Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy

Aims Slow‐release morphine may represent a much‐needed new pharmacological treatment for opioid dependence. Design In a 14‐week randomized, double‐blind, double‐dummy, cross‐over study oral slow‐release morphine was compared with methadone as a treatment for opioid dependency. During two study periods, each consisting of a 1‐week titration and a 6‐week fixed‐dose treatment phase, medication was administered daily under supervised conditions. Setting The study was carried out at the Addiction Clinic, Department of Psychiatry, Medical University Vienna. Participants Sixty‐four subjects (56 males, eight females) with opioid dependence participated in the trial. Measurements Efficacy was evaluated on the basis of retention, use of illicit substances based on urinalysis, extent of drug cravings, withdrawal symptoms and general wellbeing. Safety was assessed on the basis of adverse events and clinical and physical examination. Demographic and baseline characteristics were assessed using the European Addiction Severity Index. Findings Fifty‐five patients (86%) completed the study, with a mean methadone dose of 85 mg and a mean slow‐release morphine dose of 680 mg. No significant differences in retention or use of illicit substances (opioids, benzodiazepines, cocaine) were observed, irrespective of treatment group or medication. However, patients receiving slow‐release morphine had significantly lower depression (P < 0.001) and anxiety scores (P = 0.008) and fewer physical complaints (P < 0.001). Conclusions Oral slow‐release morphine is as effective as methadone in the treatment of opioid dependency, with comparable safety and tolerability and a greater benefit on patient wellbeing. Greater pharmaceutical diversity represents a modern development in mainstream medicine. Slow‐release morphine might represent a future treatment option that will improve long‐term outcomes for this target group.     

Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis

Despite wide use in clinical practice, acupuncture remains a controversial treatment for chronic pain. Our objective was to update an individual patient data meta-analysis to determine the effect size of acupuncture for 4 chronic pain conditions. We searched MEDLINE and the Cochrane Central Registry of Controlled Trials randomized trials published up until December 31, 2015. We included randomized trials of acupuncture needling versus either sham acupuncture or no acupuncture control for nonspecific musculoskeletal pain, osteoarthritis, chronic headache, or shoulder pain. Trials were only included if allocation concealment was unambiguously determined to be adequate. Raw data were obtained from study authors and entered into an individual patient data meta-analysis. The main outcome measures were pain and function. An additional 13 trials were identified, with data received for a total of 20,827 patients from 39 trials. Acupuncture was superior to sham as well as no acupuncture control for each pain condition (all P?<?.001) with differences between groups close to .5 SDs compared with no acupuncture control and close to .2 SDs compared with sham. We also found clear evidence that the effects of acupuncture persist over time with only a small decrease, approximately 15%, in treatment effect at 1 year. In secondary analyses, we found no obvious association between trial outcome and characteristics of acupuncture treatment, but effect sizes of acupuncture were associated with the type of control group, with smaller effects sizes for sham controlled trials that used a penetrating needle for sham, and for trials that had high intensity of intervention in the control arm. We conclude that acupuncture is effective for the treatment of chronic pain, with treatment effects persisting over time. Although factors in addition to the specific effects of needling at correct acupuncture point locations are important contributors to the treatment effect, decreases in pain after acupuncture cannot be explained solely in terms of placebo effects. Variations in the effect size of acupuncture in different trials are driven predominantly by differences in treatments received by the control group rather than by differences in the characteristics of acupuncture treatment.

The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients

Aim

Despite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical trials is limited. A multicentre AGO-OVAR-15 phase II trial reported an unfavourable effect of lonafarnib on the outcome of patients with advanced ovarian cancer. This study was performed as a genetic subgroup analysis of the AGO-OVAR-15 trial, and investigated the utility of the promoter polymorphism rs11623866 of the farnesyltransferase ß-subunit gene (FNTB) in predicting the clinical effectiveness of lonafarnib.

Methods

The influence of rs11623866 (c.-609G > C) on FNTB promoter activity was investigated by electrophoretic-mobility-shift assay, luciferase-reporter assay and RT-qPCR. A total of 57 out of 105 patients from the AGO-OVAR-15 trial, treated with carboplatin and paclitaxel ± lonafarnib, was genotyped for rs11623866 by restriction fragment length polymorphism analysis. Genotype-dependent survival analysis was performed by Kaplan–Meier analysis.

Results

The presence of the G allele was associated with increased FNTB promoter activity compared with the C allele. An unfavourable effect of lonafarnib was limited to patients carrying a GG genotype (HR_PFS 6.2, 95%CI = 2.01, 19.41, P = 0.002; HR_OS 9.6, 95%CI = 1.89, 48.54, P = 0.006). Median progression free survival (PFS) for patients with the GG genotype in the lonafarnib treated arm was 10 months, whereas median PFS without FTI-treatment was 40 months. Median overall survival (OS) in the lonafarnib-treated group was 19 months, whereas median OS was not reached in the untreated group.

Conclusions

Discrepancies between preclinical success and clinical failure may be due to the patients'' genetic variability of FNTB. Therefore, our results may encourage retrospective evaluation of FNTB polymorphisms in previous FTI studies, especially those reporting positive FTI response.     

Chronic kidney disease impairs prognosis in electrical storm

Journal of Interventional Cardiac Electrophysiology - The study sought to assess the prognostic impact of chronic kidney disease (CKD) in patients with electrical storm (ES). ES represents a...     

Replicative aging of human articular chondrocytes during ex vivo expansion

OBJECTIVE: To investigate the contribution of clinical ex vivo expansion protocols to replicative aging of human chondrocytes. METHODS: Primary human chondrocytes were cultured as monolayers after isolation from 7 articular cartilage specimens. Cells were passaged corresponding to 12-19 cell population doublings (cpd). Aliquots of the cells were collected from each passage and analyzed for telomere length and telomerase activity. RESULTS: The rate of telomere shortening was heterogeneous, ranging from 147 to 431 bp/cpd (mean +/- SD 305 +/- 122). Telomerase activity was detected at various time points during passaging in 5 of 7 primary chondrocytes analyzed, but not in native human articular cartilage specimens. According to our data, an 8-10-fold ( approximately 3 cpd) ex vivo expansion of articular chondrocytes, as typically performed for transplantation procedures, leads to telomere erosion in the range of 900 bp. This is comparable with 30 years of aging based on the in vivo rate of telomere shortening of 30 bp/year recently found in chondrocytes. CONCLUSION: If telomere shortening is an important determinant of aging in human articular cartilage, an additional telomere loss due to ex vivo expansion might affect the incidence or time of onset of age-related cartilage disorders. However, given the limited extent of expansion performed in the clinical setting to date, a significant telomere-mediated increase in the risk of malignant transformation or replicative exhaustion of the transplanted cells seems unlikely.     

Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial

OBJECTIVES: Nonsteroidal anti-inflammatory drugs vary in their impact on blood pressure and the effect of lumiracoxib 100 mg once daily has not been studied previously. To examine whether lumiracoxib 100 mg once daily would result in lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three times daily in osteoarthritis patients with controlled hypertension, a 4-week, randomized, double-blind, parallel-group study was conducted in 79 centres in nine countries. METHODS: Hypertensive osteoarthritis patients of 50 years at least whose office blood pressure was less than 140/90 mmHg on stable antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood pressure monitoring was performed at baseline and end of study. The primary outcome measure was a comparison of the change in 24-h mean systolic ambulatory blood pressure from baseline to week 4. Secondary analyses included other blood pressure-related endpoints and efficacy (pain) measurements. RESULTS: Compared with baseline, the 24-h mean systolic ambulatory blood pressure (least square mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5 mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3). Efficacy results were comparable. CONCLUSIONS: Treatment with lumiracoxib 100 mg once daily resulted in clinically significant lower blood pressure compared with ibuprofen 600 mg three times daily in osteoarthritis patients with well controlled hypertension.     

Role of allogeneic transplantation in chronic myeloid leukemia

The use of allogeneic hematopoietic stem cell transplantation for the treatment of chronic myeloid leukemia (CML) patients has changed dramatically during the past decade. It was the standard of care for all younger CML patients with a compatible donor before the introduction of imatinib. It is used now as a rescue treatment for patients for whom tyrosine kinase inhibitors have failed. Both treatments, tyrosine kinase inhibitors and allogeneic transplantation, are very powerful and able to control the disease in the long-term. It is therefore of great importance to know the place of each therapy and to integrate allogeneic hematopoietic stem cell transplantation in a risk-adapted way into the treatment plan of each individual patient.     

CANVAS: a late onset ataxia due to biallelic intronic AAGGG expansions

Journal of Neurology - The ataxias are a group of disorders that manifest with balance, movement, speech and visual problems. They can arise due to dysfunction of the cerebellum, the vestibular...