Summary Background Existing treatments for postherpetic neuralgia, and for neuropathic pain in general, are limited by modest efficacy and unfavourable side-effects. The angiotensin II type 2 ...receptor (AT2 R) is a new target for neuropathic pain. EMA401, a highly selective AT2 R antagonist, is under development as a novel neuropathic pain therapeutic agent. We assessed the therapeutic potential of EMA401 in patients with postherpetic neuralgia. Methods In this multicentre, placebo-controlled, double-blind, randomised, phase 2 clinical trial, we enrolled patients (aged 22–89 years) with postherpetic neuralgia of at least 6 months' duration from 29 centres across six countries. We randomly allocated 183 participants to receive either oral EMA401 (100 mg twice daily) or placebo for 28 days. Randomisation was done according to a centralised randomisation schedule, blocked by study site, which was generated by an independent, unmasked statistician. Patients and staff at each site were masked to treatment assignment. We assessed the efficacy, safety, and pharmacokinetics of EMA401. The primary efficacy endpoint was change in mean pain intensity between baseline and the last week of dosing (days 22–28), measured on an 11-point numerical rating scale. The primary efficacy analysis was intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000822987. Findings 92 patients were assigned to EMA401 and 91 were assigned to placebo. The patients given EMA401 reported significantly less pain compared with baseline values in the final week of treatment than did those given placebo (mean reductions in pain scores −2·29 SD 1·75 vs −1·60 1·66; difference of adjusted least square means −0·69 SE 0·25; 95% CI −1·19 to −0·20; p=0·0066). No serious adverse events related to EMA401 occurred. Overall, 32 patients reported 56 treatment-emergent adverse events in the EMA401 group compared with 45 such events reported by 29 patients given placebo. Interpretation EMA401 (100 mg twice daily) provides superior relief of postherpetic neuralgia compared with placebo at the end of 28 days of treatment. EMA401 was well tolerated by patients. Funding Spinifex Pharmaceuticals.
Abstract Purpose We aimed to determine the effects of implementing risk-stratified care for low back pain in family practice on physician's clinical behavior, patient outcomes, and costs. Methods The ...IMPaCT Back Study (IMplementation to improve Patient Care through Targeted treatment) prospectively compared separate patient cohorts in a preintervention phase (6 months of usual care) and a postintervention phase (12 months of stratified care) in family practice, involving 64 family physicians and linked physical therapy services. A total of 1,647 adults with low back pain were invited to participate. Stratified care entailed use of a risk stratification tool to classify patients into groups at low, medium, or high risk for persistent disability and provision of risk-matched treatment. The primary outcome was 6-month change in disability as assessed with the Roland-Morris Disability Questionnaire. Process outcomes captured physician behavior change in risk-appropriate referral to physical therapy, diagnostic tests, medication prescriptions, and sickness certifications. A cost-utility analysis estimated incremental quality-adjusted life-years and back-related health care costs. Analysis was by intention to treat. Results The 922 patients studied (368 in the preintervention phase and 554 in the postintervention phase) had comparable baseline characteristics. At 6 months follow-up, stratified care had a small but significant benefit relative to usual care as seen from a mean difference in Roland-Morris Disability Questionnaire scores of 0.7 (95% CI, 0.1-1.4), with a large, clinically important difference in the high risk group of 2.3 (95% CI, 0.8-3.9). Mean time off work was 50% shorter (4 vs 8 days, P = .03) and the proportion of patients given sickness certifications was 30% lower (9% vs 15%, P = .03) in the postintervention cohort. Health care cost savings were also observed. Conclusions Stratified care for back pain implemented in family practice leads to significant improvements in patient disability outcomes and a halving in time off work, without increasing health care costs. Wider implementation is recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Patterns of health-care use and comorbidities present in patients in the period before diagnosis of chronic obstructive pulmonary disease (COPD) are unknown. We investigated these factors to inform ...future case-finding strategies.
We did a retrospective analysis of a clinical cohort in the UK with data from Jan 1, 1990 to Dec 31, 2009 (General Practice Research Database and Optimum Patient Care Research Database). We assessed patients aged 40 years or older who had an electronically coded diagnosis of COPD in their primary care records and had a minimum of 3 years of continuous practice data for COPD (2 years before diagnosis up to a maximum of 20 years, and 1 year after diagnosis) and at least two prescriptions for COPD since diagnosis. We identified missed opportunites to diagnose COPD from routinely collected patient data by reviewing patterns of health-care use and comorbidities present before diagnosis. We assessed patterns of health-care use in terms of lower respiratory consultations (infective and non-infective), lower respiratory consultations with a course of antibiotics or oral steroids, and chest radiography. If these events did not lead to a diagnosis of COPD, they were deemed to be missed opportunities. This study is registered with ClinicalTrials.gov, number NCT01655667.
We assessed data for 38,859 patients. Opportunities for diagnosis were missed in 32,900 (85%) of 38,859 patients in the 5 years immediately preceding diagnosis of COPD; in 12,856 (58%) of 22,286 in the 6-10 years before diagnosis, in 3943 (42%) of 9351 in the 11-15 years before diagnosis; and in 95 (8%) of 1167 in the 16-20 years before diagnosis. Between 1990 and 2009, we noted decreases in the age at diagnosis (0·05 years of age per year, 95% CI 0·03-0·07) and yearly frequency of lower respiratory prescribing consultations (rate ratio 0·982 opportunities per year, 95% CI 0·979-0·985). Prevalence of all comorbidities present at COPD diagnosis increased except for asthma and bronchiectasis, which decreased between 1990 and 2007, from 281 (33·4%) of 842 patients to 451 of 1465 (30·8%) for asthma, and from 53 of 842 (6·3%) to 53 of 1465 (3·6%) for bronchiectasis. In the 2 years before diagnosis, of 6897 patients who had had a chest radiography, only 2296 (33%) also had spirometry.
Opportunities to diagnose COPD at an earlier stage are being missed, and could be improved by case-finding in patients with lower respiratory tract symptoms and concordant long-term comorbidities.
UK Department of Health, Research in Real Life.
Summary Background Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ...ischaemic brain damage in human beings. Methods For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12–95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov , number NCT00728182. Findings Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment—12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38–0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42–0·83). Interpretation Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. Funding NoNO Inc and Arbor Vita Corp.
Abstract Objective We sought to characterize maternal health profiles and birth outcomes among First Nations people living in Southern Ontario. Methods We performed a retrospective chart review of ...all 453 women from the Six Nations Reserve, Ontario, who were pregnant between 2005 and 2010. Maternal health behaviours, past medical history, physical measurements, birth outcomes, and newborn characteristics were abstracted. Key maternal and newborn characteristics were compared with those of a cohort of non-First Nations women recruited from nearby Hamilton, Ontario. Results The average age of women in the study cohort was 25.1 ± 6.2 (mean ± SD) years, and 75.8% were multiparous. The mean pre-pregnancy BMI was 28.3 ± 6.6 kg/m2 , and the average weight gain in pregnancy was 14.9 ± 8.3 kg. Mean weight gain during pregnancy was inversely associated with pre-pregnancy BMI, and 57.1% of women gained more than the recommended weight. The prevalence of type 2 diabetes or gestational diabetes was 4.7%, hypertension was present before or during pregnancy in 5.6%, and 35% used tobacco during pregnancy. The mean gestational age at delivery was 39.5 ± 1.7 weeks and the mean crude birth weight was 3619 ± 557 g. The main determinants of newborn weight included sex of the newborn, pre-pregnancy BMI, and weight gain during pregnancy. Compared with a contemporary cohort of 622 non-First Nations mothers and newborns, First Nations mothers were, on average, younger (25.1 vs. 32.1 years; P < 0.001), had a higher mean pre-pregnancy BMI (28.3 vs. 26.8 kg/m2 ; P < 0.001), and were more likely to use tobacco during pregnancy (35.0% vs. 14.4%; P < 0.001). First Nations newborns had significantly higher mean birth weight (+176 grams) and length (+2.3 cm) than non-First Nations newborns. Conclusion First Nations mothers from the Six Nations Reserve tended to have a high pre-pregnancy BMI, tended to gain more than the recommended weight during pregnancy, and commonly used tobacco during pregnancy. Programs to prevent overweight/ obesity and excess weight gain during pregnancy and to minimize smoking are required among women of child-bearing age in this community.
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