Victor Hasselblad

Estimation of Finite Mixtures of Distributions from the Exponential Family

Abstract General “successive substitutions” iteration equations are developed for obtaining estimates for finite mixtures of distributions from the exponential family. These, in general, correspond to relative maximums of the likelihood function. It is assumed that the number of distributions is known, and that the mixtures are from distributions of the same type, but with different parameter values. The particular equations for the Poisson, binomial, and exponential distributions are given, as well as examples of the results of the procedure for each distribution. From the examples tried, it was observed that the likelihood function increased at each iteration. Graphs of the asymptotic variances of the estimates are given, and two sampling experiments comparing estimates obtained by this scheme with moment estimates are also given.

Making Sense of Qualitative and Quantitative Findings in Mixed Research Synthesis Studies.

The synthesis of qualitative and quantitative research findings is increasingly promoted, but many of the conceptual and methodological issues it raises have yet to be fully understood and resolved. In this article, we describe how we handled issues encountered in efforts to synthesize the findings in forty-two reports of studies of antiretroviral adherence in HIV-positive women in the course of an ongoing study to develop methods to synthesize qualitative and quantitative research findings in common domains of health-related research. Working with these reports underscored the importance of looking past method claims and ideals and directly at the findings themselves, differentiating between aggregative syntheses in which findings are assimilated and interpretive syntheses in which they are configured, and understanding the judgments involved in designating relationships between findings as confirmatory, divergent, or complementary.

Comparison and meta‐analysis of randomized trials of endarterectomy for symptomatic carotid artery stenosis

Objective Comparison and meta-analysis of randomized trials of carotid endarterectomy for symptomatic stenosis of the extracranial carotid artery. Background Randomized trials (North American Symptomatic Carotid Endarterectomy Trial [NASCET], the European Carotid Surgery Trial [ECST], and the VA Cooperative Study WACS]) each show that carotid endarterectomy improves outcomes in selected symptomatic patients with high-grade extracranial carotid artery stenosis. Direct comparisons among the studies have not been possible because of differing methodologies, endpoints, and formats of data reporting. Designlmethods Data for specified endpoints and corresponding person-years at risk were obtained for each trial. The rates of nonfatal stroke, nonfatal myocardial infarction, or death for surgically or medically treated patients in the perioperative period (30 days) and thereafter were compared (both including and excluding perioperative events) and then combined using meta-analytic techniques. Data from NASCET and ECST were also analyzed for differences in outcomes by sex. Results Event rate estimates (with 95% confidence intervals [95% CI]) for the first 30 days (events per person-year, primarily nonfatal stroke) for medically treated patients were 0.44 (0.22 to 0.76) for NASCET, 0.15 (0.04 to 0.38) for ECST, and 0.27 (0.03 to 0.96) for VACS. For surgically treated patients, the corresponding rates (per person-year) were 0.78 (0.49 to 1.19), 0.63 (0.41 to 0.941, and 1.27 (0.58 to 2.43). Event rates per year after 30 days were higher for medically treated patients (0.20 [0.16 to 0.25] versus 0.08 [0.05 to 0.11] for NASCET; 0.12 [0.10 to 0.15] versus 0.07 [0.06 to 0.09] for ECST; and 0.15 [0.07 to 0.25] versus 0.07 [0.03 to 0.16] for VACS). There were no significant differences among the trials, with an overall benefit for surgical therapy (risk ratio estimate, RR = 0.67, 95% CI = 0.54 to 0.83). There were no significant sex-based differences between NASCET and ECST and the overall benefit was not significantly different for men and women (RR = 0.58, 95% CI = 0.45 to 0.74 for men; RR = 0.84, 95% CI = 0.57 to 1.25 for women). Conclusions Adjusting for primary endpoints and duration of follow-up, carotid endarterectomy has a similar benefit for symptomatic patients across trials and a similar benefit for men and women.

Conflicting Results Between Randomized Trials and Observational Studies on the Impact of Proton Pump Inhibitors on Cardiovascular Events When Coadministered With Dual Antiplatelet Therapy Systematic Review

Background— Discordant results have been reported on the effects of concomitant use of proton pump inhibitors (PPIs) and dual antiplatelet therapy (DAPT) for cardiovascular outcomes. We conducted a systematic review comparing the effectiveness and safety of concomitant use of PPIs and DAPT in the postdischarge treatment of unstable angina/non–ST-segment–elevation myocardial infarction patients. Methods and Results— We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews, from 1995 to 2012. Reviewers screened and extracted data, assessed applicability and quality, and graded the strength of evidence. We performed meta-analyses of direct comparisons when outcomes and follow-up periods were comparable. Thirty-five studies were eligible. Five (4 randomized controlled trials and 1 observational) assessed the effect of omeprazole when added to DAPT; the other 30 (observational) assessed the effect of PPIs as a class when compared with no PPIs. Random-effects meta-analyses of the studies assessing PPIs as a class consistently reported higher event rates in patients receiving PPIs for various clinical outcomes at 1 year (composite ischemic end points, all-cause mortality, nonfatal MI, stroke, revascularization, and stent thrombosis). However, the results from randomized controlled trials evaluating omeprazole compared with placebo showed no difference in ischemic outcomes, despite a reduction in upper gastrointestinal bleeding with omeprazole. Conclusions— Large, well-conducted observational studies of PPIs and randomized controlled trials of omeprazole seem to provide conflicting results for the effect of PPIs on cardiovascular outcomes when coadministered with DAPT. Prospective trials that directly compare pharmacodynamic parameters and clinical events among specific PPI agents in patients with unstable angina/non–ST-segment–elevation myocardial infarction treated with DAPT are warranted.

The Agency for Health Care Policy and Research: Smoking Cessation Clinical Practice Guideline - Findings and Implications for Psychologists

Smoking is the leading cause of preventable morbidity and mortality in the United States, and the health benefits of quitting smoking are substantial. Nevertheless, over 25% of American adults (48 million individuals) continue to smoke, and the vast majority of quit attempts are unsuccessful. The Agency for Health Care Policy and Research recently addressed the smoking problem by conducting a 2-year research project that was published as the Smoking Cessation Clinical Practice Guideline (Fiore et al., 1996). This article reviews methods, analyses, and results from the Guideline project, and highlights major Guideline recommendations. Guideline findings and recommendations are discussed with respect to their implications for psychology.

Efficacy and Tolerability of Treatments for Chronic Cough: A Systematic Review and Meta-analysis

BACKGROUND Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Original ResearchSigns and Symptoms of Chest DiseasesEfficacy and Tolerability of Treatments for Chronic Cough: A Systematic Review and Meta-analysis

BACKGROUND Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Comparative Effectiveness Review of Antiplatelet Agents in Peripheral Artery Disease

Peripheral artery disease (PAD) was identified by the Institute of Medicine as one of the top 100 priorities for comparative effectiveness research because of the large population of patients affected with significant morbidity and mortality, the multiple potential treatment options, and the high

Methods of creatine kinase-MB analysis to predict mortality in patients with myocardial infarction treated with reperfusion therapy

BackgroundLarger infarct size measured by creatine kinase (CK)-MB release is associated with higher mortality and has been used as an important surrogate endpoint in the evaluation of new treatments for ST-segment elevation myocardial infarction (STEMI). Traditional approaches to quantify infarct size include the observed CK-MB peak and calculated CK-MB area under the curve (AUC). We evaluated alternative approaches to quantifying infarct size using CK-MB values, and the relationship between infarct size and clinical outcomes.MethodsOf 1,850 STEMI patients treated with reperfusion therapy in the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) (percutaneous coronary intervention (PCI)-treated) and the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) (fibrinolytic-treated) trials, 1,718 (92.9%) (COMMA, n = 868; COMPLY, n = 850) had at least five of nine protocol-required CK-MB measures. In addition to traditional methods, curve-fitting techniques were used to determine CK-MB AUC and estimated peak CK-MB. Cox proportional hazards modeling assessed the univariable associations between infarct size and mortality, and the composite of death, heart failure, shock and stroke at 90 days.ResultsIn COMPLY, CK-MB measures by all methods were significantly associated with higher mortality (hazard ratio range per 1,000 units increase: 1.09 to 1.13; hazard ratio range per 1 standard deviation increase: 1.41 to 1.62; P <0.01 for all analyses). In COMMA, the associations were similar but did not reach statistical significance. For the composite outcome of 90-day death, heart failure, shock and stroke, the associations with all CK-MB measures were statistically significant in both the COMMA and COMPLY trials.ConclusionsSophisticated curve modeling is an alternative to infarct-size quantification in STEMI patients, but it provides information similar to that of more traditional methods. Future studies will determine whether the same conclusion applies in circumstances other than STEMI, or to studies with different frequencies and patterns of CK-MB data collection.

Adequacy of a Single Monitoring Site for Defining Mean Outdoor Concentrations of Fine Particles in a Demarcated Residential Community

Fine and coarse inhalable particle data for 60 days from five demarcated communities in U.S. cities, each with three monitoring sites, were examined to test whether the mean particle mass concentrations measured at the three sites are equivalent within each community. The result of this kind of analysis should be useful in determining how many sites in a community are adequate to provide a reliable measure of the outdoor component of an exposure estimate in that community. Only fine particles (D < 2.5 μm, aerodynamic diameter) were found to have equivalent mean concentrations, suggesting that only one monitoring site in each community is required to provide an adequate exposure estimate of the outdoor component. However, variable concentrations of total inhalable and/or coarse (2.5 μm< D < 15 μm) particles were found, which Implies a requirement for multiple monitoring sites.