Lumbar spinal stenosis: a brief review of the nonsurgical management

Purpose

The purpose of this brief narrative review is to summarize the evidence derived from randomized controlled trials pertaining to the nonsurgical treatment of lumbar spinal stenosis (LSS).

Source

The MEDLINE (January 1950 to the fourth week of January 2010) and EMBASE (January 1980 to 2009, week 53) databases, the MESH term “spinal stenosis”, and the key words, “vertebral canal stenosis” and “neurogenic claudication”, were searched. Results were limited to randomized controlled trials (RCTs) conducted on human subjects, written in English, and published in peer-reviewed journals. Only RCTs pertaining to nonsurgical treatment were considered. Studies comparing conservative and surgical management or different surgical techniques were not included in the review.

Principal findings

The search criteria yielded 13 RCTs. The average enrolment was 54 subjects per study. Blinded assessment and sample size justification were provided in 85% and 39% of RCTs, respectively. The available evidence suggests that parenteral calcitonin, but not intranasal calcitonin, can transiently decrease pain in patients with LSS. In the setting of epidural blocks, local anesthetics can improve pain and function, but the benefits seem short-lived. The available evidence does not support the addition of steroids to local anesthetic agents. Based on the limited evidence, passive physical therapy seems to provide minimal benefits in LSS. The optimal regimen for active physiotherapy remains unknown. Although benefits have been reported with gabapentin, limaprost, methylcobalamin, and epidural adhesiolysis, further trials are required to validate these findings.

Conclusions

Because of their variable quality, published RCTs can provide only limited evidence to formulate recommendations pertaining to the nonsurgical treatment of LSS. In this narrative review, no study was excluded based on factors such as sample size justification, statistical power, blinding, definition of intervention allocation, or clinical outcomes. This aspect may represent a limitation as it may serve to overemphasize evidence derived from “weaker” trials. Further well-designed RCTs are warranted.     

Dermatology and the effects of medication on the skin

Skin diseases may be treated locally or generally. Skin can also be affected by treatments that are used for healing other diseased organs; thus opening the field of drug eruptions.     

Methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy

Ifosfamide (IFOS) is used in cancer treatment. Ifosfamide-induced encephalopathy (IIE) can result in treatment delay or discontinuation as well as morbidity and mortality. Cases using methylene blue (MB) in acute and prophylactic treatments are discussed. For acute use, marked central nervous system (CNS) improvement occurred within 24h of MB administration. For prophylactic use, the severity of the symptoms decreased significantly compared with previous treatment cycles, and enabled patients to continue further IFOS therapy. MB has potential use in both the acute treatment and prophylaxis of IIE.     

Statistics on BCS Classification of Generic Drug Products Approved Between 2000 and 2011 in the USA

The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Essential Medicines to determine the distribution of BCS Class 1, 2, 3, and 4 drugs in Abbreviated New drug Applications (ANDA) submissions. To categorize solubility and intestinal permeability properties of generic drugs under development, we used a list of 61 drugs which were classified as BCS 1, 2, 3, and 4 drugs with certainty in the World Health Organization Model List of Essential Medicines. Applying this list to evaluation of 263 ANDA approvals of BCS drugs during the period of 2000 to 2011 indicated 110 approvals (41.8%) for Class 1 drugs (based on both biowaiver and in vivo bioequivalence studies), 55 (20.9%) approvals for Class 2 drugs, 98 (37.3%) approvals for Class 3 drugs, and no (0%) approvals for Class 4 drugs. The present data indicated a trend of more ANDA approvals of BCS Class 1 drugs than Class 3 or Class 2 drugs. Antiallergic drugs in Class 1, drugs for pain relief in Class 2 and antidiabetic drugs in Class 3 have received the largest number of approvals during this period.     

Background suppression in arterial spin labeling MRI with a separate neck labeling coil

In arterial spin labeling (ASL) MRI to measure cerebral blood flow (CBF), pair-wise subtraction of temporally adjacent non-labeled and labeled images often can not completely cancel the background static tissue signal because of temporally fluctuating physiological noise. While background suppression (BS) by inversion nulling improves CBF temporal stability, imperfect pulses compromise CBF contrast. Conventional BS techniques may not be applicable in small animals because the arterial transit time is short. This study presents a novel approach of BS to overcome these drawbacks using a separate 'neck' radiofrequency coil for ASL and a 'brain' radiofrequency coil for BS with the inversion pulse placed before spin labeling. The use of a separate 'neck' coil for ASL should also improve ASL contrast. This approach is referred to as the inversion-recovery BS with the two-coil continuous ASL (IR-cASL) technique. The temporal and spatial contrast-to-noise characteristics of basal CBF and CBF-based fMRI of hypercapnia and forepaw stimulation in rats at 7 Tesla were analyzed. IR-cASL yielded two times better temporal stability and 2.0-2.3 times higher functional contrast-to-noise ratios for hypercapnia and forepaw stimulation compared with cASL without BS in the same animals. The Bloch equations were modified to provide accurate CBF quantification at different levels of BS and for multislice acquisition where different slices have different degree of BS and residual degree of labeling. Improved basal CBF and CBF-based fMRI sensitivity should lead to more accurate CBF quantification and should prove useful for imaging low CBF conditions such as in white matter and stroke.     

Metabolic, toxicological, and safety considerations for drugs used to treat ADHD

INTRODUCTION: Pharmacotherapy is frequently used to treat symptoms of attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. The typically prescribed agents for ADHD have varying durations of effect and degrees of efficacy. The broad range of pharmacological treatments available allows for both single and combination therapies for achieving optimal therapeutic effects. Metabolic, toxicological, and safety information are critical for an informed evaluation of the risk/benefit considerations in prescribing practices. AREAS COVERED: This article focuses on the medications with current FDA approval for use in the treatment of ADHD in pediatric and adult populations. This review covers the stimulants (amphetamine and methylphenidate) and non-stimulants (atomoxetine, clonidine extended release, and guanfacine extended release) used to treat ADHD and presents an overview of their respective metabolic, toxicological, and safety features. A literature search and review of the relevant medications were carried out using the PubMed database up to November 2011. EXPERT OPINION: New trends in study design based on drug profiles include the use of adjuvant therapies and the inclusion of patients with comorbidities. The recent expansion of inclusion/exclusion criteria in pediatric clinical trials of ADHD allows for a more rigorous analysis of associated benefits and risks with the use of adjuvant therapy.     

Tramiprosate in mild-to-moderate Alzheimer’s disease – a randomized,double-blind,placebo-controlled,multi-centre study (the Alphase Study)

Introduction

The aim of the study was to assess the clinical efficacy, safety, and disease-modification effects of tramiprosate (homotaurine, ALZHEMED^TM) in mild-to-moderate Alzheimer’s disease (AD).

Material and methods

Double-blind, placebo-controlled, randomized trial in 67 clinical centres across North America. Patients aged ≥ 50 years, with mild-to-moderate AD (Mini-Mental State Examination score between 16 and 26) and on stable doses of cholinesterase inhibitors, alone or with memantine. Intervention: 78-week treatment with placebo, tramiprosate 100 mg or tramiprosate 150 mg BID. Measurements: Alzheimer Disease Assessment Scale – cognitive subscale (ADAS-cog) and Clinical Dementia Rating – Sum of Boxes (CDR-SB) assessments were performed at baseline and every 13 weeks. Baseline and 78-week magnetic resonance imaging (MRI) hippocampus volume (HV) measurements were conducted in a subgroup of patients.

Results

A total of 1,052 patients were enrolled and 790 (75.1%) completed the 78-week trial. Patient discontinuation and reasons for withdrawal were similar across groups. Planned analyses did not reveal statistically significant between-group differences. Lack of adequate statistical validity of the planned analysis models led to the development of revised predictive models. These adjusted models showed a trend toward a treatment effect for ADAS-cog (P = 0.098) and indicated significantly less HV loss for tramiprosate 100 mg (P = 0.035) and 150 mg (P = 0.009) compared to placebo. The incidence of adverse events was similar across treatment groups.

Conclusions

The primary planned analyses did not show a significant treatment effect, but were confounded by unexplained variance. Post-hoc analyses showed a significant treatment-related reduction in HV loss. However, there was only a trend towards slowing of decline on the ADAS-cog and no slowing of decline on the CDR-SB. These results must be interpreted in consideration of the limitations of clinical and disease-modification outcome measures and their relationship, the heterogeneity of the disease and the impact of confounding demographic and clinical variables.     

Cost-effectiveness of integrating methadone maintenance and antiretroviral treatment for HIV-positive drug users in Vietnam's injection-driven HIV epidemics

Drug use negatively affects adherence to and outcomes of antiretroviral treatment (ART). This study evaluated the cost-effectiveness of integrating methadone maintenance treatment (MMT) with ART for HIV-positive drug users (DUs) in Vietnam. A decision analytical model was developed to compare the costs and consequences of 3 HIV/AIDS treatment strategies for DUs: (1) only ART, (2) providing ART and MMT in separated sites (ART-MMT), and (3) integrating ART and MMT with direct administration (DAART-MMT). The model was parameterized using empirical data of costs and outcomes extracted from the MMT and ART cohort studies in Vietnam, and international published sources. Probabilistic sensitivity analysis was conducted to examine the model's robustness. The base-case analysis showed that the cost-effectiveness ratio of ART, DAART-MMT, and ART-MMT strategies was USD 1358.9, 1118.0 and 1327.1 per 1 Quality-Adjusted Life Year (QALY), equivalent to 1.22, 1.00, and 1.19 times Gross Domestic Product per capita (GDPpc). The incremental cost-effectiveness ratio for DAART-MMT and ART-MMT versus ART strategy was 569.4 and 1227.8, approximately 0.51 and 1.10 times GDPpc/QALY. At the willingness to pay threshold of 3 times GDPpc, the probability of being cost-effective of DAART-MMT versus ART was 86.1%. These findings indicated that providing MMT along with ART for HIV-positive DUs is a cost-effective intervention in Vietnam. Integrating MMT and ART services could facilitate the use of directly observed therapy that supports treatment adherence and brings about clinically important improvements in health outcomes. This approach is also incrementally cost-effective in this large injection-driven HIV epidemic.     

A new flavan-3-ol and the anti-inflammatory effect of flavonoids from the fruit peels of Wisteria floribunda

A new flavan-3-ol, (+)-afzelechin 5-O-β-d-glucopyranoside (2), together with 13 known flavonoids (1, 3-14), was isolated from the fruit peels of Wisteria floribunda. Their structures were assigned by detailed interpretation of NMR, MS, and CD spectroscopic data, as well as by comparing with published reports. The in vitro anti-inflammatory activity of the isolated compounds (1-14) was examined. Among them, compounds 3, 6, and 9 produced highest inhibitory effects on tumor necrosis factor alpha (TNF-α)-induced nuclear factor kappa-B activation in HepG2 cells with IC(50) values of 14.1, 16.5, and 11.9 μM, respectively. With the exception of compound 6, the compounds significantly inhibited the accumulation of pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 proteins in TNF-α-stimulated HepG2 cells at a concentration as low as 0.1 μM.