Uncontrollable hypertension in patients on hemodialysis: long-term treatment with captopril and salt subtraction

It has been suggested that an inappropriate relationship between renin and exchangeable sodium is responsible for the hypertension of patients with chronic renal failure. Long-term blockade of the renin system by captopril made it possible to test this hypothesis in 8 patients on maintenance hemodialysis. Captopril was administered orally in 2 daily doses of 25 to 200 mg. Previously, blood pressure averaged 179/105 +/- 6/3 (mean +/- SEM) pre- and 182/103 +/- 7/3 mm HG post-dialysis, despite intensive ultrafiltration and conventional antihypertensive therapy. The 4 patients with the highest plasma renin activity normalized their blood pressure with captopril alone, whereas in the 4 remaining patients, captopril therapy was complemented by salt subtraction which consisted in replacement of 1-2 liters of ultrafiltrate by an equal volume of 5% dextrose until blood pressure was controlled. After an average treatment period of 5 months, blood pressure of all 8 patients was reduced to 134/76 +/- 7/5 mm Hg (P less than 0.001) pre- and 144/81 +/- 9/5 mm Hg (P less than 0.001) post-dialysis without a significant change in body weight. The present data suggest that captopril alone or combined with salt subtraction normalizes blood pressure of patients on chronic hemodialysis with so called uncontrollable hypertension.

Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer.

BACKGROUND: To evaluate the safety and clinical feasibility of focal irreversible electroporation (IRE) of the prostate. METHODS: We assessed the toxicity profile and functional outcomes of consecutive patients undergoing focal IRE for localised prostate cancer in two centres. Eligibility was assessed by multi-parametric magnetic resonance imaging (mpMRI) and targeted and/or template biopsy. IRE was delivered under transrectal ultrasound guidance with two to six electrodes positioned transperineally within the cancer lesion. Complications were recorded and scored accordingly to the NCI Common Terminology Criteria for Adverse Events; the functional outcome was physician reported in all patients with at least 6 months follow-up. A contrast-enhanced MRI 1 week after the procedure was carried out to assess treatment effect with a further mpMRI at 6 months to rule out evidence of residual visible cancer. RESULTS: Overall, 34 patients with a mean age of 65 years (s.d.=±6) and a median PSA of 6.1 ng ml(-1) (interquartile range (IQR)= 4.3-7.7) were included. Nine (26%), 24 (71%) and 1 (3%) men had low, intermediate and high risk disease, respectively (D'Amico criteria). After a median follow-up of 6 months (range 1-24), 12 grade 1 and 10 grade 2 complications occurred. No patient had grade >/= 3 complication. From a functional point of view, 100% (24/24) patients were continent and potency was preserved in 95% (19/20) men potent before treatment. The volume of ablation was a median 12 ml (IQR=5.6-14.5 ml) with the median PSA after 6 months of 3.4 ng ml(-1) (IQR=1.9-4.8 ng ml(-1)). MpMRI showed suspicious residual disease in six patients, of whom four (17%) underwent another form of local treatment. CONCLUSIONS: Focal IRE has a low toxicity profile with encouraging genito-urinary functional outcomes. Further prospective development studies are needed to confirm the functional outcomes and to explore the oncological potential.

Les indications au traitement de l'ostéoporose [Treatment indications for osteoporosis]

The aim of this review is to better identify for which women with osteoporosis the treatment is efficient, without taking into account the bone mineral density only. The age, previous fractures, the severity of vertebral deformity identify women at high risk for subsequent fracture. The development of assessment tools for predicting fracture risk, the use of the NNT (number needed to treat), and economical analyses are particularly helpful. The number of patients needed to treat to prevent one patient having the target event expresses the magnitude of a treatment effect in a clinically useful way. Economical analyses take into account the health care resources needed to get these benefits. We analysed the NNT and the cost of the treatments which significantly reduced the risk of fracture.

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial.

ABSTRACT: Iron deficiency without anemia (IDWA) is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of an iron treatment after blood donation. METHODS: One week after donation, we randomly assigned 154 female donors with IDWA aged <50 years to a 4-week oral treatment of ferrous sulfate vs. placebo. The main outcome was the change in the level of fatigue before and after the intervention. Also evaluated were aerobic capacity, mood disorder, quality of life, compliance and adverse events. Biological markers were hemoglobin and ferritin. RESULTS: Treatment effect from baseline to 4 weeks for hemoglobin and ferritin were 5.2 g/L (p < 0.01) and 14.8 ng/mL (p < 0.01) respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 to 0.6, p = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces. CONCLUSIONS: These data are valuable as they enable us to conclude that donors with IDWA after a blood donation would not clinically benefit from iron supplementation. Trial registration: NCT00689793.

Effect of a lifestyle intervention on adiposity and fitness in socially disadvantaged subgroups of preschoolers: a cluster-randomized trial (Ballabeina).

OBJECTIVE: A multidimensional lifestyle intervention performed in 652 preschoolers (72% of migrant, 38% of low educational level (EL) parents) reduced body fat, but not BMI and improved fitness. The objective of this study is to examine whether the intervention was equally effective in children of migrant and/or low EL parents.¦METHODS: Cluster-randomized controlled single blinded trial, conducted in 2008/09 in 40 randomly selected preschools in Switzerland. The culturally tailored intervention consisted of a physical activity program and lessons on nutrition, media use and sleep. Primary outcomes included BMI and aerobic fitness. Secondary outcomes included %body fat, waist circumference and motor agility.¦RESULTS: Children of migrant parents benefitted similarly from the intervention compared to their counterparts (p for interaction≥ 0.09). However, children of low EL parents benefitted less, although these differences did not reach statistical significance (p for interaction≥ 0.06). Average intervention effect sizes for BMI were -0.10, -0.05, -0.11 and 0.04 kg/m(2) and for aerobic fitness were 0.55, 0.20, 0.37 and -0.05 stages for children of non-migrant, migrant, middle/high EL and low EL parents, respectively.¦CONCLUSIONS: This intervention was similarly effective among preschoolers of migrant parents compared to their counterparts, while children of low EL parents benefitted less.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

AIM: To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). METHODS AND RESULTS: Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES  vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). CONCLUSION: A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Sustained improvement in left ventricular function after bone marrow derived cell therapy in patients with acute ST elevation myocardial infarction. A 5-year follow-up from the Stem Cell Transplantation in Ischaemic Myocardium Study.

BACKGROUND: Intracoronary injection of autologous bone marrow-derived mononucleated cells (BM-MNC) may improve LV function shortly after acute ST elevation myocardial infarction (STEMI), but little is known about the long-term durability of the treatment effect. METHODS: In a single-centre trial a total of 60 patients with acute anterior STEMI, successful reperfusion therapy and a left ventricular ejection fraction (LVEF) of <50% were screened for the study. 23 patients were actively treated with intracoronary infusion of BM-MNC within a median of 3 days. The open-label control group consisted of 19 patients who did not consent to undergo BM-MNC treatment but agreed to undergo regular clinical and echocardiographic follow-up for up to 5 years after AMI. RESULTS: Whereas at 4 months there was no significant difference between the increase in LVEF in the BM-MNC group and the control group (+7.0%, 95%CI 3.6; 10.4) vs. +3.9%, 95%CI -2.1; 10), the absolute increase at 5 years remained stable in the BM-MNC but not in the control group (+7.95%, 95%CI 3.5; 12.4 vs. -0.5%, 95%CI -5.4; 4.4; p for interaction between groups = 0.035). DISCUSSION: In this single-centre, open-labelled study, intracoronary administration of BM-MNC is feasible and safe in the short term. It is also associated with sustained improvement of left ventricular function in patients with acute myocardial infarction, encouraging phase III studies to examine the potential BM-MNC effect on clinical outcome.

Influence of counselor characteristics and behaviors on the efficacy of a brief motivational intervention for heavy drinking in young men-a randomized controlled trial.

BACKGROUND: Brief motivational intervention (BMI) has shown promising results to reduce alcohol use in young adults. Knowledge on mechanisms that predict BMI efficacy could potentially improve treatment effect sizes through data that optimize clinical training and implementation. Particularly, little attention has been given to counselor influence on treatment mechanisms. METHODS: We investigated the influence of counselors on BMI efficacy in reducing alcohol use among non-treatment-seeking young men (age 20) screened as hazardous drinkers. Participants were randomly allocated to (i) a group receiving a single BMI from 1 of 18 counselors selected to maximize differences in several of their characteristics (gender, professional status, clinical experience, and motivational interviewing [MI] experience) or (ii) a control group receiving assessment only. Drinking at 3-month follow-up was first compared between the BMI and control groups to assess efficacy. Then, the influence of counselors' characteristics (i.e., gender, professional status, clinical experience, MI experience, BMI attitudes, and expectancies) and within-session behaviors (i.e., measured by the Motivational Interviewing Skill Code) on outcome was tested in regression analyses. RESULTS: There was a significant (p = 0.02) decrease in alcohol use among the BMI group compared to the control group. Counselors that were male, more experienced, that had more favorable BMI attitudes and expectancies, higher MI skills, but surprisingly less MI-consistent behaviors, had significantly better outcomes than the control group while their counterparts did not. CONCLUSIONS: The current study demonstrated BMI efficacy on alcohol use reduction within a sample of non-treatment-seeking young adult males. Moreover, BMI effect was related to interindividual differences among counselors, and results therefore provide recommendations for BMI training and implementation with similar populations.

The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model.

OBJECTIVES: To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. DESIGN: Decision modelling using Markov chains compared costs and effects over 5 years. SETTING: The analysis was from the perspective of the National Health Service (NHS) in England and Wales. PARTICIPANTS: The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. DATA SOURCES: We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. MAIN OUTCOME MEASURES: We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. RESULTS: Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20,000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100,000 patients compared to psychosocial support alone over the course of 5 years. CONCLUSIONS: Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. TRIAL REGISTRATION NUMBERS: This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).

Intracoronary injection of bone marrow-derived mononuclear cells early or late after acute myocardial infarction: effects on global left ventricular function.

BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Effects of a lifestyle intervention on adiposity and fitness in overweight or low fit preschoolers (Ballabeina).

OBJECTIVE: Overweight (OW) and low fit children represent cardiovascular high-risk groups. A multidimensional school-based lifestyle intervention performed in 652 preschoolers reduced skinfold thickness and waist circumference, and improved fitness, but did not affect BMI. The objective of this study is to examine whether the intervention was equally effective in OW (≥90th national percentile) and/or low fit (lowest sex- and age-adjusted quartile of aerobic fitness) children compared to their normal weight and normal fit counterparts. DESIGN AND METHODS: Cluster randomized controlled single blinded trial, conducted in 2008/09 in 40 randomly selected preschool classes in Switzerland. The intervention included a playful physical activity program and lessons on nutrition, media use and sleeps. Primary outcomes were BMI and aerobic fitness; secondary outcomes included sum of four skinfolds, waist circumference and motor agility. Modification of intervention effects by BMI-group and fitness-group was tested by interaction terms. RESULTS: Compared to their counterparts, OW children (n = 130) had more beneficial effects on waist circumference (p for interaction = 0.001) and low fit children (n = 154) more beneficial effects on all adiposity outcomes (p for interaction ≤0.03). The intervention effects on both fitness outcomes were not modified by BMI- or fitness-group (all p for interaction ≥0.2). Average intervention effect sizes for BMI were -0.12, -0.05, -0.26 and -0.02 kg/m(2) and for aerobic fitness were 0.40, 0.30, 0.12 and 0.36 stages for OW, normal weight, low fit and normal fit children, respectively. Conclusions: This multidimensional intervention was equally and for some adiposity measures even more effective in high-risk preschoolers and represents a promising option for these children.

Financial protection of patients through compensation of providers: the impact of Health Equity Funds in Cambodia

Public providers have no financial incentive to respect their legal obligation to exempt the poor from user fees. Health Equity Funds (HEFs) aim to make exemptions effective by giving NGOs responsibility for assessing eligibility and compensating providers for lost revenue. We use the geographic spread of HEFs over time in Cambodia to identify their impact on out-of-pocket (OOP) payments. Among households with some OOP payment, HEFs reduce the amount paid by 35%, on average. The effect is larger for households that are poorer and mainly use public health care. Reimbursement of providers through a government operated scheme also reduces household OOP payments but the effect is not as well targeted on the poor. Both compensation models raise household non-medical consumption but have no impact on health-related debt. HEFs reduce the probability of primarily seeking care in the private sector.

Assessing heterogeneity of effects on blood pressure in a meta-analysis of pharmacist interventions trials

Background: Recent reviews of randomized control trials have shown that pharmacist interventions improve cardiovascular diseases (CVD) risk factors in outpatients. Various interventions were evaluated in different settings, and a substantial heterogeneity was observed in the effect estimates. To better express uncertainties in the effect estimates, prediction intervals (PI) have been proposed but are, however, rarely reported. Objective: Pooling data from two systematic reviews, we estimated the effect of pharmacist interventions on systolic blood pressure (BP), computed PI, and evaluated potential causes of heterogeneity. Methods: Data were pooled from systematic reviews assessing the effect of pharmacist interventions on CVD risk factors in patients with or without diabetes, respectively. Effects were estimated using random effect models. Results: Systolic BP was the outcome in 31 trials including 12 373 patients. Pharmacist interventions included patient educational interventions, patient-reminder systems, measurement of BP, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist interventions were associated with a large reduction in systolic BP (-7.5 mmHg; 95% CI: -9.0 to -5.9). There was a substantial heterogeneity (I2: 66%). The 95% PI ranged from -13.9 to -1.0 mmHg. The effect tended to be larger if the intervention was conducted in a community pharmacy and if the pharmacist intervened at least monthly. Conclusion: On average, the effect of pharmacist interventions on BP was substantial. However, the wide PI suggests that the effect differed between interventions, with some having modest effects and others very large effects on BP. Part of the heterogeneity could be due to differences in the setting and in the frequency of the interventions.

Effectiveness of cladribine therapy in patients with pulmonary Langerhans cell histiocytosis.

BackgroundPulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterised by granulomatous proliferation of CD1a-positive histiocytes forming granulomas within lung parenchyma, in strong association with tobacco smoking, and which may result in chronic respiratory failure. Smoking cessation is considered to be critical in management, but has variable effects on outcome. No drug therapy has been validated. Cladribine (chlorodeoxyadenosine, 2-CDA) down-regulates histiocyte proliferation and has been successful in curbing multi-system Langerhans cell histiocytosis and isolated PLCH.Methods and patientsWe retrospectively studied 5 patients (aged 37¿55 years, 3 females) with PLCH who received 3 to 4 courses of cladribine therapy as a single agent (0.1 mg/kg per day for 5 consecutive days at monthly intervals). One patient was treated twice because of relapse at 1 year. Progressive pulmonary disease with obstructive ventilatory pattern despite smoking cessation and/or corticosteroid therapy were indications for treatment. Patients were administered oral trimethoprim/sulfamethoxazole and valaciclovir to prevent opportunistic infections. They gave written consent to receive off-label cladribine in the absence of validated treatment.ResultsFunctional class dyspnea improved with cladribine therapy in 4 out of 5 cases, and forced expiratory volume in 1 second (FEV1) increased in all cases by a mean of 387 ml (100¿920 ml), contrasting with a steady decline prior to treatment. Chest high-resolution computed tomography (HRCT) features improved with cladribine therapy in 4 patients. Hemodynamic improvement was observed in 1 patient with pre-capillary pulmonary hypertension. The results suggested a greater treatment effect in subjects with nodular lung lesions and/or thick-walled cysts on chest HRCT, with diffuse hypermetabolism of lung lesions on positron emission tomography (PET)-scan, and with progressive disease despite smoking cessation. Infectious pneumonia developed in 1 patient, with later grade 4 neutrocytopenia but without infection.DiscussionData interpretation was limited by the retrospective, uncontrolled study design and small sample size.ConclusionCladribine as a single agent may be effective therapy in patients with progressive PLCH.

Financial protection of patients through compensation of providers: the impact of health equity funds in Cambodia

Public providers have no financial incentive to respect their legal obligation to exempt the poor from user fees. Health Equity Funds (HEFs) aim to make exemptions effective by giving NGOs responsibility for assessing eligibility and compensating providers for lost revenue. We use the geographic spread of HEFs in Cambodia to identify their impact on out-of-pocket (OOP) payments. Among households with some OOP payment, HEFs reduce the amount by 29%, on average. The effect is larger for households that are poorer, mainly use public health care and live closer to a district hospital. HEFs are more effective in reducing OOP payments when they are operated by a NGO, rather than the government, and when they operate in conjunction with the contracting of public health services. HEFs reduce households' health-related debt by around 25%, on average. There is no significant impact on non-medical consumption and health care utilisation