Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

Ethics and methods in surgical trials.

This paper focuses on invasive therapeutic procedures, defined as procedures requiring the introduction of hands, instruments, or devices into the body via incisions or punctures of the skin or mucous membranes performed with the intent of changing the natural history of a human disease or condition for the better. Ethical and methodological concerns have been expressed about studies designed to evaluate the effects of invasive therapeutic procedures. Can such studies meet the same standards demanded of those, for example, evaluating pharmaceutical agents? This paper describes a research project aimed at examining the interplay and sometimes apparent conflict between ethical standards for human research and standards for methodological rigor in trials of invasive procedures. The paper discusses how the authors plan to develop a set of consensus standards that, if met, would result in substantial and much-needed improvements in the methodological and ethical quality of such trials.

Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration.

OBJECTIVE: To examine (1) the prevalence of depressive disorders in community-dwelling adults with advanced age-related macular degeneration (AMD) and (2) the relationship in this population between depression, visual acuity, the number of comorbid medical conditions, disability caused by vision loss as measured by the National Eye Institute-Vision Function Questionnaire (NEI-VFQ) and the vision-specific Sickness Impact Profile (SIPV), and disability caused by overall health status as measured by the Sickness Impact Profile-68 (SIP). DESIGN: Analysis of cross-sectional baseline data from a randomized clinical trial. PARTICIPANTS: Participants were 151 adults aged 60 and older (mean age, 80 years) with advanced macular degeneration whose vision was 20/60 or worse in their better eye. METHODS: Subjects were interviewed using measures of depression, disability, and chronic medical conditions. Visual acuity was obtained. Nonparametric correlation analyses and linear regression analyses were performed. MAIN OUTCOME MEASURES: Structured Clinical Interview for DSM-IV (SCID-IV), Geriatric Depression Scale (GDS), NEI-VFQ, SIPV, and SIP. RESULTS: Of the participants, 32.5% (n = 49) met SCID-IV criteria for depressive disorder, twice the rate observed in previous studies of community-dwelling elderly. Over and above depression (GDS), visual acuity aided in prediction of the level of vision-specific disability (NEI-VFQ and SIPV). CONCLUSIONS: Depressive disorder is a significant problem for the elderly afflicted with advanced macular degeneration. Further research on psychopharmacologic and psychotherapeutic interventions for depressed AMD patients is warranted to improve depression and enhance functioning. Over and above depression, visual acuity aided in predicting vision-specific disability. Treatment strategies that teach patients to cope with vision loss should be developed and evaluated.

A psychometric analysis of the measurement level of the rating scale, time trade-off, and standard gamble.

A fundamental assumption of utility-based analyses is that patient utilities for health states can be measured on an equal-interval scale. This assumption, however, has not been widely examined. The objective of this study was to assess whether the rating scale (RS), standard gamble (SG), and time trade-off (TTO) utility elicitation methods function as equal-interval level scales. We wrote descriptions of eight prostate-cancer-related health states. In interviews with patients who had newly diagnosed, advanced prostate cancer, utilities for the health states were elicited using the RS, SG, and TTO methods. At the time of the study, 77 initial and 73 follow-up interviews had. been conducted with a consecutive sample of 77 participants. Using a Rasch model, the boundaries (Thurstone Thresholds) between four equal score sub-ranges of the raw utilities were mapped onto an equal-interval logit scale. The distance between adjacent thresholds in logit units was calculated to determine whether the raw utilities were equal-interval. None of the utility scales functioned as interval-level scales in our sample. Therefore, since interval-level estimates are assumed in utility-based analyses, doubt is raised regarding the validity of findings from previous analyses based on these scales. Our findings need to be replicated in other contexts, and the practical impact of non-interval measurement on utility-based analyses should be explored. If cost-effectiveness analyses are not found to be robust to violations of the assumption that utilities are interval, serious doubt will be cast upon findings from utility-based analyses and upon the wisdom of expending millions in research dollars on utility-based studies.

Ethical dilemmas in hyperbaric medicine.

Although hyperbaric oxygen therapy (HBO2T) is the primary or adjunctive treatment for a limited number of clinical conditions, off-label use is increasing as a result of public demand. Because of unusual research problems and limited regulatory mechanisms to ensure patient safety, physicians question whether it is ethical to provide HBO2T for an unproven indication. An ethical approach to the off-label use of HBO2T is proposed. This approach requires combining a physician's clinical judgment with guidelines written by recognized organizations in hyperbaric medicine and patient informed consent. Scientific guidelines can identify which off-label uses of HBO2T are not therapeutic, which are potentially therapeutic, and to what degree. Registries or a central repository for the systematic collection of data can promote research. Ethical guidelines should require patient informed consent for approved indications, for potentially therapeutic off-label indications, and for registry or research participation. The creation of a consortium of hyperbaric clinics may improve the validity of information disseminated to the general public and promote the ethical practice of HBO2T.

Effects of storage and viral load on hepatitis C viral genotyping.

Hepatitis C virus (HCV) genotyping is important for determining the treatment protocol for hepatitis C patients. Since amplified material from the Roche HCV Monitor kit is compatible with the Innogenetics INNO-LiPA HCV II kit (line probe assay), amplicons from the Monitor assay can be used to identify the HCV genotype. The Monitor package insert recommends using amplicons within a 7-day period (at 4 degrees C) following amplification. It was hypothesized that storage of amplicons for 4 weeks and longer (at -20 degrees C) would not affect the sensitivity of the genotyping assay. After denaturation, amplicons from two genotypes were stored for 7-386 days prior to performing the genotyping assay. Storage of amplicons did not hamper the ability to identify the genotype. Additionally, the sensitivity of the assay was evaluated by analyzing five genotypes with low viral loads. HCV genotypes were detected most consistently at viral levels of 10,000 copies/mL. In conclusion, the Innogenetics genotyping assay can use stored amplicons, thus reducing the cost of the assay by avoiding additional PCR reactions. Determining the sensitivity of this assay facilitates the efficient use of this test by incorporating a sensitivity cutoff of >or=10,000 copies/mL.

A national survey of policies on disclosure of conflicts of interest in biomedical research.

BACKGROUND: Conflicts of interest pose a threat to the integrity of scientific research. The current regulations of the U.S. Public Health Service and the National Science Foundation require that medical schools and other research institutions report the existence of conflicts of interest to the funding agency but allow the institutions to manage conflicts internally. The regulations do not specify how to do so. METHODS: We surveyed all medical schools (127) and other research institutions (170) that received more than $5 million in total grants annually from the National Institutes of Health or the National Science Foundation; 48 journals in basic science and clinical medicine; and 17 federal agencies in order to analyze their policies on conflicts of interest. RESULTS: Of the 297 institutions, 250 (84 percent) responded by March 2000, as did 47 of the 48 journals and 16 of the 17 federal agencies. Fifteen of the 250 institutions (6 percent)--5 medical schools and 10 other research institutions--reported that they had no policy on conflicts of interest. Among the institutions that had policies, there was marked variation in the definition and management of conflicts. Ninety-one percent had policies that adhered to the federal threshold for disclosure ($10,000 in annual income or equity in a relevant company or 5 percent ownership), and 9 percent had policies that exceeded the federal guidelines. Only 8 percent had policies requiring disclosure to funding agencies, only 7 percent had such policies regarding journals, and only 1 percent had policies requiring the disclosure of information to the relevant institutional review boards or to research subjects. Twenty journals (43 percent) reported that they had policies requiring disclosure of conflicts of interest. Only four federal agencies had policies that explicitly addressed conflicts of interest in extramural research, and all but one of the agencies relied primarily on institutional discretion. CONCLUSIONS: There is substantial variation among policies on conflicts of interest at medical schools and other research institutions. This variation, combined with the fact that many scientific journals and funding agencies do not require disclosure of conflicts of interest, suggests that the current standards may not be adequate to maintain a high level of scientific integrity.

A trial for comparing methods for eliciting treatment preferences from men with advanced prostate cancer: results from the initial visit.

OBJECTIVE: The objective of this study was to evaluate the convergent validity of 3 types of utility measures: standard gamble, time tradeoff, and rating scale. RESEARCH DESIGN: A prospective cohort of 120 men with advanced prostate cancer were first asked to rank order 8 health states, and then utility values were obtained from each participant for each of the 8 health states through 2 of the 3 techniques evaluated (standard gamble, time tradeoff and rating scale). Participants were randomly assigned to 1 of 3 possible pairs of techniques. The validity of the 3 methods, as measured by the convergence and raw score differences of the techniques, was assessed with ANOVA. The ability of the techniques to differentiate health states was determined. The inconsistencies between rankings and utility values were also measured. Proportions of illogical utility responses were assessed as the percent of times when states with more symptoms were given higher or equal utility values than states with fewer symptoms. RESULTS: There were significant differences in raw scores between techniques, but the values were correlated across health states. Utility values were often inconsistent with the rank order of health states. In addition, utility assessment did not differentiate the health states as well as the rank order. Furthermore, utility values were often illogical in that states with more symptoms received equal or higher utility values than states with fewer symptoms. CONCLUSIONS: Use of the utility techniques in cost-effectiveness analysis and decision making has been widely recommended. The results of this study raise serious questions as to the validity and usefulness of the measures.

The prevalence of female genital operations in the Houston metropolitan area.

This study explored the prevalence of female genital operations (FGOs), also known as female circumcision, among women in the Houston metropolitan area. The medical ramifications of the procedure and the specific type of procedure undergone were examined as well as the nationality and religious background of these women and their views regarding their experience. To gather these data, we sent a questionnaire to practicing obstetrician-gynecologists in Harris County. This survey yielded a response rate greater than 36%, of which approximately 30% of physicians reported treating patients with FGOs at some time in their practice. The results of this study demonstrate that a notable proportion of women in Houston, particularly those of African background, have experienced an FGO of some type and, accordingly, our obstetrician-gynecologists and primary care physicians clearly need to be aware of this cultural practice among their patients.

A new objective digital computerized vision screening system.

PURPOSE: Fewer than 40% of children in the crucial younger-than-4 age group are evaluated for visual problems by pediatricians. This is due to impracticality from either a clinical or practice efficiency standpoint. Current photoscreening methods require trained readers and suffer from significant subjectivity and interobserver variability. We report a cross-sectional, double-masked study using new digital imaging with objective, automated, computerized image analysis. METHODS: Two-hundred six children aged 9 months to 16 years were prospectively studied in a University-based pediatric ophthalmology practice. Images were taken by volunteers with a modified digital camera which, when downloaded, were analyzed within 35 seconds by new image analysis software. The analysis was compared to a masked review of a complete pediatric ophthalmic exam. RESULTS: Overall agreement between physician and the objective computerized analysis was 86.9%. Positive predictive value was 91%, sensitivity was 89%, and specificity was 83%. CONCLUSIONS: This automated digital imaging screening system eliminates human bias and provides accurate and immediate results. The system requires no special expertise.

Managing disagreements in the management of short bowel and hypoplastic left heart syndrome.

BACKGROUND AND OBJECTIVES: When innovative, not yet fully proven therapies are introduced, physicians may have neither experience nor sufficient data in the medical literature to assist in their decision to discuss them with and/or recommend them to patients. Little is known about how physicians deal with this uncertainty. Moreover, when multiple physicians caring for a single patient have reached different conclusions regarding this new therapy, the potential for disagreement exists that could give rise to ethical issues as well as cause confusion to the patient. To explore these topics, we investigated the attitudes of specialists to therapies for two life-threatening diseases: hypoplastic left heart syndrome (HLHS) and short bowel syndrome. METHODS: A forced choice questionnaire was distributed to the heads of neonatology, pediatric cardiology, and pediatric gastroenterology training programs asking about their outcome impressions and treatment recommendations and about the local availability of treatments. In addition, responses from specialists from the same institution were linked in a confidential manner to evaluate the frequency of disagreement within the same institution. Responses were analyzed using chi(2) and Wilcoxon matched pair analysis as appropriate. RESULTS: The overall rate of response was 79%. In institutions that had both neonatology and pediatric gastroenterology training programs, there was a 59% response rate compared with a 73% response rate from institutions that had both neonatology and cardiology programs. Significant differences were noted among specialists as to who would be involved in discussions of therapeutic options with patients in both HLHS and short bowel syndrome. Differences also were noted in the willingness of specialists to discuss and recommend therapies, in the perceived survival and quality of life by various specialists after transplant and palliative surgery, and in the local availability of various options. The neonatologists and gastroenterologists at the same institution disagreed on responses in 34% of the questions with only 1 of the 25 pairs in full agreement. In contrast, the neonatologists and pediatric cardiologists at the same institution disagreed in only 14% of the questions with 7 of the 28 pairs in full agreement. CONCLUSIONS: Substantial disagreement among specialists about new interventions was found. There seem to be fewer differences among specialists when dealing with the more mature therapy, HLHS. Two major ethical issues arise. First, there seems to be no accepted professional standard to which individuals can appeal when determining whether to discuss or recommend new, not-yet-fully-proven technologies. Second, there is the potential for much patient confusion when counseling physicians recommend different options. Colleagues as individuals and specialists as groups should talk to each other before individual discussions with families to ensure that there is a clear understanding of differing beliefs.

Assessing the performance of utility techniques in the absence of a gold standard.

BACKGROUND: Utility techniques are the most commonly used means to assess patient preferences for health outcomes. However, whether utility techniques produce valid measures of preference has been difficult to determine in the absence of a gold standard. OBJECTIVE: To introduce and demonstrate two methods that can be used to evaluate how well utility techniques measure patients' preferences. SUBJECTS AND DESIGN: Patients treated for advanced prostate cancer (n = 57) first ranked eight health states in order of preference. Four utility techniques were then used to elicit patients' utilities for each health state. MEASURES: The rating scale, standard gamble, time trade-off, and a modified version of willingness-to-pay techniques were used to elicit patients' utilities. Technique performance was assessed by computing a differentiation and inconsistency score for each technique. RESULTS: Differentiation scores indicated the rating scale permitted respondents to assign unique utility values to about 70% of the health states that should have received unique values. When the other techniques were used, about 40% or less of the health states that should have received unique utility scores actually did receive unique utility scores. Inconsistency scores, which indicate how often participants assign utility scores that contradict how they value health states, indicated that the willingness-to-pay technique produced the lowest rate of inconsistency (10%). However, this technique did not differ significantly from the rating scale or standard gamble on this dimension. CONCLUSIONS: Differentiation and inconsistency offer a means to evaluate the performance of utility techniques, thereby allowing investigators to determine the extent to which utilities they have elicited for a given decision problem are valid. In the current investigation, the differentiation and inconsistency methods indicated that all four techniques performed at sub-optimal levels, though the rating scale out-performed the standard gamble, time trade-off, and willingness-to-pay techniques.

Age-related macular degeneration: a randomized clinical trial of a self-management intervention.

The purpose of this study was to conduct a randomized clinical trial to assess whether a self-management group intervention can improve mood, self-efficacy, and activity in people with central vision loss due to age-related macular degeneration (AMD). Ninety-two elderly patients with AMD (average age = 79) from a university ophthalmology clinic were randomly assigned to the self-management intervention (n = 44) or to a wait-list (n = 48). All patients were legally blind in at least one eye. The intervention consisted of 6 weekly 2-hour group sessions providing education about the disease, group discussion, and behavioral and cognitive skills training to address barriers to independence. All participants eventually completed the intervention allowing pre-post comparisons for all patients. The battery of measures included the Profile of Mood States (POMS); Quality of Well-Being Scale; and assessments of self-efficacy, participation in activities, and use of vision aids. Participants' initial psychological distress was high (mean total POMS = 59.72) and similar to distress experienced by other serious chronic illness populations (e.g. cancer, bone marrow transplant). Analysis of covariance testing the primary hypothesis revealed that intervention participants experienced significantly (p = .04) reduced psychological distress (pre mean = 61.45; post mean = 51.14) in comparison with wait-list controls (pre mean = 57.72; post mean = 62.32). Intervention participants also experienced improved (p = .02) self-efficacy (pre mean = 70.16; post mean = 77.27) in comparison with controls (pre mean = 67.71; post mean = 69.07). Further, intervention participants increased their use of vision aids (p < .001; pre mean = 3.37, post mean = 6.69). This study demonstrates that a relatively brief behavioral intervention can substantially reduce psychological distress and increase self-efficacy in elderly adults experiencing vision loss due to macular degeneration. Self-management intervention appears to improve mood, self-efficacy, and use of vision aids, further enhancing the lives of poorly sighted individuals with AMD.

The psychosocial impact of macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD), the leading cause of irreversible blindness and low vision among the elderly, has not been well studied with regard to its impact on daily life. This study was designed to demonstrate the impact of AMD on quality of life, emotional distress, and functional level. PARTICIPANTS: The study sample consisted of 86 elderly adults (average age, 79 years) with AMD who were legally blind in at least 1 eye. Participants completed a battery of measures that included the Quality of Well-being Scale, the Instrumental Activities of Daily Living index, self-rated general health status, and the Profile of Mood States. RESULTS: Persons with AMD experienced significant reductions in key aspects of daily life. Their ratings for quality of life (average Quality of Well-being Scale score=0.581) and emotional distress (average Profile of Mood States total score=65.36) were significantly worse than those for similarly aged community adults and were comparable with those reported by people with chronic illnesses (eg, arthritis, chronic obstructive pulmonary disease, acquired immunodeficiency syndrome, and bone marrow transplants). Patients with AMD were also more likely than a national sample of elderly individuals to need help with daily activities. Visual acuity was related to ability to carry out daily activities (Instrumental Activities of Daily Living, r=0.28, P=.008). Quality of life ratings were significantly related to the ability to carry out daily activities (r=-0.38, P=.001), self-rated general health status (r=-0.21, P=.05), and emotional distress (Profile of Mood States total score, r=-0.25, P=.02). Individuals with a shorter period of perceived vision loss were more likely to report high levels of emotional distress (r=-0.24, P=.03) than those with a longer period of perceived vision loss. Further, those who were blind in 1 eye were even more significantly distressed than those who were blind in both eyes. CONCLUSIONS: Elderly persons with AMD causing legal blindness in 1 or both eyes have significant emotional distress and profoundly reduced quality of life and need help with key daily activities.

Closer to home (or home alone?) The British Columbia long-term care system in transition.

Finding ways to organize and deliver long-term care that provides for quality of life at an affordable price is of increasing importance as the population ages, family size decreases, and women enter the workforce. For the past 2 decades, British Columbia has provided a model system that has apparently avoided disruptive conflicts. Although formal users' complaints are rare, this study--based on focus groups and interviews with users, their families, and advocates--identified problems users encountered toward resolving concerns about the structure, process, and outcome of long-term care. We present these findings in the context of British Columbia's current devolution from provincial to regional control that aims to save costs and keep disabled elderly persons in the community. British Columbia may be continuing to lead the way in meeting the needs of its burgeoning elderly population for long-term care. Study findings have implications for the development of US long-term care policy by pointing to the value of obtaining users' views of long-term care to identify both obvious and more subtle trouble spots.

When are placebo-controlled trials no longer appropriate?

This paper presents a standard for assessing the validity of placebo-controlled trials in circumstances in which such trials might be unjustly denying appropriate therapies to members of the control group. This standard categorizes the types of risks that can or cannot be imposed upon consenting research subjects in such control groups. The paper also shows how needed research can be conducted while respecting the proposed ethical standard. Both the problem and the proposed standard are illustrated by reference to the major trials of the thrombolytic agents.