We studied 50 consecutive patients presenting at an accident department after rear-end vehicle collisions and recorded symptoms and psychological test scores within one week of injury, at three months and at two years. The range of neck movement was noted at three months.
Concerns remain about the safety of adding long-acting β2-agonists to inhaled glucocorticoids for the treatment of asthma. In a postmarketing safety study mandated by the Food and Drug Administration, we evaluated whether the addition of formoterol to budesonide maintenance therapy increased the risk of serious asthma-related events in patients with asthma.In this multicenter, double-blind, 26-week study, we randomly assigned patients, 12 years of age or older, who had persistent asthma, were receiving daily asthma medication, and had had one to four asthma exacerbations in the previous year to receive budesonide-formoterol or budesonide alone. Patients with a history of life-threatening asthma were excluded. The primary end point was the first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization), as assessed in a time-to-event analysis. The noninferiority of budesonide-formoterol to budesonide was defined as an upper limit of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The primary efficacy end point was the first asthma exacerbation, as assessed in a time-to-event analysis.A total of 11,693 patients underwent randomization, of whom 5846 were assigned to receive budesonide-formoterol and 5847 to receive budesonide. A serious asthma-related event occurred in 43 patients who were receiving budesonide-formoterol and in 40 patients who were receiving budesonide (hazard ratio, 1.07; 95% confidence interval [CI], 0.70 to 1.65]); budesonide-formoterol was shown to be noninferior to budesonide alone. There were two asthma-related deaths, both in the budesonide-formoterol group; one of these patients had undergone an asthma-related intubation. The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P=0.002).Among adolescents and adults with predominantly moderate-to-severe asthma, treatment with budesonide-formoterol was associated with a lower risk of asthma exacerbations than budesonide and a similar risk of serious asthma-related events. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT01444430 .).
The P2X7 purinergic receptor antagonist AZD9056 was evaluated in a phase IIa study and subsequently in a phase IIb study to assess the effects of orally administered AZD9056 on the signs/symptoms of rheumatoid arthritis (RA), with American College of Rheumatology 20% response criteria (ACR20) as the primary outcome.
Methods
Both studies were randomised, double-blind, placebo-controlled, parallel-group studies in patients with RA receiving methotrexate or sulphasalazine. Phase IIa was an ascending-dose trial in two cohorts (n=75) using AZD9056 administered daily over 4 weeks. Phase IIb included an open-label etanercept treatment group. Patients were randomised to receive treatment for 6 months with 50, 100, 200 or 400 mg AZD9056 (oral, once a day) or matching placebo (oral, once a day), or subcutaneous etanercept (50 mg once a week).
Results
In phase IIa, 65% of AZD9056 recipients at 400 mg/day responded at the ACR20 level compared with 27% of placebo-treated patients. A significant reduction in swollen and tender joint count was observed in the actively treated group compared with placebo, whereas no effect on acute-phase response was observed. Of 385 randomised patients in the phase IIb study, 383 received treatment. AZD9056 (all doses) had no clinically or statistically significant effect on RA relative to placebo as measured by the proportion of patients meeting the ACR20 criteria at 6 months and further supported by secondary end points. In both studies AZD9056 was well tolerated up to 400 mg/day.
Conclusions
AZD9056 does not have significant efficacy in the treatment of RA, and the P2X7 receptor does not appear to be a therapeutically useful target in RA.
A Consensus panel approach was used in Israel to develop a list of clinical indications for which there was agreement that cholecystectomy should be performed. Nine physicians from different disciplines were asked to score a list of 266 clinical indications for cholecystectomy. Each indication was scored on a scale of 1 (inappropriate, i.e. health risks exceed health benefits) to 9 (appropriate, i.e. benefits exceed risks). Each indication also included one of four comorbidity levels (none to high). Agreement and disagreement were defined and panelists met to discuss, modify and rescore the list. The composition of the panel and definitions of agreement had a considerable impact on the preparation of a list of agreed, appropriate indications for cholecystectomy. Gastroenterologists in the panel were less likely to recommend surgery than either surgeons or general internists both before and after the panel discussion. Following the discussion the level of agreement (defined as after discarding the highest and lowest score all of the remaining seven panelists were in a 3-point range) increased from 39% to 46% (p < 0.08) and disagreement decreased from 27% to 18% (p < 0.01). Fifty-nine of the 266 indications were considered appropriate with agreement.
Background: Asthma management aims to improve control and reduce future risk of poor outcomes, including exacerbations. Inhaled fluticasone propionate/salmeterol (FP/SAL) is effective in achieving and maintaining control and reducing exacerbations. Aim: To evaluate the efficacy of FP/SAL in achieving asthma control, defined as per symptom domain control levels in GINA 2016, and absence of exacerbations. Methods: A post hoc analysis of the GOAL study including 3416 patients in the intent-to-treat population. At randomisation, patients were stratified by prior medication: inhaled corticosteroid (ICS)-naïve (Stratum [S1])/low-dose ICS (S2)/medium-dose ICS (S3), and assigned to receive FP/SAL or FP. Primary endpoint: proportion of patients that achieved well-controlled (WC) or partially-controlled (PC) asthma and no exacerbations; secondary endpoint: WC asthma and no exacerbations. Control was evaluated during the last 4 weeks of each dose titration step. Results: In all strata, more patients achieved WC/PC asthma with FP/SAL v FP: S1, 91% v 85% (p=0.003); S2, 86% v 82% (p=0.072); S3 76% v 66% (p<0.001), as well as for WC asthma: S1, 64% v 56% (p=0.005); S2, 59% v 41% (p<0.001); S3 40% v 22% (p<0.001) (Figure). Conclusion: A greater proportion of patients who entered the study with uncontrolled asthma achieved WC and PC asthma according to GINA 2016 criteria with FP/SAL than with FP alone. Funding: GSK (SAM40027)
The integration of physical and psychological assessment is frequently problematic. Psychological tests are often cumbersome and difficult to interpret. There would appear to be a need for a simple assessment method that would identify distress and help alert the clinician to the need for a more comprehensive assessment. The Distress and Risk Assessment Method is derived from a simple set of scales validated for use with patients with low-back pain. It offers a simple classification of patients into those showing no psychological distress, those at risk of developing major psychological overlay, and those clearly distressed. Four patient types can be identified on the basis of scores on two short questionnaires. The construction of the Distress and Risk Assessment Method is described and validity data (both clinical and psychological) are presented. The use of the Distress and Risk Assessment Method in the prediction of outcome of treatment is presented, and the paper concludes with general guidelines for its use.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)