Buflomedil for intermittent claudication

Background : Intermittent claudication (IC) is pain caused by chronic occlusive arterial disease, that develops in a limb during exercise and is relieved with rest. Buflomedil is a vasoactive agent used to treat peripheral vascular disease. However, its clinical efficacy for IC has not yet been critically examined. This is an update of a Cochrane review first published in 2000, and previously updated in 2007 and 2008. Objectives : To evaluate the available evidence on the efficacy of buflomedil for IC. Search methods : For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Selection criteria : Double-blinded, randomized controlled trials (RCTs) in patients with IC (Fontaine stage II) receiving oral buflomedil compared with placebo. Pain-free walking distance (PFWD) and maximum walking distance (MWD) were analysed by standardized exercise test. Data collection and analysis : Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. Main results : We included two RCTs with 127 participants. Both RCTs showed moderate improvements in PFWD for patients on buflomedil. This improvement was statistically significant for both trials (WMD 75.1 m, 95% confidence interval (CI) 20.6 to 129.6; WMD 80.6 m, 95% CI 3.0 to 158.2), the latter being a wholly diabetic population. For both RCTs, MWD gains were statistically significant with wide confidence intervals (WMD 80.7 m, 95% CI 9.4 to 152; WMD 171.4 m, 95% CI 51.3 to 291.5), respectively. Authors' conclusions : There is little evidence available to evaluate the efficacy of buflomedil for IC. Most trials were excluded due to poor quality. The two included trials showed moderately positive results; these are undermined by publication bias since we know of at least another four unpublished, irretrievable, and inconclusive studies. Buflomedil's benefit is small in relation to safety issues and its narrow therapeutic range

Silence of the limbs: pharmacological symptomatic treatment of intermittent claudication

Several oral "vasoactive" drugs claim to increase walking capacity in patients with intermittent claudication (IC). Naftidrofuryl, cilostazol, buflomedil, and pentoxifylline are the most studied molecules. Although spanning several decades, several studies underlying these claims were not properly designed, underpowered or showed clinically doubtful outcomes. The evidence for these "vasoactive" drugs has always been received with scepticism, creating the need for systematic reviews and meta-analyses. This brief review discusses the benefit-risk assessment of vasoactive drugs, by applying a systematic review to evaluate randomized, placebo-controlled trials. Oral naftidrofuryl and cilostazol have an acceptable safety profile as well as sustained evidence (documented by Cochrane analyses) of increased walking capacity. Subsequently, these drugs entered recommendations for peripheral arterial disease (PAD). In contrast, buflomedil and pentoxifylline have limited and/or doubtful evidence to increase walking capacity. Moreover, there were safety concerns about the narrow therapeutic range of buflomedil. Most other "vasoactive" drugs were either inappropriately or insufficiently tested or showed no significant if not negative effects on IC. "Vasoactive" drugs are no substitutes for lifestyle or exercise therapy but are adjuvant treatment to the well-appreciated triad of cardiovascular prevention (antiplatelet agents, statins and ACE-inhibitors), of which statins in their own right have documented claims to significantly increase walking capacity. "Vasoactive" drugs may have a place in the pharmacological management of symptomatic PAD in addition to the basic cardiovascular pharmacotherapy, when revascularization is not indicated, when exercise therapy is not feasible or when there is still insufficient benefit

Policies for replacing long-term indwelling urinary catheters in adults

We would also like to thank the foll owing Cochrane Incontinence editorial base staff members for their help and support with this re-view: Cathryn Glazener, Sheila Wallace, Mandy Fader, Peter Her-bison and Suzanne Macdonald. The review authors are grateful to Toby Lasseron for his advice. The review authors are thankful to Dr Beverly Priefer for responding to our query about Priefer 1982. Policies for replacing long‐term indwelling urinary catheters in adults, Protocol, Fergus PM Cooper, Cameron Edwin Alexander, Sanjay Sinha, Muhammad Imran Omar; https://doi.org/10.1002/14651858.CD011115; 14 May 2014Peer reviewedPublisher PD

Formoterol versus short-acting beta-agonists as relief medication for adults and children with asthma

Background Formoterol is a long-acting beta(2)-agonist but because it has a fast onset of action it can also be used as a relief medication. Objectives To asses the efficacy and safety of formoterol as reliever therapy in comparison to short-acting beta(2)-agonists in adults and children with asthma. Search strategy We searched the Cochrane Airways Group Specialised Register and websites of clinical trial registers (for unpublished trial data), and we checked the Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was February 2010. Selection criteria Randomised, parallel-arm trials of at least 12 weeks duration in patients of any age and severity of asthma. Studies randomised patients to any dose of as-needed formoterol versus short-acting beta(2)-agonist. Concomitant use of inhaled corticosteroids or other maintenance medication was allowed, as long as this was not part of the randomised treatment regimen. Data collection and analysis Two authors independently selected trials for inclusion in the review. Outcome data were extracted by one author and checked by the second author. We sought unpublished data on primary outcomes. Main results This review includes eight studies conducted in 22,604 participants (mostly adults). Six studies compared formoterol as-needed to terbutaline whilst two studies compared formoterol with salbutamol as-needed. Background maintenance therapy varied across the trials. Asthma exacerbations and serious adverse events showed a direction of treatment effect favouring formoterol, of which one outcome reached statistical significance (exacerbations requiring a course of oral corticosteroids). In patients on short-acting beta(2)-agonists, 117 people out of 1000 had exacerbations requiring oral corticosteroids over 30 weeks, compared to 101 (95% CI 93 to 108) out of 1000 for patients on formoterol as-needed. In patients on maintenance inhaled corticosteroids there were also significantly fewer exacerbations requiring a course of oral corticosteroids on formoterol as-needed (Peto OR 0.75; 95% CI 0.62 to 0.91). There was one death per 1000 people on formoterol or on short-acting beta(2)-agonists. Authors' conclusions In adults, formoterol was similar to short-acting beta(2)-agonists when used as a reliever, and showed a reduction in the number of exacerbations requiring a course of oral corticosteroids. Clinicians should weigh the relatively modest benefits of formoterol as-needed against the benefits of single inhaler therapy and the potential danger of long-term use of long-acting beta(2)-agonists in some patients. We did not find evidence to recommend changes to guidelines that suggest that long-acting beta(2)-agonists should be given only to patients already taking inhaled corticosteroids.There was insufficient information reported from children in the included trials to come to any conclusion on the safety or efficacy of formoterol as relief medication for children with asthma

The Arecibo Galaxy Environment Survey: II. A HI view of the Abell cluster 1367 and its outskirts

We present 21 cm HI line observations of 5x1 square degrees centered on the local Abell cluster 1367 obtained as part of the Arecibo Galaxy Environment Survey. One hundred sources are detected (79 new HI measurements and 50 new redshifts), more than half belonging to the cluster core and its infalling region. Combining the HI data with SDSS optical imaging we show that our HI selected sample follows scaling relations similar to the ones usually observed in optically selected samples. Interestingly all galaxies in our sample appear to have nearly the same baryon fraction independently of their size, surface brightness and luminosity. The most striking difference between HI and optically selected samples resides in their large scale distribution: whereas optical and X-ray observations trace the cluster core very well, in HI there is almost no evidence of the presence of the cluster. Some implications on the determination of the cluster luminosity function and HI distribution for samples selected at different wavelength are also discussed.Comment: 22 pages, 15 figures, 4 tables. Accepted for publication on MNRAS Main Journal. High resolution version of this paper can be downloaded at http://www.astro.cf.ac.uk/pub/Luca.Cortese/papers/ages_a1367.pdf . Datacubes and catalogs can be downloaded at http://www.naic.edu/~ages/public_data.htm

Effect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data

D-PRESSURE Collaboration: et al.[Importance]: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.[Objective]: To systematically review whether supplementation with vitamin D or its analogues reduce BP.[Data Sources]: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.[Study Selection]: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.[Data Extraction and Synthesis]: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.[Main Outcomes and Measures]: Difference in SBP and DBP measured in an office setting.[Results]: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.[Conclusions and Relevance]: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.Peer reviewe

The Millisecond Radio Sky: Transients from a Blind Single Pulse Search

We present the results of a search for transient radio bursts of between 0.125 and 32 millisecond duration in two archival pulsar surveys of intermediate galactic latitudes with the Parkes multibeam receiver. Fourteen new neutron stars have been discovered, seven of which belong to the recently identified "rotating radio transients" (RRATs) class. Here we describe our search methodology, and discuss the new detections in terms of how the RRAT population relates to the general population of pulsars. The new detections indicate (1) that the galactic z-distribution of RRATs in the surveys closely resembles the distribution of pulsars, with objects up to 0.86 kpc from the galactic plane; (2) where measurable, the RRAT pulse widths are similar to that of individual pulses from pulsars of similar period, implying a similar beaming fraction; and (3) our new detections span a variety of nulling fractions, and thus we postulate that the RRATs may simply be nulling pulsars that are only "on" for less than a pulse period. Finally, the newly discovered object PSR J0941-39 may represent a link between pulsars and RRATs. This bizarre object was discovered as an RRAT, but in follow-up observations often appeared as a bright (~10 mJy) pulsar with a low nulling fraction. It is obvious therefore that a neutron star can oscillate between being an RRAT and a pulsar. Crucially, the sites of the RRAT pulses are coincident with the pulsar's emission, implying that the two emission mechanisms are linked, and that RRATs are not just pulsars observed from different orientations.Comment: 13 pages, 9 figures, accepted by MNRA

The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review

Background: Plantar heel pain is a commonly occurring foot complaint. Stretching is frequently utilised as a treatment, yet a systematic review focusing only on its effectiveness has not been published. This review aimed to assess the effectiveness of stretching on pain and function in people with plantar heel pain. Methods: Medline, EMBASE, CINAHL, AMED, and The Cochrane Library were searched from inception to July 2010. Studies fulfilling the inclusion criteria were independently assessed, and their quality evaluated using the modified PEDro scale. Results: Six studies including 365 symptomatic participants were included. Two compared stretching with a control, one study compared stretching to an alternative intervention, one study compared stretching to both alternative and control interventions, and two compared different stretching techniques and durations. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points. The methodologies and interventions varied significantly between studies, making meta-analysis inappropriate. Most participants improved over the course of the studies, but when stretching was compared to alternative or control interventions, the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme. Another study comparing different stretching techniques, showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term. Conclusions: There were too few studies to assess whether stretching is effective compared to control or other interventions, for either pain or function. However, there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term. Appropriately powered randomised controlled trials, utilizing validated outcome measures, blinded assessors and long-term follow up are needed to assess the efficacy of stretching