Transthyretin V122I in African Americans with congestive heart failure.
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Black or African American↗
Biomedical subjects
Philip Lavori
Publications and source records attributed to Philip Lavori.
Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder.
BACKGROUND: Preliminary evidence suggests that valproate is associated with isolated features of polycystic ovarian syndrome (PCOS), while contradictory data support an association between epilepsy and PCOS. The development of PCOS features after initiation of valproate was therefore examined in women with bipolar disorder using a standardized definition of PCOS. METHODS: Three hundred women 18 to 45 years old with bipolar disorder were evaluated for PCOS at 16 Systematic Treatment Enhancement for Bipolar Disorder sites. A comparison was made between the incidence of hyperandrogenism (hirsutism, acne, male-pattern alopecia, elevated androgens) with oligoamenorrhea that developed while taking valproate versus other anticonvulsants (lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine) and lithium. Medication and menstrual cycle histories were obtained, and hyperandrogenism was assessed. RESULTS: Among 230 women who could be evaluated, oligoamenorrhea with hyperandrogenism developed in 9 (10.5%) of 86 women on valproate and in 2 (1.4%) of 144 women on a nonvalproate anticonvulsant or lithium (relative risk 7.5, 95% confidence interval [CI] 1.7-34.1, p = .002). Oligoamenorrhea always began within 12 months of valproate use. CONCLUSIONS: Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism. Monitoring for reproductive-endocrine abnormalities is important when starting and using valproate in reproductive-aged women. Prospective studies are needed to elucidate risk factors for development of PCOS on valproate.
Adolescent↗
The role of a common adenosine monophosphate deaminase (AMPD)-1 polymorphism in outcomes of ischemic and nonischemic heart failure.
BACKGROUND: A common variant of the adenosine monophosphate deaminase (AMPD)-1 gene (C34T) results in enzymatic inactivity and may increase adenosine in cardiac muscle and confer cardioprotection through ischemic preconditioning. METHODS AND RESULTS: We hypothesized that AMPD1 carriers with ischemic heart failure (HF) in the Beta-Blocker Evaluation of Survival Trial (BEST) might have a relative survival advantage. Patients (n = 1038, 20% black) with ischemic (58%) and nonischemic (42%) HF were followed for an average of 2.0 years for cardiovascular mortality. DNA was purified from blood using phenol/chloroform. Genotyping was performed by polymerase chain reaction with 5' exonuclease chemistry. Differences in survival were assessed by comparing Kaplan-Meier curves with the log-rank test. Genotype frequencies differed by ethnicity (P < .001) but not by disease etiology. AMPD1 genotype did not significantly modify survival in the entire study population (hazard ratio [HR] = 0.91, 95% CI = 0.61-1.37), among ischemics (HR = 0.73, CI = 0.44-1.22, P = .23), or ischemic non-blacks (HR = 0.74, CI = 0.44-1.24, P = .25). Genotype did not modify the effect of bucindolol on mortality. CONCLUSIONS: Results of this study failed to confirm a reported survival benefit among HF patients carrying the AMPD1 T-allele. However, further studies in larger, more homogeneous populations should explore the possibility of a modest survival advantage for patients with ischemic HF.
AMP Deaminase↗
Improving adherence to guidelines for hypertension drug prescribing: cluster-randomized controlled trial of general versus patient-specific recommendations.
OBJECTIVE: To determine whether an intervention focusing clinician attention on drug choice for hypertension treatment improves concordance between drug regimens and guidelines. STUDY DESIGN: Cluster-randomized controlled trial comparing an individualized intervention with a general guideline implementation in geographically diverse primary care clinics of a university-affiliated Department of Veterans Affairs healthcare system. METHODS: Participants were 36 attending physicians and nurse practitioners (16 in the general group and 20 in the individualized group), with findings based on 4500 hypertensive patients. A general guideline implementation for all clinicians, including education about guideline-based drug recommendations and goals for adequacy of blood pressure control, was compared with addition of a printed individualized advisory sent to clinicians at each patient visit, indicating whether or not the patient's antihypertensive drug regimen was guideline concordant. We measured change from baseline to end point in the proportion of clinicians' patients whose drug therapy was guideline concordant. RESULTS: The individualized intervention resulted in an improvement in guideline concordance more than twice that observed for the general intervention (10.9% vs 3.8%, t = 2.796, P = .008). Bootstrap analysis showed that being in the individualized group increased the odds of concordance 1.5-fold (P = .025). The proportion of patients with adequate blood pressure control increased within each study group; however, the difference between groups was not significant. CONCLUSION: An individualized advisory regarding drug therapy for hypertension given to the clinician at each patient visit was more effective in changing clinician prescribing behavior than implementation of a general guideline.
Aged↗
Enrollment in clinical trials according to patients race: experience from the VA Cooperative Studies Program (1975-2000).
BACKGROUND: Racial distribution of clinical trial participants is important because results from these studies serve to define evidence-based practice. This report summarizes the experience of the VA Cooperative Studies Program (CSP) in enrolling white, black and Hispanic patients. METHODS: An analysis of enrollment in randomized controlled trials conducted by VA CSP between 1975 and 2000. A standardized enrollment ratio for each trial was calculated by dividing the observed number of enrolled white patients in the trial by the expected number of eligible white patients based on the proportion of white patients hospitalized at the enrolling VA Medical Centers. RESULTS: 138 VA CSP clinical trials were initiated between 1975 and 2000, 83 contained information on race for 71,463 patients. Overall, 76% of enrolled patients were white, 20% were black, and 4% were Hispanic. Based on standardized enrollment ratios, 60 of the 83 trials had 95% confidence intervals that excluded 1.0. Of these, 32 studies enrolled more white patients than expected and 28 enrolled more Black and/or Hispanic patients than expected based on the racial distribution of patients hospitalized at sites involved in the trials. When trials were separated by intervention type, 13 of the 19 trials that had an invasive arm enrolled fewer minority patients than expected. In trials that targeted diseases that affect minority populations to a greater degree than whites (diabetes, hypertension and end stage renal disease), 11 of the 14 trials enrolled more minority patients than expected. CONCLUSIONS: There were several trials that enrolled either more or less minority patients than expected based on patients hospitalized at study sites. Trials that included an invasive arm enrolled fewer minority participants than expected. Trials that involve invasive therapies may wish to adopt special recruitment strategies to reach minority populations.
Cooperative Behavior↗
AACAP 2002 research forum: placebo and alternatives to placebo in randomized controlled trials in pediatric psychopharmacology.
OBJECTIVE: The use of placebo in the pediatric age group has come under increasing scrutiny. At the 2002 Annual Meeting of the American Academy of Child and Adolescent Psychiatry, the Academy's Workgroup on Research conducted a research forum. The purpose was to identify challenges and their solutions regarding the use of placebo in randomized controlled trials in pediatric psychopharmacology. METHOD: Workgroups focused on problems and solutions in five areas: ethics and human subjects, research design and statistics, partnering with consumers, U.S. Food and Drug Administration and pharmaceutical industry perspectives, and psychosocial treatments. RESULTS: In many but not all circumstances, inclusion of a placebo control is essential to meet the scientific goals of treatment outcome research. Innovative research designs; involvement of consumers in planning and implementing research; flexibility by industry, academia, the National Institutes of Health, and regulatory agencies acting in partnership; and concomitant use of evidence-based psychosocial services can and should assist in making placebo-controlled trials acceptable. CONCLUSIONS: Properly designed placebo-controlled trials remain necessary, ethical, and feasible.
Adolescent↗
Condom use by women recently diagnosed with a sexually transmitted infection: effects of study methodology on the apparent influence of hormonal/surgical contraception.
OBJECTIVE/GOAL: The objective of this study was to investigate potential predictors of consistent condom use (CCU), including the influence of hormonal contraception/surgical sterilization (HC/SS). STUDY: Regression methods were used to predict CCU and other measures of CU among 214 sexually active, 18- to 45-year-old women previously diagnosed with a sexually transmitted infection. RESULTS: CCU was significantly associated with younger age, African American ethnicity, having casual partners, recent HIV testing, condom use self-efficacy, and concern about partner relationship. HC/SS was not significantly associated with the likelihood of CCU, before (HC/SS, 21.3%, non-HC/SS, 25.3%; odds ratio [OR], 0.798; P=0.4914) or after (OR, 1.209; P=0.5995) controlling for confounders (age, ethnicity, casual partners). Controlling for age and ethnicity eliminated initial significant or near-significant inverse associations between HC/SS and 3 alternative measures of interval condom use ("any use," "number of unprotected acts," "proportion condom-protected contacts") and substantially diminished the association between HC/SS and "condom use at last sex." CONCLUSIONS: Choice of condom use measure and control of confounding variables can substantially affect results when studying potential predictors of condom use such as HC/SS.
Adolescent↗
Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study.
The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed.
Adult↗
Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD).
The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was conceived in response to a National Institute of Mental Health initiative seeking a public health intervention model that could generate externally valid answers to treatment effectiveness questions related to bipolar disorder. STEP-BD, like all effectiveness research, faces many design challenges, including how to do the following: recruit a representative sample of patients for studies of readily available treatments; implement a common intervention strategy across diverse settings; determine outcomes for patients in multiple phases of illness; make provisions for testing as yet undetermined new treatments; integrate adjunctive psychosocial interventions; and avoid biases due to subject drop-out and last-observation-carried-forward data analyses. To meet these challenges, STEP-BD uses a hybrid design to collect longitudinal data as patients make transitions between naturalistic studies and randomized clinical trials. Bipolar patients of every subtype with age >/= 15 years are accessioned into a study registry. All patients receive a systematic assessment battery at entry and are treated by a psychiatrist (trained to deliver care and measure outcomes in patients with bipolar disorder) using a series of model practice procedures consistent with expert recommendations. At every follow-up visit, the treating psychiatrist completes a standardized assessment and assigns an operationalized clinical status based on DSM-IV criteria. Patients have independent evaluations at regular intervals throughout the study and remain under the care of the same treating psychiatrist while making transitions between randomized care studies and the standard care treatment pathways. This article reviews the methodology used for the selection and certification of the clinical treatment centers, training study personnel, the general approach to clinical management, and the sequential treatment strategies offered in the STEP-BD standard and randomized care pathways for bipolar depression and relapse prevention.
Bipolar Disorder↗
A controlled trial of inpatient and outpatient geriatric evaluation and management.
BACKGROUND: Over the past 20 years, both inpatient units and outpatient clinics have developed programs for geriatric evaluation and management. However, the effects of these interventions on survival and functional status remain uncertain. METHODS: We conducted a randomized trial involving frail patients 65 years of age or older who were hospitalized at 11 Veterans Affairs medical centers. After their condition had been stabilized, patients were randomly assigned, according to a two-by-two factorial design, to receive either care in an inpatient geriatric unit or usual inpatient care, followed by either care at an outpatient geriatric clinic or usual outpatient care. The interventions involved teams that provided geriatric assessment and management according to Veterans Affairs standards and published guidelines. The primary outcomes were survival and health-related quality of life, measured with the use of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36), one year after randomization. Secondary outcomes were the ability to perform activities of daily living, physical performance, utilization of health services, and costs. RESULTS: A total of 1388 patients were enrolled and followed. Neither the inpatient nor the outpatient intervention had a significant effect on mortality (21 percent at one year overall), nor were there any synergistic effects between the two interventions. At discharge, patients assigned to the inpatient geriatric units had significantly greater improvements in the scores for four of the eight SF-36 subscales, activities of daily living, and physical performance than did those assigned to usual inpatient care. At one year, patients assigned to the outpatient geriatric clinics had better scores on the SF-36 mental health subscale, even after adjustment for the score at discharge, than those assigned to usual outpatient care. Total costs at one year were similar for the intervention and usual-care groups. CONCLUSIONS: In this controlled trial, care provided in inpatient geriatric units and outpatient geriatric clinics had no significant effects on survival. There were significant reductions in functional decline with inpatient geriatric evaluation and management and improvements in mental health with outpatient geriatric evaluation and management, with no increase in costs.
Activities of Daily Living↗
Analysis of randomized controlled trials.
Although the sophistication and flexibility of the statistical technology available to the data analyst have increased, some durable, simple principles remain valid. Hypothesis-driven analyses, which were anticipated and specified in the protocol, must still be kept separate and privileged relative to the important, but risky data mining made possible by modern computers. Analyses that have a firm basis in the randomization are interpreted more easily than those that rely heavily on statistical models. Outcomes--such as quality of life, symptoms, and behaviors--that require the cooperation of subjects to be measured will come to be more and more important as trials move away from mortality as the main outcome. Inevitably, such trials will have to deal with more missing data, especially because of dropout and noncompliance. There are fundamental limits on the ability of statistical methods to compensate for such problems, so they must be considered when studies are designed. Finally, it must be emphasized that the availability of software is not a substitute for experience and statistical expertise.
Data Interpretation, Statistical↗
Treatment predictors of extrapyramidal side effects in patients with tardive dyskinesia: results from Veterans Affairs Cooperative Study 394.
Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD.
Adult↗