OBJECTIVES: Our main objective was to assess the effectiveness of antimicrobial impregnation, coating or bonding on CVCs in reducing clinically-diagnosed sepsis, catheter-related blood stream infection (CRBSI), all-cause mortality, catheter colonization and other catheter-related infections in adult participants who required central venous catheterization, along with their safety and cost effectiveness where data were available. We undertook the following comparisons: 1) catheters with antimicrobial modifications in the form of antimicrobial impregnation, coating or bonding, against catheters without antimicrobial modifications and 2) catheters with one type of antimicrobial impregnation against catheters with another type of antimicrobial impregnation. We planned to analyse the comparison of catheters with any type of antimicrobial impregnation against catheters with other antimicrobial modifications, e.g. antiseptic dressings, hubs, tunnelling, needleless connectors or antiseptic lock solutions, but did not find any relevant studies. Additionally, we planned to conduct subgroup analyses based on the length of catheter use, settings or levels of care (e.g. intensive care unit, standard ward and oncology unit), baseline risks, definition of sepsis, presence or absence of co-interventions and cost-effectiveness in different currencies.
SEARCH METHODS: We used the standard search strategy of the Cochrane Anaesthesia, Critical and Emergency Care Review Group (ACE). In the updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), MEDLINE (OVID SP; 1950 to March 2015), EMBASE (1980 to March 2015), CINAHL (1982 to March 2015), and other Internet resources using a combination of keywords and MeSH headings. The original search was run in March 2012.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) that assessed any type of impregnated catheter against either non-impregnated catheters or catheters with another type of impregnation in adult patients cared for in the hospital setting who required CVCs. We planned to include quasi-RCT and cluster-RCTs, but we identified none. We excluded cross-over studies.
DATA COLLECTION AND ANALYSIS: We extracted data using the standard methodological procedures expected by Cochrane. Two authors independently assessed the relevance and risk of bias of the retrieved records. We expressed our results using risk ratio (RR), absolute risk reduction (ARR) and number need to treat to benefit (NNTB) for categorical data and mean difference (MD) for continuous data, where appropriate, with their 95% confidence intervals (CIs).
MAIN RESULTS: We included one new study (338 participants/catheters) in this update, which brought the total included to 57 studies with 16,784 catheters and 11 types of impregnations. The total number of participants enrolled was unclear, as some studies did not provide this information. Most studies enrolled participants from the age of 18, including patients in intensive care units (ICU), oncology units and patients receiving long-term total parenteral nutrition. There were low or unclear risks of bias in the included studies, except for blinding, which was impossible in most studies due to the catheters that were being assessed having different appearances. Overall, catheter impregnation significantly reduced catheter-related blood stream infection (CRBSI), with an ARR of 2% (95% CI 3% to 1%), RR of 0.62 (95% CI 0.52 to 0.74) and NNTB of 50 (high-quality evidence). Catheter impregnation also reduced catheter colonization, with an ARR of 9% (95% CI 12% to 7%), RR of 0.67 (95% CI 0.59 to 0.76) and NNTB of 11 (moderate-quality evidence, downgraded due to substantial heterogeneity). However, catheter impregnation made no significant difference to the rates of clinically diagnosed sepsis (RR 1.0, 95% CI 0.88 to 1.13; moderate-quality evidence, downgraded due to a suspicion of publication bias), all-cause mortality (RR 0.92, 95% CI 0.80 to 1.07; high-quality evidence) and catheter-related local infections (RR 0.84, 95% CI 0.66 to 1.07; 2688 catheters, moderate quality evidence, downgraded due to wide 95% CI).In our subgroup analyses, we found that the magnitudes of benefits for impregnated CVCs varied between studies that enrolled different types of participants. For the outcome of catheter colonization, catheter impregnation conferred significant benefit in studies conducted in ICUs (RR 0.70;95% CI 0.61 to 0.80) but not in studies conducted in haematological and oncological units (RR 0.75; 95% CI 0.51 to 1.11) or studies that assessed predominantly patients who required CVCs for long-term total parenteral nutrition (RR 0.99; 95% CI 0.74 to 1.34). However, there was no such variation for the outcome of CRBSI. The magnitude of the effects was also not affected by the participants' baseline risks.There were no significant differences between the impregnated and non-impregnated groups in the rates of adverse effects, including thrombosis/thrombophlebitis, bleeding, erythema and/or tenderness at the insertion site.
AUTHORS' CONCLUSIONS: This review confirms the effectiveness of antimicrobial CVCs in reducing rates of CRBSI and catheter colonization. However, the magnitude of benefits regarding catheter colonization varied according to setting, with significant benefits only in studies conducted in ICUs. A comparatively smaller body of evidence suggests that antimicrobial CVCs do not appear to reduce clinically diagnosed sepsis or mortality significantly. Our findings call for caution in routinely recommending the use of antimicrobial-impregnated CVCs across all settings. Further randomized controlled trials assessing antimicrobial CVCs should include important clinical outcomes like the overall rates of sepsis and mortality.
OBJECTIVES: We assessed the effectiveness and safety of antimicrobial (antiseptic or antibiotic) dressings in reducing CVC-related infections in newborn infants. Had there been relevant data, we would have evaluated the effects of antimicrobial dressings in different subgroups, including infants who received different types of CVCs, infants who required CVC for different durations, infants with CVCs with and without other antimicrobial modifications, and infants who received an antimicrobial dressing with and without a clearly defined co-intervention.
SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2015, Issue 9), MEDLINE (PubMed), EMBASE (EBCHOST), CINAHL and references cited in our short-listed articles using keywords and MeSH headings, up to September 2015.
SELECTION CRITERIA: We included randomised controlled trials that compared an antimicrobial CVC dressing against no dressing or another dressing in newborn infants.
DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the CNRG. Two review authors independently assessed the eligibility and risk of bias of the retrieved records. We expressed our results using risk difference (RD) and risk ratio (RR) with 95% confidence intervals (CIs).
MAIN RESULTS: Out of 173 articles screened, three studies were included. There were two comparisons: chlorhexidine dressing following alcohol cleansing versus polyurethane dressing following povidone-iodine cleansing (one study); and silver-alginate patch versus control (two studies). A total of 855 infants from level III neonatal intensive care units (NICUs) were evaluated, 705 of whom were from a single study. All studies were at high risk of bias for blinding of care personnel or unclear risk of bias for blinding of outcome assessors. There was moderate-quality evidence for all major outcomes.The single study comparing chlorhexidine dressing/alcohol cleansing against polyurethane dressing/povidone-iodine cleansing showed no significant difference in the risk of CRBSI (RR 1.18, 95% CI 0.53 to 2.65; RD 0.01, 95% CI -0.02 to 0.03; 655 infants, moderate-quality evidence) and sepsis without a source (RR 1.06, 95% CI 0.75 to 1.52; RD 0.01, 95% CI -0.04 to 0.06; 705 infants, moderate-quality evidence). There was a significant reduction in the risk of catheter colonisation favouring chlorhexidine dressing/alcohol cleansing group (RR 0.62, 95% CI 0.45 to 0.86; RD -0.09, 95% CI -0.15 to -0.03; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 7 to 33; 655 infants, moderate-quality evidence). However, infants in the chlorhexidine dressing/alcohol cleansing group were significantly more likely to develop contact dermatitis, with 19 infants in the chlorhexidine dressing/alcohol cleansing group having developed contact dermatitis compared to none in the polyurethane dressing/povidone-iodine cleansing group (RR 43.06, 95% CI 2.61 to 710.44; RD 0.06, 95% CI 0.03 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 13 to 33; 705 infants, moderate-quality evidence). The roles of chlorhexidine dressing in the outcomes reported were unclear, as the two assigned groups received different co-interventions in the form of different skin cleansing agents prior to catheter insertion and during each dressing change.In the other comparison, silver-alginate patch versus control, the data for CRBSI were analysed separately in two subgroups as the two included studies reported the outcome using different denominators: one using infants and another using catheters. There were no significant differences between infants who received silver-alginate patch against infants who received standard line dressing in CRBSI, whether expressed as the number of infants (RR 0.50, 95% CI 0.14 to 1.78; RD -0.12, 95% CI -0.33 to 0.09; 1 study, 50 participants, moderate-quality evidence) or as the number of catheters (RR 0.72, 95% CI 0.27 to 1.89; RD -0.05, 95% CI -0.20 to 0.10; 1 study, 118 participants, moderate-quality evidence). There was also no significant difference between the two groups in mortality (RR 0.55, 95% CI 0.15 to 2.05; RD -0.04, 95% CI -0.13 to 0.05; two studies, 150 infants, I² = 0%, moderate-quality evidence). No adverse skin reaction was recorded in either group.
AUTHORS' CONCLUSIONS: Based on moderate-quality evidence, chlorhexidine dressing/alcohol skin cleansing reduced catheter colonisation, but made no significant difference in major outcomes like sepsis and CRBSI compared to polyurethane dressing/povidone-iodine cleansing. Chlorhexidine dressing/alcohol cleansing posed a substantial risk of contact dermatitis in preterm infants, although it was unclear whether this was contributed mainly by the dressing material or the cleansing agent. While silver-alginate patch appeared safe, evidence is still insufficient for a recommendation in practice. Future research that evaluates antimicrobial dressing should ensure blinding of caregivers and outcome assessors and ensure that all participants receive the same co-interventions, such as the skin cleansing agent. Major outcomes like sepsis, CRBSI and mortality should be assessed in infants of different gestation and birth weight.
METHODS: We conducted a search of PubMed, EMBASE and Cochrane databases until 31st December 2014 for randomized control trials (RCTs) in HF evaluating statins versus placebo. Identified RCTs and their respective abstracted information were grouped according to statin type evaluated and analyzed separately. Outcomes were initially pooled with the Peto's one-step method, producing odd ratios (OR) and 95 % confidence intervals (CI) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons of lipophilic versus hydrophilic statin for each outcome.
RESULTS: Thirteen studies involving 10,966 patients were identified and analyzed. Lipophilic statins were superior to hydrophilic rosuvastatin regarding all-cause mortality (OR 0 · 50; 95 % CI, 0 · 11-0 · 89; p = 0 · 01), cardiovascular mortality (OR 0 · 61; 0 · 25-0 · 97; p = 0 · 009), and hospitalization for worsening HF (OR 0 · 52; 0 · 21-0 · 83; p = 0 · 0005). However, both statins were comparable with regards to cardiovascular hospitalization [OR 0 · 80 (0 · 31, 1 · 28); p = 0 · 36].
CONCLUSIONS: Lipophilic statin treatment shows significant decreases in all-cause mortality, cardiovascular mortality and hospitalization for worsening HF compared with rosuvastatin treatment. This meta-analysis provides preliminary evidence that lipophilic statins offer better clinical outcomes in HF till data from head to head comparisons are available.
OBJECTIVES: We aimed to assess the effectiveness of co-bedding compared with separate (individual) care for stable preterm twins in the neonatal nursery in promoting growth and neurodevelopment and reducing short- and long-term morbidities, and to determine whether co-bedding is associated with significant adverse effects.As secondary objectives, we sought to evaluate effects of co-bedding via the following subgroup analyses: twin pairs with different weight ranges (very low birth weight [VLBW] < 1500 grams vs non-VLBW), twins with versus without significant growth discordance at birth, preterm versus borderline preterm twins, twins co-bedded in incubator versus cot at study entry, and twins randomized by twin pair versus neonatal unit.
SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG). We used keywords and medical subject headings (MeSH) to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (via PubMed), EMBASE (hosted by EBSCOHOST), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and references cited in our short-listed articles, up to February 29, 2016.
SELECTION CRITERIA: We included randomized controlled trials with randomization by twin pair and/or by neonatal unit. We excluded cross-over studies.
DATA COLLECTION AND ANALYSIS: We extracted data using standard methods of the CNRG. Two review authors independently assessed the relevance and risk of bias of retrieved records. We contacted the authors of included studies to request important information missing from their published papers. We expressed our results using risk ratios (RRs) and mean differences (MDs) when appropriate, along with 95% confidence intervals (95% CIs). We adjusted the unit of analysis from individual infants to twin pairs by averaging measurements for each twin pair (continuous outcomes) or by counting outcomes as positive if developed by either twin (dichotomous outcomes).
MAIN RESULTS: Six studies met the inclusion criteria; however, only five studies provided data for analysis. Four of the six included studies were small and had significant limitations in design. As each study reported outcomes differently, data for most outcomes were effectively contributed by a single study. Study authors reported no differences between co-bedded twins and twins receiving separate care in terms of rate of weight gain (MD 0.20 grams/kg/d, 95% CI -1.60 to 2.00; one study; 18 pairs of twins; evidence of low quality); apnea, bradycardia, and desaturation (A/B/D) episodes (RR 0.85, 95% CI 0.18 to 4.05; one study; 62 pairs of twins; evidence of low quality); episodes in co-regulated states (MD 0.96, 95% CI -3.44 to 5.36; one study; three pairs of twins; evidence of very low quality); suspected or proven infection (RR 0.84, 95% CI 0.30 to 2.31; three studies; 65 pairs of twins; evidence of very low quality); length of hospital stay (MD -4.90 days, 95% CI -35.23 to 25.43; one study; three pairs of twins; evidence of very low quality); and parental satisfaction measured on a scale of 0 to 55 (MD -0.38, 95% CI -4.49 to 3.73; one study; nine pairs of twins; evidence of moderate quality). Although co-bedded twins appeared to have lower pain scores 30 seconds after heel lance on a scale of 0 to 21 (MD -0.96, 95% CI -1.68 to -0.23; two studies; 117 pairs of twins; I(2) = 75%; evidence of low quality), they had higher pain scores 90 seconds after the procedure (MD 1.00, 95% CI 0.14 to 1.86; one study; 62 pairs of twins). Substantial heterogeneity in the outcome of infant pain response after heel prick at 30 seconds post procedure and conflicting results at 30 and 90 seconds post procedure precluded clear conclusions.
AUTHORS' CONCLUSIONS: Evidence on the benefits and harms of co-bedding for stable preterm twins was insufficient to permit recommendations for practice. Future studies must be adequately powered to detect clinically important differences in growth and neurodevelopment. Researchers should assess harms such as infection, along with medication errors and caregiver satisfaction.
OBJECTIVES: To assess the effectiveness and safety of various interventions for the treatment of oro-antral communications and fistulae due to dental procedures.
SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (whole database, to 3 July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2015, Issue 6), MEDLINE via OVID (1946 to 3 July 2015), EMBASE via OVID (1980 to 3 July 2015), US National Institutes of Health Trials Registry (http://clinicaltrials.gov) (whole database, to 3 July 2015) and the World Health Organization (WHO) International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/) (whole database, to 3 July 2015). We also searched the reference lists of included and excluded trials for any randomised controlled trials (RCTs).
SELECTION CRITERIA: We included RCTs evaluating any intervention for treating oro-antral communications or oro-antral fistulae due to dental procedures. We excluded quasi-RCTs and cross-over trials. We excluded studies on participants who had oro-antral communications, fistulae or both related to Caldwell-Luc procedure or surgical excision of tumours.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials. Two review authors assessed trial risk of bias and extracted data independently. We estimated risk ratios (RR) for dichotomous data, with 95% confidence intervals (CI). We assessed the overall quality of the evidence using the GRADE approach.
MAIN RESULTS: We included only one study in this review, which compared two surgical interventions: pedicled buccal fat pad flap and buccal flap for the treatment of oro-antral communications. The study involved 20 participants. The risk of bias was unclear. The relevant outcome reported in this trial was successful (complete) closure of oro-antral communication.The quality of the evidence for the primary outcome was very low. The study did not find evidence of a difference between interventions for the successful (complete) closure of an oro-antral communication (RR 1.00, 95% Cl 0.83 to 1.20) one month after the surgery. All oro-antral communications in both groups were successfully closed so there were no adverse effects due to treatment failure.We did not find trials evaluating any other intervention for treating oro-antral communications or fistulae due to dental procedures.
AUTHORS' CONCLUSIONS: We found very low quality evidence from a single small study that compared pedicled buccal fat pad and buccal flap. The evidence was insufficient to judge whether there is a difference in the effectiveness of these interventions as all oro-antral communications in the study were successfully closed by one month after surgery. Large, well-conducted RCTs investigating different interventions for the treatment of oro-antral communications and fistulae caused by dental procedures are needed to inform clinical practice.
OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.
SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .
SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.
MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (
QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (
QUALITY OF EVIDENCE: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (
QUALITY OF EVIDENCE: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (
QUALITY OF EVIDENCE: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (
QUALITY OF EVIDENCE: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (QUALITY OF EVIDENCE for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.
AUTHORS' CONCLUSIONS: The very low quality evidence gathered in this review does not suggest that TES provides a benefit for children with chronic constipation. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.
OBJECTIVES: To assess the effects of skin antisepsis as part of CVC care for reducing catheter-related BSIs, catheter colonisation, and patient mortality and morbidities.
SEARCH METHODS: In May 2016 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations and Epub Ahead of Print); Ovid EMBASE and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies. There were no restrictions with respect to language, date of publication or study setting.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed any type of skin antiseptic agent used either alone or in combination, compared with one or more other skin antiseptic agent(s), placebo or no skin antisepsis in patients with a CVC in place.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for their eligibility, extracted data and assessed risk of bias. We expressed our results in terms of risk ratio (RR), absolute risk reduction (ARR) and number need to treat for an additional beneficial outcome (NNTB) for dichotomous data, and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: Thirteen studies were eligible for inclusion, but only 12 studies contributed data, with a total of 3446 CVCs assessed. The total number of participants enrolled was unclear as some studies did not provide such information. The participants were mainly adults admitted to intensive care units, haematology oncology units or general wards. Most studies assessed skin antisepsis prior to insertion and regularly thereafter during the in-dwelling period of the CVC, ranging from every 24 h to every 72 h. The methodological quality of the included studies was mixed due to wide variation in their risk of bias. Most trials did not adequately blind the participants or personnel, and four of the 12 studies had a high risk of bias for incomplete outcome data.Three studies compared different antisepsis regimens with no antisepsis. There was no clear evidence of a difference in all outcomes examined, including catheter-related BSI, septicaemia, catheter colonisation and number of patients who required systemic antibiotics for any of the three comparisons involving three different antisepsis regimens (aqueous povidone-iodine, aqueous chlorhexidine and alcohol compared with no skin antisepsis). However, there were great uncertainties in all estimates due to underpowered analyses and the overall very low quality of evidence presented.There were multiple head-to-head comparisons between different skin antiseptic agents, with different combinations of active substance and base solutions. The most frequent comparison was chlorhexidine solution versus povidone-iodine solution (any base). There was very low quality evidence (downgraded for risk of bias and imprecision) that chlorhexidine may reduce catheter-related BSI compared with povidone-iodine (RR of 0.64, 95% CI 0.41 to 0.99; ARR 2.30%, 95% CI 0.06 to 3.70%). This evidence came from four studies involving 1436 catheters. None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine, alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality (and were generally underpowered). Mortality was only reported in a single study.There was very low quality evidence that skin antisepsis with chlorhexidine may also reduce catheter colonisation relative to povidone-iodine (RR of 0.68, 95% CI 0.56 to 0.84; ARR 8%, 95% CI 3% to 12%; ; five studies, 1533 catheters, downgraded for risk of bias, indirectness and inconsistency).Evaluations of other skin antiseptic agents were generally in single, small studies, many of which did not report the primary outcome of catheter-related BSI. Trials also poorly reported other outcomes, such as skin infections and adverse events.
AUTHORS' CONCLUSIONS: It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing. Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine. These results are based on very low quality evidence, which means the true effects may be very different. Moreover these results may be influenced by the nature of the antiseptic solution (i.e. aqueous or alcohol-based). Further RCTs are needed to assess the effectiveness and safety of different skin antisepsis regimens in CVC care; these should measure and report critical clinical outcomes such as sepsis, catheter-related BSI and mortality.
OBJECTIVES: To determine the effectiveness of rapamycin or rapalogs in people with tuberous sclerosis complex for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects.
SEARCH METHODS: Relevant studies were identified by authors from the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and clinicaltrials.gov. Relevant resources were also searched by the authors, such as conference proceedings and abstract books of conferences, from e.g. the Tuberous Sclerosis Complex International Research Conferences, other tuberous sclerosis complex-related conferences and the Human Genome Meeting. We did not restrict the searches by language as long as English translations were available for non-English reports.Date of the last searches: 14 March 2016.
SELECTION CRITERIA: Randomized or quasi-randomized studies of rapamycin or rapalogs in people with tuberous sclerosis complex.
DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors using standard acquisition forms. The data collection was verified by one author. The risk of bias of each study was independently assessed by two authors and verified by one author.
MAIN RESULTS: Three placebo-controlled studies with a total of 263 participants (age range 0.8 to 61 years old, 122 males and 141 females, with variable lengths of study duration) were included in the review. We found high-quality evidence except for response to skin lesions which was judged to be low quality due to the risk of attrition bias. Overall, there are 175 participants in the treatment arm (rapamycin or everolimus) and 88 in the placebo arm. Participants all had tuberous sclerosis complex as proven by consensus diagnostic criteria as a minimum. The quality in the description of the study methods was mixed, although we assessed most domains as having a low risk of bias. Blinding of treatment arms was successfully carried out in all of the studies. However, two studies did not report allocation concealment. Two of the included studies were funded by Novartis Pharmaceuticals.Two studies (235 participants) used oral (systemic) administration of everolimus (rapalog). These studies reported response to tumour size in terms of the number of individuals with a reduction in the total volume of tumours to 50% or more relative to baseline. Significantly more participants in the treatment arm (two studies, 162 participants, high quality evidence) achieved a 50% reduction in renal angiomyolipoma size, risk ratio 24.69 (95% confidence interval 3.51 to 173.41) (P = 0.001). For the sub-ependymal giant cell astrocytoma, our analysis of one study (117 participants, high quality evidence) showed significantly more participants in the treatment arm achieved a 50% reduction in tumour size, risk ratio 27.85 (95% confidence interval 1.74 to 444.82) (P = 0.02). The proportion of participants who showed a skin response from the two included studies analysed was significantly increased in the treatment arms, risk ratio 5.78 (95% confidence interval 2.30 to 14.52) (P = 0.0002) (two studies, 224 participants, high quality evidence). In one study (117 participants), the median change of seizure frequency was -2.9 in 24 hours (95% confidence interval -4.0 to -1.0) in the treatment group versus -4.1 in 24 hour (95% confidence interval -10.9 to 5.8) in the placebo group. In one study, one out of 79 participants in the treatment group versus three of 39 in placebo group had increased blood creatinine levels, while the median percentage change of forced expiratory volume at one second in the treatment arm was -1% compared to -4% in the placebo arm. In one study (117 participants, high quality evidence), we found that those participants who received treatment had a similar risk of experiencing adverse events compared to those who did not, risk ratio 1.07 (95% confidence interval 0.96 - 1.20) (P = 0.24). However, as seen from two studies (235 participants, high quality evidence), the treatment itself led to significantly more adverse events resulting in withdrawal, interruption of treatment, or reduction in dose level, risk ratio 3.14 (95% confidence interval 1.82 to 5.42) (P < 0.0001).One study (28 participants) used topical (skin) administration of rapamycin. This study reported response to skin lesions in terms of participants' perception towards their skin appearance following the treatment. There was a tendency of an improvement in the participants' perception of their skin appearance, although not significant, risk ratio 1.81 (95% confidence interval 0.80 to 4.06, low quality evidence) (P = 0.15). This study reported that there were no serious adverse events related to the study product and there was no detectable systemic absorption of the rapamycin during the study period.
AUTHORS' CONCLUSIONS: We found evidence that oral everolimus significantly increased the proportion of people who achieved a 50% reduction in the size of sub-ependymal giant cell astrocytoma and renal angiomyolipoma. Although we were unable to ascertain the relationship between the reported adverse events and the treatment, participants who received treatment had a similar risk of experiencing adverse events as compared to those who did not receive treatment. Nevertheless, the treatment itself significantly increased the risk of having dose reduction, interruption or withdrawal. This supports ongoing clinical applications of oral everolimus for renal angiomyolipoma and subependymal giant cell astrocytoma. Although oral everolimus showed beneficial effect on skin lesions, topical rapamycin only showed a non-significant tendency of improvement. Efficacy on skin lesions should be further established in future research. The beneficial effects of rapamycin or rapalogs on tuberous sclerosis complex should be further studied on other manifestations of the condition.
OBJECTIVES: To assess the effect of mother-infant rooming-in versus separation on the duration of breastfeeding (exclusive and total duration of breastfeeding).
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 May 2016) and reference lists of retrieved studies.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) investigating the effect of mother-infant rooming-in versus separate care after hospital birth or at home on the duration of breastfeeding, proportion of breastfeeding at six months and adverse neonatal and maternal outcomes.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.
MAIN RESULTS: We included one trial (involving 176 women) in this review. This trial included four groups with a factorial design. The factorial design took into account two factors, i.e. infant location in relation to the mother and the type of infant apparel. We combined three of the groups as the intervention (rooming-in) group and the fourth group acted as the control (separate care) and we analysed the results as a single pair-wise comparison. Primary outcomesThe primary outcome, duration of any breastfeeding, was reported by authors as median values because the distribution was found to be skewed. They reported the overall median duration of any breastfeeding to be four months, with no difference found between groups. Duration of exclusive breastfeeding and the proportion of infants being exclusively breastfed at six months of age was not reported in the trial. There was no difference found between the two groups in the proportion of infants receiving any breastfeeding at six months of age (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.51 to 1.39; one trial; 137 women; low-quality evidence). Secondary outcomesThe mean frequency of breastfeeds per day on day four postpartum for the rooming-in group was 8.3 (standard deviation (SD) 2.2), slightly higher than the separate care group, i.e. seven times per day. However, between-group comparison of this outcome was not appropriate since every infant in the separate care group was breastfed at a fixed schedule of seven times per day (SD = 0) resulting in no estimable comparison. The rate of exclusive breastfeeding on day four postpartum before discharge from hospital was significantly higher in the rooming-in group 86% (99 of 115) compared with separate care group, 45% (17 of 38), (RR 1.92; 95% CI 1.34 to 2.76; one trial, 153 women; low-quality evidence). None of our other pre-specified secondary outcomes were reported.
AUTHORS' CONCLUSIONS: We found little evidence to support or refute the practice of rooming-in versus mother-infant separation. Further well-designed RCTs to investigate full mother-infant rooming-in versus partial rooming-in or separate care including all important outcomes are needed.
OBJECTIVES: To assess the effect of restricted versus unrestricted pacifier use in healthy full-term newborns whose mothers have initiated breastfeeding and intend to exclusively breastfeed, on the duration of breastfeeding, other breastfeeding outcomes and infant health.
SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2016) and reference lists of retrieved studies.
SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing restricted versus unrestricted pacifier use in healthy full-term newborns who have initiated breastfeeding.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS: We found three trials (involving 1915 babies) for inclusion in the review, but have included only two trials (involving 1302 healthy full-term breastfeeding infants) in the analysis. Meta-analysis of the two combined studies showed that pacifier use in healthy breastfeeding infants had no significant effect on the proportion of infants exclusively breastfed at three months (risk ratio (RR) 1.01; 95% confidence interval (CI) 0.96 to 1.07, two studies, 1228 infants), and at four months of age (RR 1.01; 95% CI 0.94 to 1.09, one study, 970 infants, moderate-quality evidence), and also had no effect on the proportion of infants partially breastfed at three months (RR 1.00; 95% CI 0.98 to 1.02, two studies, 1228 infants), and at four months of age (RR 0.99; 95% CI 0.97 to 1.02, one study, 970 infants). None of the included trials reported data on the other primary outcomes, i.e. duration of partial or exclusive breastfeeding, or secondary outcomes: breastfeeding difficulties (mastitis, cracked nipples, breast engorgement); infant's health (dental malocclusion, otitis media, oral candidiasis; sudden infant death syndrome (SIDS)); maternal satisfaction and level of confidence in parenting. One study reported that avoidance of pacifiers had no effect on cry/fuss behavior at ages four, six, or nine weeks and also reported no effect on the risk of weaning before age three months, however the data were incomplete and so could not be included for analysis.
AUTHORS' CONCLUSIONS: Pacifier use in healthy term breastfeeding infants, started from birth or after lactation is established, did not significantly affect the prevalence or duration of exclusive and partial breastfeeding up to four months of age. Evidence to assess the short-term breastfeeding difficulties faced by mothers and long-term effect of pacifiers on infants' health is lacking.
OBJECTIVES: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.
METHODS: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.
MEASUREMENTS AND MAIN RESULTS: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.
CONCLUSIONS: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
METHODS: RCTs comparing the early complication rates following LVSG and LRYGB between 2000 and 2015 were selected from PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane database. The outcome variables analyzed included 30-day mortality, major and minor complications and interventions required for their management, length of hospital stay, readmission rates, operating time, and conversions from laparoscopic to open procedures.
RESULTS: Six RCTs involving a total of 695 patients (LVSG n = 347, LRYGB n = 348) reported on early major complications. A statistically significant reduction in relative odds of early major complications favoring the LVSG procedure was noted (p = 0.05). Five RCTs representing 633 patients (LVSG n = 317, LRYGB n = 316) reported early minor complications. A non-statically significant reduction in relative odds of 29 % favoring the LVSG procedure was observed for early minor complications (p = 0.4). However, other outcomes directly related to complications which included reoperation rates, readmission rate, and 30-day mortality rate showed comparable effect size for both surgical procedures.
CONCLUSIONS: This meta-analysis and systematic review of RCTs suggests that fewer early major and minor complications are associated with LVSG compared with LRYGB procedure. However, this does not translate into higher readmission rate, reoperation rate, or 30-day mortality for either procedure.
OBJECTIVES: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA).
SEARCH STRATEGY: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour.
SELECTION CRITERIA: We selected trials including pregnant women between 24 and 36(6/7) weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment.
DATA COLLECTION AND ANALYSIS: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed.
MAIN RESULTS: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01).
CONCLUSION: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice.
TWEETABLE ABSTRACT: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation.
OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.
SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .
SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.
MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (Quality of evidence: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (Quality of evidence: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (Quality of evidence: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (Quality of evidence for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.
AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.
OBJECTIVES: To assess the effectiveness, safety and appropriate dose regimen of hydroxyurea in people with non-transfusion dependent beta thalassaemia (haemoglobin E combined with beta thalassaemia and beta thalassaemia intermedia).
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of relevant journals. We also searched ongoing trials registries and the reference lists of relevant articles and reviews.Date of last search: 30 April 2016.
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of hydroxyurea in people with non-transfusion dependent beta thalassaemia comparing hydroxyurea with placebo or standard treatment or comparing different doses of hydroxyurea.
DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria in order to select trials for inclusion. Both authors assessed the risk of bias of trials and extracted the data. A third author verified these assessments.
MAIN RESULTS: No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks.Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported.The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment.
AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.