Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting.

BACKGROUND AND OBJECTIVES: Treatment for individuals receiving medication for opioid use disorder (MOUD) should follow an informed patient-centered approach. To better support patient autonomy in the decision-making process, clinicians should be aware of patient preferences and be prepared to educate and assist patients in transitioning from one MOUD to another, when clinically indicated. This posthoc analysis describes the characteristics of clinical trial participants (NCT02696434) with a history of opioid use disorder (OUD) seeking to transition from buprenorphine (BUP) to extended-release naltrexone (XR-NTX). METHODS: The posthoc analysis included adults with OUD currently receiving BUP (≤8 mg/day) and seeking transition to XR-NTX (N = 101) in a residential setting. Baseline participant characteristics and OUD treatment history were reviewed. All patients completed a screening questionnaire that asked about their reasons for seeking transition to XR-NTX and for choosing BUP. RESULTS: The most common reasons for initiating a transition to XR-NTX were "Seeking to be opioid-free" (63.4%) and "Tired of daily pill taking" (25.7%). Positive predictors of transition included a more extensive BUP treatment history and a history of prescription opioid abuse. Most participants stated they were not aware of XR-NTX as a treatment option when initiating BUP (78.2%). DISCUSSIONS AND CONCLUSIONS: Patients' reasons for seeking XR-NTX transition, more extensive BUP treatment history, and a history of prescription opioid abuse, may positively predict outcomes. SCIENTIFIC SIGNIFICANCE: These findings may assist clinicians in optimizing outcomes of the BUP to XR-NTX transition and supporting patients to make better informed MOUD decisions.

Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone.

BACKGROUND: Pharmacologic treatment is recommended for many individuals with opioid use disorder (OUD). For patients who select opioid antagonist treatment, effective management of opioid withdrawal symptoms during transition to antagonist treatment requires consideration of the patient experience. OBJECTIVES: To compare patterns of opioid withdrawal between those withdrawing from untreated opioid use and those withdrawing from buprenorphine. METHODS: We performed a post hoc, cross-study comparison of the temporal pattern of opioid withdrawal during 1-week induction onto extended-release naltrexone by similar protocols enrolling two participant populations: participants with OUD entering a study with untreated opioid use (N = 378, NCT02537574) or on stable buprenorphine (BUP) treatment (N = 101, NCT02696434). RESULTS: The temporal pattern of withdrawal from induction day 1 through day 7 differed between the two participant populations for Clinical Opiate Withdrawal Score (COWS) and Subjective Opiate Withdrawal Score (SOWS): participants with untreated OUD prior to study entry were more likely to experience an earlier relative peak in opioid withdrawal followed by a gradual decline, whereas participants on stable BUP treatment prior to study entry were more likely to experience a relatively later, though still mild, peak opioid withdrawal. The peak COWS was reached at a mean (standard deviation) of 1.9 (1.5) days for participants with untreated OUD and 5.0 (1.5) days for participants on stable BUP. Daily peak cravings were generally higher for participants with untreated OUD than participants on stable BUP. CONCLUSION: Awareness of population-specific variations in the patient experience of opioid withdrawal may help clinicians anticipate the expected course of withdrawal.

Handwriting Kinematics in Patients with Schizophrenia Treated with Long-Acting Injectable Atypical Antipsychotics: Results From the ALPINE Study.

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis). Treatment response was defined as ≥20% reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 4. Two HWK measures, peak velocity (decreases with greater dysfunction) and percentage of nonballistic movements (%NBM; increases with greater dysfunction), were captured in 4 handwriting tasks (complex loops, maximum speed circles, overlay circles, and left-right loops). Peak velocity and %NBM at baseline were compared between responders and nonresponders. The analysis included 143 patients (mean baseline PANSS total score, 94.5). PANSS responders (n = 67 [46.9%]) had a lower mean peak velocity (i.e., slower pen movements) on all HWK tasks at baseline compared with nonresponders (n = 76): complex loops, 8.8 versus 12.1 cm/s; maximum speed circles, 18.0 versus 23.7 cm/s; overlay circles, 12.6 versus 17.2 cm/s; and left-right loops, 11.2 versus 14.6 cm/s. PANSS responders had a greater %NBM on 3 tasks compared with nonresponders: complex loops, 57.1% versus 47.4%; overlay circles, 30.6% versus 24.3%; and left-right loops, 58.7% versus 47.0%. In this exploratory analysis, PANSS responders to aripiprazole lauroxil or paliperidone palmitate treatment at week 4 had lower baseline HWK movement velocities and greater baseline %NBM versus nonresponders, suggesting that baseline HWKs might predict response to these antipsychotic drugs.

Different types of distrust in clinical research among whites and African Americans.

BACKGROUND: African Americans are thought to be more distrustful of clinical research compared to elderly whites, but it is unknown whether specific types of distrust in clinical research, such as interpersonal or societal distrust, vary according to race. The primary objective was to identify racial differences in interpersonal or societal distrust in clinical research among African Americans and whites. METHODS: Seven hundred seventy-six older African Americans and whites were surveyed about their interpersonal and societal distrust using a 7-item index of distrust in clinical research. We combined the 2 societal distrust items into a societal distrust subscale. We also assessed trust in primary care physicians, access to care, health/functional status, previous exposure to clinical research, awareness of the Tuskegee Syphilis Study, perceived discrimination in health care, and sociodemographic characteristics. RESULTS: High societal distrust was more common among African Americans compared to whites (21% vs 7% in the top quartile of the societal distrust, p < .0001), but there were no racial differences in responses to the individual interpersonal distrust index items. In sequentially built multivariable analyses, the relationship between African American race and societal distrust (odds ratio, 2.2; 95% CI, 1.2-3.7) was not completely explained by other factors such as trust in one's physician, previous discrimination, or awareness of the Tuskegee Syphilis Study. CONCLUSIONS: Racial differences according to the type of distrust in clinical research may warrant assessing specific types of distrust separately among racially diverse populations in future studies.

Willingness to participate in clinical trials among African Americans and whites previously exposed to clinical research.

The objective of this study was to identify racial differences in willingness to participate in a population with previous exposure to clinical research. A survey instrument was administered to community-dwelling whites and African Americans who were voluntarily receiving a lay research and health education newsletter from a local Boston geriatric clinical research institution. The survey instrument assessed willingness to participate in 3 hypothetical clinical trials (diet trial for obesity, medication trial for hypertension [HTN], chemotherapy trial for cancer). Surveys were received from 473 whites and 279 African Americans (53% response rate) with mean age 74 (SD +/- 9). In multivariate models, race was not significantly related to willingness to participate in the multivariate models for any of the 3 trials. Previous trial participation was related to a higher odds of willingness to participate in the diet trial only (OR 1.8, 95% CI 1.2, 2.6). Lower levels of trust in one's primary care physician were associated with a lower odds of willingness to participate in clinical trials for the diet and HTN trials (OR 0.5, 95% CI 0.3, 0.8 and OR 0.6, 95% CI 0.3, 0.9, respectively). These findings suggest that, within populations previously exposed to clinical research, African Americans are no less willing to participate in clinical trials compared to whites.

Association between language and risk factor levels among Hispanic adults with hypertension, hypercholesterolemia, or diabetes.

BACKGROUND: The association of acculturation and cardiovascular risk factor control among populations with high proportions of immigrants has not been well studied. METHODS: We studied 1,492 Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with hypertension, hypercholesterolemia, and/or diabetes. We used linear regression to examine the cross-sectional relationships between acculturation measures and cardiovascular risk factor levels. Outcome measures included systolic blood pressure (mm Hg), fasting low-density lipoprotein (LDL) cholesterol (mg/dL), and fasting blood glucose (mg/dL). Covariates included education, income, health insurance, physical activity, dietary factors, risk factor-specific medication use, duration of medication use, smoking, and body mass index. RESULTS: There were 580 Hispanics with hypertension, 539 with hypercholesterolemia, and 248 with diabetes. After adjustment for age and gender, Spanish-speaking Hispanics with cardiovascular risk factors had higher systolic blood pressure, fasting LDL cholesterol, and fasting blood glucose compared to English-speaking Hispanics. Differences in systolic blood pressure were accounted for mainly by education, whereas differences in LDL cholesterol were almost entirely accounted for by cholesterol-lowering medication use. Differences in fasting glucose were partly accounted for by socioeconomic variables but were augmented after adjustment for dietary factors. Similar associations were observed between proportion of life in the United States and risk factor levels. CONCLUSIONS: Among those with cardiovascular risk factors, Hispanics who spoke Spanish at home and lived less time in the United States had worse control of cardiovascular risk factors. Treatment strategies that focus on Hispanics with low levels of acculturation may improve cardiovascular risk factor control.

Acculturation and cardiovascular risk factor control among Hispanic adults in the United States.

OBJECTIVES: We sought to determine whether low acculturation, based on language measures, leads to disparities in cardiovascular risk factor control in U.S. Hispanic adults. METHODS: We studied 4729 Hispanic adults aged 18 to 85 years from the National Health and Nutrition Examination Survey, 1999-2004. We examined the association between acculturation and control of low-density lipoprotein (LDL) cholesterol, blood pressure, and hemoglobin A1c based on national guidelines among participants with hypercholesterolemia, hypertension, and diabetes, respectively. We used weighted logistic regression adjusting for age, gender, and education. We then examined health insurance, having a usual source of care, body mass index, fat intake, and leisure-time physical activity as potential mediators. RESULTS: Among participants with hypercholesterolemia, Hispanic adults with low acculturation were significantly more likely to have poorly controlled LDL cholesterol than Hispanic adults with high acculturation after multivariable adjustment (odds ratio [OR] = 3.4, 95% confidence interval [CI] 1.2, 9.5). Insurance status mildly attenuated the difference in LDL cholesterol control. After adjusting for diet and physical activity, the magnitude of the association increased. Other covariates had little influence on the observed relationship. Among those with diabetes and hypertension, we did not observe statistically significant associations between low acculturation and control of hemoglobin A1c (OR = 0.5, 95% CI 0.2, 1.2), and blood pressure (OR = 1.1, 95% CI 0.6, 1.7), respectively. CONCLUSIONS: Low levels of acculturation may be associated with increased risk of inadequate LDL cholesterol control among Hispanic adults with hypercholesterolemia. Further studies should examine the mechanisms by which low acculturation might adversely impact lipid control among Hispanic adults in the U.S.

An overview of practical approaches for handling missing data in clinical trials.

For a variety of reasons including poorly designed case report forms (CRFs), incomplete or invalid CRF data entries, and premature treatment or study discontinuations, missing data is a common phenomenon in controlled clinical trials. With the widely accepted use of the intent-to-treat (ITT) analysis dataset as the primary analysis dataset for the analysis of controlled clinical trial data, the presence of missing data could lead to complicated data analysis strategies and subsequently to controversy in the interpretation of trial results. In this article, we review the mechanisms of missing data and some common approaches to analyzing missing data with an emphasis on study dropouts. We discuss the importance of understanding the reasons for study dropouts with ways to assess the mechanisms of missingness. Finally, we discuss the results of a comparative Monte Carlo investigation of the performance characteristics of commonly utilized statistical methods for the analysis of clinical trial data with dropouts. The methods investigated include the mixed effects model for repeated measurements (MMRM), weighted and unweighted generalized estimating equations (GEE) method for the available case data, multiple-imputation-based GEE (MI-GEE), complete case (CC) analysis of covariance (ANCOVA), and last observation carried forward (LOCF) ANCOVA. Simulation experiments for the repeated measures model with missing at random (MAR) dropout, under varying dropout rates and intrasubject correlation, show that the LOCF, ANCOVA, and weighted GEE methods perform poorly in terms of percent relative bias for estimating a difference in means effect, while the MI-GEE and weighted GEE methods both have less power for rejecting a zero difference in means hypothesis.

Characteristics of yoga users: results of a national survey.

BACKGROUND: There are limited data on the characteristics of yoga users in the U.S. OBJECTIVE: To characterize yoga users, medical reasons for use, perceptions of helpfulness, and disclosure of use to medical professionals. METHODS: Utilizing cross-sectional survey data from the 2002 National Health Interview Survey (NHIS) Alternative Medicine Supplement (n = 31044), we examined correlates of yoga use for health. The estimated prevalence from 2002 NHIS of yoga for health was 5.1% corresponding to over 10 million adults. RESULTS: In 2002, yoga users were predominately Caucasian (85%) and female (76%) with a mean age of 39.5 years. Compared to non-yoga users, yoga users were more likely female (OR 3.76, 95% CI 3.11-4.33); less likely black than white (OR 0.65, 95% CI 0.53-0.80); tended to be younger; and more likely college educated (OR 2.70, 95% CI 2.37-3.08). Musculoskeletal conditions (OR 1.61, 95% CI 1.42-1.83), mental health conditions (OR 1.43, 95% CI 1.22-1.67), severe sprains in the last 12 months (OR 1.49, 95% CI 1.22-1.81), and asthma (OR 1.27, 95% CI 1.05-1.54) were independently associated with higher yoga use, while hypertension (OR 0.78, 95% CI 0.64-0.95) and chronic obstructive lung disease (OR 0.69, 95% CI 0.48-1.00) were associated with lower use. Yoga was most commonly used to treat musculoskeletal or mental health conditions, and most users reported yoga to be helpful for these conditions. A majority of yoga users (61%) felt yoga was important in maintaining health, though only 25% disclosed yoga practice to their medical professional. CONCLUSIONS: We found that yoga users are more likely to be white, female, young and college educated. Yoga users report benefit for musculoskeletal conditions and mental health, indicating that further research on the efficacy of yoga for the treatment and/or prevention of these conditions is warranted.

Patient expectations as predictors of outcome in patients with acute low back pain.

BACKGROUND: Few studies have evaluated the association between patient expectations for recovery and clinical outcomes, and no study has evaluated whether asking patients to choose their therapy modifies such an association. OBJECTIVE: To evaluate the association between patients' expectations and functional recovery in patients with acute low back pain (LBP), and to determine whether that association is affected by giving patients choice of therapy. DESIGN AND PARTICIPANTS: A secondary analysis of a randomized controlled trial comparing usual care alone to usual care plus choice of chiropractic, acupuncture, or massage in 444 adults with acute LBP, lasting less than 21 days. MEASUREMENTS AND MAIN RESULTS: Primary outcome was functional disability (Roland score) at 5 and 12 weeks. Patients' general expectations for improvement were associated with improvement in functional status (beta = 0.96, 95% CI = 0.56, 1.36). A 1-point increase in general expectations was associated with a 0.96-point improvement in Roland score. The association of expectation with outcome was 2-3 times greater in the usual care group than the choice group. However, these differences did not reach statistical significance. CONCLUSIONS: In patients with acute LBP, higher expectations for recovery are associated with greater functional improvement. Eliciting patient expectations for improvement may be a simple way to identify patients with the highest (or lowest) likelihood of experiencing functional improvement. Incorporating questions about patient expectations in future trials may clarify the role of this important correlate of clinical outcomes.

Acupuncture for treatment of persistent arm pain due to repetitive use: a randomized controlled clinical trial.

OBJECTIVE: To compare true and sham acupuncture in their abilities to relieve arm pain and improve arm function in individuals with arm pain due to repetitive use. METHODS: Participants with persistent arm pain (N=123) were randomly assigned to true or sham acupuncture groups and received 8 treatments over 4 weeks. The primary outcome was intensity of pain (10-point scale) and secondary outcomes were arm symptoms, arm function, and grip strength. Outcomes were measured during treatment (at 2 and 4 wk) and 1 month after treatment ended. RESULTS: Arm pain scores improved in both groups during the treatment period, but improvements were significantly greater in the sham group than in the true acupuncture group. This difference disappeared by 1 month after treatment ended. The true acupuncture group experienced more side effects, predominantly mild pain at time of treatments. DISCUSSION: Sham acupuncture reduced arm pain more than true acupuncture during treatment, but the difference did not persist after 1 month. Mild side effects from true acupuncture may have blunted any positive treatment effects. Overall, this study did not find evidence to support the effectiveness of true acupuncture in treatment of persistent arm pain due to repetitive use.

Primary care for low-income populations: comparing health care delivery systems.

Amidst recent policy discussions about the health care safety net there has been relatively little information about whether the actual site of care affects care quality. We therefore used National Health Interview Survey data to describe low-income adults seeking primary care at different types of sites and the quality of access and preventive care at these sites. After adjusting for sociodemographic characteristics and illness burden, hospital-outpatient- department patients were more likely to receive vaccinations for influenza (adjusted odds ratio [AOR] 1.3, 95% confidence interval [CI] 1.0-1.6) and pneumococcus (AOR 1.4, 95% CI 1.1-1.8) than were those at clinics or health centers. Hospital-clinic patients were more likely to report delays in care due to office administrative difficulties (AOR 1.3, 95% CI 1.1-1.7) and more likely to have more than one emergency room visit (AOR 1.9, 95% CI 1.5-2.3). Physicians' office or HMO patients were less likely to report administrative delays in care than those at clinics or health centers, but there were no other differences in quality between these two site types. Policymakers and health care services analysts and providers must monitor quality as they decide how best to deliver care to vulnerable populations.

Cytokine release following recruitment maneuvers.

BACKGROUND: There are reports of rigors and/or clinical deterioration following recruitment maneuvers (RMs), leading us to question whether the use of sustained high-pressure inflation could lead to release of inflammatory mediators. METHODS: Prospective cohort study of 26 patients with ARDS receiving mechanical ventilation. A single RM was performed during which the mean airway pressure was increased to 40 cm H2O and held constant for a period of 30 s. The concentration of nine cytokines (interleukin [IL]-1, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-alpha, Fas ligand, vascular endothelial growth factor, TNF receptor 1, TNF receptor 2) was measured longitudinally at three time points: prior to initiation of the RM, 5 min after the RM, and 60 min after the RM. RESULTS: RMs were tolerated well from a hemodynamic perspective. Oxygenation improved as reflected by an increased Pao2/fraction of inspired oxygen (Fio2) ratio from 140+/-49 at baseline to 190+/-78 (mean+/-SD) at 5 min after the RM (p=0.01). At 60 min, the increase in Pao2/Fio2 ratio, to 172+/-76, was no longer significant (p=0.1). There were no important changes in the levels of any of the measured cytokines at 5 min or 60 min following RM as compared with the baseline levels. CONCLUSIONS: The results of our study demonstrate that recruitment maneuvers are well tolerated in patients with ARDS. Our data suggest no major hemodynamic or immunologic evidence of deterioration within the first hour of RM. In particular, cytokines, previously related to worsening lung injury and distal organ failure in patients with ARDS, are not elevated by use of an RM. Registered at: www.clinicaltrials.gov as NCT00127491.

Factors associated with dietary supplement use among prescription medication users.

BACKGROUND: We examined the patterns of nonvitamin dietary supplement (NVDS) use among adult prescription medication users in the United States. METHODS: Using the 2002 National Health Interview Survey, we analyzed factors associated with NVDS use and prescription medication use in the prior 12 months with descriptive, chi(2), and logistic regression analysis. RESULTS: In the United States, 21% of adult prescription medication users reported using NVDSs in the prior 12 months. Of the respondents who used both prescription medications and NVDSs in the prior 12 months, 69% did not discuss this use with a conventional medical practitioner. Among adults who used prescription medications in the prior 12 months, the most commonly used supplements included echinacea, ginseng, ginkgo, garlic, and glucosamine chondroitin. Prescription medication users with menopause and chronic gastrointestinal disorders had the highest rates of NVDS use (33% and 28%, respectively), and prescription medication users with coronary heart disease and history of myocardial infarction had the lowest rates of use (12% each). In the adjusted analysis, factors associated with increased use of NVDSs by prescription medication users included being female, being Hispanic, having more years of education, living in the West, lacking medical insurance, and having chronic conditions. Elderly respondents were less likely to use NVDSs. CONCLUSION: One in 4 prescription medication users took an NVDS in the prior 12 months, yet the majority did not share this with a conventional medical professional.

The association of language with prevalence of undiagnosed hypertension among older Mexican Americans.

OBJECTIVE: Language barriers have been shown to negatively impact health care for immigrants. We evaluated the association between language use and the diagnosis of hypertension among elderly Mexican Americans. STUDY POPULATION: We studied subjects from the Hispanic Established Populations for Epidemiologic Studies of the Elderly, a cohort of 3050 Mexican American subjects age > or =65. PREDICTORS: Measures of language included Spanish and/or English language read/spoken, language used in social situations, and language of mass media use. OUTCOME MEASURE: Undiagnosed hypertension on physical exam was defined as systolic blood pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg in persons who did not report previous hypertension diagnosis or were not current users of anti-hypertensive medications. RESULTS: The age- and sex-adjusted prevalence of diagnosed hypertension and undiagnosed hypertension were 50.5% and 19.3%, respectively. Among 1347 older adults without previous diagnosis of hypertension that were included in the primary analysis, the mean age was 72 years and 43% were immigrants. After adjusting for age, gender, and education, Spanish use more often than English use in mass media was significantly associated with undiagnosed hypertension (adjusted OR 2.2 [1.3-3.6]). Other measures of acculturation were not independently associated with undiagnosed hypertension. In analyses restricted to persons with hypertension, similar language factors distinguished those who had been diagnosed from those whose hypertension was undiagnosed. CONCLUSIONS: Mexican American elders who reported using Spanish more often than English use in mass media were more likely to have undiagnosed hypertension compared to those using English language in mass media. Further studies are needed to elucidate the role of mass media language in hypertension awareness and management among Hispanic elders.

Factors associated with herbal therapy use by adults in the United States.

OBJECTIVE: To examine the patterns of herbal therapy use among adults in the United States and to describe factors associated with herb use. DESIGN: We examined the use of natural herbs from the 2002 National Health Interview Survey (NHIS). We analyzed factors associated with herb use and reasons for herb use with logistic regression. RESULTS: Factors associated with herb use include the following: age (45-64 years old), being uninsured, being female, having a higher education, living in the West, using prescription medications or over-the-counter (OTC) medications, and self-identified as "non-Hispanic other." Factors associated with no herb use include being non-Hispanic black and living in the South or Midwest. Seventy-two percent of those who used herbs used prescription medications, and 84% of those who used herbs also used an OTC medication in the prior 12 months. Among adults who used herbs, the most commonly mentioned were echinacea (41%), ginseng (25%), gingko (22%), and garlic (20%). The most frequent conditions for herb use were head or chest cold (30%), musculoskeletal conditions (16%), and stomach or intestinal illness (11%). Among those who used herbs in the prior year, factors associated with using herbs because conventional medical treatments were too expensive included being uninsured, having poor health, and being 25-44 years old. CONCLUSIONS: Nearly 1 in 5 people in the US population report using an herb for treatment of health conditions and/or health promotion. More than half did not disclose this information to a conventional medical professional.

Factors associated with herb and dietary supplement use by young adults in the United States.

BACKGROUND: Little is known about the association between use of herbs and dietary supplements (HDS) and lifestyle/behavior factors in young adults in the US. METHODS: Analyzing the 2002 National Health Interview Survey (NHIS), we examined the patterns of HDS (excluding vitamins/minerals) use among young adults in the United States using descriptive statistics and logistic regression. RESULTS: In our sample of 18 to 30 year olds (n = 6666), 26% were current smokers, 24% were moderate/heavy drinkers, 43% had high physical activity, and 54% and 76% use prescription and over the counter (OTC) medications respectively. Non-vitamin, non-mineral HDS was used by 17% of the overall sample in the last 12 months. In the multivariable analysis, the lifestyle and behavioral factors associated with HDS use include: current smoking (odds ratio 1.41 95% CI [1.16-1.72]); being a former smoker (1.50 [1.15-1.95]); moderate/heavy alcohol use (2.02 [1.53-2.65]); high physical activity levels (2.45 [1.98-3.03]); and prescription medication use (1.51 [1.26-1.81]). Among HDS users, only 24% discussed their use with a health care professional. CONCLUSION: Nearly one in five young adults report using non-vitamin/non-mineral HDS.

Investigating placebo effects in irritable bowel syndrome: a novel research design.

Little is known about placebo effects with scientific precision. Poor methodology has confounded our understanding of the magnitude and even the existence of the placebo effect. Investigating placebo effects presents special research challenges including: the design of appropriate controls for studying placebo effects including separating such effects from natural history and regression to the mean, the need for large sample sizes to capture expected small effects, and the need to understand such potential effects from a patient's perspective. This article summarizes the methodology of an ongoing NIH-funded randomized controlled trial aimed at investigating whether the placebo effect in irritable bowel syndrome (IBS) exists and whether the magnitude of such an effect can be manipulated to vary in a manner analogous to "dose dependence." The trial also uses an innovative combination of quantitative and qualitative methods.

Decision-making and outcomes in severe symptomatic aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Aortic stenosis (AS) remains the most common valvular disease of the elderly in the United States. Though valve replacement has proven effective among older adults, decision-making regarding surgery is difficult for these patients and their physicians. Herein, the clinical outcomes and decision-making process for elderly patients with severe symptomatic AS was assessed. METHODS: A retrospective cohort study of patients aged > or = 60 years with severe AS was conducted at two large urban teaching hospitals. Severe AS was defined by a mean valve gradient > or = 50 mmHg or valve area < 0.8 cm2 by echocardiogram, and associated symptoms (angina, congestive heart failure, dyspnea, fatigue, or exercise intolerance). Demographic and clinical data and information about decision-making were obtained from inpatient and outpatient medical records. RESULTS: Of the 124 patients studied, 49 (39.5%) had aortic valve replacement (AVR) surgery. In a logistic regression analysis adjusting for gender, comorbidity and baseline functional status, those patients aged < 80 years were significantly more likely to have surgery than older patients. Surgery was associated with a large reduction in mortality in all age groups. At one-year follow up, 87.8% of all patients (87.5% of those aged > or = 80 years) who had undergone surgery were alive, while only 54.7% (49.1% of those aged > or = 80 years) who did not receive surgery were alive. Postoperative complications were similar among older and younger elderly patients. Comorbidity and age were the most common reasons for not offering elderly patients valve replacement. CONCLUSION: The results of the present study showed that AVR surgery improves the survival of elderly patients with severe AS, and patients aged > 80 years experience benefits similar to younger patients. Nevertheless, these findings suggest that surgery may not always be offered to elderly patients who might benefit from it.

Predicting severe head injury after light motor vehicle crashes: implications for automatic crash notification systems.

Motor vehicle crashes (MVC) are a leading public health problem. Improving notification times and the ability to predict which crashes will involve severe injuries may improve trauma system utilization. This study was undertaken to develop and validate a model to predict severe head injury following MVC using information readily incorporated into an automatic crash notification system. A cross-sectional study with derivation and validation sets was performed. The cohort was drawn from drivers of vehicles involved in MVC obtained from the National Automotive Sampling System (NASS). Independent multivariable predictors of severe head injury were identified. The model was able to stratify drivers according to their risk of severe head injury indicating its validity. The areas under the receiver-operating characteristic (ROC) curves were 0.7928 in the derivation set and 0.7940 in the validation set. We have developed a prediction model for head injury in MVC. As the development of automatic crash notification systems improves, models such as this one will be necessary to permit triage of what would be an overwhelming increase in crash notifications to pre-hospital responders.