Laparoscopically assisted ventriculoperitoneal shunt placement: a prospective randomized controlled trial

OBJECT In ventriculoperitoneal (VP) shunt surgery, laparoscopic assistance can be used for placement of the peritoneal catheter. Until now, the efficacy of laparoscopic shunt placement has been investigated only in retrospective and nonrandomized prospective studies, which have reported decreased distal shunt dysfunction rates in patients undergoing laparascopic placement compared with mini-laparotomy cohorts. In this randomized controlled trial the authors compared rates of shunt failure in patients who underwent laparoscopic surgery for peritoneal catheter placement with rates in patients who underwent traditional mini-laparotomy. METHODS One hundred twenty patients scheduled for VP shunt surgery were randomized to laparoscopic surgery or mini-laparotomy for insertion of the peritoneal catheter. The primary endpoint was the rate of overall shunt complication or failure within the first 12 months after surgery. Secondary endpoints were distal shunt failure, overall complication/ failure, duration of surgery and hospitalization, and morbidity. RESULTS The overall shunt complication/failure rate was 15% (9 of 60 cases) in the laparoscopic group and 18.3% (11 of 60 cases) in the mini-laparotomy group (p = 0.404). Patients in the laparoscopic group had no distal shunt failures; in contrast, 5 (8%) of 60 patients in the mini-laparotomy group experienced distal shunt failure (p = 0.029). Intraoperative complications occurred in 2 patients (both in the laparoscopic group), and abdominal pain led to catheter removal in 1 patient per group. Infections occurred in 1 patient in the laparoscopic group and 3 in the mini-laparotomy group. The mean durations of surgery and hospitalization were similar in the 2 groups. CONCLUSIONS While overall shunt failure rates were similar in the 2 groups, the use of laparoscopic shunt placement significantly reduced the rate of distal shunt failure compared with mini-laparotomy.

Stochastic Resonance Whole-Body Vibration Improves Postural Control in Health Care Professionals: A Worksite Randomized Controlled Trial

Slip, trip, and fall injuries are frequent among health care workers. Stochastic resonance whole-body vibration training was tested to improve postural control. Participants included 124 employees of a Swiss university hospital. The randomized controlled trial included an experimental group given 8 weeks of training and a control group with no intervention. In both groups, postural control was assessed as mediolateral sway on a force plate before and after the 8-week trial. Mediolateral sway was significantly decreased by stochastic resonance whole-body vibration training in the experimental group but not in the control group that received no training (p < .05). Stochastic resonance whole-body vibration training is an option in the primary prevention of balance-related injury at work.

Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874

Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV

PURPOSE Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival. PATIENTS AND METHODS Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival. RESULTS Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression. CONCLUSION MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.

Safety and efficacy of imatinib in CML over a period of 10 years: data from the randomized CML-study IV.

Tyrosine kinase inhibitors (TKI) have changed the natural course of chronic myeloid leukemia (CML). With the advent of second-generation TKI safety and efficacy issues have gained interest. The randomized CML - Study IV was used for a long-term evaluation of imatinib (IM). 1503 patients have received IM, 1379 IM monotherapy. After a median observation of 7.1 years, 965 patients (64%) still received IM. At 10 years, progression-free survival was 82%, overall survival 84%, 59% achieved MR(5), 72% MR(4.5), 81% MR(4), 89% major molecular remission and 92% MR(2) (molecular equivalent to complete cytogenetic remission). All response levels were reached faster with IM800 mg except MR(5). Eight-year probabilities of adverse drug reactions (ADR) were 76%, of grades 3-4 22%, of non-hematologic 73%, and of hematologic 28%. More ADR were observed with IM800 mg and IM400 mg plus interferon α (IFN). Most patients had their first ADR early with decreasing frequency later on. No new late toxicity was observed. ADR to IM are frequent, but mostly mild and manageable, also with IM 800 mg and IM 400 mg+IFN. The deep molecular response rates indicate that most patients are candidates for IM discontinuation. After 10 years, IM continues to be an excellent initial choice for most patients with CML.Leukemia advance online publication, 13 March 2015; doi:10.1038/leu.2015.36.

Efficacy of motivational enhancement therapy on alcohol use disorders in patients with chronic hepatitis C: a randomized controlled trial

AIMS: To determine the efficacy of motivational enhancement therapy (MET) on alcohol use in patients with the hepatitis C virus (HCV) and an alcohol use disorder (AUD). DESIGN: Randomized, single-blind, controlled trial comparing MET to a control education condition with 6-month follow-up. SETTING: Patients were recruited from hepatitis clinics at the Minneapolis, Minnesota and Portland, Oregon Veterans Affairs Health Care Systems, USA. PARTICIPANTS AND INTERVENTION: Patients with HCV, an AUD and continued alcohol use (n = 139) were randomized to receive either MET (n = 70) or a control education condition (n = 69) over 3 months. MEASUREMENTS: Data were self-reported percentage of days abstinent from alcohol and number of standard alcohol drinks per week 6 months after randomization. FINDINGS: At baseline, subjects in MET had 34.98% days abstinent, which increased to 73.15% at 6 months compared to 34.63 and 59.49% for the control condition. Multi-level models examined changes in alcohol consumption between MET and control groups. Results showed a significant increase in percentage of days abstinent overall (F(1120.4)  = 28.04, P < 0.001) and a significant group × time effect (F(1119.9)  = 5.23, P = 0.024) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition. There were no significant differences between groups for drinks per week. The effect size of the MET intervention was moderate (0.45) for percentage of days abstinent. CONCLUSION: Motivational enhancement therapy (MET) appears to increase the percentage of days abstinent in patients with chronic hepatitis C, alcohol use disorders and ongoing alcohol use. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

A Randomized, Controlled Trial of an Aerosolized Vaccine against Measles.

Background Aerosolized vaccine can be used as a needle-free method of immunization against measles, a disease that remains a major cause of illness and death. Data on the immunogenicity of aerosolized vaccine against measles in children are inconsistent. Methods We conducted an open-label noninferiority trial involving children 9.0 to 11.9 months of age in India who were eligible to receive a first dose of measles vaccine. Children were randomly assigned to receive a single dose of vaccine by means of either aerosol inhalation or a subcutaneous injection. The primary end points were seropositivity for antibodies against measles and adverse events 91 days after vaccination. The noninferiority margin was 5 percentage points. Results A total of 1001 children were assigned to receive aerosolized vaccine, and 1003 children were assigned to receive subcutaneous vaccine; 1956 of all the children (97.6%) were followed to day 91, but outcome data were missing for 331 children because of thawed specimens. In the per-protocol population, data on 1560 of 2004 children (77.8%) could be evaluated. At day 91, a total of 662 of 775 children (85.4%; 95% confidence interval [CI], 82.5 to 88.0) in the aerosol group, as compared with 743 of 785 children (94.6%; 95% CI, 92.7 to 96.1) in the subcutaneous group, were seropositive, a difference of -9.2 percentage points (95% CI, -12.2 to -6.3). Findings were similar in the full-analysis set (673 of 788 children in the aerosol group [85.4%] and 754 of 796 children in the subcutaneous group [94.7%] were seropositive at day 91, a difference of -9.3 percentage points [95% CI, -12.3 to -6.4]) and after multiple imputation of missing results. No serious adverse events were attributable to measles vaccination. Adverse-event profiles were similar in the two groups. Conclusions Aerosolized vaccine against measles was immunogenic, but, at the prespecified margin, the aerosolized vaccine was inferior to the subcutaneous vaccine with respect to the rate of seropositivity. (Funded by the Bill and Melinda Gates Foundation; Measles Aerosol Vaccine Project Clinical Trials Registry-India number, CTRI/2009/091/000673 .).

Acupuncture-induced changes of pressure pain threshold are mediated by segmental inhibition-a randomized controlled trial

Our aim was to distinguish between spinal and supraspinal mechanisms in the intact nervous system by comparing homosegmental and heterosegmental effects of electroacupuncture (EA) and manual acupuncture (MA) on sensory perception in healthy volunteers by means of quantitative sensory testing. Seventy-two healthy volunteers were randomly assigned to receive either MA or EA at SP 6, SP 9, GB 39, and ST 36 at the left leg or relaxed for 30 minutes (control group [CG]). Blinded examiners assessed 13 sensory modalities (thermal and mechanical detection and pain thresholds) at the upper arms and lower legs before and after intervention by means of a standardized quantitative sensory testing battery. Change scores of all 13 sensory thresholds were compared between groups. The main outcome measure was the change score of the pressure pain threshold (PPT). There were no baseline differences between groups. Pressure pain threshold change scores at the lower left leg, in the same segment as the needling site, differed significantly (P = 0.008) between the EA (median: 103.01 kPa) and CG groups (median: 0.00 kPa) but not between the MA (median: 0.00 kPa) and CG groups. No further significant change score differences were found between one of the acupuncture groups and the CG. The PPT can be changed by EA. The PPT increase was confined to the segment of needling, which indicates that it is mainly mediated by segmental inhibition in the spinal cord. This underscores the importance of segmental needling and electrical stimulation in clinical practice.