Paper 246-2009 Getting the Most out of the SAS ® Survey Procedures: Repeated Replication Methods, Subpopulation Analysis, and Missing Data Options in SAS ® v9.2

This paper presents practical guidance on three common survey data analysis techniques: repeated replication methods for variance estimation, subpopulation analyses, and techniques for handling missing data. A number of new features in the SAS ® 9.2 survey procedures are demonstrated: Jackknife and Balanced Repeated Replication methods for variance estimation, subpopulation analysis with use of the DOMAIN option and the subsetting approach and the use of the NOMCAR (not missing completely at random) and multiple imputation options for handling missing data. Descriptive statistics as well as logistic regression are demonstrated. The analytic techniques presented can be used on any operating system and are intended for an intermediate level audience

Recovery from PTSD following Hurricane Katrina

Background: We examined patterns and correlates of speed of recovery of estimated posttraumatic stress disorder (PTSD) among people who developed PTSD in the wake of Hurricane Katrina. Method: A probability sample of prehurricane residents of areas affected by Hurricane Katrina was administered a telephone survey 7–19 months following the hurricane and again 24–27 months posthurricane. The baseline survey assessed PTSD using a validated screening scale and assessed a number of hypothesized predictors of PTSD recovery that included sociodemographics, prehurricane history of psychopathology, hurricane‐related stressors, social support, and social competence. Exposure to posthurricane stressors and course of estimated PTSD were assessed in a follow‐up interview. Results: An estimated 17.1% of respondents had a history of estimated hurricane‐related PTSD at baseline and 29.2% by the follow‐up survey. Of the respondents who developed estimated hurricane‐related PTSD, 39.0% recovered by the time of the follow‐up survey with a mean duration of 16.5 months. Predictors of slow recovery included exposure to a life‐threatening situation, hurricane‐related housing adversity, and high income. Other sociodemographics, history of psychopathology, social support, social competence, and posthurricane stressors were unrelated to recovery from estimated PTSD. Conclusions: The majority of adults who developed estimated PTSD after Hurricane Katrina did not recover within 18–27 months. Delayed onset was common. Findings document the importance of initial trauma exposure severity in predicting course of illness and suggest that pre‐ and posttrauma factors typically associated with course of estimated PTSD did not influence recovery following Hurricane Katrina. Depression and Anxiety, 2011.  © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87167/1/20790_ftp.pd

Sample designs and sampling methods for the Collaborative Psychiatric Epidemiology Studies (CPES)

This paper provides an overview of the probability sample designs and sampling methods for the Collaborative Psychiatric Epidemiology Studies (CPES): the National Comorbidity Survey Replication (NCS-R), the National Study of American Life (NSAL) and the National Latino and Asian American Study of Mental Health (NLAAS). The multi-stage sample design and respondent selection procedures used in these three studies are based on the University of Michigan Survey Research Center's National Sample designs and operations. The paper begins with a general overview of these designs and procedures and then turns to a more detailed discussion of the adaptation of these general methods to the three specific study designs. The detailed discussions of the individual study samples focus on design characteristics and outcomes that are important to analysts of the CPES data sets and to researchers and statisticians who are planning future studies. The paper describes how the expected survey cost and error structure for each of these surveys influenced the original design of the samples and how actual field experience led to changes and adaptations to arrive at the final samples of each survey population. Copyright © 2004 Whurr Publishers Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34225/1/179_ftp.pd

The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Hypertriglyceridemia may be associated with important complications. The aim of this study is to estimate the magnitude of association and quality of supporting evidence linking hypertriglyceridemia to cardiovascular events and pancreatitis.</p> <p>Methods</p> <p>We conducted a systematic review of multiple electronic bibliographic databases and subsequent meta-analysis using a random effects model. Studies eligible for this review followed patients longitudinally and evaluated quantitatively the association of fasting hypertriglyceridemia with the outcomes of interest. Reviewers working independently and in duplicate reviewed studies and extracted data.</p> <p>Results</p> <p>35 studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate to low with fair level of multivariable adjustments and adequate exposure and outcome ascertainment. Fasting hypertriglyceridemia was significantly associated with cardiovascular death (odds ratios (OR) 1.80; 95% confidence interval (CI) 1.31-2.49), cardiovascular events (OR, 1.37; 95% CI, 1.23-1.53), myocardial infarction (OR, 1.31; 95% CI, 1.15-1.49), and pancreatitis (OR, 3.96; 95% CI, 1.27-12.34, in one study only). The association with all-cause mortality was not statistically significant.</p> <p>Conclusions</p> <p>The current evidence suggests that fasting hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis.</p> <p>Précis: hypertriglyceridemia is associated with increased risk of cardiovascular death, MI, cardiovascular events, and possibly acute pancreatitis</p

The epidemiology of major depressive episodes: results from the International Consortium of Psychiatric Epidemiology (ICPE) surveys

Absence of a common diagnostic interview has hampered cross-national syntheses of epidemiological evidence on major depressive episodes (MDE). Community epidemiological surveys using the World Health Organization Composite International Diagnostic Interview administered face-to-face were carried out in 10 countries in North America (Canada and the US), Latin America (Brazil, Chile, and Mexico), Europe (Czech Republic, Germany, the Netherlands, and Turkey), and Asia (Japan). The total sample size was more than 37,000. Lifetime prevalence estimates of hierarchy-free DSM-III-R/DSM-IV MDE varied widely, from 3% in Japan to 16.9% in the US, with the majority in the range of 8% to 12%. The 12-month/lifetime prevalence ratio was in the range 40% to 55%, the 30-day/12-month prevalence ratio in the range 45% to 65%, and median age of onset in the range 20 to 25 in most countries. Consistent socio-demographic correlates included being female and unmarried. Respondents in recent cohorts reported higher lifetime prevalence, but lower persistence than those in earlier cohorts. Major depressive episodes were found to be strongly co-morbid with, and temporally secondary to, anxiety disorders in all countries, with primary panic and generalized anxiety disorders the most powerful predictors of the first onset of secondary MDE. Major depressive episodes are a commonly occurring disorder that usually has a chronic-intermittent course. Effectiveness trials are needed to evaluate the impact of early detection and treatment on the course of MDE as well as to evaluate whether timely treatment of primary anxiety disorders would reduce the subsequent onset, persistence, and severity of secondary MDE. Copyright © 2003 Whurr Publishers Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34221/1/138_ftp.pd

Structure, Function, and Evolution of the Thiomonas spp. Genome

Bacteria of the Thiomonas genus are ubiquitous in extreme environments, such as arsenic-rich acid mine drainage (AMD). The genome of one of these strains, Thiomonas sp. 3As, was sequenced, annotated, and examined, revealing specific adaptations allowing this bacterium to survive and grow in its highly toxic environment. In order to explore genomic diversity as well as genetic evolution in Thiomonas spp., a comparative genomic hybridization (CGH) approach was used on eight different strains of the Thiomonas genus, including five strains of the same species. Our results suggest that the Thiomonas genome has evolved through the gain or loss of genomic islands and that this evolution is influenced by the specific environmental conditions in which the strains live

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value &lt; 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p &lt; 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation