Is paromomycin an effective and safe treatment against cutaneous leishmaniasis? A meta-analysis of 14 randomized controlled trials.

BACKGROUND: High cost, poor compliance, and systemic toxicity have limited the use of pentavalent antimony compounds (SbV), the treatment of choice for cutaneous leishmaniasis (CL). Paromomycin (PR) has been developed as an alternative to SbV, but existing data are conflicting. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials, without language restriction, through August 2007, to identify randomized controlled trials that compared the efficacy or safety between PR and placebo or SbV. Primary outcome was clinical cure, defined as complete healing, disappearance, or reepithelialization of all lesions. Data were extracted independently by two investigators, and pooled using a random-effects model. Fourteen trials including 1,221 patients were included. In placebo-controlled trials, topical PR appeared to have therapeutic activity against the old world and new world CL, with increased local reactions, when used with methylbenzethonium chloride (MBCL) compared to when used alone (risk ratio [RR] for clinical cure, 2.58 versus 1.01: RR for local reactions, 1.60 versus 1.07). In SbV-controlled trials, the efficacy of topical PR was not significantly different from that of intralesional SbV in the old world CL (RR, 0.70; 95% confidence interval, 0.26-1.89), whereas topical PR was inferior to parenteral SbV in treating the new world CL (0.67; 0.54-0.82). No significant difference in efficacy was found between parenteral PR and parenteral SbV in the new world CL (0.88; 0.56-1.38). Systemic side effects were fewer with topical or parenteral PR than parenteral SbV. CONCLUSIONS/SIGNIFICANCE: Topical PR with MBCL could be a therapeutic alternative to SbV in selected cases of the old world CL. Development of new formulations with better efficacy and tolerability remains to be an area of future research.

Exploring the Association Between Household Food Insecurity, Parental Self-Efficacy, and Fruit and Vegetable Parenting Practices Among Parents of 5- to 8-Year-Old Overweight Children

Background: Food insecurity may negatively impact children’s nutritional status by affecting parenting quality. Because parents have a strong influence on their children’s eating and food choices, examining the effects of food insecurity on parenting may provide important insights into obesity prevention efforts. Objectives: This study explored whether food insecurity was associated with parental self-efficacy and parenting practices related to fruit and vegetable consumption. Methods: Secondary analysis was performed using baseline data from 31 mothers of 5-8 year old overweight or obese children who had participated in a pilot obesity treatment program. Household food security status, fruit and vegetable parental self-efficacy (modeling/socialization, planning/encouraging and availability/accessibility) and fruit and vegetable parenting practices (structure, responsiveness, non-directive control, and external control) were assessed using validated measures. Students' t-test investigated differences in subscales by food security status. Results: There were no significant differences in fruit and vegetable parenting practices and parental self-efficacy between food secure and insecure groups. There was a trend towards a decrease in parental self-efficacy for making fruit and vegetables available in the home among food insecure parents (p=.06). Conclusions: In this small sample no significant associations were found between food insecurity and fruit and vegetable parenting practices and parental self-efficacy. However, the trend observed in this exploratory analysis supports further hypothesis-driven research with a larger sample size able to detect more subtle differences.

Motivation as a predictor of drinking outcomes after residential treatment programs for alcohol dependence

OBJECTIVES: Patients' motivation to change their substance use is usually viewed as a crucial component of successful treatment. The objective of this study was to examine whether motivation contributes to drinking outcomes after residential treatment for alcohol dependence. METHODS: Our sample included 415 Swiss patients from 12 residential alcohol treatment programs. We statistically controlled for important predictors, such as sex, employment, alcohol consumption before admission, severity of alcohol dependence, severity of psychiatric symptoms at admission, and alcohol-related self-efficacy at discharge. Abstinence, alcohol consumption, and time to first drink were used as primary outcome measures and were assessed 1 year after discharge from treatment. RESULTS: Action-oriented motivation to change substance use had a modest impact on drinking outcomes. At the 1-year follow-up, only the Taking Steps subscale of the Stages of Change Readiness and Treatment Eagerness Scale and alcohol-related self-efficacy were found to be significant predictors of abstinence and the number of standard drinks. CONCLUSIONS: The impact of action-oriented motivation at admission to residential treatment is modest but still relevant, compared with other outcome predictors. It may be useful to focus treatment on improving action-oriented motivation to reduce substance use

Efficacy of a dilemma-focused intervention for unipolar depression: study protocol for a multicenter randomized controlled trial

BACKGROUND: Depression is one of the more severe and serious health problems because of its morbidity, disabling effects and for its societal and economic burden. Despite the variety of existing pharmacological and psychological treatments, most of the cases evolve with only partial remission, relapse and recurrence.Cognitive models have contributed significantly to the understanding of unipolar depression and its psychological treatment. However, success is only partial and many authors affirm the need to improve those models and also the treatment programs derived from them. One of the issues that requires further elaboration is the difficulty these patients experience in responding to treatment and in maintaining therapeutic gains across time without relapse or recurrence. Our research group has been working on the notion of cognitive conflict viewed as personal dilemmas according to personal construct theory. We use a novel method for identifying those conflicts using the repertory grid technique (RGT). Preliminary results with depressive patients show that about 90% of them have one or more of those conflicts. This fact might explain the blockage and the difficult progress of these patients, especially the more severe and/or chronic. These results justify the need for specific interventions focused on the resolution of these internal conflicts. This study aims to empirically test the hypothesis that an intervention focused on the dilemma(s) specifically detected for each patient will enhance the efficacy of cognitive behavioral therapy (CBT) for depression. DESIGN: A therapy manual for a dilemma-focused intervention will be tested using a randomized clinical trial by comparing the outcome of two treatment conditions: combined group CBT (eight, 2-hour weekly sessions) plus individual dilemma-focused therapy (eight, 1-hour weekly sessions) and CBT alone (eight, 2-hour group weekly sessions plus eight, 1-hour individual weekly sessions). METHOD: Participants are patients aged over 18 years meeting diagnostic criteria for major depressive disorder or dysthymic disorder, with a score of 19 or above on the Beck depression inventory, second edition (BDI-II) and presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct) as assessed using the RGT. The BDI-II is the primary outcome measure, collected at baseline, at the end of therapy, and at 3- and 12-month follow-up; other secondary measures are also used. DISCUSSION: We expect that adding a dilemma-focused intervention to CBT will increase the efficacy of one of the more prestigious therapies for depression, thus resulting in a significant contribution to the psychological treatment of depression. TRIAL REGISTRATION: ISRCTN92443999; ClinicalTrials.gov Identifier: NCT01542957.

Transcatheter renal denervation for the treatment of resistant arterial hypertension: the Swiss expert consensus

Transcatheter (or percutaneous) renal denervation is a novel technique developed for the treatment of resistant hypertension. So far, only one randomised controlled trial has been published, which has shown a reduction of office blood pressure. The Swiss Society of Hypertension, the Swiss Society of Cardiology, The Swiss Society of Angiology and the Swiss Society of Interventional Radiology decided to establish recommendations to practicing physicians and specialists for good clinical practice. The eligibility of patients for transcatheter renal denervation needs (1.) confirmation of truly resistant hypertension, (2.) exclusion of secondary forms of hypertension, (3.) a multidisciplinary decision confirming the eligibility, (4.) facilities that guarantee procedural safety and (5.) a long-term follow-up of the patients, if possible in cooperation with a hypertension specialist. These steps are essential until long-term data on safety and efficacy are available.

Internet-based individually versus group guided self-help treatment for social anxiety disorder: protocol of a randomized controlled trial

BACKGROUND: Social anxiety disorder (SAD) is one of the most common mental disorders and causes subjective suffering and economic burden worldwide. Although effective treatments are available, a lot of cases go untreated. Internet-based self-help is a low-threshold and flexible treatment alternative for SAD. Various studies have already shown that internet-based self-help can be effective to reduce social phobic symptoms significantly. Most of the interventions tested include therapist support, whereas the role of peer support within internet-based self-help has not yet been fully understood. There is evidence suggesting that patients' mutual exchange via integrated discussion forums can increase the efficacy of internet-based treatments. This study aims at investigating the added value of therapist-guided group support on the treatment outcome of internet-based self-help for SAD. METHODS/DESIGN: The study is conducted as a randomized controlled trial. A total of 150 adults with a diagnosis of SAD are randomly assigned to either a waiting-list control group or one of the active conditions. The participants in the two active conditions use the same internet-based self-help program, either with individual support by a psychologist or therapist-guided group support. In the group guided condition, participants can communicate with each other via an integrated, protected discussion forum. Subjects are recruited via topic related websites and links; diagnostic status will be assessed with a telephone interview. The primary outcome variables are symptoms of SAD and diagnostic status after the intervention. Secondary endpoints are general symptomology, depression, quality of life, as well as the primary outcome variables 6 months later. Furthermore, process variables such as group processes, the change in symptoms and working alliance will be studied. DISCUSSION: The results of this study should indicate whether group-guided support could enhance the efficacy of an internet-based self-help treatment for SAD. This novel treatment format, if shown effective, could represent a cost-effective option and could further be modified to treat other conditions, as well.

Effects of Motive-Oriented Therapeutic Relationship in a Ten-Session General Psychiatric Treatment of Borderline Personality Disorder: A Randomized Controlled Trial

Background: Motive-oriented therapeutic relationship (MOTR) was postulated to be a particularly helpful therapeutic ingredient in the early treatment phase of patients with personality disorders, in particular with borderline personality disorder (BPD). The present randomized controlled study using an add-on design is the first study to test this assumption in a 10-session general psychiatric treatment with patients presenting with BPD on symptom reduction and therapeutic alliance. Methods: A total of 85 patients were randomized. They were either allocated to a manual-based short variant of the general psychiatric management (GPM) treatment (in 10 sessions) or to the same treatment where MOTR was deliberately added to the treatment. Treatment attrition and integrity analyses yielded satisfactory results. Results: The results of the intent-to-treat analyses suggested a global efficacy of MOTR, in the sense of an additional reduction of general problems, i.e. symptoms, interpersonal and social problems (F 1, 73 = 7.25, p < 0.05). However, they also showed that MOTR did not yield an additional reduction of specific borderline symptoms. It was also shown that a stronger therapeutic alliance, as assessed by the therapist, developed in MOTR treatments compared to GPM (Z 55 = 0.99, p < 0.04). Conclusions: These results suggest that adding MOTR to psychiatric and psychotherapeutic treatments of BPD is promising. Moreover, the findings shed additional light on the perspective of shortening treatments for patients presenting with BPD.

Efficacy and Safety of Natalizumab in Crohn’s Disease Patients Treated at 6 Boston Academic Hospitals

BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not currently enrolled in a clinical trial. METHODS: A retrospective case review of patients treated with natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on natalizumab were collected. At the start of treatment, patients' disease duration was 12 years. A high proportion of patients were women (68%), presented with perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%), methotrexate (58%), and at least two anti-tumor necrosis factor agent failures (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation had a partial or complete clinical response. Loss of response was 13% after an average of 1 year of treatment. Adverse events were infusion reactions, headaches, fever, and infections. No case of progressive multifocal leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside the context of a clinical trial, natalizumab is largely reserved for CD patients with extensive ileocolonic disease who have failed conventional immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug is, however, well tolerated and offers significant clinical improvement for more than a year in one-third of these difficult-to-treat CD patients.

Treatment modalities for T1N0 esophageal cancers: a comparative analysis of local therapy versus surgical resection

BACKGROUND To investigate the role of nonsurgical treatment for early-stage esophageal cancer, we compared the outcomes of local therapy to esophagectomy, using a large, national database. METHODS Five-year cancer-specific and overall survival (OS) of patients, with T1N0M0 squamous cell or adenocarcinoma of the mid or distal esophagus treated with either surgery or local therapy, with ablative and/or excision techniques, in the Surveillance Epidemiology and End Results cancer registry from 1998 to 2008, were compared using the Kaplan-Meier approach, and multivariable and propensity-score adjusted Cox proportional hazard, and competing risk models. RESULTS Of 1458 patients with T1N0 esophageal cancer, 1204 (83%) had surgery and 254 (17%) had local therapy only. The use of local therapy increased significantly from 8.1% in 1998 to 24.1% in 2008 (p < 0.001). The 5-year OS after local excisional therapy and surgery was not significantly different (55.5% versus 64.1% respectively, p = 0.07), and 5-year cancer-specific survival (CSS) also did not differ (81.7% versus 75.8%, p = 0.10). However, after propensity-score adjustment, CSS was better for patients who underwent local therapy compared with those who underwent surgery (hazard ratio: 0.46, 95% confidence interval: 0.27-0.77, p = 0.003), whereas OS remained similar. CONCLUSION The use of local therapy for T1N0 esophageal cancers increased significantly from 1998 to 2008. Compared with those treated with esophagectomy, patients treated with local therapy had similar OS but improved CSS, indicating a higher chance of dying from other causes. Further studies are needed to confirm the oncologic efficacy of local therapy when used in patients whose lifespans are not limited by conditions other than esophageal cancer.

Differences in coping, self-efficacy, and external control beliefs between patients at-risk for psychosis and patients with first-episode psychosis

Patients with first-episode psychosis (FEP) often show dysfunctional coping patterns, low self-efficacy, and external control beliefs that are considered to be risk factors for the development of psychosis. Therefore, these factors should already be present in patients at-risk for psychosis (AR). We compared frequencies of deficits in coping strategies (Stress-Coping-Questionnaires, SVF-120/SVF-KJ), self-efficacy, and control beliefs (Competence and Control Beliefs Questionnaire, FKK) between AR (n=21) and FEP (n=22) patients using a cross-sectional design. Correlations among coping, self-efficacy, and control beliefs were assessed in both groups. The majority of AR and FEP patients demonstrated deficits in coping skills, self-efficacy, and control beliefs. However, AR patients more frequently reported a lack of positive coping strategies, low self-efficacy, and a fatalistic externalizing bias. In contrast, FEP patients were characterized by being overly self-confident. These findings suggest that dysfunctional coping, self-efficacy, and control beliefs are already evident in AR patients, though different from those in FEP patients. The pattern of deficits in AR patients closely resembles that of depressive patients, which may reflect high levels of depressiveness in AR patients. Apart from being worthwhile treatment targets, these coping and belief patterns are promising candidates for predicting outcome in AR patients, including the conversion to psychosis

Treatment for outpatients with comorbid schizophrenia and substance use disorders: a review

Aims: This review provides evidence of which interventions need to be part of effective outpatient integrated treatment for patients with comorbid schizophrenia and substance use disorders. Methods: A total of 14 randomized controlled trials were included. Effect sizes are provided to assess the magnitude of the treatments’ efficacy. Results: Despite the studies’ heterogeneity, we can conclude that certain programs (e.g., Behavioral Treatment for Substance Abuse in Schizophrenia) and specific interventions (e.g., motivational interviewing, family interventions) seem to be effective. Moreover, programs integrating multiple interventions are more likely to be positively related to better outcomes than single interventions. Finally, the lack of difference between effect sizes of assertive community treatment compared to case management suggests that a lower caseload is not necessary for positive treatment outcomes. Conclusion: Integrated treatment seems advantageous, although effect sizes are mostly modest. More homogeneous and qualitative sound studies are needed.

Efficacy of lead-in silibinin and subsequent triple therapy in difficult-to-treat HIV/hepatitis C virus-coinfected patients

OBJECTIVES: The efficacy of current hepatitis C virus (HCV) triple therapy, including a protease inhibitor, is limited in HIV/HCV-coinfected patients with advanced liver fibrosis and nonresponse to previous peginterferon-ribavirin. These patients have a low chance (only 30%) of achieving a sustained virological response (SVR) during triple therapy and cannot wait for next-generation anti-HCV drugs. In a pilot study, we investigated the efficacy of a lead-in therapy with silibinin before triple therapy in difficult-to-treat patients. METHODS: Inclusion criteria were HIV/HCV coinfection with advanced liver fibrosis and documented failure of previous peginterferon-ribavirin treatment. Intervention was lead-in therapy with intravenous silibinin 20 mg/kg/day for 14 days. Subsequently, peginterferon-ribavirin combined with telaprevir was initiated for 12 weeks, followed by peginterferon-ribavirin dual therapy until week 48 after initiation of triple therapy. The outcome measurements were HCV RNA after silibinin lead-in, at weeks 2, 4 and 12 of triple therapy, and SVR at week 24 after the end of treatment. RESULTS: We examined six HIV/HCV-coinfected patients (four infected with genotype 1a). All had fibrosis grade METAVIR ≥F3 and were on fully suppressive antiretroviral therapy. Mean HCV RNA decline after silibinin therapy was 2.6 log10 IU/mL (range 2-3 log10 IU/mL). Five of the six patients were virologically suppressed at weeks 2 and 4, and all six at week 12 of triple therapy. One experienced a viral breakthrough thereafter. Four of five patients (80%) showed an SVR 24. One patient had an SVR 12 but has not yet reached week 24. CONCLUSIONS: A lead-in with silibinin before triple therapy is highly effective and increases the probability of HCV treatment success in difficult-to-treat HIV/HCV-coinfected patients with advanced liver fibrosis and previous failure of peginterferon-ribavirin.

Safety and efficacy of thrombolysis with intravenous alteplase in older stroke patients.

Stroke is a common cause of death and persisting disability worldwide, and thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. Older age is the most important non-modifiable risk factor for stroke, and demographic changes are also resulting in an increasingly ageing population. However, clinical trial evidence for the use of intravenous alteplase is limited for the older age group where stroke incidence is highest. In this article, the current evidence regarding the safety and efficacy of intravenous thrombolytic therapy in stroke patients aged ≥80 years is critically analysed and the gap in current knowledge highlighted. In summary, intravenous thrombolysis in stroke patients aged ≥80 years seems to be associated with less favourable clinical outcomes and higher mortality than in younger patients, which is consistent with the natural course in untreated patients. The risk of symptomatic intracranial haemorrhage does not appear to be significantly higher in the elderly group, suggesting that intracranial bleeding complications are unlikely to outweigh the potential benefit in this age group. Overall, withholding thrombolytic treatment in ischaemic stroke on the basis of advanced age alone is no longer justifiable.

Virologic and immunologic responses in treatment-naive patients to ritonavir-boosted atazanavir or efavirenz with a common backbone

Background: Atazanavir boosted with ritonavir (ATV/r) and efavirenz (EFV) are both recommended as first-line therapies for HIV-infected patients. We compared the 2 therapies for virologic efficacy and immune recovery. Methods: We included all treatment-naïve patients in the Swiss HIV Cohort Study starting therapy after May 2003 with either ATV/r or EFV and a backbone of tenofovir and either emtricitabine or lamivudine. We used Cox models to assess time to virologic failure and repeated measures models to assess the change in CD4 cell counts over time. All models were fit as marginal structural models using both point of treatment and censoring weights. Intent-to-treat and various as-treated analyses were carried out: In the latter, patients were censored at their last recorded measurement if they changed therapy or if they were no longer adherent to therapy. Results: Patients starting EFV (n = 1,097) and ATV/r (n = 384) were followed for a median of 35 and 37 months, respectively. During follow-up, 51% patients on EFV and 33% patients on ATV/r remained adherent and made no change to their first-line therapy. Although intent-to-treat analyses suggest virologic failure was more likely with ATV/r, there was no evidence for this disadvantage in patients who adhered to first-line therapy. Patients starting ATV/r had a greater increase in CD4 cell count during the first year of therapy, but this advantage disappeared after one year. Conclusions: In this observational study, there was no good evidence of any intrinsic advantage for one therapy over the other, consistent with earlier clinical trials. Differences between therapies may arise in a clinical setting because of differences in adherence to therapy.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis

OBJECTIVES Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. METHODS We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. RESULTS Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. CONCLUSIONS Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children.