Shared decision-making for people with asthma.

BACKGROUND: Asthma is a chronic inflammatory disease that affects the airways and is common in both adults and children. It is characterised by symptoms including wheeze, shortness of breath, chest tightness, and cough. People with asthma may be helped to manage their condition through shared decision-making (SDM). SDM involves at least two participants (the medical practitioner and the patient) and mutual sharing of information, including the patient's values and preferences, to build consensus about favoured treatment that culminates in an agreed action. Effective self-management is particularly important for people with asthma, and SDM may improve clinical outcomes and quality of life by educating patients and empowering them to be actively involved in their own health. OBJECTIVES: To assess benefits and potential harms of shared decision-making for adults and children with asthma. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which contains studies identified in several sources including CENTRAL, MEDLINE, and Embase. We also searched clinical trials registries and checked the reference lists of included studies. We conducted the most recent searches on 29 November 2016. SELECTION CRITERIA: We included studies of individual or cluster parallel randomised controlled design conducted to compare an SDM intervention for adults and children with asthma versus a control intervention. We included studies available as full-text reports, those published as abstracts only, and unpublished data, and we placed no restrictions on place, date, or language of publication. We included interventions targeting healthcare professionals or patients, their families or care-givers, or both. We included studies that compared the intervention versus usual care or a minimal control intervention, and those that compared an SDM intervention against another active intervention. We excluded studies of interventions that involved multiple components other than the SDM intervention unless the control group also received these interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened searches, extracted data from included studies, and assessed risk of bias. Primary outcomes were asthma-related quality of life, patient/parent satisfaction, and medication adherence. Secondary outcomes included exacerbations of asthma, asthma control, acceptability/feasibility from the perspective of healthcare professionals, and all adverse events. We graded and presented evidence in a 'Summary of findings' table.We were unable to pool any of the extracted outcome data owing to clinical and methodological heterogeneity but presented findings in forest plots when possible. We narratively described skewed data. MAIN RESULTS: We included four studies that compared SDM versus control and included a total of 1342 participants. Three studies recruited children with asthma and their care-givers, and one recruited adults with asthma. Three studies took place in the United States, and one in the Netherlands. Trial duration was between 6 and 24 months. One trial delivered the SDM intervention to the medical practitioner, and three trials delivered the SDM intervention directly to the participant. Two paediatric studies involved use of an online portal, followed by face-to-face consultations. One study delivered an SDM intervention or a clinical decision-making intervention through a mixture of face-to-face consultations and telephone calls. The final study randomised paediatric general practice physicians to receive a seminar programme promoting application of SDM principles. All trials were open-label, although one study, which delivered the intervention to physicians, stated that participants were unaware of their physicians' involvement in the trial. We had concerns about selection and attrition bias and selective reporting, and we noted that one study substantially under-recruited participants. The four included studies used different approaches to measure fidelity/intervention adherence and to report study findings.One study involving adults with poorly controlled asthma reported improved quality of life (QOL) for the SDM group compared with the control group, using the Asthma Quality of Life Questionnaire (AQLQ) for assessment (mean difference (MD) 1.90, 95% confidence interval (CI) 1.24 to 2.91), but two other trials did not identify a benefit. Patient/parent satisfaction with the performance of paediatricians was greater in the SDM group in one trial involving children. Medication adherence was better in the SDM group in two studies - one involving adults and one involving children (all medication adherence: MD 0.21, 95% CI 0.11 to 0.31; mean number of controlled medication prescriptions over 26 weeks: 1.1 in the SDM group (n = 26) and 0.7 in the control group (n = 27)). In one study, asthma-related visit rates were lower in the SDM group than in the usual care group (1.0/y vs 1.4/y; P = 0.016), but two other studies did not report a difference in exacerbations nor in prescriptions for short courses of oral steroids. Finally, one study described better odds of reporting no asthma problems in the SDM group than in the usual care group (odds ratio (OR) 1.90, 95% CI 1.26 to 2.87), although two other studies reporting asthma control did not identify a benefit with SDM. We found no information about acceptability of the intervention to the healthcare professional and no information on adverse events. Overall, our confidence in study results ranged from very low to moderate, and we downgraded outcomes owing to risk of bias, imprecision, and indirectness. AUTHORS' CONCLUSIONS: Substantial differences between the four included randomised controlled trials (RCTs) indicate that we cannot provide meaningful overall conclusions. Individual studies demonstrated some benefits of SDM over control, in terms of quality of life; patient and parent satisfaction; adherence to prescribed medication; reduction in asthma-related healthcare visits; and improved asthma control. Our confidence in the findings of these individual studies ranges from moderate to very low, and it is important to note that studies did not measure or report adverse events.Future trials should be adequately powered and of sufficient duration to detect differences in patient-important outcomes such as exacerbations and hospitalisations. Use of core asthma outcomes and validated scales when possible would facilitate future meta-analysis. Studies conducted in lower-income settings and including an economic evaluation would be of interest. Investigators should systematically record adverse events, even if none are anticipated. Studies identified to date have not included adolescents; future trials should consider their inclusion. Measuring and reporting of intervention fidelity is also recommended

Genotype–phenotype correlation in migraine without aura focusing on the rs1835740 variant on 8q22.1

A large two-stage GWAS by Antilla et al. reported the minor allele of rs1835740 on 8q22.1 to be associated with common types of migraine. The objective of the present study was to determine the clinical correlate of the variant in migraine without aura (MO). Clinical data on 339 successfully genotyped MO patients (patients with attacks of migraine without aura and no attacks of migraine with aura) were obtained by an extensive validated semi-structured telephone interview performed by a physician or a trained senior medical student. Reliable, systematic and extensive data on symptoms, age of onset, attack frequencies and duration, relevant comorbidity, specific provoking factors including different hormonal factors in females, and effect and use of medication, both abortive and prophylactic, were thereby obtained. A comparison of carriers and non-carriers were performed. Comparison of homozygotes with heterozygotes was not performed as the number of homozygotes was too small for statistical purposes. Data from other MO populations in the GWAS by Antilla et al. were not included as phenotype and clinical data were obtained differently. While thousands of patients are needed to detect a genetic variant like rs1835740, 339 are sufficient to detect meaningful clinical differences. 136 of 339 patients were carriers of the variant, 15 were homozygous. Comparison of carriers with non-carriers showed no significant difference in any of the parameters studied. In conclusion, the rs1835740 variant has no significant influence on the clinical expression of MO

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

BACKGROUND: There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether or not regular (continuous, intermittent or pulsed) treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was performed on 27 July 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methods. Two independent review authors selected studies for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. MAIN RESULTS: We included 14 studies involving 3932 participants in this review. We identified two further studies meeting inclusion criteria but both were terminated early without providing results. All studies were published between 2001 and 2015. Nine studies were of continuous macrolide antibiotics, two studies were of intermittent antibiotic prophylaxis (three times per week) and two were of pulsed antibiotic regimens (e.g. five days every eight weeks). The final study included one continuous, one intermittent and one pulsed arm. The antibiotics investigated were azithromycin, erythromycin, clarithromycin, doxycyline, roxithromycin and moxifloxacin. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the pooled results were of moderate quality. The risk of bias of the included studies was generally low.The studies recruited participants with a mean age between 65 and 72 years and mostly at least moderate-severity COPD. Five studies only included participants with frequent exacerbations and two studies recruited participants requiring systemic steroids or antibiotics or both, or who were at the end stage of their disease and required oxygen. One study recruited participants with pulmonary hypertension secondary to COPD and a further study was specifically designed to asses whether eradication of Chlamydia pneumoniae reduced exacerbation rates.The co-primary outcomes for this review were the number of exacerbations and quality of life.With use of prophylactic antibiotics, the number of participants experiencing one or more exacerbations was reduced (odds ratio (OR) 0.57, 95% CI 0.42 to 0.78; participants = 2716; studies = 8; moderate-quality evidence). This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The number needed to treat for an additional beneficial outcome with prophylactic antibiotics given for three to 12 months to prevent one person from experiencing an exacerbation (NNTB) was 8 (95% CI 5 to 17). The test for subgroup difference suggested that continuous and intermittent antibiotics may be more effective than pulsed antibiotics (P = 0.02, I² = 73.3%).The frequency of exacerbations per patient per year was also reduced with prophylactic antibiotic treatment (rate ratio 0.67; 95% CI 0.54 to 0.83; participants = 1384; studies = 5; moderate-quality evidence). Although we were unable to pool the result, six of the seven studies reporting time to first exacerbation identified an increase (i.e. benefit) with antibiotics, which was reported as statistically significant in four studies.There was a statistically significant improvement in quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) with prophylactic antibiotic treatment, but this was smaller than the four unit improvement that is regarded as being clinically significant (mean difference (MD) -1.94, 95% CI -3.13 to -0.75; participants = 2237; studies = 7, high-quality evidence).Prophylactic antibiotics showed no significant effect on the secondary outcomes of frequency of hospital admissions, change in forced expiratory volume in one second (FEV1), serious adverse events or all-cause mortality (moderate-quality evidence). There was some evidence of benefit in exercise tolerance, but this was driven by a single study of lower methodological quality.The adverse events that were recorded varied among the studies depending on the antibiotics used. Azithromycin was associated with significant hearing loss in the treatment group, which was in many cases reversible or partially reversible. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.The development of antibiotic resistance in the community is of major concern. Six studies reported on this, but we were unable to combine results. One study found newly colonised participants to have higher rates of antibiotic resistance. Participants colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. A further study with three active treatment arms found an increase in the degree of antibiotic resistance of isolates in all three arms after 13 weeks treatment. AUTHORS' CONCLUSIONS: Use of continuous and intermittent prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All studies of continuous and intermittent antibiotics used macrolides, hence the noted benefit applies only to the use of macrolide antibiotics prescribed at least three times per week. The impact of pulsed antibiotics remains uncertain and requires further research.The studies in this review included mostly participants who were frequent exacerbators with at least moderate-severity COPD. There were also older individuals with a mean age over 65 years. The results of these studies apply only to the group of participants who were studied in these studies and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse. Monitoring of significant side effects including hearing loss, tinnitus, and long QTc in the community in this elderly patient group may require extra health resources

Evolution And Medicine In Undergraduate Education: A Prescription For All Biology Students

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91331/1/j.1558-5646.2011.01552.x.pd

Surgical wounds healing by secondary intention: characterising and quantifying the problem, identifying effective treatments, and assessing the feasibility of conducting a randomised controlled trial of negative pressure wound therapy versus usual care

Background: Most surgical incisions heal by primary intention (i.e. wound edges are apposed with sutures, clips or glue); however some heal by secondary intention (i.e. the wound is left open and heals by formation of granulation tissue). There is, however, a lack of evidence regarding the epidemiology, management, and impact on patients’ quality of life of these surgical wounds healing by secondary intention (SWHSI), resulting in uncertainty regarding effective treatments and difficulty in planning care and research. Objectives: To derive a better understanding of the nature, extent, costs, impact and outcomes of SWHSI, effective treatments and the value and nature of further research. Design: Cross-sectional survey; inception cohort; cost-effectiveness and value of implementation analyses; qualitative interviews; and a pilot, feasibility randomised controlled trial (RCT). Setting: Acute and community care settings in Leeds and Hull, Yorkshire, UK. Participants: Adults with (or for qualitative interviews, patients or practitioners with previous experience of) a SWHSI. Inclusion criteria varied between the individual Workstreams. Interventions: The pilot, feasibility RCT compared negative pressure wound therapy (NPWT) – a device applying a controlled vacuum to a wound via a dressing - with Usual Care (no NPWT). Results: Survey data estimated that treated SWHSI have a point prevalence of 4.1 per 10,000 population (95% CI: 3.5 to 4.7). SWHSI most frequently occurred following colorectal surgery (n=80, 42.8% - Cross-sectional survey, n=136, 39.7% - Inception cohort), and were often planned before surgery (n=89, 47.6% - Survey, n=236, 60.1% - Cohort). Wound care was frequently delivered in community settings (n=109, 58.3%) and most patients (n=184, 98.4%) received active wound treatment. Cohort data identified hydrofibre dressings (n=259, 65.9%) as the most common treatment, although 29.3% (n=115) participants used NPWT at some time during the study. SWHSI healing occurred in 81.4% (n=320) of participants at a median of 86 days (95% CI: 75 to 103). Baseline wound area (p=<0.01), surgical wound contamination (determined during surgery) (p=0.04) and wound infection at any time (p=<0.01) (i.e. at baseline or post-operatively) were found to be predictors of prolonged healing. Econometric models, using observational, cohort study data, identified that with little uncertainty, that NPWT treatment is more costly and less effective than standard dressing treatment for the healing of open surgical wounds: Model A (ordinary least squares with imputation): Effectiveness: 73 days longer than those who did not receive NPWT (95% Credible Interval (CrI): 33.8 to 112.8); Cost Effectiveness (Associated incremental quality adjusted life years): -0.012 (SE 0.005) (Observables); -0.008 (SE 0.011) (Unobservables) , Model B (Two Stage Model – Logistic and linear regression): Effectiveness: 46 days longer the those who did not receive NPWT (95% CrI: 19.6 to 72.5); Cost Effectiveness (Associated incremental quality adjusted life years): -0.007 (Observables) and -0.027 (Unobservables) (SE 0.017). Patient interviews (n=20) identified initial reactions to SWHSI of shock and disbelief. Impaired quality of life characterised the long healing process, with particular impact on daily living for patients with families or in paid employment. Patients were willing to try any treatment promising wound healing. Health professionals (n=12) had variable knowledge of SWHSI treatments, and frequently favoured NPWT despite the lack of robust evidence, The pilot, feasibility RCT screened 248 patients for eligibility and subsequently recruited and randomised 40 participants to receive NPWT or Usual Care (no NPWT). Data indicated that it was feasible to complete a full RCT to provide definitive evidence for the effectiveness of NPWT as a treatment for SWHSI. Key elements and recommendations for a larger RCT were identified. Limitations: This research programme was conducted in a single geographical area (Yorkshire and the Humber, UK) and local guidelines and practices may have affected treatment availability and so may not represent UK wide treatment choices. A wide range of wound types were included, however, some wound types may be underrepresented meaning this research may not represent the overall SWHSI population. The lack of RCT data on the relative effects of NPWT in SWHSI resulted in much of the economic modelling being based on observational data. Observational data, even with adjustment, does not negate the potential for unresolved confounding to affect the results. This may reduce confidence in the conclusions drawn and may lead to calls for definitive evidence from an RCT. Conclusions: This research has provided new information regarding the nature, extent, costs, impacts and outcomes of SWHSI, treatment effectiveness and the value and nature of future research; addressing previous uncertainties regarding the problem of SWHSI. Aspects of our research indicate that NPWT is more costly and less effective than standard dressing for the healing of open surgical wounds. However, because this conclusion is based solely on observational data it may be affected by unresolved confounding. Should a future RCT be considered necessary, its design should reflect careful consideration of the findings of this programme of research