Trends in Health Service Utilization After Enrollment in an Interdisciplinary Primary Care Clinic for Veterans with Addiction, Social Determinants of Health, or Other Vulnerabilities.

BACKGROUND: Models of interdisciplinary primary care (IPC) may improve upon traditional primary care approaches in addressing addiction and social determinants of health. OBJECTIVE: To compare the trends in health care utilization in the year before and after enrollment in an IPC clinic model, and explore the variations in temporal patterns for patients with histories of high emergency department (ED) use, homelessness, and/or substance use disorders (SUDs). DESIGN AND PARTICIPANTS: Interrupted time series study of utilization among IPC patients. MAIN MEASURES: Quarterly ED, inpatient, primary care, and behavioral health visits were abstracted from administrative data before and after IPC enrollment. Negative binomial segmented regressions estimated changes in health care utilization over time. We used interactions to test for statistical differences in temporal patterns for IPC subgroups. RESULTS: Among IPC patients (n=994), enrollment was associated with overall reductions in ED, inpatient, and behavioral health visits (p's<0.001) and increases in primary care (p's<0.001). Temporal patterns of ED visits, hospitalizations, and behavioral health differed across IPC subgroups (interaction p's<0.001). For those with histories of high ED use (n=265), ED, inpatient, and behavioral health visits decreased after enrollment (level change incidence rate ratios [IRRs]=0.57-0.69) and continued to decline over time (post-enrollment IRRs=0.80-0.88). Among other patients with homeless experiences (n=123), there were initial declines in hospitalizations (IRR=0.33) and overall declines in behavioral health visits (level change and post-enrollment IRRs=0.46-0.94). Other patients with SUDs had initial declines in hospitalizations (IRR=0.46), and post-enrollment declines in rates of specialty SUD visits (IRR=0.92). For all patients, primary care visits initially increased (level change IIRs=2.47-1.34) then gradually declined (post-enrollment IRRs=0.92-0.92). CONCLUSIONS: An IPC model of care reduces acute care and behavioral health service use, particularly for patients with historically high ED use. IPC models may improve patient and system outcomes of vulnerable patient populations with social, clinical, and addiction morbidities.

Physical therapists' attitudes are associated with their confidence in and the frequency with which they engage in prescription opioid medication misuse management practices with their patients. A cross-sectional study.

Background: In the US, prescription opioid medication misuse (POMM) necessitates engagement of physical therapists (PTs). We (1) evaluated the attitudes of (PT) related to their management of patients with POMM and (2) examined the association between these attitudes and PTs confidence in POMM-related management abilities and the frequency with which they engaged in POMM-related management practices. Methods: We conducted a national survey of PTs that included a modified Drug and Drug Problems Perception Questionnaire (DDPPQ). Confidence in POMM-related abilities and the frequency of engaging in POMM-related management practices were measured. Logistic regression evaluated the association between the DDPPQ subscales (role adequacy, role legitimacy, role self-esteem, role support, job satisfaction) and confidence and frequency outcomes. Results: The analysis included 402 respondents. Role adequacy and legitimacy subscales were associated with confidence and frequency outcomes (p<.05), indicating that more favorable role adequacy and legitimacy attitudes are associated with greater odds of having more confidence in POMM-related management abilities and of engaging in more frequent POMM-related management practices. Conclusions: PTs with a greater sense of preparedness to engage in POMM-related management were more likely to report greater confidence in POMM-related management abilities and engage in POMM-related management practices with greater frequency.

The association between advanced orthopedic certification and confidence and engagement in prescription opioid medication misuse management practices: a cross-sectional study.

In the United States, attaining the orthopedic certified specialist (OCS) credential or the orthopedic subspecialty credential of Fellow of the American Academy of Orthopedic Manual Physical Therapists (FAAOMPT), may lead to a higher level of orthopedic practice. It is unknown whether attaining these credentials influences physical therapist confidence in and frequency of engagement in prescription opioid medication misuse (POMM) management practices. A national cross-sectional web-based survey of PTs identified whether respondents had an OCS or FAAOMPT credential. Self-report confidence in POMM-related management practices and the frequency of engaging in these practices were assessed. Logistic regression evaluated association between credential status and confidence in, and frequency of, engagement in POMM-related management practices. The analysis included 402 respondents with a mean age of 41.0 (SD = 11.2) and 203 (50.4%) females. There were 91 (22.6%) PTs with a FAAOMPT credential, 143 (35.6%) with an OCS but with no FAAOMPT credential and 168 (41.8%) had neither credential. Compared to those with an OCS credential, FAAOMPTs reported greater confidence in, and greater frequency of engagement in, POMM-related management practices (p< .05). Compared to those without an OCS or FAAOMPT credential and compared to those with an FAAOMPT credential, those with an OCS did not report greater confidence or greater engagement in any POMM-related management practice (p≥ .05). Obtain the FAAOMPT credential may increase PTs' confidence in some POMM-related management practices. Research is needed to determine why FAAOMPTs report greater confidence and engagement in POMM-related management practices.

Associations of Body Mass Index and Waist Circumference in Young Adulthood with Later Life Incident Diabetes.

CONTEXT: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied. OBJECTIVE: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (≥40 years). DESIGN: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis. SETTING: Population-based cohort studies. PARTICIPANTS: 30 780 participants (56.1% female, 69.8% non-Hispanic white) without a diagnosis of diabetes by age 40. INTERVENTIONS: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. MAIN OUTCOME MEASURE(S): Incident diabetes defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of diabetes medications. RESULTS: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI ≥ 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49% and 44% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations. CONCLUSIONS: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator.

Cognition and 20-year subsequent sleep disturbances.

INTRODUCTION: There is a paucity of data exploring the extent that preclinical cognitive changes are predictive of subsequent sleep outcomes. METHODS: Logistic regression models were used to evaluate data from a cohort of 196 African American adults who had measures of cognitive function assessed at 2 time points during a 20-year period across the mid- to late-life transition. Cognitive testing included the Delayed Word Recall, the Digit Symbol Substitution, and the Word Fluency tests, which were summarized as a composite cognitive z-score. Sleep apnea was measured by in-home sleep apnea testing and sleep duration and quality were derived from 7-day wrist actigraphy at the end of the study period. RESULTS: A one standard deviation (SD) lower composite cognitive z-score at baseline was significantly associated with greater odds of low sleep efficiency (<85%) (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.13, 3.04) and greater odds of increased wakefulness after sleep onset time (WASO; >60 minutes) (OR = 1.65, 95% CI = 1.05, 2.60) in adjusted models. A one SD faster rate of cognitive decline over the study period was significantly associated with greater odds of low sleep efficiency (OR = 1.68, 95% CI = 1.04, 2.73), greater odds of sleep fragmentation (>35%); (OR = 1.73, 95% CI = 1.05, 2.85), and greater odds of increased WASO (OR = 1.85, 95% CI = 1.15, 2.95) in adjusted models. Neither baseline cognitive z-score nor rate of cognitive decline was associated with sleep apnea or the total average sleep duration. CONCLUSION: Cognition at baseline and change over time predicts sleep quality and may reflect common neural mechanisms and vulnerabilities.

Association of mid-life serum lipid levels with late-life brain volumes: The atherosclerosis risk in communities neurocognitive study (ARICNCS).

BACKGROUND: Limited information exists regarding the association between midlife lipid levels and late-life total and regional brain volumes. METHODS: We studied 1872 participants in the longitudinal community-based Atherosclerosis Risk in Communities Neurocognitive Study. Serum lipid levels were measured in 1987-1989 (mean age, 53 ± 5 years). Participants underwent 3T brain MRI scans in 2011-2013. Brain volumes were measured using FreeSurfer image analysis software. Linear regression models were used to assess the associations between serum lipids and brain volumes modeled in standard deviation (SD) units, adjusting for potential confounders. RESULTS: In adjusted analyses, one SD higher low-density lipoprotein cholesterol (LDL) levels were associated with larger total brain volumes (ß 0.033, 95% CI 0.006-0.060) as well as larger volumes of the temporal (ß 0.038, 95% CI 0.003-0.074) and parietal lobes (ß 0.044, 95% CI 0.009-0.07) and Alzheimer disease-related region (ß 0.048, 95% CI 0.048-0.085). Higher triglyceride levels were associated with smaller total brain volumes (ß -0.033, 95% CI -0.060, -0.007). The associations between LDL levels and brain volumes were modified by age (P for interaction <0.001), with higher LDL levels associated with larger total and regional brain volumes only among adults >53 years at baseline, and were attenuated after application of weights to account for informative attrition, although associations with the parietal and Alzheimer's disease-related region remained significant. High-density lipoprotein cholesterol was not associated with brain volumes. CONCLUSION: Higher LDL levels in late midlife were associated with larger brain volumes later in life, while higher triglyceride levels were associated with smaller brain volumes. These associations were driven by adults >53 years at baseline.

Sex-specific associations of inflammation markers with cognitive decline.

BACKGROUND/OBJECTIVE: Inflammation is implicated in cognitive decline; however, there is a paucity of data for African American populations and for sex-specific associations. DESIGN: Prospective cohort study. SETTING: Genetic Epidemiology Network of Arteriopathy/Genetics of Microangiopathic Brain Injury studies. PARTICIPANTS: African-American sibships (N = 1010). MEASUREMENTS: Neurocognitive tests assessed global cognition and four cognitive domains: processing speed, memory, language, and executive function at two time points over seven years. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor receptor (TNFR)-1 and TNFR2 were measured at study baseline. Linear mixed models were used to investigate the association between inflammation markers and cognitive decline. RESULTS: Among men, a one SD increase in CRP was associated with an increased rate of decline over 7 years in global cognitive Z-score (adjusted difference in slopes = -0.31, p = 0.006) and in processing speed Z-score (adjusted difference in slopes = -0.10, p = 0.02), but not declines in memory, language, or executive function Z-scores. Also among men, a one SD increase in IL-6 was associated with an increased decline rate in global cognitive Z-score (adjusted difference in slopes = -0.33, p = 0.002) and in processing speed Z-score (adjusted difference in slopes = -0.12, p = 0.007). There was no difference in decline rates by CRP or IL-6 level in adjusted analyses among women for any cognitive scores. Among men and women combined, a one SD increase in baseline sTNFR1 was associated with a faster rate of decline in memory Z-score (adjusted difference in slopes = -0.09, p = 0.02). Baseline sTNFR2 levels did not significantly predict rate of cognitive decline in any cognitive domains. CONCLUSIONS: Circulating markers of CRP and IL-6 may be differential risk factors for men and women in relation to cognitive decline. A novel inflammation marker, sTNFR1, may be a useful predictor of memory decline in older adults.

Associations of serum uric acid with incident dementia and cognitive decline in the ARIC-NCS cohort.

INTRODUCTION: Elevated serum uric acid (SUA) is associated with cardiovascular risk factors, which often contribute to dementia and dementia-like morbidity, yet several cross-sectional studies have shown protective associations with cognition, which would be consistent with other work showing benefits of elevated SUA through its antioxidant properties. METHODS: We studied 11,169 participants free of dementia and cardiovascular disease from the Atherosclerosis Risk in Communities (ARIC) cohort. SUA was measured in blood samples collected in 1990-92, baseline for this study (age range 47-70 years). Incident dementia was ascertained based on clinical assessments in 2011-13 and 2016-17, surveillance based on dementia screeners conducted over telephone interviews, hospitalization discharge codes, and death certificates. Cognitive function was assessed up to four times between 1990 and 92 and 2016-17. We estimated the association of SUA, categorized into quartiles, with incidence of dementia using Cox regression models adjusting for potential confounders. The association between cognitive decline and SUA was assessed using generalized estimating equations. RESULTS: Over a median follow-up period of 24.1 years, 2005 cases of dementia were identified. High baseline SUA was associated with incident dementia (HR, 1.29; 95% CI, 1.12, 1.47) when adjusted for sociodemographic variables. However, after further adjustment including cardiovascular risk factors, this relationship disappeared (HR, 1.03; 95% CI, 0.88, 1.21). Elevated baseline SUA was associated with faster cognitive decline even after further adjustment (25-year global z-score difference, -0.149; 95% CI, -0.246, -0.052). CONCLUSION: Higher levels of mid-life SUA were associated with faster cognitive decline, but not necessarily with higher risk of dementia.

Neuroimaging findings in midlife and risk of late-life dementia over 20 years of follow-up.

OBJECTIVE: To examine the association between neuroimaging features in a predominantly middle-aged cohort and risk of late-life dementia. METHODS: Cerebral MRI was performed on 1,881 individuals with no history of stroke from the Atherosclerosis Risk in Communities Study cohort in 1993 to 1995. White matter hyperintensities (WMH), ventricular size, and sulcal size were graded on a semiquantitative scale, and presence of silent cerebral infarcts was identified. In 2011 to 2013, dementia was determined from neuropsychological testing, informant interview, hospital ICD-9 codes, and death certificate dementia codes. Cox regression was used to evaluate associations between MRI findings and dementia. RESULTS: Over 20 years of follow-up, dementia developed in 279 participants (14.8%). High-grade WMH and high-grade ventricular size were independently associated with increased dementia risk (hazard ratio [HR] for WMH 1.62, 95% confidence interval [CI] 1.14-2.30; HR for ventricular size 1.46, 95% CI 1.06-2.03). There was an increased risk of dementia for diabetic participants with silent infarcts (HR 2.56, 95% CI 1.23-5.31) but not among nondiabetic participants (HR 0.87, 95% CI 0.56-1.37). Each 1-unit increase in the total number of high-grade cerebral abnormalities at baseline (count values range 0-4) showed increased dementia risk, with a considerably higher risk among diabetic participants (HR for diabetes mellitus 1.97, 95% CI 1.44-2.69; HR for no diabetes mellitus 1.20, 95% CI 1.03-1.39). CONCLUSION: In adults without evidence of clinical stroke, MRI-detected WMH and ventricular enlargement in midlife may represent markers of brain injury that increase risk for later-life cognitive impairment. The presence of diabetes mellitus may modify the association between silent infarcts and dementia.

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.

Adiposity, Change in Adiposity, and Cognitive Decline in Mid- and Late Life.

OBJECTIVES: To examine associations between adiposity and adiposity change (loss, stable, gain) and subsequent longitudinal cognitive performance in African Americans in mid and late life. DESIGN: Cohort study using linear mixed models. SETTING: Genetic Epidemiology Network of Arteriopathy. PARTICIPANTS: African-American sibships with hypertension in Jackson, Mississippi (N = 1,108). MEASUREMENTS: Waist circumference and body mass index (BMI) were measured at two examinations 5 years apart. Stable adiposity was defined as values within 5% of the first measure. A composite cognitive Z-score was derived from individual cognitive test Z-scores at two study visits 6 years apart. RESULTS: Larger waist circumference was associated with greater rate of cognitive decline during follow-up (beta = -0.0009 per year, P = .001); BMI, change in waist circumference, and change in BMI were not associated with rate of decline. Loss of adiposity in midlife was associated with higher cognitive Z-scores in middle-aged individuals, and loss of adiposity in late life was associated with lower Z-scores in older adults (P = .01 for interaction between waist circumference and age; P = .04 for interaction between BMI and age). Simultaneous inclusion of waist circumference and BMI in the cross-sectional model suggested an association between larger waist circumference and poorer cognitive performance (beta = -0.009, P = .006) and between higher BMI and better cognitive performance (beta = 0.014, P = .06). CONCLUSION: The results suggested a differential pattern of the relationship between adiposity and cognition according to age (mid- or late life) and regional distribution of adiposity.

Cognitive decline and the PPAR-γ Pro12Ala genotype: variation by sex and ethnicity.

Objective: We investigated the association between the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12Ala polymorphism and cognitive decline in older adults. Methods: Participants from a population-based cohort of older Hispanic and non-Hispanic white adults (n = 492) were administered the Mini Mental State Examination (MMSE), a multi-domain cognitive screening tool, and the Behavioral Dyscontrol Scale (BDS), a measure of executive cognitive function, at baseline and at follow-up, an average of 22 months later. Multiple linear regression was used to investigate the association between the two cognitive test scores and the Pro12Ala polymorphism. Results: At baseline, presence of the Ala12 allele was not significantly associated with MMSE score (P = 0.62) nor with BDS score (P = 0.85). Heterogeneity was present for cognitive decline as measured by the MMSE among ethnic, sex and Ala12 allele status (P = 0.04 for three-way interaction term). Stratification by the cross-classification of sex and ethnicity revealed significantly greater declines in MMSE score among male Hispanic carriers of the Ala12 allele compared to male Hispanic non-carriers (decline = 4.0 versus 1.6 points; P = 0.02). A significant difference in decline between Ala12 carriers and non-carriers was not present among the other sex/ethnic groups. Conclusions: Carriers of the PPAR-γ Ala12 allele showed greater cognitive decline compared to non-carriers as detected by the MMSE but the risk varied across sex and ethnic groups. Male Ala12 carriers of Hispanic origin may be a high-risk group for cognitive decline.

Ultrasound versus MRI: is there a difference in measurements of the fetal lateral ventricles?

OBJECTIVE: To evaluate whether fetal brain lateral ventricle measurements differ between ultrasound (US) and MRI. METHODS: We evaluated 115 fetuses with US and MRI performed within 24 h of each other. Ventricular measurements were performed in the axial plane at the level of the atria for both modalities and the right and left ventricles were evaluated separately. We compared mean measurements; mean differences, association with gestational age (GA), association with the presence of a brain anomaly, and agreement between MRI and US. RESULTS: The LV and RV were measured in 65 and 64 cases, respectively. LV and RV size estimates were significantly greater when measured by MRI compared with US (p < 0.001). Therefore, LV and RV were 0.87 mm and 0.89 mm larger in MRI versus US, respectively. Neither GA at measurement or presence/absence of a brain anomaly was significantly associated with differences in measurements. When comparing the agreement between the US and MRI measurements for ventriculomegaly; the kappa level of agreement for the LV and RV was 0.74 for each. CONCLUSION: MRI measurements of ventricles are significantly larger than the measurements by US by ∼1 mm. There is a good level of agreement when categorizing by normal, mild and severe ventriculomegaly.

Children with minimal chance for cure: parent proxy of the child's health-related quality of life and the effect on parental physical and mental health during treatment.

To assess health-related quality of life (HRQOL) from the time of diagnosis until disease progression in a cohort of children with diffuse intrinsic pontine glioma (DIPG). The assessment was collected from the perspectives of the child and their parents and evaluated the effect of the child's HRQOL on their parents' physical and mental well-being, thus providing insight into the optimal timing of palliative consultation, including anticipatory grief and bereavement services. This longitudinal study assessed 25 parents and their children, ages 2-17 years of age with DIPG across five time-points, baseline and weeks 2, 4, 6, 16, 24. Assessments included the PedsQL 4.0 Core Scales, PedsQL 3.0 Brain Tumor Scale, and Short-Form 36. HRQOL instruments were completed by the child (age ≥5 years) and parent-proxy (ages 2-17 years), with the parent completing the SF-36. Children's reports and parents' proxy of their child's HRQOL indicated poor physical functioning and increased anxiety at the initiation of therapy. A trending improvement in the children's HRQOL was reported by children and parents from baseline to week 6, with a decline at week 16. The childs' parent proxy reported cognitive problems, procedural anxiety and lower overall brain tumor HRQOL were assoicated with poorer self-reported parental mental status. Palliative care consultation should be initiated at the time of diagnosis and is supported in the high physical and emotional symptom burden reported by our patients, with heightened involvement initiated at 16 weeks. Prompt palliative care involvement, mitigating anxiety associated with clinic visits and procedures, management of brain tumor specific symptoms, advanced care planning, anticipatory grief and bereavement services, and care coordination may maximize HRQOL for patients and ensure positive long-term outcomes for parents of children with DIPG.

Corticosteroid Treatment and Growth Patterns in Ambulatory Males with Duchenne Muscular Dystrophy.

OBJECTIVES: To evaluate growth patterns of ambulatory males with Duchenne muscular dystrophy (DMD) treated with corticosteroids compared with ambulatory, steroid-naïve males with DMD and age-matched unaffected general-population males and to test associations between growth and steroid treatment patterns among treated males. STUDY DESIGN: Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network, we identified a total of 1768 height, 2246 weight, and 1755 body mass index (BMI) measurements between age 2 and 12 years for 324 ambulatory males who were treated with corticosteroids for at least 6 months. Growth curve comparisons and linear mixed-effects modeling, adjusted for race/ethnicity and birth year, were used to evaluate growth and steroid treatment patterns (age at initiation, dosing interval, duration, cumulative dose). RESULTS: Growth curves for ambulatory males treated with corticosteroids showed significantly shorter stature, heavier weight, and greater BMI compared with ambulatory, steroid-naïve males with DMD and general-population US males. Adjusted linear mixed-effects models for ambulatory males treated with corticosteroids showed that earlier initiation, daily dosing, longer duration, and greater dosages predicted shorter stature with prednisone. Longer duration and greater dosages predicted shorter stature for deflazacort. Daily prednisone dosing predicted lighter weight, but longer duration, and greater dosages predicted heavier weight. Early initiation, less than daily dosing, longer duration, and greater doses predicted greater BMIs. Deflazacort predicted shorter stature, but lighter weight, compared with prednisone. CONCLUSION: Prolonged steroid use is significantly associated with short stature and heavier weight. Growth alterations associated with steroid treatment should be considered when making treatment decisions for males with DMD.

Age at onset of first signs or symptoms predicts age at loss of ambulation in Duchenne and Becker Muscular Dystrophy: Data from the MD STARnet.

PURPOSE: We investigated the prognostic utility of onset age at first signs and symptoms (SS) to predict onset age at loss of ambulation (LOA) for childhood-onset Duchenne and Becker Muscular Dystrophies (DBMD). METHODS: Our cohort comprised male cases with DBMD ascertained by the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models for associations between onset ages of first SS and LOA. Covariates controlled for were corticosteroid use, family history of DBMD, birth year, race/ethnicity, and MD STARnet site. Onset age at first SS was considered as a continuous and as a categorical variable. RESULTS: A one-year increase in onset age at first SS was significantly associated with a 10% reduction in annual risk of LOA (HR = 0.90, CI = 0.87-0.94). Treating onset age at first SS as a categorical variable yielded a similar association (≥ 5 years: referent; ≥ 3 to < 5 years: HR = 1.36, CI = 1.02-1.81; 18 months to < 3 years: HR = 1.72, CI = 1.31-2.26; < 18 months: HR = 1.52, CI = 1.14-2.02). CONCLUSIONS: Earlier onset age at first SS is associated with earlier onset age at LOA and may have clinical utility in differentiating childhood-onset Duchenne and Becker muscular dystrophies.

The Relationship of Longitudinal Levels of Complement Bb During Pregnancy with Preeclampsia.

PROBLEM: To determine the understudied relationship between complement Bb during pregnancy in subjects with preeclampsia compared with normotensive controls. METHOD OF STUDY: Nested case-control study. RESULTS: Average Bb levels significantly decreased over time in pregnancy [weekly slope (S.E.): -0.0094 (0.0005), P < 0.01]. Cross-sectionally, at less than 10 weeks, Bb levels decreased with increasing gestational age in women who remained normotensive [weekly slope (S.E.): -0.007 (0.02) and for women who developed preeclampsia (weekly slope (S.E.): -0.059 (0.03) P = 0.12]. Among women who developed preeclampsia, Bb levels were greatest when samples were drawn in the gestational window of 15-20 weeks [(weekly slope (S.E.): 0.06 (0.02)], while levels among normotensive women were inversely related with gestational age [weekly slope (S.E.): -0.02 (0.01)]. The differences in slopes between cases and controls between 10 and 21 weeks' gestation were statistically significant (P = 0.003). CONCLUSIONS: We suggest dysregulation of Bb activation between 10 and 20 weeks' gestation in women who develop preeclampsia.

Prescription opioid exposures and adverse outcomes among older adults.

PURPOSE: A high prevalence of chronic pain and high rates of polypharmacy among older adults suggest that this age group may be particularly susceptible to unintentional misuse of prescription opioids. We examined recent trends in misuse of prescription opioids and associated medical outcomes among older-aged adults (60+ years) and compared the patterns with trends among younger-aged adults (20-59 years). METHODS: Linear regression trend analysis was used to analyze 57 681 misuse cases reported to participating US poison centers during 2006-2014. RESULTS: Population rates of misuse of prescription opioids were higher for older adults than for younger adults, and this disparity increased over time. Rates among the older ages increased each year, although the rate of increase slowed over time (p < 0.0001 for negative quadratic trend). In contrast, among the younger adults, there was a significant negative quadratic trend in population rates (p < 0.0001) with a rise in rates during 2006-2010 followed by a decline during 2011-2014. Rates of serious medical outcomes among the older ages followed an increasing linear trend (p < 0.0001); in contrast, rates among younger adults rose and fell during the period, with recent rates trending downward (p < 0.0001 for quadratic trend). CONCLUSIONS: Recent increases in rates of misuse of prescription opioids and associated unfavorable medical outcomes among older adults have important implications as the USA undergoes a rapid expansion of its elderly population. Copyright © 2015 John Wiley & Sons, Ltd.

Fetal weight estimation in diabetic pregnancies using the gestation-adjusted projection method: comparison of two timing strategies for third-trimester sonography.

OBJECTIVES: The gestation-adjusted projection method extrapolates birth weight using third-trimester sonography. This technique is shown to be more accurate for sonographic examinations from 34 weeks to 36 weeks 6 days than 37 weeks to 38 weeks 6 days. Our objective was to determine whether even earlier sonographic examinations (31 weeks-33 weeks 6 days) further improves birth weight prediction in patients with diabetes. METHODS: We conducted a retrospective cohort analysis of 388 pregnant women with pregestational or gestational diabetes who delivered at 37 weeks or later and had a sonographic examination performed between 31 weeks and 36 weeks 6 days. Sonographic examinations were categorized as "early" if performed at 31 weeks to 33 weeks 6 days or "late" if performed at 34 weeks to 36 weeks 6 days. We estimated birth weight using the gestation-adjusted projection method, compared errors in prediction of birth weight using the t test and Mann-Whitney U test, and performed a 2-sample test of proportions to compare prediction of macrosomia (birth weight >4000 g). RESULTS: The early and late groups had similar mean gestational ages at birth (38 weeks 4 days versus 38 weeks 5 days; P = .13) and rates of macrosomia (10.7% versus 12.4%; P = .63). The early group had a greater mean absolute error (336 versus 297 g; P = .03) and percent error (9.9% versus 7.9%; P = .01) in birth weight prediction but a lower mean birth weight (3303 versus 3426 g; P = .02). Sensitivity for prediction of macrosomia was 19% in the early group versus 45% in the late group (P = .07), whereas specificity was similar (98% versus 96%; P = .27). CONCLUSIONS: Using the gestation-adjusted projection method in our patients with diabetes, we found that sonographic examinations performed at 34 weeks to 36 weeks 6 days better predicted birth weight than those performed at 31 weeks to 33 weeks 6 days.