3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors and the Risk of Cancer

Background During the past 15 years there has been an exponential increase in the number of prescriptions for lipid-lowering drugs. Uncertainties remain about the long-term impact of these medications on cancer, which is particularly bothersome given that the duration of these treatments may extend for several decades.\ud Objective To explore the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence.\ud Methods Using the administrative health databases of the Régie de l'Assurance-Maladie du Québec we performed a nested case-control study. We selected a cohort of 6721 beneficiaries of the health care plan of Quebec who were free of cancer for at least 1 year at cohort entry, 65 years and older, and treated with lipid-modifying agents. Cohort members were selected between 1988 and 1994 and were followed up for a median period of 2.7 years. From the cohort, 542 cases of first malignant neoplasm were identified, and 5420 controls were randomly selected. Users of HMG-CoA reductase inhibitors were compared with users of bile acid–binding resins as to their risk of cancer. Specific cancer sites were also considered.\ud Results Users of HMG-CoA reductase inhibitors were found to be 28% less likely than users of bile acid–binding resins to be diagnosed as having any cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific cancer sites under study were found to be not or inversely associated with the use of HMG-CoA reductase inhibitors.\ud Conclusion The results of our study provide some degree of reassurance about the safety of HMG-CoA reductase inhibitors

A case of intermittent left bundle branch block

An 82-year-old woman with uncontrolled hypertension and occasional exertional dyspnea was found to be in intermittent left bundle branch block (LBBB). Her laboratory results, echocardiogram, and ischemic workup were unremarkable. This case highlights that intermittent LBBB is not always associated with coronary ischemia, vasospasm, blunt cardiac injury, drugs, and high catecholaminergic or inflammatory states

Pulmonary rehabilitation following exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Guidelines have provided positive recommendations for pulmonary rehabilitation after exacerbations of chronic obstructive pulmonary disease (COPD), but recent studies indicate that postexacerbation rehabilitation may not always be effective in patients with unstable COPD. OBJECTIVES: To assess effects of pulmonary rehabilitation after COPD exacerbations on hospital admissions (primary outcome) and other patient-important outcomes (mortality, health-related quality of life (HRQL) and exercise capacity). SEARCH METHODS: We identified studies through searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PEDro (Physiotherapy Evidence Database) and the Cochrane Airways Review Group Register of Trials. Searches were current as of 20 October 2015, and handsearches were run up to 5 April 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing pulmonary rehabilitation of any duration after exacerbation of COPD versus conventional care. Pulmonary rehabilitation programmes had to include at least physical exercise (endurance or strength exercise, or both). We did not apply a criterion for the minimum number of exercise sessions a rehabilitation programme had to offer to be included in the review. Control groups received conventional community care without rehabilitation. DATA COLLECTION AND ANALYSIS: We expected substantial heterogeneity across trials in terms of how extensive rehabilitation programmes were (i.e. in terms of number of completed exercise sessions; type, intensity and supervision of exercise training; and patient education), duration of follow-up (< 3 months vs ≥ 3 months) and risk of bias (generation of random sequence, concealment of random allocation and blinding); therefore, we performed subgroup analyses that were defined before we carried them out. We used standard methods expected by Cochrane in preparing this update, and we used GRADE for assessing the quality of evidence. MAIN RESULTS: For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self-management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive.Eight studies involving 810 participants contributed data on hospital readmissions. Moderate-quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I(2) = 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta-analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I(2) = 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies.High-quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health-related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) -7.80, 95% CI -12.12 to -3.47; I(2) = 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High-quality evidence shows that six-minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I(2) = 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health-related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review.Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event. AUTHORS' CONCLUSIONS: Overall, evidence of high quality shows moderate to large effects of rehabilitation on health-related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self-management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality

Evidenzbasierte Psychotherapie der Panikstörung mit und ohne Agoraphobie : ein Überblick zur S1-Leitlinie der Deutschen Gesellschaft für Psychologie

Alpers GW, Gerlach AL, Heinrichs N. Evidence-based psychotherapy of panic disorder with or without agoraphobia. Psychotherapeut. 2011;56(6):535-548.From the evidence reported in the recent guidelines [Heinrichs et al. (2009) Evidenzbasierte Leitlinie zur Psychotherapie der Panikstorung mit und ohne Agoraphobie. Hogrefe, Gottingen] the following conclusions can be drawn with respect to the treatment of panic disorder with or without agoraphobia, as well as for agoraphobia without panic disorder: Every psychotherapy should be preceded by suitable diagnostics and a case formulation. The effectiveness of every psychotherapy should be evaluated with well established measures. For the treatment of panic disorder without agoraphobia, cognitive behavioral treatment (CBT) and applied relaxation have been shown to be effective (evidence grade 1). For panic disorder with agoraphobia, CBT, combination treatment (CBT plus medication), as well as panic-focused psychodynamic psychotherapy in the outpatient setting have shown short-term effectiveness (evidence grade 1). Longer lasting effects have been documented for CBT (evidence grade 1). For agoraphobia without panic disorder, CBT with a focus on situational exposure can be recommended (evidence grade 1)

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis

Background: Respiratory tract infection with Pseudomonas aeruginosa occurs inmost people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate. This is an update of a Cochrane review first published in 2003, and previously updated in 2006 and 2009. Objectives: To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms). Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 08 September 2014. Selection criteria: We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls. Data collection and analysis: Both authors independently selected trials, assessed risk of bias and extracted data. Main results: The search identified 49 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used. Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months. One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% confidence interval 0.02 to 0.79). One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non- inferiority or equivalence. A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups. A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures. An analysis performed in this review (not adjusted for age) showed fewer participants in the cycled therapy group with one or more isolates of Pseudomonas aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28). Authors’ conclusions: We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials of two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis

Getting It Right: Being Smarter about Clinical Trials

A major NIH meeting led to recommendations for conducting better clinical trials

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

CONTEXT: Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance. OBJECTIVE: To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls. DESIGN: Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs. SETTING: Referral practice and research center. PARTICIPANTS: 60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test. MAIN OUTCOME MEASURES: Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof. RESULTS: CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests. CONCLUSION: A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition