OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects.
SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015.
SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen.
DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments.
MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure.
AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
OBJECTIVES: This study sought to conduct a systematic published data review and meta-analysis of RCTs comparing RM with IO follow-up.
METHODS: Electronic databases and reference lists were searched for RCTs reporting clinical outcomes in ICD patients who did or did not undergo RM. Data were extracted from 9 RCTs, including 6,469 patients, 3,496 of whom were randomized to RM and 2,973 to IO follow-up.
RESULTS: In the RCT setting, RM demonstrated clinical outcomes comparable with office follow-up in terms of all-cause mortality (odds ratio [OR]: 0.83; p = 0.285), cardiovascular mortality (OR: 0.66; p = 0.103), and hospitalization (OR: 0.83; p = 0.196). However, a reduction in all-cause mortality was noted in the 3 trials using home monitoring (OR: 0.65; p = 0.021) with daily verification of transmission. Although the odds of receiving any ICD shock were similar in RM and IO patients (OR: 1.05; p = 0.86), the odds of inappropriate shock were reduced in RM patients (OR: 0.55; p = 0.002).
CONCLUSIONS: Meta-analysis of RCTs demonstrates that RM and IO follow-up showed comparable overall outcomes related to patient safety and survival, with a potential survival benefit in RCTs using daily transmission verification. RM benefits include more rapid clinical event detection and a reduction in inappropriate shocks.
OBJECTIVES: To assess the effects of EMT on the healing of venous leg ulcers.
SEARCH METHODS: For this fourth update, we searched The Cochrane Wounds Group Specialised Register (searched 30 January 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 12).
SELECTION CRITERIA: Randomised controlled trials comparing EMT with sham-EMT or other treatments.
DATA COLLECTION AND ANALYSIS: Standard Cochrane Collaboration methods were employed. At least two review authors independently scrutinised search results and obtained full reports of potentially eligible studies for further assessment. We extracted and summarised details of eligible studies using a data extraction sheet, and made attempts to obtain missing data by contacting study authors. A second review author checked data extraction, and we resolved disagreements after discussion between review authors.
MAIN RESULTS: Three randomised controlled trials (RCTs) of low or unclear risk of bias, involving 94 people, were included in the original review; subsequent updates have identified no new trials. All the trials compared the use of EMT with sham-EMT. Meta-analysis of these trials was not possible due to heterogeneity. In the two trials that reported healing rates; one small trial (44 participants) reported that significantly more ulcers healed in the EMT group than the sham-EMT group however this result was not robust to different assumptions about the outcomes of participants who were lost to follow up. The second trial that reported numbers of ulcers healed found no significant difference in healing. The third trial was also small (31 participants) and reported significantly greater reductions in ulcer size in the EMT group however this result may have been influenced by differences in the prognostic profiles of the treatment groups.
AUTHORS' CONCLUSIONS: It is not clear whether electromagnetic therapy influences the rate of healing of venous leg ulcers. Further research would be needed to answer this question.
OBJECTIVES: To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non-tertiary hospitals, with the need for sensitivity analysis determined by trial quality.At the 2008 update, the objectives were modified to include preterm infants with respiratory failure.
SEARCH METHODS: We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled-trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO).
SELECTION CRITERIA: All random or quasi-random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary.
DATA COLLECTION AND ANALYSIS: We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author.
MAIN RESULTS: We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials.Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants).
AUTHORS' CONCLUSIONS: In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration.
OBJECTIVES: To assess the effects of EMT on the healing of pressure ulcers.
SEARCH METHODS: For this update we searched the Cochrane Wounds Group Specialised Register (searched 10 June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 6); Ovid MEDLINE (2014 to 10 June 2015); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 10 June 2015); Ovid EMBASE (2014 to 10 June 2015); and EBSCO CINAHL (2014 to 6 July 2012).
SELECTION CRITERIA: Randomised controlled trials comparing EMT with sham EMT or other (standard) treatment.
DATA COLLECTION AND ANALYSIS: For this update two review authors independently scrutinised the results of the search to identify relevant RCTs and obtained full reports of potentially eligible studies. In previous versions of the review we made attempts to obtain missing data by contacting study authors. A second review author checked data extraction and disagreements were resolved after discussion between review authors.
MAIN RESULTS: We identified no new trials for this update.Two randomised controlled trials (RCTs), involving 60 participants, at unclear risk of bias were included in the original review. Both trials compared the use of EMT with sham EMT, although one of the trials included a third arm in which only standard therapy was applied. Neither study found a statistically significant difference in complete healing in people treated with EMT compared with those in the control group. In one trial that assessed percentage reduction in wound surface area, the difference between the two groups was reported to be statistically significant in favour of EMT. However, this result should be interpreted with caution as this is a small study and this finding may be due to chance. Additionally, the outcome, percentage reduction in wound area, is less clinically meaningful than complete healing.
AUTHORS' CONCLUSIONS: The results provide no strong evidence of benefit in using EMT to treat pressure ulcers. However, the possibility of a beneficial or harmful effect cannot be ruled out because there were only two included trials, both with methodological limitations and small numbers of participants. Further research is recommended.
OBJECTIVES: The objective of this review is to compare SFH measurement with serial ultrasound measurement of fetal parameters or clinical palpation to detect abnormal fetal growth (IUGR and large-for-gestational age), and improving perinatal outcome.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 July 2015) and reference lists of retrieved articles.
SELECTION CRITERIA: Randomised controlled trials including quasi-randomised and cluster-randomised trials involving pregnant women with singleton fetuses at 20 weeks' gestation and above comparing tape measurement of SFH with serial ultrasound measurement of fetal parameters or clinical palpation using anatomical landmarks.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.
MAIN RESULTS: One trial involving 1639 women was included. It compared SFH measurement with clinical abdominal palpation.There was no difference in the two reported primary outcomes of incidence of small-for-gestational age (risk ratio (RR) 1.32; 95% confidence interval (CI) 0.92 to 1.90, low quality evidence) or perinatal death.(RR 1.25, 95% CI 0.38 to 4.07; participants = 1639, low quality evidence). There were no data on the neonatal detection of large-for-gestational age (variously defined by authors). There was no difference in the reported secondary outcomes of neonatal hypoglycaemia, admission to neonatal nursery, admission to the neonatal nursery for IUGR (low quality evidence), induction of labour and caesarean section (very low quality evidence). The trial did not address the other outcomes specified in the 'Summary of findings' table (intrauterine death; neurodevelopmental outcome in childhood). GRADEpro software was used to assess the quality of evidence, downgrading of evidence was based on including a small single study with unclear risk of bias and a wide confidence interval crossing the line of no effect.
AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether SFH measurement is effective in detecting IUGR. We cannot therefore recommended any change of current practice. Further trials are needed.
METHODS: Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas.
RESULTS: Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%).
CONCLUSION: Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.
OBJECTIVES: To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 21 September 2015.We also searched the following resources (24 March 2015): Latin American and Carribean Health Science Literature Database (LILACS); WHO International Clinical Trials Registry Platforms (ICTRP); and ClinicalTrials.gov.
SELECTION CRITERIA: Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, the risk of bias of the included trials and extracted and analysed data. We contacted the trial authors for additional information.
MAIN RESULTS: Two trials (341 eyes of 238 children and adults) were included comparing efficacy and safety of laser photocoagulation to no therapy in people with proliferative sickle retinopathy. There were 121 males and 117 females with an age range from 13 to 67 years. The laser photocoagulation technique used was different in the two trials; one single-centre trial employed sectoral scatter laser photocoagulation using an argon laser; and the second, two-centre trial, employed feeder vessel coagulation using argon laser in one centre and xenon arc in the second centre. The follow-up period ranged from a mean of 21 to 32 months in one trial and 42 to 47 months in the second. Both trials were at risk of selection bias (random sequence generation) because of the randomisation method employed for participants with bilateral disease. One study was considered to be at risk of reporting bias.Using sectoral scatter laser photocoagulation, one trial (174 eyes) reported that complete regression of proliferative sickle retinopathy was seen in 30.2% in the laser group and 22.4% in the control group (no difference between groups). The same trial reported the development of new proliferative sickle retinopathy in 34.3% of laser-treated eyes and in 41.3% of eyes given no treatment; again, there was no difference between treatment groups. The second trial, using feeder vessel coagulation, did not present full data for either treatment group for these outcomes.There was evidence from both trials (341 eyes) that laser photocoagulation using scatter laser or feeder vessel coagulation may prevent the loss of vision in eyes with proliferative sickle retinopathy (at median follow up of 21 to 47 months). Data from both trials indicated that laser treatment prevented the occurrence of vitreous haemorrhage with both argon and xenon laser; with the protective effect being greater with feeder vessel laser treatment compared to scatter photocoagulation.Regarding adverse effects, the incidence of retinal tear was minimal, with only one event reported. Combined data from both trials were available for 341 eyes; there was no difference between the laser and control arms for retinal detachment. In relation to choroidal neovascularization, treatment with xenon arc was found to be associated with a significantly higher risk, but visual loss related to this complication is uncommon with long-term follow up of three years or more.Data regarding quality of life and other adverse effects were not reported in the included trials.
AUTHORS' CONCLUSIONS: Our conclusions are based on the data from two trials conducted over 20 years ago. In the absence of further evidence, laser treatment for sickle cell disease-related retinopathy should be considered as a one of therapeutic options for preventing visual loss and vitreous haemorrhage. However, it does not appear to have a significant different effect on other clinical outcomes such as regression of proliferative sickle retinopathy and development of new ones. No evidence is available assessing efficacy in relation to patient-important outcomes (such as quality of life or the loss of a driving licence). There is limited evidence on safety, overall, scatter argon laser photocoagulation is superior in terms of adverse effects, although feeder vessel coagulation has a better effect in preventing vitreous haemorrhage. Further research is needed to examine the safety of laser treatment compared to other interventions such as intravitreal injection of anti-vascular endothelial growth factors. In addition, patient-important outcomes as well as cost-effectiveness should be addressed.
DESIGN: Retrospective observational analysis.
SETTING: 56 acute stroke hospitals in eight countries.
PARTICIPANTS: 1074 trial physiotherapists, nurses, and other clinicians.
OUTCOME MEASURES: Number of babies born during trial recruitment per trial participant recruited.
RESULTS: With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average.
CONCLUSION: The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators' meetings and helped maintain a cohesive collaborative group.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry no 12606000185561.
DISCLAIMER: Participation in a rehabilitation trial does not guarantee successful reproductive activity.
METHODS: The addressed focused question was "Is aPDT effective in the treatment of AgP?" MEDLINE/PubMed, EMBASE, Scopus, ISI Web of knowledge and Google-Scholar databases were searched from 1977 till May 2015 using combinations of the following keywords: antimicrobial; photochemotherapy; photodynamic therapy; photosensitizing agents; AgP; scaling and root-planing (SRP). Reviews, case reports, commentaries, and articles published in languages other than English were excluded.
RESULTS: Seven studies were included. In 5 studies, aPDT was performed as an adjunct to SRP. Laserwavelengths and duration of irradiation ranged between 660-690 nm and 60-120 s, respectively. Laser power output as reported in 2 studies was 75 mW. One study showed significant improvement in periodontal parameters for subjects receiving aPDT as an adjunct to SRP as compared to treatment with SRP alone at follow up. However, comparable periodontal parameters were reported when aPDT as an adjunct to SRP was compared to SRP alone in the treatment of AgP in one study. One study showed comparable outcomes when aPDT was compared to SRP in the treatment of AgP. In two studies, adjunctive antibiotic administration to SRP showed significantly better outcomes when compared to application of adjunctive use of aPDT to SRP.
CONCLUSION: aPDT is effective as an adjunct to SRP for the management of AgP, however, further randomized clinical trials with well defined control groups are needed in this regard.