Guideline on the design and conduct of cystic fibrosis clinical trials: The European Cystic Fibrosis Society–Clinical Trials Network (ECFS-CTN)

We describe the rationale for disease specific research networks in general as well as the aims and function of the European Cystic Fibrosis Society-Clinical Trials Network (ECFS-CTN) specifically. The ECFS-CTN was founded in 2009 with the aim of improving the quality and quantity of clinical research in the area of cystic fibrosis (CF) in Europe. A network of 18 clinical trial sites in 8 European countries was established according to uniform state-of-the-art quality criteria. To support the ECFS-CTN in the acquisition, planning and conduct of clinical trials, the network is equipped with a coordinating centre, steering and executive committees, and committees for protocol review, standardization, training and networking as well as a data safety monitoring board. A strong partnership with European CF patient parent organizations aims to increase awareness of the need for efficient clinical research and the participation of patients in clinical trials.

A psycho-educational intervention for family caregivers of patients receiving palliative care:a randomized controlled trial

This study describes an evaluation of a psycho-educational intervention for family caregivers of patients dying of cancer at home. In a randomized controlled trial, participants (n = 106) received standard home-based palliative care services (n = 52) or these services plus the new intervention (n = 54). Data were collected at three time points: upon commencement of home-based palliative care (Time 1), five weeks later (Time 2), and then eight weeks following patient death (Time 3). No intervention effects were identified with respect to preparedness to care, self-efficacy, competence, and anxiety. However, participants who received the intervention reported a significantly more positive caregiver experience than those who received standard care at both Times 2 and 3. The findings indicate that it is possible to increase caregiver rewards despite being immersed in challenging circumstances that often yield considerable negative psychosocial sequelae. Furthermore, it is feasible for health professionals to discuss emotive topics, such as impending death, with caregivers without adverse effects.

Interventions for late trabeculectomy bleb leak

BACKGROUND: Late trabeculectomy bleb leaks are a common complication after filtering glaucoma surgery. Although asymptomatic, late bleb leaks may lead to hypotony and are associated with bleb related infections.

OBJECTIVES: To assess the effects of interventions for late trabeculectomy bleb leak.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 18 July 2012.

SELECTION CRITERIA: We included randomised and quasi-randomised trials in which any treatments for eyes with late bleb leak (interventional and non-interventional) were compared with each other.

DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors when additional information was needed.

MAIN RESULTS: The review included one multicentre trial based in the USA with 30 eyes of 30 participants. The trial compared two surgical procedures (conjunctival advancement and amniotic membrane transplant) to cover a filtering bleb leak. Conjunctival advancement has been shown to be more effective in sealing filtering bleb leaks.

AUTHORS' CONCLUSIONS: Although a variety of treatments have been proposed for bleb leaks, there is no evidence of their comparative effectiveness.The evidence in this review was provided by a single trial that compared two surgical procedures (conjunctival advancement and amniotic membrane transplant). The trial did show a superiority of conjunctival advancement, which was regarded as standard treatment, to amniotic membrane transplantation. There is a need for more randomised trials to validate the findings of this single trial and provide more information on the different types of interventions, especially non-surgical treatments compared to surgical procedures. We recommend that any intervention should be compared to a standard procedure, which is to date conjunctival advancement.

Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years.

Early-onset child conduct problems are common and costly. A large number of studies and some previous reviews have focused on behavioural and cognitive-behavioural group-based parenting interventions, but methodological limitations are commonplace and evidence for the effectiveness and cost-effectiveness of these programmes has been unclear. To assess the effectiveness and cost-effectiveness of behavioural and cognitive-behavioural group-based parenting programmes for improving child conduct problems, parental mental health and parenting skills. We searched the following databases between 23 and 31 January 2011: CENTRAL (2011, Issue 1), MEDLINE (1950 to current), EMBASE (1980 to current), CINAHL (1982 to current), PsycINFO (1872 to current), Social Science Citation Index (1956 to current), ASSIA (1987 to current), ERIC (1966 to current), Sociological Abstracts (1963 to current), Academic Search Premier (1970 to current), Econlit (1969 to current), PEDE (1980 to current), Dissertations and Theses Abstracts (1980 to present), NHS EED (searched 31 January 2011), HEED (searched 31 January 2011), DARE (searched 31 January 2011), HTA (searched 31 January 2011), mRCT (searched 29 January 2011). We searched the following parent training websites on 31 January 2011: Triple P Library, Incredible Years Library and Parent Management Training. We also searched the reference lists of studies and reviews. We included studies if: (1) they involved randomised controlled trials (RCTs) or quasi-randomised controlled trials of behavioural and cognitive-behavioural group-based parenting interventions for parents of children aged 3 to 12 years with conduct problems, and (2) incorporated an intervention group versus a waiting list, no treatment or standard treatment control group. We only included studies that used at least one standardised instrument to measure child conduct problems. Two authors independently assessed the risk of bias in the trials and the methodological quality of health economic studies. Two authors also independently extracted data. We contacted study authors for additional information. This review includes 13 trials (10 RCTs and three quasi-randomised trials), as well as two economic evaluations based on two of the trials. Overall, there were 1078 participants (646 in the intervention group; 432 in the control group). The results indicate that parent training produced a statistically significant reduction in child conduct problems, whether assessed by parents (standardised mean difference (SMD) -0.53; 95% confidence interval (CI) -0.72 to -0.34) or independently assessed (SMD -0.44; 95% CI -0.77 to -0.11). The intervention led to statistically significant improvements in parental mental health (SMD -0.36; 95% CI -0.52 to -0.20) and positive parenting skills, based on both parent reports (SMD -0.53; 95% CI -0.90 to -0.16) and independent reports (SMD -0.47; 95% CI -0.65 to -0.29). Parent training also produced a statistically significant reduction in negative or harsh parenting practices according to both parent reports (SMD -0.77; 95% CI -0.96 to -0.59) and independent assessments (SMD -0.42; 95% CI -0.67 to -0.16). Moreover, the intervention demonstrated evidence of cost-effectiveness. When compared to a waiting list control group, there was a cost of approximately $2500 (GBP 1712; EUR 2217) per family to bring the average child with clinical levels of conduct problems into the non-clinical range. These costs of programme delivery are modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Behavioural and cognitive-behavioural group-based parenting interventions are effective and cost-effective for improving child conduct problems, parental mental health and parenting skills in the short term. The cost of programme delivery was modest when compared with the long-term health, social, educational and legal costs associated with childhood conduct problems. Further research is needed on the long-term assessment of outcomes.

Laser peripheral iridoplasty for angle-closure

BACKGROUND: Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations.

OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles (PACs), PAC and PACG.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 January 2012.

SELECTION CRITERIA: We included only randomised controlled trials (RCTs) in this review. Patients with narrow angles, PAC or PACG were eligible. We excluded studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis.

DATA COLLECTION AND ANALYSIS: No analysis was carried out as only one trial was included in the review.

MAIN RESULTS: We included one RCT with 158 participants. The trial reported laser peripheral iridoplasty as an adjunct to laser peripheral iridotomy compared to iridotomy alone. The authors report no superiority in using iridoplasty as an adjunct to iridotomy for IOP, number of medications or need for surgery.

AUTHORS' CONCLUSIONS: There is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.

Laser peripheral iridoplasty for angle-closure

BACKGROUND: Angle-closure glaucoma is a leading cause of irreversible blindness in the world. Treatment is aimed at opening the anterior chamber angle and lowering the IOP with medical and/or surgical treatment (e.g. trabeculectomy, lens extraction). Laser iridotomy works by eliminating pupillary block and widens the anterior chamber angle in the majority of patients. When laser iridotomy fails to open the anterior chamber angle, laser iridoplasty may be recommended as one of the options in current standard treatment for angle-closure. Laser peripheral iridoplasty works by shrinking and pulling the peripheral iris tissue away from the trabecular meshwork. Laser peripheral iridoplasty can be used for crisis of acute angle-closure and also in non-acute situations. OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of narrow angles (i.e. primary angle-closure suspect), primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) in non-acute situations when compared with any other intervention. In this review, angle-closure will refer to patients with narrow angles, PAC and PACG. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library), MEDLINE, EMBASE and LILACS (Latin American and Caribbean Literature on Health Sciences). The databases were last searched on 11 February 2008. SELECTION CRITERIA: Only randomised controlled trials (RCTs) were eligible for inclusion in this review. Patients with narrow angles, PAC or PACG were eligible. Studies that included only patients with acute presentations, using laser peripheral iridoplasty to break acute crisis were excluded. DATA COLLECTION AND ANALYSIS: No analysis was carried out due to lack of trials. MAIN RESULTS: There were no RCTs assessing laser peripheral iridoplasty in the non-acute setting of angle-closure. AUTHORS' CONCLUSIONS: There is currently no strong evidence for laser peripheral iridoplasty's use in treating angle-closure.

Meta-analysis of randomised controlled trials comparing latanoprost with timolol in the treatment of patients with open angle glaucoma or ocular hypertension

Aim - To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs). Methods - Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects. Results - Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk = 2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6). Conclusion - This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.

Interventions to improve the appropriate use of polypharmacy for older people

Background
Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing.

Objectives
This review sought to determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people.

Search methods
In November 2013, for this first update, a range of literature databases including MEDLINE and EMBASE were searched, and handsearching of reference lists was performed. Search terms included 'polypharmacy', 'medication appropriateness' and 'inappropriate prescribing'.

Selection criteria
A range of study designs were eligible. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people 65 years of age and older in which a validated measure of appropriateness was used (e.g. Beers criteria, Medication Appropriateness Index (MAI)).

Data collection and analysis
Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. Study-specific estimates were pooled, and a random-effects model was used to yield summary estimates of effect and 95% confidence intervals (CIs). The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall quality of evidence for each pooled outcome.

Main results
Two studies were added to this review to bring the total number of included studies to 12. One intervention consisted of computerised decision support; 11 complex, multi-faceted pharmaceutical approaches to interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals, such as prescribers and pharmacists. Appropriateness of prescribing was measured using validated tools, including the MAI score post intervention (eight studies), Beers criteria (four studies), STOPP criteria (two studies) and START criteria (one study). Interventions included in this review resulted in a reduction in inappropriate medication usage. Based on the GRADE approach, the overall quality of evidence for all pooled outcomes ranged from very low to low. A greater reduction in MAI scores between baseline and follow-up was seen in the intervention group when compared with the control group (four studies; mean difference -6.78, 95% CI -12.34 to -1.22). Postintervention pooled data showed a lower summated MAI score (five studies; mean difference -3.88, 95% CI -5.40 to -2.35) and fewer Beers drugs per participant (two studies; mean difference -0.1, 95% CI -0.28 to 0.09) in the intervention group compared with the control group. Evidence of the effects of interventions on hospital admissions (five studies) and of medication-related problems (six studies) was conflicting.

Authors' conclusions
It is unclear whether interventions to improve appropriate polypharmacy, such as pharmaceutical care, resulted in clinically significant improvement; however, they appear beneficial in terms of reducing inappropriate prescribing.

Effectiveness of medicines review with web-based pharmaceutical treatment algorithms in reducing potentially inappropriate prescribing in older people in primary care:a cluster randomized trial (OPTI-SCRIPT study protocol)

Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care.

Home-based child development interventions for preschool children from socially disadvantaged families

BACKGROUND
Social disadvantage can have a significant impact on early child development, health and wellbeing. What happens during this critical period is important for all aspects of development. Caregiving competence and the quality of the environment play an important role in supporting development in young children and parents have an important role to play in optimising child development and mitigating the negative effects of social disadvantage. Home-based child development programmes aim to optimise children's developmental outcomes through educating, training and supporting parents in their own home to provide a more nurturing and stimulating environment for their child.

OBJECTIVES
To determine the effects of home-based programmes aimed specifically at improving developmental outcomes for preschool children from socially disadvantaged families.

SEARCH STRATEGY
We searched the following databases between 7 October and 12 October 2010: Cochrane Central Register of Controlled Trials (CENTRAL) (2010, Issue 4), MEDLINE (1950 to week 4, September 2010), EMBASE (1980 to Week 39, 2010), CINAHL (1937 to current), PsycINFO (1887 to current), ERIC (1966 to current), ASSIA (1987 to current), Sociological Abstracts (1952 to current), Social Science Citation Index (1970 to current). We also searched reference lists of articles.

SELECTION CRITERIA
Randomised controlled trials comparing home-based preschool child development interventions with a 'standard care' control. Participants were parents with children up to the age of school entry who were socially disadvantaged in respect of poverty, lone parenthood or ethnic minority status.

DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed the trials' risk of bias and extracted data.

RESULTS
We included seven studies, which involved 723 participants. We assessed four of the seven studies as being at high risk of bias and three had an unclear risk of bias; the quality of the evidence was difficult to assess as there was often insufficient detail reported to enable any conclusions to be drawn about the methodological rigour of the studies. Four trials involving 285 participants measured cognitive development and we synthesised these data in a meta-analysis. Compared to the control group, there was no statistically significant impact of the intervention on cognitive development (standardised mean difference (SMD) 0.30; 95% confidence interval -0.18 to 0.78). Only three studies reported socioemotional outcomes and there was insufficient data to combine into a meta-analysis. No study reported on adverse effects.

AUTHORS’ CONCLUSIONS
This review does not provide evidence of the effectiveness of home-based interventions that are specifically targeted at improving developmental outcomes for preschool children from socially disadvantaged families. Future studies should endeavour to better document and report their methodological processes.

A randomized controlled trial of a self-management psychosocial intervention for men with prostate cancer and their partners: a study protocol.

Background
Little is known about interventions to help men and their partners cope with the after effects of prostate cancer treatment. The lack of in-depth descriptions of the intervention content is hindering the identification of which intervention (or component of an intervention) works.

Aim
To describe the development and evaluation of the content of a self-management psychosocial intervention for men with prostate cancer and their partners.

Design
A feasibility randomized controlled trial including structure, process, and outcome analysis.

Methods
This 9-week intervention commences on completion of treatment and consists of three group and two telephone sessions. The intervention focuses on symptom management, sexual dysfunction, uncertainty management, positive thinking and couple communication. Forty-eight couples will be assigned to either the intervention or a control group receiving usual care. Participants will be assessed at baseline, immediately postintervention and at 1 and 6 months postintervention. Outcome measures for patients and caregivers include self-efficacy, quality of life, symptom distress, uncertainty, benefits of illness, health behaviour, and measures of couple communication and support. An additional caregiver assessment will be completed by the partner.

Discussion
The main purpose of this feasibility study is to investigate the acceptability of the CONNECT programme to men with prostate cancer and their partners and to gain feedback from the participants and facilitators to make changes to and enhance the programme. Reasons why men do not want to participate will be collated to enhance recruitment in the future. We will also test recruitment strategies, randomization procedures, and the acceptability of the questionnaires. Ethical approval granted December 2010.

Strategies for multivessel revascularization in patients with diabetes

In some randomized trials comparing revascularization strategies for patients with diabetes, coronary-artery bypass grafting (CABG) has had a better outcome than percutaneous coronary intervention (PCI). We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease.

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome:baseline and post intervention effects

Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.

Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort:associations with gender and glycemia

To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes.

Appealing to the Republic of Letters: An Autopsy of Anti-venereal Trials in Eighteenth-century Mexico

This study analyses the narrative elements of a little-known report into anti-venereal trials written by an Irish military physician-surgeon, Daniel O'Sullivan (1760–c.1797). It explores the way in which O'Sullivan as the narrator of the Historico-critical report creates medical heroes and anti-heroes as a means to criticise procedures initiated by staff in the Hospital General de San Andrés, Mexico City. The resulting work depicts a much less positive picture of medical trials and hospital authorities in this period than has been recorded to date, and provides a critical and complicated assessment of one of Spain's leading physicians of the nineteenth century, Francisco Javier Balmis (1753–1819).