Significant Improvement In Change Research Articles

Asthma control in normal weight and overweight/obese asthmatic children following adenotonsillectomy.

Childhood adenotonsillar hypertrophy (ATH) with sleep-disordered breathing (SDB) frequently occurs concomitant with asthma. Adenotonsillectomy and reduction in asthma severity association has been reported. We describe changes in asthma control in nonobese or normal weight and obese/overweight children undergoing adenotonsillectomy for SDB. This prospective, nonrandomized cohort trial with 6-month follow-up at a tertiary children's hospital enrolled 41 children with persistent asthma undergoing adenotonsillectomy for SDB. Children with significant chronic medical conditions, premature birth (< 28weeks), or recent respiratory infection were excluded. Patients were stratified by baseline BMI into nonobese or normal weight (BMI < 85 percentile) and obese/overweight (BMI > 85%). The primary outcome was change in Childhood Asthma Control Test (cACT) scores 3 and 6 months following adenotonsillectomy. Secondary outcome examined improvement in Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ) 3 and 6months following adenotonsillectomy. Baseline characteristics were similar except for anthropometric measures and mean PACQLQ (P = .03). Children with nonobese or normal weight (n = 26) had statistically significant improvement in change in cACT at 3 (22.80 ± 2.33 vs. 17.86 ± 3.53, P < .001) and 6 (20.71±3.29 vs. 18.24 ± 4.16, P = .044) months compared with baseline. PACQLQ scores also improved at 3 (6.20 ± 0.87 vs. 4.56 ± 1.12, P < .001) and 6 (6.36 ± 0.72 vs. 4.93 ± 0.96, P < .001) months. Obese/overweight children (n = 10) had significant improvement in cACT scores at 6months (20.00 ± 3.90 vs. 15.00 ± 6.90, P = .048). Change of cACT scores at 3months (17.86 ± 3.53 vs. 14.86 ± 6.31, P = .272) was not significantly different. PACQLQ scores improved at 3 (5.47 ± 1.09 vs. 3.70 ± 0.85, P < .001) and 6 (5.75 ± 2.19 vs. 3.67 ± 1.04, P = .016) months. Nonobese or normal-weight children undergoing adenotonsillectomy demonstrated significant improvement in asthma control scores at 3 and 6 and obese/overweight children at 6 months. Using the PACQLQ, caregiver quality of life improved for all children at 3 and 6 months. Surgical management of ATH in children with comorbid SBD and asthma is a good treatment option.

The effectiveness of e-textiles in providing thermal comfort: A systematic review and meta-analysis

Thermal electronic textiles (e-textiles) are increasingly common in the market and aim to provide thermal comfort in cold environments. Currently, however, there is a paucity of information on the relative effectiveness of the different types of thermal e-textile. This study sets out to compare the effectiveness of a range of such textiles reported in the relevant literature. The study addresses the issue of heating effectiveness in terms of gender and particular body regions. Among the results reported, three primary categories emerged for investigation: (a) metabolic response, comprising metabolic rate and heart rate; (b) respiratory response i.e. mean skin temperature; and (c) perceptual response, including thermal sensation and comfort sensation. Eight eligible studies with a total of 83 subjects aged 23.4 ± 1.49 years, 40.96% male and 37.35% female and 21.69% in which gender was not reported, were investigated for the meta-analysis. Results show a significant improvement in changes in mean skin temperature and thermal sensation between the control and experimental groups via heating intervention ( p &lt; 0.05), but results were not significant for changes in metabolic rate, heart rate, and comfort sensation ( p &gt; 0.05). Regarding gender, thermal e-textiles significantly enhanced the changes in mean skin temperature in males and thermal sensation in both males and females ( p &lt; 0.05). With regard to different body regions being heated, there were significant effects on changes in mean skin temperature, thermal sensation, and comfort sensation in heating the upper torso ( p &lt; 0.05) and on changes in thermal sensation in heating the feet and toes ( p &lt; 0.05). The results reported here may serve as reference points for the further development of smart heating textile technology.

The effects of Baduanjin exercise vs. brisk walking on physical fitness and cognition in middle-aged patients with schizophrenia: A randomized controlled trial.

ObjectivePatients with schizophrenia have deficits in physical and cognitive function that may become salient in their middle ages. These deficits need active intervention to prevent functional decline. Baduanjin and brisk walking show promise as interventions in patients with schizophrenia. This study investigated the effects of Baduanjin exercise vs. brisk walking in middle-aged patients with schizophrenia.MethodsIn this single-blind, 2-arm, parallel, randomized controlled trial, 48 participants aged older than 40 years were enrolled and assigned to the intervention group (Baduanjin) or the control group (brisk walking). The training of both groups took place twice a week, 60 min per session, for 12 weeks. The participants were evaluated with physical, cognitive, and functional outcomes at baseline, postintervention, and 4 weeks after the intervention.ResultsThe results of the study demonstrated significant time effects in walking distance (p = 0.035, η2 = 0.094) and lower extremity strength (p = 0.006, η2 = 0.152). Post-hoc analysis revealed both groups had significant improvement in changes from baseline to the postintervention assessment (ps < 0.05) and follow-up (ps < 0.05). The results demonstrated a significant group-by-time interaction in change scores of global cognition (F = 7.01, p = 0.011, η2 = 0.133). Post-hoc analysis revealed a significant improvement in the Baduanjin group from baseline to postintervention (p = 0.021), but the improvements were not maintained at the follow-up assessment (p = 0.070). The results also demonstrated significant group effects in balance function (p < 0.001, η2 = 0.283), motor dual-task performance (p = 0.026, η2 = 0.103), and cognitive dual-task performance (p < 0.001, η2 = 0.307). Post-hoc analysis revealed that the Baduanjin group improved more than the brisk walking group in the above outcomes (ps < 0.05).ConclusionThis study demonstrated the differential effects of Baduanjin exercise and brisk walking in middle-aged patients with schizophrenia. Baduanjin might be a beneficial regimen for improving physical and cognitive function in this population. Further research with a larger sample is warranted.Clinical trial registration[ClinicalTrials.gov], identifier [202000817B0C602].

Meta-analyses of deflazacort versus prednisone/prednisolone in patients with nonsense mutation Duchenne muscular dystrophy.

Aim: Compare efficacies of deflazacort and prednisone/prednisolone in providing clinically meaningful delays in loss of physical milestones in patients with nonsense mutation Duchenne muscular dystrophy. Materials & methods: Placebo data from Phase IIb (ClinicalTrials.gov Identifier: NCT00592553) and ACT DMD (ClinicalTrials.gov Identifier: NCT01826487) ataluren nonsense mutation Duchenne muscular dystrophy clinical trials were retrospectively combined in meta-analyses (intent-to-treat population; for change from baseline to week 48 in 6-min walk distance [6MWD] and timed function tests). Results: Significant improvements in change in 6-min walk distance with deflazacort versus prednisone/prednisolone (least-squares mean difference 39.54m [95% CI: 13.799, 65.286; p=0.0026]). Significant and clinically meaningful improvements in 4-stair climb and 4-stair descend for deflazacort versus prednisone/prednisolone. Conclusion: Deflazacort provides clinically meaningful delays in loss of physical milestones over 48weeks compared with prednisone/prednisolone for patients withnonsense mutation Duchenne muscular dystrophy.

Effects of roflumilast on arterial stiffness in COPD (ELASTIC): A randomized trial.

Cardiovascular risk is substantially increased in patients with COPD and can be quantified via arterial stiffness. The PDE-IV inhibitor roflumilast revealed a potential reduction of COPD-related cardiovascular risk. We aimed to investigate the effects of roflumilast on arterial stiffness by quantification of pulse wave velocity (PWV) in stable COPD. In this randomized placebo-controlled trial, 80 COPD patients received roflumilast or placebo for 24 weeks. The primary outcome was the change in cf-PWV. Secondary outcomes comprised markers of vascular function (e.g. Aix and RHI), systemic inflammation (e.g. IL-6 and TNF-α) and clinical characteristics of COPD (e.g. CAT and 6MWT). A total of 33 and 34 patients completed the roflumilast and placebo arm, respectively (age, median (IQR): 64.5 (61-69.5) vs 64.5 (56-72) years; FEV1 , median (IQR): 34.5 (25.5-48.6) vs 35.3 (27-46.8) % predicted; 6MWT, median (IQR): 428 (340-558) vs 456 (364-570) m). Change from baseline PWV did not show a significant difference between roflumilast and placebo (+5.0 (95% CI: -2.0 to +13.0) vs 0.0 (95% CI: -7.0 to +7.0)%, P = 0.268). Roflumilast did not improve markers of vascular function or systemic inflammation. We observed a significant improvement in change from baseline 6MWT with roflumilast versus placebo (+53.0 (95% CI: +19.1 to +86.9) vs -0.92 (95% CI: -35.1 to +33.3) m, P = 0.026). Our study revealed no beneficial effects of roflumilast on arterial stiffness. Further studies are needed to test a potential improvement of exercise capacity with roflumilast in COPD.

Impact of Mind-Body Medicine Professional Skills Training on Healthcare Professional Burnout.

BackgroundHealthcare professional burnout has reached epidemic proportions, with downstream effects on personal and patient health and on our institutions. Solutions lie in the domains of work culture, operational efforts, and personal strategies.ObjectivesTo evaluate the impact of a 5-day mind–body medicine professional training program on burnout and quality of life.MethodsWe conducted pre- and postevaluation of a mind–body medicine skills training for healthcare professionals on 6 wellness domains using 2 validated instruments: the Maslach Burnout Inventory and the Professional Quality of Life Survey.ResultsThere was a statistically significant improvement in changes in emotional exhaustion, depersonalization, personal accomplishment, compassion satisfaction, burnout, and secondary traumatic stress which was sustained at 12 months. Largest relative improvements occurred in emotional exhaustion and depersonalization, 22% and 21%, respectively.ConclusionIn addition to providing an important patient care skill set, mind–body medicine training may be an effective way to mitigate burnout and improve healthcare professional well-being.

Bioimpedance spectroscopy-guided fluid management in peritoneal dialysis patients with residual kidney function: A randomized controlled trial.

Bioimpedance spectroscopy (BIS) allows volume status to be assessed objectively. This study evaluated the effect of BIS-guided fluid management on residual kidney function (RKF), volume status, and cardiovascular events in peritoneal dialysis (PD) patients. A multicenter, prospective, randomized, controlled trial was conducted over 12 months in 2013-2017. Non-anuric PD patients (urine volume ≥ 500 mL/day) were randomized to clinical method-guided management (n = 98) or BIS-guided management (n = 103). The volume in the BIS group was controlled with BIS, with the aim of achieving the target overhydration (OH) goal of -2.0 to +2.0 L. The volume in the control group was controlled by clinical assessment alone. The groups were compared in terms of change in RKF and volume status at 12 months relative to baseline and in terms of cardiovascular event rates during a median follow-up period of 36 months. Compared with the controls, the BIS group did not show a significant improvement in change in OH, after adjustments were made for covariates (P = 0.191). The two groups did not differ in terms of delta OH, renal creatinine and urea clearance, and 24 h urine volume. The control and BIS groups also did not differ significantly in terms of change in peritoneal ultrafiltration volume, blood pressure, body weight and echocardiographic variables or in cardiovascular event rates (10.2% vs 11.3%; P = 0.953). Bioimpedance spectroscopy-guided fluid management did not show an additional benefit to achieve euvolemia, and did not affect the decline in RKF in non-anuric PD patients.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We also searched online trials registries for any ongoing trials (01 July 2018).Last search of the Group's Haemoglobinopathies Trials Register: 08 October 2018. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria, including 524 people with sickle cell disease aged between 12 and 65 years of age. One study tested the effectiveness of zinc sulphate as compared to placebo and the remaining two assessed senicapoc versus placebo. No deaths were seen in any of the studies (low-quality evidence). The zinc sulphate study showed a significant reduction in painful crises (in a total of 145 participants) over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (moderate-quality evidence). However, analysis was restricted due to limited statistical data. Changes to red blood cell parameters and blood counts were inconsistent (very low-quality evidence). No serious adverse events were noted in the study. The Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo showed that the high dose senicapoc showed significant improvement in change in hemoglobin level, the number and proportion of dense red blood cells, red blood cell count and indices and hematocrit value (very low-quality evidence). The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups (low-quality evidence). A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red blood cell survival (depending on dose), this did not lead to fewer painful crises.Given this is no longer an active area of research, this review will no longer be regularly updated.

DUPILUMAB REDUCES SEVERE EXACERBATION RATE AND IMPROVES LUNG FUNCTION IN ADOLESCENT PATIENTS WITH UNCONTROLLED, MODERATE-TO-SEVERE ASTHMA: FROM THE LIBERTY ASTHMA QUEST STUDY

DUPILUMAB REDUCES SEVERE EXACERBATION RATE AND IMPROVES LUNG FUNCTION IN ADOLESCENT PATIENTS WITH UNCONTROLLED, MODERATE-TO-SEVERE ASTHMA: FROM THE LIBERTY ASTHMA QUEST STUDY

Characteristics of cardio-Cerebrovascular modulation in patients with generalized anxiety disorder: an observational study

BackgroundGeneralized anxiety disorder (GAD) has been shown in previous studies to display abnormal cerebral blood flow velocity (CBFV); however, the characteristics of cardio-cerebrovascular modulation are unknown. We aimed to analyze cardio-cerebrovascular modulation using parameters from a supine-to-standing test.MethodsThere are 2 parts to this study; in Part 1, 125 participants with Hamilton Anxiety scale scores ≥14 were enrolled, and 33 age- and sex-matched medically and psychiatrically healthy volunteers were recruited as control participants. Patients were divided by score into mild, moderate, and severe anxiety groups. The cardio-cerebrovascular modulation using the parameters of dynamic changes of CBFV and heart rate in response to an orthostatic challenge were investigated. In Part 2, we followed up the severe GAD patients for 6 months and repeated the supine-to-standing test, and severe GAD patients were divided into recovery and non-recovery groups.ResultsIn part 1, the GAD group displayed more marked CBFV and heart rate changes than the healthy group, but there was no difference in the CBFV and heart rate changes from the supine to upright position in mild, moderate, and severe anxiety groups. In part 2, The recovery group demonstrated significant improvement in changes in the CBFV and heart rate values from the supine to the upright position after treatment compared with before treatment. In the non-recovery group, the CBFV and heart rate changes were significantly higher than the healthy group regardless of treatment.ConclusionsCardio-cerebrovascular modulation is compromised in patients with GAD, however, this impairment can be restored to normal after the disappearance of anxiety.

Efficacy of rasagiline for the treatment of Parkinson’s disease: an updated meta-analysis

Objective: Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson’s disease (PD), both as monotherapy and combination therapy.Methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson’s disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson’s disease rating scale (UPDRS) and the three subscales.Results: Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores.Conclusions: Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols.KEY MESSAGESRasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales.Both monotherapy and combination therapy significantly improved total UPDRS scores.Effect of rasagiline on total UPDRS scores was not dose-dependent.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 28 November 2015. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published.

Flibanserin: First agent for female sexual dysfunction

Flibanserin: First agent for female sexual dysfunction

A randomized, three-period crossover study of umeclidinium as monotherapy in adult patients with asthma

To our knowledge, no studies in patients with asthma have assessed a long-acting muscarinic antagonist in the absence of inhaled corticosteroids (ICS). Evaluate the dose-response, efficacy, and safety of umeclidinium (UMEC) in patients with asthma not receiving ICS. In this double-blind, three-period crossover study, 350 subjects were randomized toa sequence of three of eight inhaled treatments: UMEC 15.6, 31.25, 62.5, 125, or 250mcg oncedaily (OD), UMEC 15.6 or 31.25mcg twice daily (BID), or placebo, administered for 14 days (12-14-day washout). Trough forced expiratory volume in one second (FEV1), 0-24-hweighted mean (WM) FEV1, and safety were assessed. Serial spirometry and pharmacokinetic assessments were performed in a subgroup. Subjects had a mean baseline pre- and post-bronchodilator FEV1 of 71% and 88% predicted, respectively. Significant improvements in change from baseline trough FEV1 were observed for UMEC 15.6 OD (0.066L; p=0.036) and UMEC 125 OD (0.088L; p=0.005) versusplacebo, but not other OD or BID doses. UMEC increased 0-24-hWM FEV1 versus placebo (0.068-0.121L [p≤0.017] with no clear dose-response). Treatment differences were similar for corresponding OD and BID doses in serial assessments. UMEC was rapidly absorbed, with evidence of some accumulation. The incidence of on-treatment adverse events was 9-21% for UMEC and 12% for placebo. There were no treatment-related effects on laboratory parameters. The modest trough FEV1 improvements did not conclusively support a therapeutic benefit of UMEC in non-ICS treated patients with asthma. NCT01641692.

Effects of Adding Ezetimibe to Fluvastatin on Kidney Function in Patients with Hypercholesterolemia: a Randomized Control Trial

Statins not only reduce low-density lipoprotein (LDL) cholesterol, but also prevent the progression of kidney dysfunction. Ezetimibe, a cholesterol-absorption inhibitor, also lowers LDL cholesterol levels when added to statins; however, the effect of add-on ezetimibe on kidney function has had conflicting results. We conducted an open-labeled, randomized, 12-month trial, comparing the effects of daily therapy with 20 mg fluvastatin either with or without 10 mg ezetimibe in 54 patients with dyslipidemia. The prespecified primary outcome was the percent change from baseline in kidney function, which was defined by the estimated glomerular filtration rate. The secondary outcomes were the changes in surrogate atherosclerotic markers. All analyses were by intention to treat. The primary outcome, the percent change from baseline (±SE) of the estimated glomerular filtration rate, was -5.5±1.9% in the fluvastatin-only group and 6.6±1.9% in the fluvastatin-plus-ezetimibe (combined-therapy) group (p=0.0002). Secondary outcomes, consisting of the cardioankle vascular index, augmentation index, ankle-brachial index, and maximum intima-media thickness of the carotid arteries, did not differ significantly between the two groups. At the end of the study, the mean (±SD) LDL cholesterol was 122±23 mg per deciliter in the fluvastatin group and 111±29 mg per deciliter in the combined-therapy group (a between-group difference of 9.2%, p= 0.036). Side-effect and safety profiles were similar in the two groups. Combined therapy with fluvastatin 20 mg plus ezetimibe 10 mg daily resulted in a significant improvement in changes in the estimated glomerular filtration rate.

Gastro-oesophageal reflux treatment for prolonged non-specific cough in children and adults

Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H(2)-antagonist and proton pump inhibitors (PPI)) and fundoplication. To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease, i.e. non-specific chronic cough. We searched the Cochrane Airways Group Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, review articles and reference lists of relevant articles. The date of last search was 8 April 2010. All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease. Two review authors independently assessed trial quality and extracted data. We contacted study authors for further information. We included 19 studies (six paediatric, 13 adults). None of the paediatric studies could be combined for meta-analysis. A single RCT in infants found that PPI (compared to placebo) was not efficacious for cough outcomes (favouring placebo OR 1.61; 95% CI 0.57 to 4.55) but those on PPI had significantly increased adverse events (OR 5.56; 95% CI 1.18 to 26.25) (number needed to treat for harm in four weeks was 11 (95% CI 3 to 232)). In adults, analysis of H(2) antagonist, motility agents and conservative treatment for GORD was not possible (lack of data) and there were no controlled studies of fundoplication. We analysed nine adult studies comparing PPI (two to three months) to placebo for various outcomes in the meta-analysis. Using intention-to-treat, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough (OR 0.46; 95% CI 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). We only found significant differences in sensitivity analyses. We found a significant improvement in change of cough scores at end of intervention (two to three months) in those receiving PPI (standardised mean difference -0.41; 95% CI -0.75 to -0.07) using generic inverse variance analysis on cross-over trials. Two studies reported improvement in cough after five days to two weeks of treatment. PPI is not efficacious for cough associated with GORD symptoms in very young children (including infants) and should not be used for cough outcomes. There is insufficient data in older children to draw any valid conclusions. In adults, there is insufficient evidence to conclude definitely that GORD treatment with PPI is universally beneficial for cough associated with GORD. Clinicians should be cognisant of the period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double-blind, randomised controlled and parallel-design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.

Practice Guideline Dissemination and Implementation Strategies for Healthcare Teams and Team-Based Practice: a systematic review.

The objective of this systematic review is to describe and identify the effectiveness of different practice guideline implementation strategies on team-based practice and/or patient outcomes. A systematic review was conducted, using a comprehensive, reproducible search strategy that revealed 88 studies that met the inclusion criteria. A descriptive analysis revealed multiple approaches using teams of health care providers with 72.7% of the studies reporting statistically significant results in knowledge, practice and/or outcomes. Of 10 dissemination strategies the most effective were reminders, and audit and feedback. The most popular strategy was education meetings. A secondary analysis revealed different populations with chronic or complex disorders where a team approach was effective in practice guideline dissemination and implementation. Many of the studies provided caveats to explain how or why the strategies did or did not demonstrate improvements. Overall, authors described complex health care requiring increasingly complex approaches to ensure evidence based guidelines were utilised in practice, including using multiple dissemination and implementation strategies. The review has provided evidence that a multi-pronged approach to dissemination and implementation of practice guidelines will assist in gaining significant improvements in change in knowledge, practice and patient outcomes.

C.17.03 Increasing compliance with anti-depressant treatment

To analyze the available evidence from randomized clinical trials regarding the effective dose range and optimal dose of quetiapine when treating bipolar I disorder patients with acute mania.Patients with acute mania were treated with quetiapine as monotherapy (for 12 weeks) or in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 69.5 μg/mL) (Li/DVP) (for 3–6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule. Guidance for the dosing of quetiapine involved increasing the first day's dose (100 mg/day) by 100 mg on a daily basis until Day 4 (400 mg/day), then adjusting the dose up to 600 mg/day at Day 5, and up to 800 mg/day thereafter. Pooled data from the two monotherapy studies and the two combination therapy studies have been used to evaluate the effective quetiapine dose range. As the dose was flexible, effective dose was estimated by the mean last-week dose among responders. The mean last-week dose was defined as the median dose during the 7 days before the last available Young Mania Rating Scale (YMRS) assessment. Patients who achieved a ≥ 50% decrease in the YMRS total score from baseline to end of treatment with quetiapine were considered responders. Tolerability was assessed from direct patient reports.According to randomized clinical trials, administration of quetiapine compared with placebo achieved a statistically significant improvement in change from baseline YMRS score within the first week and onward, as monotherapy or in combination with Li/DVP. The average quetiapine dose (± SD) in responders during the last week of treatment was 575 (± 175) at Day 21 and 598 (± 198) mg/day at Day 84 for monotherapy, and 584 ± 208 mg/day at Day 21 for combination therapy, with most responders receiving doses within the range of 400–800 mg/day. Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance. This dose administration schedule was generally well tolerated.The mean last-week median dose among responders suggests that 600 mg/day of quetiapine is an effective target dose in acute mania.

Quetiapine in the treatment of acute mania: Target dose for efficacious treatment

Objective To analyze the available evidence from randomized clinical trials regarding the effective dose range and optimal dose of quetiapine when treating bipolar I disorder patients with acute mania. Methods Patients with acute mania were treated with quetiapine as monotherapy (for 12 weeks) or in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 69.5 μg/mL) (Li/DVP) (for 3–6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule. Guidance for the dosing of quetiapine involved increasing the first day's dose (100 mg/day) by 100 mg on a daily basis until Day 4 (400 mg/day), then adjusting the dose up to 600 mg/day at Day 5, and up to 800 mg/day thereafter. Pooled data from the two monotherapy studies and the two combination therapy studies have been used to evaluate the effective quetiapine dose range. As the dose was flexible, effective dose was estimated by the mean last-week dose among responders. The mean last-week dose was defined as the median dose during the 7 days before the last available Young Mania Rating Scale (YMRS) assessment. Patients who achieved a ≥ 50% decrease in the YMRS total score from baseline to end of treatment with quetiapine were considered responders. Tolerability was assessed from direct patient reports. Results According to randomized clinical trials, administration of quetiapine compared with placebo achieved a statistically significant improvement in change from baseline YMRS score within the first week and onward, as monotherapy or in combination with Li/DVP. The average quetiapine dose (± SD) in responders during the last week of treatment was 575 (± 175) at Day 21 and 598 (± 198) mg/day at Day 84 for monotherapy, and 584 ± 208 mg/day at Day 21 for combination therapy, with most responders receiving doses within the range of 400–800 mg/day. Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance. This dose administration schedule was generally well tolerated. Conclusions The mean last-week median dose among responders suggests that 600 mg/day of quetiapine is an effective target dose in acute mania.

Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria.

OBJECTIVE: To evaluate the efficiency of mitoxantrone in multiple sclerosis. METHODS: Forty two patients with confirmed multiple sclerosis, selected as having a very active disease on clinical and MRI criteria...