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.

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.

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.

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.

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.

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.

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.

Visual hallucinations in dementia: a prospective community-based study with autopsy.

OBJECTIVE: Several studies have demonstrated that specific neuropathologic features may be associated with the presence of visual hallucinations in dementia patients, but the clinical usefulness of these studies has been limited because their subjects were selected on the basis of neuropathologic findings rather than clinical presentations. This study seeks to investigate the demographic, clinical, and neuropathologic features of community-based dementia subjects with and without visual hallucations. DESIGN: A prospective examination of the clinical and neuropathologic correlates of visual hallucinations in community-based dementia subjects. PARTICIPANTS: One hundred forty-eight subjects with sufficient clinical and neuropathologic data from a community-based incident dementia autopsy case series. RESULTS: Subjects were classified according to the presence or absence of visual hallucinations and subjects with visual hallucinations (N = 27) were younger at intake and more likely to exhibit agitation, delusions, and apathy than subjects without visual hallucinations (N = 121). Subjects with visual hallucinations were also more likely than subjects without visual hallucinations to have Lewy-related pathology (LRP) (78% versus 45%). In addition, a higher frequency of visual hallucinations was observed in subjects with neocortical LRP than subjects with limbic-, amygdala-, or brainstem-predominant LRP. Although Alzheimer disease with concomitant LRP was the most common neuropathologic subtype in the visual hallucinations-positive group (59%), the frequency of subjects with Alzheimer disease pathology did not differ significantly between those with and without visual hallucinations (74% versus 62%). CONCLUSIONS: Subjects with visual hallucinations were more likely to have concomitant postural and gait disturbance, additional neuropsychiatric symptoms, and neocortical LRP than subjects without visual hallucinations. Visual hallucinations accompanying dementia have distinct clinical and neuropathologic characteristics that are important for prognosis and clinical management.

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.

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.

Evaluating and interpreting exposure-response relationships for manganese and neurobehavioral outcomes.

Exposure-response relationships (ERRs) are of interest in many areas of epidemiology. In occupational and environmental epidemiology in particular, the nature of such associations may have practical implications for policy and the setting of standards. We use a study undertaken to estimate the association between neurobehavioral test scores and manganese exposure to illustrate that tests for linear trend may be significant in the presence of highly non-linear ERRs. We illustrate this point further with simulated data where the form of the ERR is known. We provide guidelines for exploring the nature of ERRs, in the absence of a priori knowledge of the response of the outcome of interest to exposure.

Predicting lewy body pathology in a community-based sample with clinical diagnosis of Alzheimer's disease.

Accurate antemortem prediction of Lewy body pathology in patients with dementia is problematic. This study generates a model that better predicts Lewy body pathology in community-based patients with clinical Alzheimer's disease. Lewy body pathology was detected in 80 of 152 participants (52.6%) with an initial diagnosis of probable Alzheimer's disease. In a stepwise logistic regression model, female gender, lower education, being married, bradykinesia, hallucinations, and absence of irritability predicted the greatest likelihood of Lewy body pathology. The predictive model correctly diagnosed Lewy body pathology with an estimated sensitivity of 75%, specificity of 68%, and accuracy of 72%; the area under the receiver operating characteristic curve was 0.75. In a community-based autopsy sample, this predictive model confirmed parkinsonism and hallucinations as important predictors of Lewy body pathology in patients with clinical Alzheimer's disease. The model also identified other demographic and clinical characteristics that might enhance the prediction of Lewy body pathology.

The nervous system effects of occupational exposure to manganese--measured as respirable dust--in a South African manganese smelter.

OBJECTIVES: A major recent review of occupational exposure limits for manganese (Mn) has proposed a respirable dust level of 0.1 mg/m3. There is, however, no theoretical basis for using this exposure metric to estimate the systemic effects of Mn, and little in the way of empirical data relating respirable Mn to neurobehavioural and other non-pulmonary effects. Cross-sectional data from a study showing few and unconvincing neurobehavioural effects of inhalable dust in Mn smelter workers published just prior to this review were reanalyzed here using respirable Mn. The hypotheses tested were that respirable Mn exposure is a more appropriate predictor of neurobehavioural effects than inhalable Mn where such effects exist, and that there should be no observed effects at respirable dust levels below 0.1 mg/m3. METHODS: Five hundred and nine production workers and 67 external referents were studied. Exposure measures from personal sampling included the Mn content of respirable dust as a concentration-time integrated cumulative exposure index (CEI) and as average intensity (INT) over a working lifetime. Neurobehavioural endpoints included items from the Swedish nervous system questionnaire (Q16), World Health Organisation neurobehavioural core test battery (WHO NCTB), Swedish performance evaluation system (SPES), Luria-Nebraska (LN), and Danish Product Development (DPD) test batteries, and a brief clinical examination. RESULTS: The median respirable Mn exposure was 0.058 mg/m3 (range=0-0.51; IQR=0.02-0.16) amongst the exposed, with 30% having average intensities above the proposed 0.1 mg/m3 and 44% above the proposed supplemental limit of 0.5 mg/m3 inhalable dust. As in the study of inhalable Mn effects, there were few respirable Mn effects showing clear continuity of response with increasing exposure. CONCLUSION: These data did not provide empirical support for a respirable, as opposed to an inhalable, dust metric being more sensitive in the identification of Mn effects. Neither metric showed convincing effects within the exposure range studied. Further study is needed to determine a threshold for respirable Mn effects, if such exist, and to verify our findings.

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.

A case-control study of maternal recreational physical activity and risk of gestational diabetes mellitus.

Despite the maternal and infant morbidity associated with gestational diabetes mellitus (GDM), few modifiable risk factors have been identified. We explored the relation between recreational physical activity performed during the year before and during the first 20 weeks of pregnancy and the risk of GDM. 155 GDM cases and 386 normotensive, non-diabetic pregnant controls provided information about the type, intensity, frequency, and duration of physical activity performed during these time periods. Women who participated in any recreational physical activity during the first 20 weeks of pregnancy, as compared with inactive women, experienced a 48% reduction in risk of GDM (odds ratio [OR] = 0.52; 95% confidence interval [CI] 0.33-0.80). The number of hours spent performing recreational activities and the energy expended were related to a decrease in GDM risk. No clear patterns related to distance walked and pace of walking emerged. Daily stair climbing, when compared with no stair climbing, was associated with a 49-78% reduction in GDM risk (P for trend <0.011). Recreational physical activity performed during the year before the index pregnancy was also associated with statistically significant reductions in GDM risk, but women who engaged in physical activity during both time periods experienced the greatest reduction in risk (OR = 0.40; 95% CI 0.23-0.68). These data suggest that recreational physical activity performed before and/or during pregnancy is associated with a reduced risk of GDM.

Nervous system effects of occupational manganese exposure on South African manganese mineworkers.

Occupational exposure to airborne manganese dust has been shown to produce adverse effects on the central nervous system. Four hundred and eighty-nine blue and white collar manganese mineworkers from South Africa were studied cross-sectionally to investigate the nervous system effects of medium to low occupational manganese exposures. The different facilities included underground mines, surface processing plants, and office locations. A job exposure matrix was constructed using routine occupational hygiene data. Exposure variables included years of service, a cumulative exposure index (CEI) and average intensity of exposure (AINT) across all jobs, and blood manganese. Endpoints included items from the Q16, WHO-NCTB, SPES, and Luria-Nebraska test batteries, and a brief clinical examination. Potential confounders and effect modifiers included age, level of education, past medical history including previous head injury, previous neurotoxic job exposures, tobacco use, alcohol use and home language. Associations were evaluated by multiple linear and logistic regression modeling. Average exposure intensity across all jobs was 0.21mg/m(3) manganese dust. Multivariate analyses showed that none of the symptom nor test results were associated with any measure of exposure including blood manganese, after adjustment for confounders. This relatively large null study indicates that manganese miners exposed on average across all jobs to MnO(2) at levels near the American Conference of Governmental Industrial Hygienists Threshold Limit Value (ACGIH TLV) are unlikely to have a subclinical neurotoxicity problem.