with risk for the composite cardiovascular outcome in men without or with prevalent cardiovascular disease (HR, 0.91; 95% CI, 0.80-1.04; HR, 0.98; 95% CI, 0.89-1.09, respectively). Conclusions In a large cohort of men without a history of myocardial infarction, stroke, or venous thromboembolism, testosterone treatment was not associated with increased risk for incident composite cardiovascular events.

Urban upgrading and levels of interpersonal violence in Cape Town, South Africa: The violence prevention through urban upgrading programme.

Violence Prevention through Urban Upgrading applies second generation crime prevention through environmental design, which includes built environment interventions alongside social programmes and community participation initiatives in Khayelitsha, one of South Africa's poorest and most violent suburbs. We conducted a retrospective population-based study using survey data from 3625 geo-located households collected between 2013 and 2015 and mapped alcohol outlets to assess the association between the intervention and reported experience of violence. The analysis used generalised linear models to estimate and compare selfreported experience of violence adjusting for known confounders, which included area and household deprivation as well as alcohol outlet density. Living in close proximity to the upgraded urban infrastructure was associated with a 34% reduced exposure to interpersonal violence after adjusting for confounders. This association was consistent across age and gender. Access to additional social programmes alongside the urban upgrading intervention was not associated with further reduction in risk. The association between urban-upgrading and reduced exposure to interpersonal violence supports its inclusion among interventions in national and local crime prevention policies to address social and structural environments.

Testosterone treatment and the risk of aggressive prostate cancer in men with low testosterone levels.

PURPOSE: Testosterone treatment of men with low testosterone is common and, although relatively short-term, has raised concern regarding an increased risk of prostate cancer (CaP). We investigated the association between modest-duration testosterone treatment and incident aggressive CaP. MATERIALS AND METHODS: Retrospective inception cohort study of male Veterans aged 40 to 89 years with a laboratory-defined low testosterone measurement from 2002 to 2011 and recent prostate specific antigen (PSA) testing; excluding those with recent testosterone treatment, prostate or breast cancer, high PSA or prior prostate biopsy. Histologically-confirmed incident aggressive prostate cancer or any prostate cancer were the primary and secondary outcomes, respectively. RESULTS: Of the 147,593 men included, 58,617 were treated with testosterone. 313 aggressive CaPs were diagnosed, 190 among untreated men (incidence rate (IR) 0.57 per 1000 person years, 95% CI 0.49-0.65) and 123 among treated men (IR 0.58 per 1000 person years; 95% CI 0.48-0.69). After adjusting for age, race, hospitalization during year prior to cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP (HR 0.89; 95% CI 0.70-1.13) or any CaP (HR 0.90; 95% CI 0.81-1.01). No association between cumulative testosterone dose or formulation and CaP was observed. CONCLUSIONS: Among men with low testosterone levels and normal PSA, testosterone treatment was not associated with an increased risk of aggressive or any CaP. The clinical risks and benefits of testosterone treatment can only be fully addressed by large, longer-term randomized controlled trials.

Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study.

BACKGROUND/OBJECTIVES: Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI). DESIGN: A prospective cohort study. SETTING: Community-dwelling members of a U.S. health maintenance organization. PARTICIPANTS: Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315). MEASUREMENTS: Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. RESULTS: Increased cognitive decline relative to "normal" aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0-3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE ε4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε4 genotype, but not by education. CONCLUSION: Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis.

The development and validation of the AMPREDICT model for predicting mobility outcome after dysvascular lower extremity amputation.

OBJECTIVE: The objective of this study was the development of AMPREDICT-Mobility, a tool to predict the probability of independence in either basic or advanced (iBASIC or iADVANCED) mobility 1 year after dysvascular major lower extremity amputation. METHODS: Two prospective cohort studies during consecutive 4-year periods (2005-2009 and 2010-2014) were conducted at seven medical centers. Multiple demographic and biopsychosocial predictors were collected in the periamputation period among individuals undergoing their first major amputation because of complications of peripheral arterial disease or diabetes. The primary outcomes were iBASIC and iADVANCED mobility, as measured by the Locomotor Capabilities Index. Combined data from both studies were used for model development and internal validation. Backwards stepwise logistic regression was used to develop the final prediction models. The discrimination and calibration of each model were assessed. Internal validity of each model was assessed with bootstrap sampling. RESULTS: Twelve-month follow-up was reached by 157 of 200 (79%) participants. Among these, 54 (34%) did not achieve iBASIC mobility, 103 (66%) achieved at least iBASIC mobility, and 51 (32%) also achieved iADVANCED mobility. Predictive factors associated with reduced odds of achieving iBASIC mobility were increasing age, chronic obstructive pulmonary disease, dialysis, diabetes, prior history of treatment for depression or anxiety, and very poor to fair self-rated health. Those who were white, were married, and had at least a high-school degree had a higher probability of achieving iBASIC mobility. The odds of achieving iBASIC mobility increased with increasing body mass index up to 30 kg/m2 and decreased with increasing body mass index thereafter. The prediction model of iADVANCED mobility included the same predictors with the exception of diabetes, chronic obstructive pulmonary disease, and education level. Both models showed strong discrimination with C statistics of 0.85 and 0.82, respectively. The mean difference in predicted probabilities for those who did and did not achieve iBASIC and iADVANCED mobility was 33% and 29%, respectively. Tests for calibration and observed vs predicted plots suggested good fit for both models; however, the precision of the estimates of the predicted probabilities was modest. Internal validation through bootstrapping demonstrated some overoptimism of the original model development, with the optimism-adjusted C statistic for iBASIC and iADVANCED mobility being 0.74 and 0.71, respectively, and the discrimination slope 19% and 16%, respectively. CONCLUSIONS: AMPREDICT-Mobility is a user-friendly prediction tool that can inform the patient undergoing a dysvascular amputation and the patient's provider about the probability of independence in either basic or advanced mobility at each major lower extremity amputation level.

Periconceptional seafood intake and pregnancy complications.

OBJECTIVE: To investigate associations of maternal periconceptional shellfish, lean fish and fatty fish intake with risk of pregnancy complications. DESIGN: In this prospective cohort study, we collected information on intake of seafood subtypes using FFQ. We categorized seafood intake into frequencies of 1 servings/week. We ascertained gestational hypertension, pre-eclampsia, gestational diabetes and preterm birth diagnoses from medical records. Using generalized linear models with a log link, the Poisson family and robust standard errors, we estimated risk ratios and 95 % confidence intervals across seafood intake categories. SETTING: The Omega study, a study of risk factors for pregnancy complications among women recruited from prenatal clinics in Washington State, USA, 1996-2008. SUBJECTS: The current study included 3279 participants from the Omega study. RESULTS: Median (interquartile range) shellfish, lean fish and fatty fish intake was 0·3 (0-0·9), 0·5 (0-1·0) and 0·5 (0·1-1·0) servings/week, respectively. Lean fish intake of >1 servings/week (v. <0·2 servings/month) was associated with a 1·55-fold higher risk of preterm birth (95 % CI 1·04, 2·30) and was not associated with the other pregnancy complications. Higher intake of seafood (total or other subtypes) was not associated with pregnancy complications (separately or combined). CONCLUSIONS: Higher intake of lean fish, but not fatty fish or shellfish, was associated with a higher risk of preterm birth; these findings may have significance for preterm birth prevention. Studies of mechanisms and potential contributing factors (including seafood preparation and nutrient/contaminant content) are warranted.

Weight Change Trajectories After Incident Lower-Limb Amputation.

OBJECTIVE: To characterize weight change after amputation by identifying typical weight trajectories in men with incident lower-limb amputation (LLA) and describing characteristics associated with each trajectory. DESIGN: Retrospective cohort study and analyzed using group-based trajectory modeling. SETTING: Administrative data. PARTICIPANTS: Veterans who were men (N=759), living in the Northwest United States, and who had an incident toe, foot, or leg amputation between 1997 and 2008 and at least 18 months of amputation-free survival thereafter. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Postamputation weight and body mass index change. RESULTS: The mean weight at baseline was 91.6±24 kg (202±53 lb), and average follow-up was 2.4 years. We identified 4 trajectory groups for weight change: weight loss (13%), stable weight (47%), slow weight gain (33%), and rapid weight gain (7%). Men with a toe or foot amputation most frequently were assigned to the stable weight group (58%), whereas men with transtibial or transfemoral amputations were most commonly assigned to the slow weight gain group (42% each). Men who died during follow-up were more likely to be assigned to the weight loss group (24%) than men who did not die (11%). CONCLUSIONS: We identified distinct weight change trajectories that represent heterogeneity in weight change after LLA. An improved understanding of factors predictive of weight gain or loss in people with LLA may help better target rehabilitation and prosthetic prescription. Additional research is needed to fully understand the relation between weight change and health status after amputation.

Lower-limb amputation and body weight changes in men.

Little is known about the relationship between lower-limb amputation (LLA) and subsequent changes in body weight. We conducted a retrospective cohort study using clinical and administrative databases to identify and follow weight changes in 759 males with amputation (partial foot amputation [PFA], n = 396; transtibial amputation [TTA], n = 267; and transfemoral amputation [TFA], n = 96) and 3,790 nondisabled persons frequency-matched (5:1) on age, body mass index, diabetes, and calendar year from eight Department of Veterans Affairs medical care facilities in the Pacific Northwest. We estimated and compared longitudinal percent weight change from baseline during up to 39 mo of follow-up in participants with and without amputation. Weight gain in the 2 yr after amputation was significantly more in men with an amputation than without, and in men with a TTA or TFA (8%-9% increase) than in men with a PFA (3%-6% increase). Generally, percent weight gain peaked at 2 yr and was followed by some weight loss in the third year. These findings indicate that LLA is often followed by clinically important weight gain. Future studies are needed to better understand the reasons for weight gain and to identify intervention strategies to prevent excess weight gain and the deleterious consequences that may ensue.

Periconceptional Seafood Intake and Fetal Growth.

BACKGROUND: Previous reports of associations of maternal seafood intake with fetal growth were inconsistent. Further, little is known whether associations differ across seafood subtypes or fetal growth indices. METHODS: Among 3141 participants of the Omega study, a pregnancy cohort study, we investigated associations of periconceptional shell, lean, and fatty fish intake with fetal growth indices. We categorised food frequency questionnaire reported seafood intake into frequencies of: <0.2 servings/month, 0.2 servings/month -<0.5 servings/week, 0.5-1 servings/week, and >1 servings/week. We abstracted birthweight, birth length, and head circumference from medical records. Using generalised linear models with a log link, the Poisson family, and robust standard errors, we estimated relative risks and 95% confidence intervals (CI) for low birthweight (LBW, <2500 g) and linear regression models to estimate mean differences for continuous fetal growth indices across seafood intake categories. RESULTS: Medians (interquartile range) of shell, lean, and fatty fish intake were 0.3 (0-0.9), 0.5 (0-1.0), and 0.5 (0.1-1.0) servings/week, respectively. Lean fish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 2.2-fold higher risk of LBW (95% CI 1.2, 4.1). Shellfish intake of >1 servings/week (vs. <0.2 servings/month) was associated with a 0.6 kg/m(3) higher mean ponderal index (95% CI 0.0, 1.2 kg/m(3) ). There was no evidence for associations of total seafood or seafood subtype intake with other fetal growth indices. CONCLUSIONS: Higher intakes of lean fish and shellfish were associated with a higher risk of LBW and higher mean ponderal index, respectively. Findings highlight the importance of considerations of seafood subtype in similar investigations.

Physical activity barriers and enablers in older Veterans with lower-limb amputation.

Little is known about the types of physical activities that older individuals with lower-limb loss perform, correlates of regular physical activity (PA), and barriers and facilitators to PA. We conducted an exploratory study in 158 older Veterans from the Pacific Northwest with a partial foot (35%), below-knee (39%) and above-knee (26%) amputation. Ninety-eight percent of survey respondents were male, on average 65 yr of age and 15 yr postamputation; 36% of amputations were trauma-related. The most commonly reported physical activities were muscle strengthening (42%), yard work and/or gardening (30%), and bicycling (11%). Forty-three percent were classified as physically active based on weekly moderate- and vigorous-intensity PA. History of vigorous preamputation PA was positively associated with being active, while low wealth and watching ≥5 h/d of television/videos were inversely associated. While pain- and resource-related barriers to PA were most frequently reported, only knowledge-related and interest/motivation-related barriers were inversely associated with being active. Family support and financial assistance to join a gym were the most commonly reported factors that would facilitate PA. To increase PA in the older amputee population, interventions should address motivational issues, knowledge gaps, and television watching; reduce financial barriers to exercising; and consider involving family members.

The association of maternal adult weight trajectory with preeclampsia and gestational diabetes mellitus.

BACKGROUND: Preeclampsia (PE) and gestational diabetes mellitus (GDM) adversely affect pregnancy outcomes and the subsequent health of both mother and infant. It is known that elevated pre-pregnancy body mass index (BMI) is associated with increased risk of these obstetrical complications. However, little is known about the role of adult weight patterns prior to pregnancy. METHODS: Self-reported weight at ages prior to the current pregnancy was recorded in a prospective cohort study of 3567 pregnant women, allowing assessment of longitudinal pre-pregnancy weight trajectories and their association with subsequent PE and GDM in the study pregnancy. RESULTS: Women who would subsequently experience PE or GDM in the study pregnancy experienced on average almost double the rate of adult weight gain than other women [PE: additional 0.30 kg/year, 95% confidence interval (CI) 0.09, 0.51 and GDM: additional 0.34 kg/year, 95% CI 0.21, 0.48]. Women with mean adult annual weight gain above the 90th percentile (1.4 kg/year) had elevated risk of subsequent PE and GDM independent of their BMI at age 18 and of their obesity status at the time of the study pregnancy. Finite mixture trajectory modelling identified four monotonely ordered, increasing mean weight trajectories. Relative to the second lowest (most common) weight trajectory, women in the highest trajectory were at greater risk of PE [odds ratio (OR) 5.0, 95% CI 2.9, 8.8] and GDM (OR 2.8, 95% CI 1.7, 4.5). CONCLUSIONS: These results indicate that higher adult weight gain trajectories prior to pregnancy may play a role in predisposing women to PE or GDM.

Firearm and nonfirearm homicide in 5 South African cities: a retrospective population-based study.

OBJECTIVE: We assessed the effectiveness of South Africa's Firearm Control Act (FCA), passed in 2000, on firearm homicide rates compared with rates of nonfirearm homicide across 5 South African cities from 2001 to 2005. METHODS: We conducted a retrospective population-based study of 37 067 firearm and nonfirearm homicide cases. Generalized linear models helped estimate and compare time trends of firearm and nonfirearm homicides, adjusting for age, sex, race, day of week, city, year of death, and population size. RESULTS: There was a statistically significant decreasing trend regarding firearm homicides from 2001, with an adjusted year-on-year homicide rate ratio of 0.864 (95% confidence interval [CI] = 0.848, 0.880), representing a decrease of 13.6% per annum. The year-on-year decrease in nonfirearm homicide rates was also significant, but considerably lower at 0.976 (95% CI = 0.954, 0.997). Results suggest that 4585 (95% CI = 4427, 4723) lives were saved across 5 cities from 2001 to 2005 because of the FCA. CONCLUSIONS: Strength, timing and consistent decline suggest stricter gun control mediated by the FCA accounted for a significant decrease in homicide overall, and firearm homicide in particular, during the study period.

Organochlorine pesticides and risk of endometriosis: findings from a population-based case-control study.

BACKGROUND: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. OBJECTIVE: We investigated endometriosis risk in relation to environmental exposure to OCPs. METHODS: We conducted the present analyses using data from the Women's Risk of Endometriosis (WREN) study, a population-based case-control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. RESULTS: Our data suggested increased endometriosis risk associated with serum concentrations of ß-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum ß-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). CONCLUSIONS: In our case-control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of ß-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women.

Phthalates and risk of endometriosis.

BACKGROUND: Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. OBJECTIVE: To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. METHODS: We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. RESULTS: The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1-0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ∑DEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. CONCLUSIONS: Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women.

The South African Triage Scale (adult version) provides reliable acuity ratings.

OBJECTIVE: To estimate the inter- and intra-rater reliability of triage ratings on Emergency Centre patients by South African nurses and doctors using the South African Triage Scale (SATS). METHODS: A cross-sectional reliability study was performed. Five emergency physicians and ten enrolled nursing assistants independently assigned triage categories to 100 written vignettes unaware of the ratings given by others. Four different quantitative reliability measures were calculated and compared. Graphical displays portrayed rating distributions for vignettes with mean ratings at different acuity categories. RESULTS: The estimated quadratically weighted kappa for the group of emergency physicians was 0.76 (95% CI: 0.67-0.84) and for the group of nurses 0.66 (95% CI: 0.58-0.74). These values were close to the estimated intra-class correlation coefficients. For intra-rater reliability, the average exact agreement was 84%. The graphical displays showed that the least variability was evident in the vignettes that had a mean rating of 'emergency', 'very urgent' or 'routine'. CONCLUSION: This study indicates good inter- and intra-rater reliability among nurses and doctors using the SATS. It suggests that the SATS is reliably applied, and supports the feasibility of further implementation of the SATS in similar settings.

Temporal relationship between depression and dementia: findings from a large community-based 15-year follow-up study.

CONTEXT: Late-life depression is associated with increased risk of dementia, but the temporal relationship between depression and development of dementia remains unclear. OBJECTIVES: To examine the association between risk of dementia and baseline depressive symptoms; history of depression, particularly early-life (<50 years) vs late-life depression (≥50 years); and individual domains of the Center for Epidemiologic Studies Depression Scale. DESIGN: A large cohort with initially nondemented participants was followed up biennially for up to 15 years. Baseline depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale; presence of significant depressive symptoms was defined as a score of 11 or greater. Self-reported history of depression was collected at the baseline interview. Cox proportional hazards regression was used to assess the association between depression and dementia risk. SETTING: Population-based cohort drawn from members of the Group Health Cooperative in Seattle, Washington. PARTICIPANTS: A cohort of 3410 participants without dementia aged at least 65 years. RESULTS: During a mean of 7.1 years of follow-up, 658 participants (19.3%) developed dementia. At baseline, 9.4% of participants had presence of significant depressive symptoms, and 21.2% reported a history of depression. The adjusted hazard ratio for dementia associated with baseline depressive symptoms was 1.71 (95% confidence interval, 1.37-2.13), after adjusting for age at entry, sex, educational level, and wave of enrollment. Compared with participants without depression history, those with late-life depression were at increased dementia risk (adjusted hazard ratio, 1.46; 95% confidence interval, 1.16-1.84), but early-life depression had no association with dementia risk (1.10 [0.83-1.47]). Depressed mood (adjusted hazard ratio, 1.48; 95% confidence interval, 1.25-1.76) and perceived performance difficulty (1.39 [1.15-1.67]) were independently associated with dementia. CONCLUSION: This study confirmed that late-life depression is associated with increased risk of dementia and supplied evidence that late-life depression may be an early manifestation of dementia rather than increasing risk for dementia.

Association between lifetime cigarette smoking and lewy body accumulation.

Cigarette smoking has been associated repeatedly in observational studies with decreased risk of Parkinson's disease (PD), but its relationship to the risk of dementia or Alzheimer's disease (AD) is inconsistent. All of these studies have used clinical diagnoses of disease. We tested the hypothesis that lifetime cigarette use might be associated with reduced risk of neuropathologic changes of Lewy-related pathology (LRP) in multiple brain regions or with reduced risk of consensus neuropathologic changes of AD in a prospective community-based study of brain aging and dementia, the Adult Changes in Thought (ACT) study. We observed that heavy lifetime cigarette smoking (>50 pack years) was associated with significantly reduced relative risk (RR) for LRP, but not AD-type pathologic changes, after correcting for selection bias, and with significantly reduced frequency of LRP in the substantia nigra. These findings are the first of which we are aware to associate reduced LRP in human brain with any exposure, and substantiate observational studies that have associated cigarette smoking with reduced risk of PD. Although cigarette smoking is too toxic to suggest as a treatment, if confirmed, these findings may guide future therapeutic strategies that attempt to suppress LRP in human brain by other means.

Modelling the association of blood pressure during pregnancy with gestational age and body mass index.

Improved understanding of the determinants of blood pressure (BP) changes during pregnancy is essential for decreasing the morbidity and mortality borne by women and their families worldwide. While most epidemiological studies consider associations based on categorical risk factor classifications, using measurements on a continuous scale has been advocated as a means of gaining richer insights into biological processes. We modelled the relationship during pregnancy of continuous systolic (S) and diastolic (D) BP distributions with gestational age and pre-pregnancy body mass index (BMI) using fractional polynomials. We used information, including antenatal BP values abstracted from medical records, from a prospective cohort of 1733 women recruited before 20 weeks' gestation. The percentiles for SBP and DBP changed over pregnancy, with DBP percentiles decreasing initially, followed by an increase starting about mid-second trimester. Modelling the joint impact of BMI and gestational age on mean BP indicated an increase in mean BP with increasing BMI that was attenuated at higher BMI levels, later in pregnancy. This attenuation persisted in a variety of sub-analyses which explored the possibility that it was caused by confounding or by influential groupings of subjects. Estimated longitudinal percentiles that characterise the BP distribution across gestation may facilitate evaluation of BP during pregnancy. BP patterns observed over pregnancy and, in particular, the attenuation of BP increases at high BMI, late in pregnancy, can provide insights towards elucidating the mechanisms that drive BP changes during pregnancy.