Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Reducing stillbirths: behavioural and nutritional interventions before and during pregnancy. Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age. Preliminary data on an acceptance-based emotion regulation group intervention for deliberate self-harm among women with borderline personality disorder. ABT-578-eluting stents. The promising successor of sirolimus- and paclitaxel-eluting stent concepts? Effects of maternal multiple micronutrient supplementation on fetal growth: a double-blind randomized controlled trial in rural Burkina Faso. Methadone treatment and HIV and hepatitis B and C risk reduction among injectors in the Seattle area. [Therapy of suspected intrauterine fetal retardation]. Randomized trial of brief family interventions for general populations: adolescent substance use outcomes 4 years following baseline. Double-blind, placebo-controlled trial of selegiline transdermal system (STS) for the treatment of cocaine dependence. Omega-3 fatty acids in bipolar disorder: clinical and research considerations.
Alcohol withdrawal syndrome (AWS) is a serious complication of alcohol dependence and often requires intensive medical treatment. Antiepileptic drugs (AEDs) have been shown to be as efficacious in the treatment of AWS in several controlled trials as benzodiazepines and superior to placebo in relieving alcohol withdrawal symptoms. Oxcarbazepine (OXC), a newer anticonvulsive drug, has a favorable safety profile over carbamazepine (CBZ) and other older AEDs due to its excellent efficacy and better side-effect profile.
                The efficacy and tolerability of OXC versus placebo were investigated in 50 inpatients during a 6-day treatment of alcohol withdrawal in a 4-site, double-blind, randomized, placebo-controlled pilot study. The amount of rescue medication of clomethiazole (CLO) capsules needed was chosen as the primary variable. The data were collected between May 2003 and September 2004.
                No initial differences were found regarding sociodemographic data and alcohol-related parameters, indicating successful randomization. No differences were found in the need for rescue medication CLO, decrease of withdrawal symptoms, or craving for alcohol between the OXC and the placebo group. Subjectively experienced side effects, normalization of vegetative parameters, craving, or improvement of psychopathological parameters were not different between the groups.
                Despite the negative finding, which may be attributable to the design of the study, OXC still poses an interesting alternative to CBZ and other drugs because other studies have found it not only as efficient but also as having no addictive potential, while additionally possessing an anti-craving effect. Therefore, well-designed investigations with larger cohorts are required to further elucidate this issue. The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase women's risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.
                This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.
                From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.
                Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care - particularly including diagnosis and management of high-risk pregnancies - that pregnant women receive. It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture.
                The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants.
                We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly.
                Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables.
                The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture. Borderline personality disorder (BPD) and deliberate self-harm are clinically important conditions for which additional economically and clinically feasible interventions are needed. Literature on both the emotion regulating and experientially avoidant function of self-harm and the role of emotional dysfunction in BPD provided the rationale for developing a group intervention targeting emotion dysregulation among self-harming women with BPD. This study provides preliminary data on the efficacy of this new, 14-week, emotion regulation group intervention, designed to teach self-harming women with BPD more adaptive ways of responding to their emotions so as to reduce the frequency of their self-harm behavior. Participants were matched on level of emotion dysregulation and lifetime frequency of self-harm and randomly assigned to receive this group in addition to their current outpatient therapy (N = 12), or to continue with their current outpatient therapy alone for 14 weeks (N = 10). Results indicate that the group intervention had positive effects on self-harm, emotion dysregulation, experiential avoidance, and BPD-specific symptoms, as well as symptoms of depression, anxiety, and stress. Participants in the group treatment condition evidenced significant changes over time on all measures, and reached normative levels of functioning on most. While these preliminary results are promising, the study's limitations require their replication in a larger-scale randomized controlled trial. ABT-578 is a new synthetic analog of rapamycin, designed to inhibit smooth muscle cell proliferation-a key contributor to restenosis-by blocking the function of the mTOR cell cycle regulatory protein. Given these pharmacodynamics, ABT-578 was considered beneficial for intracoronary delivery to arrest the process responsible for neointimal hyperplasia after angioplasty and stenting. Consequently, the ABT-578-eluting ENDEAVOR stent system has been created, representing a potential new alternative for treating patients with coronary heart disease. In order to evaluate safety, feasibility and efficacy of this stent design, the ENDEAVOR clinical program has been started, including three randomized clinical trials. ENDEAVOR I is the first-in-man trial including 100 patients with native de novo coronary lesions. The 4-month follow-up data, recently presented, demonstrated safety and feasibility of this new drug-eluting stent (DES) concept with a 4-month MACE (major adverse cardiac events) rate of 2.0%. In order to evaluate this stent system in a larger patient population as well as more complex lesion subsets, the multicenter study ENDEAVOR II has been started including a total of 1,200 patients. The enrollment of this study was completed in January 2004. The aim of the US multicenter study ENDEAVOR III is a head-to-head comparison of the ENDEAVOR ABT-578-eluting stent system with the already approved sirolimus-eluting Cypher stent in 369 patients. If the results of both pivotal studies ENDEAVOR II and III confirm the efficacy of the ENDEAVOR stent design observed so far, the ENDEAVOR stent will be established as a new and promising contender in the field of DES. Intrauterine growth retardation is a major predictor of child health in developing countries.
                We tested whether providing pregnant women with the UNICEF/WHO/UNU international multiple micronutrient preparation (UNIMMAP), rather than iron and folic acid alone, improved fetal growth and its correlates.
                An intention-to-treat, double-blind, randomized controlled trial including 1426 pregnancies was carried out in rural Burkina Faso. Tablet intake was directly observed.
                Pregnancy outcome was known in 96.3% of the participants. After adjustment for gestational age at delivery, both birth weight (52 g; 95% CI: 4, 100; P = 0.035) and birth length (3.6 mm; 95% CI: 0.8, 6.3; P = 0.012) were significantly higher in the UNIMMAP group. UNIMMAP had a differential effect by percentiles of birth weight and length distributions: the risk of large-for-gestational-age infants was higher in the UNIMMAP group (OR: 1.58; 95% CI: 1.04, 2.38; P = 0.03), although the risk of low birth weight remained unchanged. The effect of UNIMMAP on birth size was modified by maternal body mass index at enrollment and could be more important in multiparous women and women taking sulfadoxine-pyrimethamine. Unexpectedly, the risk of perinatal death was marginally significantly increased in the UNIMMAP group (OR: 1.78; 95% CI: 0.95, 3.32; P = 0.07), and this seemed to affect mainly primiparous women (OR: 3.44; 95% CI: 1.1, 10.7; P for interaction = 0.11).
                Maternal UNIMMAP modestly but significantly increased fetal growth. The resulting benefit on infant growth and survival needs to be assessed. The possible lack of benefit and potential harm in primiparous women should be further investigated. This trial was registered at clinicaltrials.gov as NCT00642408. Drug treatment has the potential to reduce incidence of blood-borne infections by helping injection drug users (IDUs) achieve abstinence or by decreasing the frequency of injection and sharing practices. We studied the associations between retention in methadone treatment and drug use behaviors and incidence of hepatitis B and C in a cohort of IDUs in the Seattle, Washington, area. Data on IDUs entering methadone treatment at four centers in King County, Washington, were collected through face-to-face interviews using a standardized questionnaire at baseline and 12-month follow-up between October 1994 and January 1998. Blood specimens were obtained and tested for human immunodeficiency virus (HIV) and hepatitis B and C. Drug treatment status at follow-up was analyzed in relation to study enrollment characteristics and potential treatment outcomes, including injection risk behaviors, cessation or reduced frequency of injection, and incidence of hepatitis B and C. Of 716 IDUs, 292 (41%) left treatment, 198 (28%) disrupted (left and returned) treatment, and 226 (32%) continued treatment throughout the 1-year follow-up period. Compared to those who left treatment, subjects who disrupted or continued were less likely to inject at follow-up (odds ratio [OR] = 0.5, 95% CI 0.3-0.7; and OR = 0.1, 95% CI 0.1-0.2, respectively). Among the 468 (65%) subjects who continued injecting, those who continued treatment injected less frequently, were less likely to pool money to buy drugs (OR = 0.5, 95% CI 0.3-0.8) and inject with used needles (OR = 0.5, 95% CI 0.2-0.8) compared to those who left treatment. Cooker or cotton sharing was not associated with retention in treatment, but hepatitis B incidence was lowest among those who continued treatment. The results of this study suggest drug use risk reduction is more likely to be achieved by those who remain in drug treatment and by those who stop injecting, but that those who drop out and return and those who continue to inject while in treatment may also benefit. This supports the role of consistent drug treatment in an overall harm-reduction strategy. In a randomized prospective study, performed on 45 pregnancies with clinical and sonographic suspicion for intrauterine fetal growth retardation, examinations were done to evaluate the therapeutic effect of bed rest and of additional daily administered glucose infusions or oral galactose applications respectively on the fetal growth, the hemodynamic, respiratory and endocrine insufficiency of the materno-feto-placental unit as well as selected biochemical parameters of the umbilical blood. There is no positive therapeutic effect, either on the impaired endocrine partial function nor on the reduced respiratory function of the feto-placental unit. It is obvious, that despite the improvement of the nutritional supply of the fetus and the revival of the regular fetal growth, the previous lack of fetal growth can not be altered. This can be demonstrated in all three therapeutic groups due to the fact of a resulting high hypotrophy-rate of the newborns. The results prove that the additional supply of the fetus with glucose or galactose does not remarkably improve the therapeutic effectivity as opposed by strict bed rest alone. This study examined the long-term substance use outcomes of 2 brief interventions designed for general population families of young adolescents. Thirty-three public schools were randomly assigned to 3 conditions: the 5-session Preparing for the Drug Free Years Program, the 7-session Iowa Strengthening Families Program, and a minimal contact control condition. The pretest involved 667 6th graders and their families. Assessments included multiple measures of initiation and current use of alcohol, tobacco, and marijuana. Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade. Significant intervention-control differences in initiation and current use were found for both interventions. It is concluded that brief family skills-training interventions designed for general populations have the potential to reduce adolescent substance use and thus have important public health implications. Cocaine dependence is a major public health problem for which there is no FDA-approved pharmacological treatment. Selegiline is an irreversible selective inhibitor of monoamine oxidase type B (MAO-B) which may affect cocaine addiction through several potential mechanisms. In this study, selegiline transdermal system (STS) was compared to placebo as a treatment for cocaine dependence. This multi-site, double-blind trial of 300 subjects with cocaine dependence assessed the efficacy of selegiline using subject self-reported cocaine use substantiated by urine benzoylecgonine (BE) as the primary outcome measure. Analysis of the data did not show a significant effect for selegiline over placebo. This study does not support a role for selegiline in treating cocaine dependence. The contrast of this result to earlier, promising preclinical and human pilot data could be due to factors associated with sample size, patient characteristics, dose, or poor predictive validity of preclinical models. Several lines of evidence suggest that omega-3 fatty acids may be important in the pathophysiology, treatment or prevention of bipolar disorder (BD). Electronic and manual searches were conducted in order to review the literature relevant to the etiology and treatment of BDs with omega-3 fatty acids. We also present data from a randomized, double-blind, placebo-controlled pilot study conducted at three sites (N = 10) comparing an omega-3 fatty acid (docosahexaenoic acid, DHA) versus placebo, added to psychosocial treatment for women with BD who chose to discontinue standard pharmacologic treatment while attempting to conceive. While some epidemiologic and preclinical data support the role of omega-3 fatty acids in BD, clinical trials to date have yielded conflicting results. In our pilot study of 10 Caucasian women taking DHA while attempting to conceive (BP1 = 9, BPII = 1), age 27-42 years, DHA was well tolerated and suggests that a larger study would be feasible. The elucidation of the potential role of omega-3 fatty acids as a treatment for BD requires further study. The current data are not sufficient to support a recommendation of monotherapy treatment as a substitute for standard pharmacologic treatments. However, judicious monotherapy in selected clinical situations, or adjunctive use, may be warranted pending further data from adequately powered controlled clinical trials. Our pilot trial of DHA in women who plan to stop conventional psychotropics in order to conceive suggests that such trials are feasible.
Larger, well-designed studies are needed to evaluate the effects of betamimetics on fetal growth. Since there is potential for adverse effects due to the pharmacological characteristics of this group of drugs, data related to any potential harms should be collected in addition to beneficial effects.