Patterns of alcohol consumption in bipolar patients comorbid for alcohol abuse or dependence

OBJECTIVES: Despite a high prevalence rate, patients with bipolar disorder and active alcohol use are routinely excluded from controlled clinical trials leaving clinicians with little evidence-based medicine to guide treatment. This report evaluates preliminary data of alcohol consumption patterns utilizing the Alcohol Timeline Followback (TLFB) method in actively drinking patients with bipolar disorder. METHODS: A sample of 30 patients underwent a Structured Diagnostic Interview for DSM-IV (SCID-IV) as well as completing various measures of alcohol use and associated morbidity. RESULTS: In the month prior to study entry, the TLFB reported 18.4/30+/-9.12 drinking days, 9.9+/-4.73 drinks per drinking day and 169.4+/-101.71 total standard drinks for this study group. There was a significant difference in the number of drinks per drinking day between those diagnosed with rapid cycling than non-rapid cycling bipolar disorder and those with a new diagnosis versus established diagnosis of bipolar disorder. DISCUSSION: This study highlights heavy alcohol use in patients with bipolar disorder and alcohol comorbidity. The TLFB method provides 'real world' quantification of use. Further studies are encouraged to elucidate implications of heavy drinking patterns as found in our rapid cycling and newly diagnosed cohorts.     

Comparison of "B" readers' interpretations of chest radiographs for asbestos related changes

RATIONALE AND OBJECTIVES: The purpose of this study was to determine if chest radiographic interpretations by physicians retained by attorneys representing persons alleging respiratory changes from occupational exposure to asbestos would be confirmed by independent consultant readers. MATERIALS AND METHODS: For 551 chest radiographs read as positive for lung changes by initial "B" readers retained by plaintiffs' attorneys, 492 matching interpretative reports were made available to the authors. Six consultants in chest radiology, also B readers, agreed to re-interpret the radiographs independently without knowledge of their provenance. The film source, patient name, and other identifiers on each film were masked. The International Labor Office 1980 Classification of Chest Radiographs(ILO 80) was used with forms designed by the US National Institute of Occupational Safety and Health to record the consult-ants' findings. The results were compared with initial readings for film quality, complete negativity, parenchymal abnormalities,small opacities profusion, and pleural abnormalities using chi-square tests and kappa statistics.Results. Initial readers interpreted study radiographs as positive for parenchymal abnormalities (ILO small opacity profusion category of 1/0 or higher) in 95.9% of 492 cases. Six consultants classified the films as 1/0 or higher in 4.5% of 2,952 readings. Statistical tests of these and other comparable data from the study showed highly significant differences between the interpretations of the initial readers and the findings of the consultants. CONCLUSION: The magnitude of the differences between the interpretations by initial readers and the six consultants is too great to be attributed to interobserver variability. There is no support in the literature on x-ray studies of workers exposed to asbestos and other mineral dusts for the high level of positive findings recorded by the initial readers in this report.     

Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder

BACKGROUND: Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine. METHOD: A randomized, single-blind, parallel-group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions-Improvement scale (CGI-I), with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response, i.e., remission. RESULTS: At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg. CONCLUSION: Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later.     

Dementia caregiver intervention research: in search of clinical significance

PURPOSE: We reviewed intervention studies that reported dementia caregiver outcomes published since 1996, including psychosocial interventions for caregivers and environmental and pharmacological interventions for care recipients. Our goal was to focus on issues of clinical significance in caregiver intervention research in order to move the field toward a greater emphasis on achieving reliable and clinically meaningful outcomes. DESIGN AND METHODS: MEDLINE, PsycINFO, and Cumulative Index to Nursing & Allied Health databases from 1996 through 2001 were searched to identify articles and book chapters mapping to two medical subject headings: caregivers and either dementia or Alzheimer's disease. Articles were evaluated on two dimensions, outcomes in four domains thought to be important to the individual or society and the magnitude of reported effects for these outcomes in order to determine if they were large enough to be clinically meaningful. RESULTS: Although many studies have reported small to moderate statistically significant effects on a broad range of outcomes, only a small proportion of these studies achieved clinically meaningful outcomes. Nevertheless, caregiving intervention studies have increasingly shown promise of affecting important public health outcomes in areas such as service utilization, including delayed institutionalization; psychiatric symptomatology, including the successful treatment of major and minor depression; and providing services that are highly valued by caregivers. IMPLICATIONS: Assessment of clinical significance in addition to statistical significance is needed in this research area. Specific recommendations on design, measurement, and conceptual issues are made to enhance the clinical significance of future research.     

Lithium and the kidney: an updated review.

Despite the availability of alternative agents, lithium continues to be the standard against which all mood stabilisers, prescribed for acute and maintenance treatment of bipolar (and, to a lesser extent, unipolar) mood disorders, are compared. As a medication often used on a maintenance basis for a lifelong disorder, the potential for lithium to cause long term organ toxicity has generated appropriate concern. Foremost among these concerns are its renal effects. Lithium adversely affects renal tubular function, causing polyuria secondary to a deficit in urine concentrating ability. This effect is probably progressive for the first decade of lithium therapy, i.e. it correlates with duration of lithium therapy. Although this effect of lithium is probably functional and reversible early in treatment, it may become structural and irreversible over time. In contrast, the effect of lithium on glomerular function is not progressive. Conclusions in this area are hampered by the evidence that patients with psychiatric disorders who are not receiving lithium also show defects in certain aspects of renal function. Despite the generally sanguine data on glomerular function, a very small group of patients may develop renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, for the vast majority of patients, the renal effects of lithium are benign. Current strategies for minimising the renal effects of lithium include: (i) assiduously avoiding episodes of renal toxicity; (ii) monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentration; (iii) monitoring serum creatinine levels on a yearly basis, getting further medical evaluation when the serum creatinine level consistently rises above 140 mmol/L (1.6 mg/dl); and (iv) possibly administering lithium once a day.     

Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.     

Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading

Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (FALS). We tested this hypothesis by ablating the gene encoding the copper chaperone for SOD1 (CCS) in a series of FALS-linked SOD1 mutant mice. Metabolic 64Cu labeling in SOD1-mutant mice lacking the CCS showed that the incorporation of copper into mutant SOD1 was significantly diminished in the absence of CCS. Motor neurons in CCS-/- mice showed increased rate of death after facial nerve axotomy, a response documented for SOD1-/- mice. Thus, CCS is necessary for the efficient incorporation of copper into SOD1 in motor neurons. Although the absence of CCS led to a significant reduction in the amount of copper-loaded mutant SOD1, however, it did not modify the onset and progression of motor neuron disease in SOD1-mutant mice. Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models.