Test For Subgroup Differences Research Articles

Additional behavioural support as an adjunct to pharmacotherapy for smoking cessation.

Effective pharmacotherapies are available to help people who are trying to stop smoking, but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further. To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. We searched the Cochrane Tobacco Addiction Group Specialised Register in May 2015 for records with any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline that evaluated the addition of personal support or compared two or more intensities of behavioural support. Randomized or quasi-randomized controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount of behavioural support. The intervention condition had to involve person-to-person contact. The control condition could receive less intensive personal contact, or just written information. We did not include studies that used a contact-matched control to evaluate differences between types or components of support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. One author prescreened search results and two authors agreed inclusion or exclusion of potentially relevant trials. One author extracted data and another checked them.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically-validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. Forty-seven studies met the inclusion criteria with over 18,000 participants in the relevant arms. There was little evidence of statistical heterogeneity (I² = 18%) so we pooled all studies in the main analysis. There was evidence of a small but statistically significant benefit from more intensive support (RR 1.17, 95% CI 1.11 to 1.24) for abstinence at longest follow-up. All but four of the included studies provided four or more sessions of support to the intervention group. Most trials used NRT. We did not detect significant effects for studies where the pharmacotherapy was nortriptyline (two trials) or varenicline (one trial), but this reflects the absence of evidence.In subgroup analyses, studies that provided at least four sessions of personal contact for the intervention and no personal contact for the control had slightly larger estimated effects (RR 1.25, 95% CI 1.08 to 1.45; 6 trials, 3762 participants), although a formal test for subgroup differences was not significant. Studies where all intervention counselling was via telephone (RR 1.28, 95% CI 1.17 to 1.41; 6 trials, 5311 participants) also had slightly larger effects, and the test for subgroup differences was significant, but this subgroup analysis was not prespecified. In this update, the benefit of providing additional behavioural support was similar for the subgroup of trials in which all participants, including controls, had at least 30 minutes of personal contact (RR 1.18, 95% CI 1.06 to 1.32; 21 trials, 5166 participants); previously the evidence of benefit in this subgroup had been weaker. This subgroup was not prespecified and a test for subgroup differences was not significant. We judged the quality of the evidence to be high, using the GRADE approach. We judged a small number of trials to be at high risk of bias on one or more domains, but findings were not sensitive to their exclusion. Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 25%, based on a pooled estimate from 47 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support.

Workplace interventions to prevent work disability in workers on sick leave.

Work disability has serious consequences for individuals as well as society. It is possible to facilitate resumption of work by reducing barriers to return to work (RTW) and promoting collaboration with key stakeholders. This review was first published in 2009 and has now been updated to include studies published up to February 2015. To determine the effectiveness of workplace interventions in preventing work disability among sick-listed workers, when compared to usual care or clinical interventions. We searched the Cochrane Work Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO databases on 2 February 2015. We included randomised controlled trials (RCTs) of workplace interventions that aimed to improve RTW for disabled workers. We only included studies where RTW or conversely sickness absence was reported as a continuous outcome. Two review authors independently extracted data and assessed risk of bias of the studies. We performed meta-analysis where possible, and we assessed the quality of evidence according to GRADE criteria. We used standard methodological procedures expected by Cochrane. We included 14 RCTs with 1897 workers. Eight studies included workers with musculoskeletal disorders, five workers with mental health problems, and one workers with cancer. We judged six studies to have low risk of bias for the outcome sickness absence.Workplace interventions significantly improved time until first RTW compared to usual care, moderate-quality evidence (hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.20 to 2.01). Workplace interventions did not considerably reduce time to lasting RTW compared to usual care, very low-quality evidence (HR 1.07, 95% CI 0.72 to 1.57). The effect on cumulative duration of sickness absence showed a mean difference of -33.33 (95% CI -49.54 to -17.12), favouring the workplace intervention, high-quality evidence. One study assessed recurrences of sick leave, and favoured usual care, moderate-quality evidence (HR 0.42, 95% CI 0.21 to 0.82). Overall, the effectiveness of workplace interventions on work disability showed varying results.In subgroup analyses, we found that workplace interventions reduced time to first and lasting RTW among workers with musculoskeletal disorders more than usual care (HR 1.44, 95% CI 1.15 to 1.82 and HR 1.77, 95% CI 1.37 to 2.29, respectively; both moderate-quality evidence). In studies of workers with musculoskeletal disorders, pain also improved (standardised mean difference (SMD) -0.26, 95% CI -0.47 to -0.06), as well as functional status (SMD -0.33, 95% CI -0.58 to -0.08). In studies of workers with mental health problems, there was a significant improvement in time until first RTW (HR 2.64, 95% CI 1.41 to 4.95), but no considerable reduction in lasting RTW (HR 0.79, 95% CI 0.54 to 1.17). One study of workers with cancer did not find a considerable reduction in lasting RTW (HR 0.88, 95% CI 0.53 to 1.47).In another subgroup analysis, we did not find evidence that offering a workplace intervention in combination with a cognitive behavioural intervention (HR 1.93, 95% CI 1.27 to 2.93) is considerably more effective than offering a workplace intervention alone (HR 1.35, 95% CI 1.01 to 1.82, test for subgroup differences P = 0.17).Workplace interventions did not considerably reduce time until first RTW compared with a clinical intervention in workers with mental health problems in one study (HR 2.65, 95% CI 1.42 to 4.95, very low-quality evidence). We found moderate-quality evidence that workplace interventions reduce time to first RTW, high-quality evidence that workplace interventions reduce cumulative duration of sickness absence, very low-quality evidence that workplace interventions reduce time to lasting RTW, and moderate-quality evidence that workplace interventions increase recurrences of sick leave. Overall, the effectiveness of workplace interventions on work disability showed varying results. Workplace interventions reduce time to RTW and improve pain and functional status in workers with musculoskeletal disorders. We found no evidence of a considerable effect of workplace interventions on time to RTW in workers with mental health problems or cancer.We found moderate-quality evidence to support workplace interventions for workers with musculoskeletal disorders. The quality of the evidence on the effectiveness of workplace interventions for workers with mental health problems and cancer is low, and results do not show an effect of workplace interventions for these workers. Future research should expand the range of health conditions evaluated with high-quality studies.

Planned caesarean section for term breech delivery.

Planned caesarean section for term breech delivery.

Granulocyte transfusions for preventing infections in people with neutropenia or neutrophil dysfunction.

Despite modern antimicrobials and supportive therapy, bacterial and fungal infections are still major complications in people with prolonged disease-related or therapy-related neutropenia. Since the late 1990s there has been increasing demand for donated granulocyte transfusions to treat or prevent severe infections in people who lack their own functional granulocytes. This is an update of a Cochrane review first published in 2009. To determine the effectiveness and safety of prophylactic granulocyte transfusions compared with a control population not receiving this intervention for preventing all-cause mortality, mortality due to infection, and evidence of infection due to infection or due to any other cause in people with neutropenia or disorders of neutrophil function. We searched for randomised controlled trials (RCTs) and quasi-RCTs in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), CINAHL (from 1937), theTransfusion Evidence Library (from 1980) and ongoing trial databases to April 20 2015. Randomised controlled trials (RCTs) and quasi-RCTs comparing people receiving granulocyte transfusions to prevent the development of infection with a control group receiving no granulocyte transfusions. Neonates are the subject of another Cochrane review and were excluded from this review. There was no restriction by outcomes examined, but this review focuses on mortality, mortality due to infection and adverse events. We used standard methodological procedures expected by The Cochrane Collaboration. Twelve trials met the inclusion criteria. One trial is still ongoing, leaving a total of 11 trials eligible involving 653 participants. These trials were conducted between 1978 and 2006 and enrolled participants from fairly comparable patient populations. None of the studies included people with neutrophil dysfunction. Ten studies included only adults, and two studies included children and adults. Ten of these studies contained separate data for each arm and were able to be critically appraised. One study re-randomised people and therefore quantitative analysis was unable to be performed.Overall, the quality of the evidence was very low to low across different outcomes according to GRADE methodology. This was due to many of the studies being at high risk of bias, and many of the outcome estimates being imprecise.All-cause mortality was reported for nine studies (609 participants). There was no difference in all-cause mortality over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (seven studies; 437 participants; RR 0.92, 95% CI 0.63 to 1.36, very low-quality evidence).Mortality due to infection was reported for seven studies (398 participants). There was no difference in mortality due to infection over 30 days between people receiving prophylactic granulocyte transfusions and those that did not (six studies; 286 participants; RR 0.69, 95% CI 0.33 to 1.44, very low-quality evidence).The number of people with localised or systemic bacterial or fungal infections was reported for nine studies (609 participants). There were differences between the granulocyte dose subgroups (test for subgroup differences P = 0.01). There was no difference in the number of people with infections over 30 days between people receiving prophylactic granulocyte transfusions and those that did not in the low-dose granulocyte group (< 1.0 x 10(10) granulocytes per day) (four studies, 204 participants; RR 0.84, 95% CI 0.58 to 1.20; very low-quality evidence). There was a decreased number of people with infections over 30 days in the people receiving prophylactic granulocyte transfusions in the intermediate-dose granulocyte group (1.0 x 10(10) to 4.0 x 10(10) granulocytes per day) (4 studies; 293 participants; RR 0.40, 95% CI 0.26 to 0.63, low-quality evidence).There was a decreased number of participants with bacteraemia and fungaemia in the participants receiving prophylactic granulocyte transfusions (nine studies; 609 participants; RR 0.45, 95% CI 0.30 to 0.65, low-quality evidence).There was no difference in the number of participants with localised bacterial or fungal infection in the participants receiving prophylactic granulocyte transfusions (six studies; 296 participants; RR 0.75, 95% CI 0.50 to 1.14; very low-quality evidence).Serious adverse events were only reported for participants receiving granulocyte transfusions and donors of granulocyte transfusions. In people who are neutropenic due to myelosuppressive chemotherapy or a haematopoietic stem cell transplant, there is low-grade evidence that prophylactic granulocyte transfusions decrease the risk of bacteraemia or fungaemia. There is low-grade evidence that the effect of prophylactic granulocyte transfusions may be dose-dependent, a dose of at least 10 x 10(10) per day being more effective at decreasing the risk of infection. There is insufficient evidence to determine any difference in mortality rates due to infection, all-cause mortality, or serious adverse events.

Efficacy of low-level laser therapy on myofascial trigger point: a systematic review and meta-analysis of randomized clinical trials

BACKGROUND: A myofascial trigger point (MTrP) is defined as a hyperirritable spot in a palpable taut band of skeletal muscle fibers. It can produce referred pain, either on digital compression or spontaneously. Various approaches for MTrP treatment are available, such as massage, stretching, ischemic compression, dry needling and application of physical agents. . Among the latter, low-level laser therapy (LLLT), defined as non-invasive light source treatment that generates a single wavelength of light, might be considered as an option for treating patients with MTrPs. PURPOSE: To explore the evidence regarding the efficacy of LLLT to reduce pain in patients with MTrPs in the upper quarter muscles. METHODS: Pubmed, Scopus and PEDro electronic databases were consulted for articles published up to July 2014. Search strategy used the following keywords: ‘laser therapy, low-level’ ‘trigger points’ and ‘Pain Measurement’. Identified studies were screened against the following inclusion criteria: randomized controlled trial (RCT), at least one MTrP in the upper quarter muscles, and LLLT treatment for trigger point-related pain. RCTs that met these criteria were assessed for internal validity using the Cochrane Collaboration's tool for assessing risk of bias. RESULTS: Eleven studies were included in the review. The methodological quality was generally moderate-to-low, in particular the monitoring of pharmacological co-interventions in studies was lacking. A meta-analysis including ten trials was performed for estimate the efficacy of LLLT on pain rated with VAS. The estimated effect in standardized mean difference (SMD) was 1.01 (95%CI, 0.56 to 1.47) favouring laser therapy. Performing a subgroup analysis, according to the presence of uncontrolled pharmacological co-interventions, the meta-analysis revealed that in three studies in which co-interventions were absent, the estimated effect of laser was not statistically significant in reducing pain with a SMD of 0.16 (95% CI, -0.35 to 0.68) against those in which pharmacological co-intervention were not monitored with SMD of 1.34 (95% CI, 1.06 to 1.62). The test for subgroup differences resulted: Chi² = 15.56, df = 1 (P < 0.0001), I² = 93.6%. CONCLUSION: LLLT seems to be effective for reducing MTrP pain. However its effect is minimal when used as unique treatment. Due to the lacking of monitoring pharmacological co-interventions it is not possible to drew firm conclusion on the efficacy of the LLLT in reducing myofascial pain. Well-designed studies with an accurate monitoring of co-interventions that could interfere with the effect of the laser therapy are needed to support its use as approach for MTrP treatment. IMPLICATIONS: The effect of the laser therapy should not be widespread recommended as unique treatment of MTrP pain

Virtual reality for lower limb-related functions in stroke rehabilitation: systematic review and meta-analysis

MTrP treatment are available, such as massage, stretching, ischemic compression, dry needling and application of physical agents. Among the latter, low-level laser therapy (LLLT), defined as non-invasive light source treatment that generates a single wavelength of light, might be considered as an option for treating patients with MTrPs. Purpose: To explore the evidence regarding the efficacy of LLLT to reduce pain in patients with MTrPs in the upper quarter muscles. Methods: Pubmed, Scopus and PEDro electronic databases were consulted for articles published up to July 2014. Search strategy used the following keywords: ‘laser therapy, low-level’ ‘trigger points’ and ‘Pain Measurement’. Identified studies were screened against the following inclusion criteria: randomized controlled trial (RCT), at least one MTrP in the upper quarter muscles, and LLLT treatment for trigger point-related pain. RCTs that met these criteria were assessed for internal validity using the Cochrane Collaboration’s tool for assessing risk of bias. Results: Eleven studies were included in the review. The methodological quality was generally moderate-tolow, in particular the monitoring of pharmacological co-interventions in studies was lacking. A meta-analysis including ten trials was performed for estimate the efficacy of LLLT on pain rated with VAS. The estimated effect in standardized mean difference (SMD) was 1.01 (95%CI, 0.56 to 1.47) favouring laser therapy. Performing a subgroup analysis, according to the presence of uncontrolled pharmacological co-interventions, the meta-analysis revealed that in three studies in which cointerventions were absent, the estimated effect of laser was not statistically significant in reducing pain with a SMD of 0.16 (95%CI,−0.35 to 0.68) against those in which pharmacological co-intervention were not monitored with SMD of 1.34 (95%CI, 1.06 to 1.62). The test for subgroup differences resulted: Chi2 = 15.56, df = 1 (P< 0.0001), I2 = 93.6%. Conclusion(s): LLLT seems to be effective for reducing MTrP pain. However its effect is minimal when used as unique treatment. Due to the lacking of monitoring pharmacological co-interventions it is not possible to drew firm conclusion on the efficacy of the LLLT in reducing myofascial pain. Well-designed studies with an accurate monitoring of co-interventions that could interfere with the effect of the laser therapy are needed to support its use as approach for MTrP treatment. Implications: The effect of the laser therapy should not be widespread recommended as unique treatment of MTrP pain.

Dehydroepiandrosterone for women in the peri- or postmenopausal phase.

During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels. This can lead to the development of various perimenopausal and postmenopausal symptoms (for example hot flushes, night sweats, vaginal dryness). Dehydroepiandrosterone (DHEA) is one of the main precursors of androgens, which in turn are converted to testosterone and estrogens. It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function (for example libido, dyspareunia, satisfaction). Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety. This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of randomised controlled trials. To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase. The databases that we searched (3 June 2014) with no language restrictions applied were the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We also searched conference abstracts and citation lists in the ISI Web of Knowledge. Ongoing trials were searched in the trials registers. Reference lists of retrieved articles were checked. We included randomised controlled trials comparing any dose and form of DHEA by any route of administration versus any other active intervention, placebo or no treatment for a minimal treatment duration of seven days in peri- and postmenopausal women. Two authors independently extracted data after assessing eligibility for inclusion and quality of studies. Authors were contacted for additional information. Twenty-eight trials with 1273 menopausal women were included in this review. Data could be extracted from 16 trials to conduct the meta-analysis. The overall quality of the studies was moderate to low with the majority of studies that were included in the meta-analysis having reasonable methodology. Compared to placebo, DHEA did not improve quality of life (standardised mean difference (SMD) 0.16, 95% confidence interval (CI) -0.03 to 0.34, P = 0.10, 8 studies, 287 women (132 from parallel and 155 from crossover trials), I² = 0%, moderate quality evidence; one trial of the nine that reported on this outcome was removed in a sensitivity analysis as it was judged to be at high risk of bias). DHEA was found to be associated with androgenic side effects (mainly acne) (odds ratio (OR) 3.77, 95% CI 1.36 to 10.4, P = 0.01, 5 studies, 376 women, I² = 10%, moderate quality evidence) when compared to placebo. No associations were found with other adverse effects. It was unclear whether DHEA affected menopausal symptoms as the results from the trials were inconsistent and could not easily be pooled to provide an overall effect due to different types of measurement (for example continuous, dichotomous, change and end scores). DHEA was found to improve sexual function (SMD 0.31, 95% CI 0.07 to 0.55, P = 0.01, 5 studies, 261 women (239 women from parallel trials and 22 women from crossover trials), I² = 0%; one trial judged to be at high risk of bias was removed during sensitivity analysis) compared to placebo.There was no difference in the acne associated with DHEA when comparing studies that used oral DHEA (OR 2.16, 95% CI 0.47 to 9.96, P = 0.90, 3 studies, 136 women, I² = 5%, very low quality evidence) to one study that used skin application of DHEA (OR 2.74, 95% CI 0.10 to 74.87, P = 0.90, 1 study, 22 women, very low quality evidence). The effects did not differ for sexual function when studies using oral DHEA (SMD 0.11, 95% CI -0.13 to 0.35, P = 0.36, 5 studies, 340 women, I² = 0) were compared to a study using intravaginal DHEA (SMD 0.42, 95% CI 0.03 to 0.81, 1 study, 218 women). Test for subgroup differences: Chi² = 1.77, df = 1 (P = 0.18), I² = 43.4%. Insufficient data were available to assess quality of life and menopausal symptoms for this comparison.There were insufficient data available to compare the effects of DHEA to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects. No large differences in treatment effects were found for sexual function when comparing DHEA to HT (mean difference (MD) 1.26, 95% CI -0.21 to 2.73, P = 0.09, 2 studies, 41 women, I² = 0%). There is no evidence that DHEA improves quality of life but there is some evidence that it is associated with androgenic side effects. There is uncertainty whether DHEA decreases menopausal symptoms, but DHEA may slightly improve sexual function compared with placebo.

Interventions for improving upper limb function after stroke.

Improving upper limb function is a core element of stroke rehabilitation needed to maximise patient outcomes and reduce disability. Evidence about effects of individual treatment techniques and modalities is synthesised within many reviews. For selection of effective rehabilitation treatment, the relative effectiveness of interventions must be known. However, a comprehensive overview of systematic reviews in this area is currently lacking. To carry out a Cochrane overview by synthesising systematic reviews of interventions provided to improve upper limb function after stroke. We comprehensively searched the Cochrane Database of Systematic Reviews; the Database of Reviews of Effects; and PROSPERO (an international prospective register of systematic reviews) (June 2013). We also contacted review authors in an effort to identify further relevant reviews. We included Cochrane and non-Cochrane reviews of randomised controlled trials (RCTs) of patients with stroke comparing upper limb interventions with no treatment, usual care or alternative treatments. Our primary outcome of interest was upper limb function; secondary outcomes included motor impairment and performance of activities of daily living. When we identified overlapping reviews, we systematically identified the most up-to-date and comprehensive review and excluded reviews that overlapped with this. Two overview authors independently applied the selection criteria, excluding reviews that were superseded by more up-to-date reviews including the same (or similar) studies. Two overview authors independently assessed the methodological quality of reviews (using a modified version of the AMSTAR tool) and extracted data. Quality of evidence within each comparison in each review was determined using objective criteria (based on numbers of participants, risk of bias, heterogeneity and review quality) to apply GRADE (Grades of Recommendation, Assessment, Development and Evaluation) levels of evidence. We resolved disagreements through discussion. We systematically tabulated the effects of interventions and used quality of evidence to determine implications for clinical practice and to make recommendations for future research. Our searches identified 1840 records, from which we included 40 completed reviews (19 Cochrane; 21 non-Cochrane), covering 18 individual interventions and dose and setting of interventions. The 40 reviews contain 503 studies (18,078 participants). We extracted pooled data from 31 reviews related to 127 comparisons. We judged the quality of evidence to be high for 1/127 comparisons (transcranial direct current stimulation (tDCS) demonstrating no benefit for outcomes of activities of daily living (ADLs)); moderate for 49/127 comparisons (covering seven individual interventions) and low or very low for 77/127 comparisons.Moderate-quality evidence showed a beneficial effect of constraint-induced movement therapy (CIMT), mental practice, mirror therapy, interventions for sensory impairment, virtual reality and a relatively high dose of repetitive task practice, suggesting that these may be effective interventions; moderate-quality evidence also indicated that unilateral arm training may be more effective than bilateral arm training. Information was insufficient to reveal the relative effectiveness of different interventions.Moderate-quality evidence from subgroup analyses comparing greater and lesser doses of mental practice, repetitive task training and virtual reality demonstrates a beneficial effect for the group given the greater dose, although not for the group given the smaller dose; however tests for subgroup differences do not suggest a statistically significant difference between these groups. Future research related to dose is essential.Specific recommendations for future research are derived from current evidence. These recommendations include but are not limited to adequately powered, high-quality RCTs to confirm the benefit of CIMT, mental practice, mirror therapy, virtual reality and a relatively high dose of repetitive task practice; high-quality RCTs to explore the effects of repetitive transcranial magnetic stimulation (rTMS), tDCS, hands-on therapy, music therapy, pharmacological interventions and interventions for sensory impairment; and up-to-date reviews related to biofeedback, Bobath therapy, electrical stimulation, reach-to-grasp exercise, repetitive task training, strength training and stretching and positioning. Large numbers of overlapping reviews related to interventions to improve upper limb function following stroke have been identified, and this overview serves to signpost clinicians and policy makers toward relevant systematic reviews to support clinical decisions, providing one accessible, comprehensive document, which should support clinicians and policy makers in clinical decision making for stroke rehabilitation.Currently, no high-quality evidence can be found for any interventions that are currently used as part of routine practice, and evidence is insufficient to enable comparison of the relative effectiveness of interventions. Effective collaboration is urgently needed to support large, robust RCTs of interventions currently used routinely within clinical practice. Evidence related to dose of interventions is particularly needed, as this information has widespread clinical and research implications.

Physical Rehabilitation Approaches for the Recovery of Function and Mobility After Stroke

Physical Rehabilitation Approaches for the Recovery of Function and Mobility After Stroke

Tiotropium versus placebo for chronic obstructive pulmonary disease.

Tiotropium is an anticholinergic agent which has gained widespread acceptance as a once daily maintenance therapy for symptoms and exacerbations of stable chronic obstructive pulmonary disease (COPD). In the past few years there have been several systematic reviews of the efficacy of tiotropium, however, several new trials have compared tiotropium treatment with placebo, including those of a soft mist inhaler, making an update necessary. To evaluate data from randomised controlled trials (RCTs) comparing the efficacy of tiotropium and placebo in patients with COPD, upon clinically important endpoints. We searched the Cochrane Airways Group's Specialised Register of Trials (CAGR) and ClinicalTrials.gov up to February 2012. We included parallel group RCTs of three months or longer comparing treatment with tiotropium against placebo for patients with COPD. Two review authors independently assessed studies for inclusion and then extracted data on study quality and the outcome results. We contacted study authors and trial sponsors for additional information, and collected information on adverse effects from all trials. We analysed the data using Cochrane Review Manager 5, RevMan 5.2. This review included 22 studies of good methodological quality that had enrolled 23,309 participants with COPD. The studies used similar designs, however, the duration varied from three months to four years. In 19 of the studies, 18 mcg tiotropium once daily via the Handihaler dry powder inhaler was evaluated, and in three studies, 5 or 10 mcg tiotropium once daily via the Respimat soft mist inhaler was evaluated. Compared to placebo, tiotropium treatment significantly improved the mean quality of life (mean difference (MD) -2.89; 95% confidence interval (CI) -3.35 to -2.44), increased the number of participants with a clinically significant improvement (odds ratio (OR) 1.52; 95% CI 1.38 to 1.68), and reduced the number of participants with a clinically significant deterioration (OR 0.65; 95% CI 0.59 to 0.72) in quality of life (measured by the St George's Respiratory Questionnaire (SGRQ)). Tiotropium treatment significantly reduced the number of participants suffering from exacerbations (OR 0.78; 95% CI 0.70 to 0.87). This corresponds to a need to treat 16 patients (95% CI 10 to 36) with tiotropium for a year in order to avoid one additional patient suffering exacerbations, based on the average placebo event rate of 44% from one-year studies. Tiotropium treatment led to fewer hospitalisations due to exacerbations (OR 0.85; 95% CI 0.72 to 1.00), but there was no statistically significant difference in all-cause hospitalisations (OR 1.00; 95% CI 0.88 to 1.13) or non-fatal serious adverse events (OR 1.03; 95% CI 0.97 to 1.10). Additionally, there was no statistically significant difference in all-cause mortality between the tiotropium and placebo groups (Peto OR 0.98; 95% CI 0.86 to 1.11). However, subgroup analysis found a significant difference between the studies using a dry powder inhaler and those with a soft mist inhaler (test for subgroup differences: P = 0.01). With the dry powder inhaler there were fewer deaths in the tiotropium group (Peto OR 0.92; 95% CI 0.80 to 1.05) than in the placebo group (yearly rate 2.8%), but with the soft mist inhaler there were significantly more deaths in the tiotropium group (Peto OR 1.47; 95% CI 1.04 to 2.08) than in the placebo group (yearly rate 1.8%). It is noted that the rates of patients discontinuing study treatment were uneven, with significantly fewer participants withdrawing from tiotropium treatment than from placebo treatment (OR 0.66; 95% CI 0.59 to 0.73). Participants on tiotropium had improved lung function at the end of the study compared with those on placebo (trough forced expiratory volume in one second (FEV1) MD 118.92 mL; 95% CI 113.07 to 124.77). This review shows that tiotropium treatment was associated with a significant improvement in patients' quality of life and it reduced the risk of exacerbations, with a number needed to treat to benefit (NNTB) of 16 to prevent one exacerbation. Tiotropium also reduced exacerbations leading to hospitalisation but no significant difference was found for hospitalisation of any cause or mortality. Thus, tiotropium appears to be a reasonable choice for the management of patients with stable COPD, as proposed in guidelines. The trials included in this review showed a difference in the risk of mortality when compared with placebo depending on the type of tiotropium delivery device used. However, these results have not been confirmed in a recent trial when 2.5 mcg or 5 mcg of tiotropium via Respimat was used in a direct comparison to the 18 mcg Handihaler.

Ultrasound and shockwave therapy for acute fractures in adults.

Ultrasound and shockwave therapy for acute fractures in adults.

The effectiveness of exercise for the prevention and treatment of antenatal depression: systematic review with meta-analysis.

Antenatal depression can have harmful consequences for the mother and fetus. Exercise may be a useful intervention to prevent and treat antenatal depression. This systematic review aims to establish whether there is sufficient evidence to conclude that exercise is an effective intervention for preventing and treating antenatal depression. Searches using electronic databases from MEDLINE, Cochrane Library, CINAHL, EMBASE, AMED and PsycINFO were performed. Randomised controlled trials (RCT) that compared any type of exercise intervention with any comparator in pregnant women were eligible for inclusion. Meta-analysis was performed calculating standardised mean differences (SMD). Six trials (seven comparisons) were eligible for inclusion. Meta-analysis showed a significant reduction in depression scores (SMD -0.46, 95% CI -0.87 to -0.05, P = 0.03, I(2) = 68%) for exercise interventions relative to comparator groups. The test for subgroup differences in women who were non-depressed (one trial) (SMD -0.74, 95%CI -1.22 to -0.27, P = 0.002) and depressed (five trials) (SMD -0.41, 95% CI -0.88 to 0.07, P = 0.09) at baseline was not significant (P = 0.32). The test for subgroup differences between aerobic (one trial) and non-aerobic exercise (five trials) was also nonsignificant (P = 0.32). We found some evidence that exercise may be effective in treating depression during pregnancy but this conclusion is based on a small number of low-moderate quality trials with significant heterogeneity and wide confidence intervals.

Adjuvant chemotherapy for advanced endometrial cancer.

Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison. There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.

Physical rehabilitation approaches for the recovery of function and mobility following stroke.

Various approaches to physical rehabilitation may be used after stroke, and considerable controversy and debate surround the effectiveness of relative approaches. Some physiotherapists base their treatments on a single approach; others use a mixture of components from several different approaches. To determine whether physical rehabilitation approaches are effective in recovery of function and mobility in people with stroke, and to assess if any one physical rehabilitation approach is more effective than any other approach.For the previous versions of this review, the objective was to explore the effect of 'physiotherapy treatment approaches' based on historical classifications of orthopaedic, neurophysiological or motor learning principles, or on a mixture of these treatment principles. For this update of the review, the objective was to explore the effects of approaches that incorporate individual treatment components, categorised as functional task training, musculoskeletal intervention (active), musculoskeletal intervention (passive), neurophysiological intervention, cardiopulmonary intervention, assistive device or modality.In addition, we sought to explore the impact of time after stroke, geographical location of the study, dose of the intervention, provider of the intervention and treatment components included within an intervention. We searched the Cochrane Stroke Group Trials Register (last searched December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 12, 2012), MEDLINE (1966 to December 2012), EMBASE (1980 to December 2012), AMED (1985 to December 2012) and CINAHL (1982 to December 2012). We searched reference lists and contacted experts and researchers who have an interest in stroke rehabilitation. Randomised controlled trials (RCTs) of physical rehabilitation approaches aimed at promoting the recovery of function or mobility in adult participants with a clinical diagnosis of stroke. Outcomes included measures of independence in activities of daily living (ADL), motor function, balance, gait velocity and length of stay. We included trials comparing physical rehabilitation approaches versus no treatment, usual care or attention control and those comparing different physical rehabilitation approaches. Two review authors independently categorised identified trials according to the selection criteria, documented their methodological quality and extracted the data. We included a total of 96 studies (10,401 participants) in this review. More than half of the studies (50/96) were carried out in China. Generally the studies were heterogeneous, and many were poorly reported.Physical rehabilitation was found to have a beneficial effect, as compared with no treatment, on functional recovery after stroke (27 studies, 3423 participants; standardised mean difference (SMD) 0.78, 95% confidence interval (CI) 0.58 to 0.97, for Independence in ADL scales), and this effect was noted to persist beyond the length of the intervention period (nine studies, 540 participants; SMD 0.58, 95% CI 0.11 to 1.04). Subgroup analysis revealed a significant difference based on dose of intervention (P value < 0.0001, for independence in ADL), indicating that a dose of 30 to 60 minutes per day delivered five to seven days per week is effective. This evidence principally arises from studies carried out in China. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.003, for independence in ADL).We found physical rehabilitation to be more effective than usual care or attention control in improving motor function (12 studies, 887 participants; SMD 0.37, 95% CI 0.20 to 0.55), balance (five studies, 246 participants; SMD 0.31, 95% CI 0.05 to 0.56) and gait velocity (14 studies, 1126 participants; SMD 0.46, 95% CI 0.32 to 0.60). Subgroup analysis demonstrated a significant difference based on dose of intervention (P value 0.02 for motor function), indicating that a dose of 30 to 60 minutes delivered five to seven days a week provides significant benefit. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.05, for independence in ADL).No one physical rehabilitation approach was more (or less) effective than any other approach in improving independence in ADL (eight studies, 491 participants; test for subgroup differences: P value 0.71) or motor function (nine studies, 546 participants; test for subgroup differences: P value 0.41). These findings are supported by subgroup analyses carried out for comparisons of intervention versus no treatment or usual care, which identified no significant effects of different treatment components or categories of interventions. Physical rehabilitation, comprising a selection of components from different approaches, is effective for recovery of function and mobility after stroke. Evidence related to dose of physical therapy is limited by substantial heterogeneity and does not support robust conclusions. No one approach to physical rehabilitation is any more (or less) effective in promoting recovery of function and mobility after stroke. Therefore, evidence indicates that physical rehabilitation should not be limited to compartmentalised, named approaches, but rather should comprise clearly defined, well-described, evidenced-based physical treatments, regardless of historical or philosophical origin.

Intermittent androgen deprivation is a rational standard-of-care treatment for all stages of progressive prostate cancer: results from a systematic review and meta-analysis

The optimal hormone treatment strategy in prostate cancer is uncertain, particularly in patients with metastatic disease. We aimed to compare the relative benefits and harms of intermittent androgen deprivation (IAD) to continuous androgen deprivation (CAD) in all stages of prostate cancer. We included eight randomised control trials (4668 patients) in our systematic review and meta-analysis. Median follow-up ranged from 29 to 118 months. Pooled hazard ratios (HRs) were calculated for overall survival (OS), cancer-specific survival, time to cancer progression and mortality unrelated to prostate cancer. The relative effect of treatment in patients with metastatic and those with non-metastatic disease was compared using pre-planned subgroup analysis. There was no difference in OS between patients treated with IAD and CAD (HR 1.01, 95% confidence interval (CI) 0.93-1.10); nor was there any difference in cancer-specific survival (HR 1.03; 95% CI 0.88-1.21). There was a non-significant trend towards longer time to prostate cancer progression for IAD (HR 0.93, 95% CI 0.84-1.04), raising the possibility of slower selection for castrate resistance. There was no significant difference in OS when analysis was restricted to patients with metastatic disease (HR 1.04, 95% CI 0.91-1.19) or patients without metastatic disease (HR 1.06, 95% CI 0.91-1.23) (test for subgroup differences P=0.84). Most studies found an improvement in quality of life or toxicity profile with IAD. IAD is non-inferior to CAD in terms of OS and cancer-specific survival, and is at least non-inferior in terms of time to progression. This meta-analysis confirms IAD as a valid standard of care for managing prostate cancer patients.

Efficacy and Safety of Trabeculectomy vs Nonpenetrating Surgical Procedures

To date, only a few studies have directly compared nonpenetrating surgery (NPS) and trabeculectomy (TE). Therefore, there is no strong evidence as to which surgical technique leads to the best results in terms of ocular hypotensive effect and safety. To compare the hypotensive effect and safety of NPS and TE in terms of intraocular pressure (IOP) reduction and incidence of complications. The MEDLINE and EMBASE databases were searched for studies potentially eligible in any language published up to March 31, 2013. Systematic review and meta-analysis of comparative studies of 2 or more surgical techniques (1 of which had to be TE), including patients with open-angle glaucoma. The considered interventions were TE, deep sclerectomy (DS), viscocanalostomy, and canaloplasty. The primary outcome was the mean between-group difference in the reduction in diurnal IOP from baseline to the 6- or 12-month follow-up evaluation. We also considered the incidence of complications, expressed as relative risk. Eighteen articles, accounting for 20 comparisons, were selected for data extraction and analysis. Analysis of the 6-month follow-up data showed that the pooled estimate of the mean between-group difference was -2.15 mm Hg (95% CI, -2.85 to -1.44) in favor of TE. There was no difference between the NPS subgroups. In the subgroup antimetabolite analysis, the addition of mitomycin C to TE and DS decreased the difference in the reduction in IOP (TE and DS without mitomycin C: -2.65 mm Hg [95% CI, -3.90 to -1.39]; TE and DS with mitomycin C: -0.83 mm Hg [95% CI, -2.40 to 0.74]). In the subgroup analysis by implant addition, no significant difference induced by DS with or without drainage devices was detected (test for subgroup differences: χ(2)(1) = 0.24; P = .62). The absolute risk of hypotony, choroidal effusion, cataract, and flat or shallow anterior chamber was higher in the TE group than in the NPS group. Trabeculectomy seems to be the most effective surgical procedure for reducing IOP in patients with open-angle glaucoma. However, as expected, it was associated with a higher incidence of complications when compared with NPS.

Trial sequential analysis: The role of the number needed-to-treat in evaluating the clinical relevance of relative risk reduction values in the intra-aortic balloon pump support

In a recent meta-analysis we evaluated the effectiveness of prophylactic intra-aortic balloon pump (IABP) support in patients at high-risk PCI (HR-PCI) on 7 randomized controlled trials (RCTs) and 4 Observational studies (Obs.) [1]. The primary endpoint was the in-hospital mortality and the composite of major adverse cardiac and cardiovascular events (MACCE) was considered the secondary endpoint. Data on MACCE were available only in 5 RCTs and in 3 Obs. The best level of evidence coming from RCTs was in agreement with the results obtained from Obs., as showed by the test for subgroup differences which always showed a value of I2 equal to zero, for both RR and RD, on the primary and the secondary endpoints [1].

Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B: systematic review and meta-analysis

ObjectivesThe effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo...

Cognitive rehabilitation for spatial neglect following stroke

Unilateral spatial neglect causes difficulty attending to one side of space. Various rehabilitation interventions have been used but evidence of their benefit is lacking. To assess whether cognitive rehabilitation improves functional independence, neglect (as measured using standardised assessments), destination on discharge, falls, balance, depression/anxiety and quality of life in stroke patients with neglect measured immediately post-intervention and at longer-term follow-up; and to determine which types of interventions are effective and whether cognitive rehabilitation is more effective than standard care or an attention control. We searched the Cochrane Stroke Group Trials Register (last searched June 2012), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL (1983 to June 2011), PsycINFO (1974 to June 2011), UK National Research Register (June 2011). We handsearched relevant journals (up to 1998), screened reference lists, and tracked citations using SCISEARCH. We included randomised controlled trials (RCTs) of cognitive rehabilitation specifically aimed at spatial neglect. We excluded studies of general stroke rehabilitation and studies with mixed participant groups, unless more than 75% of their sample were stroke patients or separate stroke data were available. Two review authors independently selected studies, extracted data, and assessed study quality. For subgroup analyses, review authors independently categorised the approach underlying the cognitive intervention as either 'top-down' (interventions that encourage awareness of the disability and potential compensatory strategies) or 'bottom-up' (interventions directed at the impairment but not requiring awareness or behavioural change, e.g. wearing prisms or patches). We included 23 RCTs with 628 participants (adding 11 new RCTs involving 322 new participants for this update). Only 11 studies were assessed to have adequate allocation concealment, and only four studies to have a low risk of bias in all categories assessed. Most studies measured outcomes using standardised neglect assessments: 15 studies measured effect on activities of daily living (ADL) immediately after the end of the intervention period, but only six reported persisting effects on ADL. One study (30 participants) reported discharge destination and one study (eight participants) reported the number of falls.Eighteen of the 23 included RCTs compared cognitive rehabilitation with any control intervention (placebo, attention or no treatment). Meta-analyses demonstrated no statistically significant effect of cognitive rehabilitation, compared with control, for persisting effects on either ADL (five studies, 143 participants) or standardised neglect assessments (eight studies, 172 participants), or for immediate effects on ADL (10 studies, 343 participants). In contrast, we found a statistically significant effect in favour of cognitive rehabilitation compared with control, for immediate effects on standardised neglect assessments (16 studies, 437 participants, standardised mean difference (SMD) 0.35, 95% confidence interval (CI) 0.09 to 0.62). However, sensitivity analyses including only studies of high methodological quality removed evidence of a significant effect of cognitive rehabilitation.Additionally, five of the 23 included RCTs compared one cognitive rehabilitation intervention with another. These included three studies comparing a visual scanning intervention with another cognitive rehabilitation intervention, and two studies (three comparison groups) comparing a visual scanning intervention plus another cognitive rehabilitation intervention with a visual scanning intervention alone. Only two small studies reported a measure of functional disability and there was considerable heterogeneity within these subgroups (I² > 40%) when we pooled standardised neglect assessment data, limiting the ability to draw generalised conclusions.Subgroup analyses exploring the effect of having an attention control demonstrated some evidence of a statistically significant difference between those comparing rehabilitation with attention control and those with another control or no treatment group, for immediate effects on standardised neglect assessments (test for subgroup differences, P = 0.04). The effectiveness of cognitive rehabilitation interventions for reducing the disabling effects of neglect and increasing independence remains unproven. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. However, there is some very limited evidence that cognitive rehabilitation may have an immediate beneficial effect on tests of neglect. This emerging evidence justifies further clinical trials of cognitive rehabilitation for neglect. However, future studies need to have appropriate high quality methodological design and reporting, to examine persisting effects of treatment and to include an attention control comparator.

Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data

BackgroundThe prognosis of patients with gastroesophageal adenocarcinoma is poor. There is conflicting evidence regarding effects of preoperative chemotherapy on survival and other outcomes. MethodsWe conducted a meta-analysis with aggregate and individual patient data (IPD) to assess the effect of preoperative chemotherapy for gastroesophageal adenocarcinoma on survival and other outcomes. Two independent reviewers identified eligible randomised controlled trials (RCTs) comparing chemotherapy+/–radiotherapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. IPD was solicited from all trials. Meta-analyses were performed using the two stage method. ResultsWe identified 14 RCTs (2422 patients). For eight RCTs (1049 patients; 43.3%) we obtained IPD. Preoperative chemotherapy was associated with longer overall survival (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.73–0.89; p<0.0001). There were larger treatment effects in tumours of the gastroesophageal junction and for chemoradiotherapy compared to chemotherapy, but the tests for subgroup differences were not statistically significant. Preoperative chemotherapy was associated with longer disease-free survival, higher likelihood of R0 resection and more favourable post-treatment tumour stage, but not perioperative complications. ConclusionPreoperative chemotherapy for locoregional gastroesophageal adenocarcinoma increases survival compared to surgery alone. It should be offered to all eligible patients. There appear to be larger survival advantages in tumours of the gastroesophageal junction and for chemoradiotherapy, but these findings require prospective confirmation.