Date Of Last Search Research Articles

Quality of Life and Medico-Legal Implications Following Iatrogenic Bile Duct Injuries.

In this review we aimed to evaluate quality of life after bile duct injury and the consequent medico-legal implications. A comprehensive English languageliterature search was performed on MEDLINE, Embase, Science Citation Index and Google™ Scholar databases for articles published between January 2000 and April 2016. The last date of search was 11 April 2016. Key search words included bile duct injury, iatrogenic, cholecystectomy, prevention, risks, outcomes, quality of life, litigation and were used in combination with the Boolean operators AND, OR and NOT. Long-term survival after bile duct injury is significantly impaired (all-cause long-termmortality approximately 21%) along with the quality of life (especially psychological/mental state remains affected). Bile duct injury is associated with high rates of litigation. Monetary compensation varied from £2500 to £216,000 in the UK, €9826-€55,301 in the Netherlands and $628,138-$2,891,421 in the USA. Bile duct injuries have profound implications for patients, medical personnel and healthcare providers as they cause significant morbidity and mortality, high rates of litigation and raised healthcare expenditure.

Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome).

Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X-linked disease caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those individuals with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II. This is an update of a previously published version of this review. To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 23 November 2015).We also searched Embase, PubMed and the Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS) (date of last search 28 November 2015). Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation). Two authors independently screened the trials identified, appraised quality of papers and extracted data. One study (96 male participants) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. This trial was considered to be of overall good quality. Following 53 weeks of treatment, participants in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of participants at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels. The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in people with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy.

Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues. To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis. We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors. We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women. Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate. Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction. Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.

Intratympanic therapy in Meniere's syndrome or disease: up to date evidence for clinical practice.

Meniere's syndrome or disease (MS/D) is typically characterised by episodic vertigo, aural fullness, tinnitus and fluctuating hearing loss. There are multiple options available for treatment with variation in consensus on the best intervention. To evaluate the evidence on the efficacy of intratympanic therapies [steroids, gentamicin, antivirals and other therapies] on the frequency and severity of vertigo and other symptoms of MS/D. A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders group trials register using various MeSH. The search was restricted to English and human subjects, and the last date of search was December 2014. Randomised controlled trials of intratympanic therapies [steroids, gentamicin antivirals and latanoprost] versus a placebo or another treatment. We analysed 8 RCT's comparing intratympanic steroids, gentamicin, ganciclovir (antiviral) and latanoprost versus another form of intratympanic treatment or placebo. On the basis of 6 RCT's (n = 242), there is evidence to support the effectiveness of intratympanic steroids and gentamicin to control symptoms of vertigo in MS/D albeit with a risk of hearing loss with gentamicin. However, there was no consensus found on doses or treatment protocols. There was no evidence to support the use of other forms of intratympanic therapy (antivirals and latanoprost) in MS/D.

Laser therapy for retinopathy in sickle cell disease.

Sickle cell disease includes a group of inherited haemoglobinopathies affecting multiple organs including the eyes. Some people with the disease develop ocular manifestations due to vaso-occlusion. Vision-threatening complications of sickle cell disease are mainly due to proliferative sickle retinopathy which is characterized by proliferation of new blood vessels. Laser photocoagulation is widely applicable in proliferative retinopathies such as proliferative sickle retinopathy and proliferative diabetic retinopathy. It is important to evaluate the efficacy and safety of laser photocoagulation in the treatment of proliferative sickle retinopathy to prevent sight-threatening complications. To evaluate the effectiveness of various techniques of laser photocoagulation therapy in sickle cell disease-related retinopathy. 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. Randomised controlled trials comparing laser photocoagulation to no treatment in children and adults. 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. 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. 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.

Ménière's Syndrome or Disease: Time Trends in Management and Quality of Evidence Over the Last Two Decades.

To evaluate the evidence and trends in published literature on the treatment of Ménière's syndrome or disease (MS/D) by comparing studies published in the last two decades. A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders groups trials register using a combination of MeSH. The date of last search was October 2014. Two hundred five studies (104 in decade I and 101 in decade II) were evaluated to report trends in the management of this condition, the differing levels of evidence published for each treatment modality, evaluate whether the guidelines published by the AAOHNS-Committee on Hearing and Equilibrium had been correctly employed, and whether the randomized controlled trials (RCTs) were compliant with the CONSORT guidelines. The number of published RCTs almost tripled from decade I (1994-2003) to decade II (2004-2103). There was a significant decline in the use of surgical intervention (p = 0.013); however, the number of studies involving the use of intratympanic injection remained largely unchanged. There was a shift in the level of evidence in published studies; studies with level 1 evidence tripled from decade I to II (4.8 to 17.8%, respectively) (p = 0.03); however, compliance with the AAOHNS-CHE criteria for reporting treatment outcomes and the CONSORT checklist was still poor. Although the evidence base on published literature on MS/D has improved over the last decade with an increase in emphasis on RCTs and quality of life (QoL) studies, a significant number of studies failed to follow AAOHNS-CHE criteria for reporting treatment outcome and the CONSORT criteria for reporting RCTs.

The Effect of Early Initiation of Antiretroviral Therapy in TB/HIV-Coinfected Patients: A Systematic Review and Meta-Analysis.

The importance of early initiation of antiretroviral therapy (ART) for tuberculosis (TB) and HIV-coinfected patients is controversial. We conducted a systematic review and meta-analysis to assess the effect of early initiation of ART (within 2-4 weeks of TB treatment) on several treatment outcomes among TB/HIV-coinfected patients. A systematic search of clinical trials was performed in PubMed, Embase, Google Scholar, Science Direct, Medscape, and the Cochrane library. Clinical trials which were published in any language before the last date of search (March 31, 2015) were included. The qualities of the studies were assessed using criteria from the Cochrane Library. Heterogeneity test was conducted to assess the variations among study outcomes. For each study outcome, the risk ratio (RR) with 95% confidence interval (CI) was calculated as a measure of intervention effect. The Mantel-Haenszel method was used to estimate the RR using a fixed-effects model. A total of 2272 study participants from 6 trials were included in the meta-analysis. Early ART initiation during TB treatment was associated with reduced all-cause mortality (RR = 0.78; 95% CI = 0.63-0.98) and increased rate of TB-associated immune reconstitution inflammatory syndrome (TB-IRIS; RR = 2.19; 95% CI = 1.77- 2.70) and death related to TB-IRIS (RR = 6.94; 95% CI = 1.26-38.22). However, the time of ART initiation has no association with TB cure rate (RR = 0.99; 95% CI = 0.81-1.07), rate of drug toxicity (RR = 1.00; 95% CI = 0.93-1.08), death associated with drug toxicity (RR = 0.40; 95% CI = 0.14- 1.16), rate of low viral load (less than 400 copies/mL; RR = 1.00; 95% CI = 0.96-1.04), and rate of new AIDS-defining illness (RR = 0.84; 95% CI = 0.60-1.18). Immunological response in early ART arms of study participant in different trials showed a greater or equal response compared with late ART arms. This systematic review presents conclusive evidence on the reduction of all-cause mortality as a result of early initiation of ART. However, this study also confirms the high rate of TB-IRIS and death associated with it. Operational and implementation research are required to maintain the benefit of early ART initiation and proper management of TB-IRIS. Studies on the timing of ART in extrapulmonary and multidrug-resistant TB are recommended.

Systematic review with meta-analysis: Saccharomyces boulardii supplementation and eradication of Helicobacter pylori infection.

Unsatisfactory Helicobacter pylori eradication rates and therapy-associated side effects remain a problem. To update our 2010 meta-analysis on the effects of Saccharomyces boulardii as supplementation to a standard eradication regimen on H. pylori eradication rates and therapy-associated side effects. The Cochrane Library, MEDLINE and EMBASE databases were searched from July 2010 (end date of last search) to February 2015, with no language restrictions, for randomised controlled trials (RCTs); additional references were obtained from reviewed articles. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines. Eleven RCTs (2200 participants, among them 330 children) met the inclusion criteria. Of the 853 patients in the S. boulardii group, 679 (80%, 95% CI 77-82) experienced eradication compared with 608 of the 855 patients (71%, 95% CI 68-74) in the control group [relative risk (RR) 1.11, 95% confidence interval (CI) 1.06-1.17; moderate quality evidence]. S. boulardii compared with control reduced the risk of overall H. pylori therapy-related adverse effects (RR 0.44, 95% CI 0.31-0.64; moderate quality evidence), particularly of diarrhoea (RR 0.51, 95% CI 0.42-0.62; high quality evidence) and nausea [RR 0.6, 95% CI 0.44-0.83 (moderate quality of evidence)]. In the populations studied, the effectiveness of standard triple therapy was unsatisfactory. The addition of S. boulardii significantly increased the eradication rate, but it was still below the desired level of success. Saccharomyces boulardii significantly decreased some therapy-related side effects.

Rituximab for treating inhibitors in people with inherited severe hemophilia.

Hemophilia A and B are inherited coagulation disorders characterized by a reduced or absent level of factor VIII or factor IX respectively. The severe form is characterized by a factor level less than 0.01 international units (IU) per milliliter. The development of inhibitors in hemophilia is the main complication of treatment, because the presence of these antibodies, reduces or even nullifies the efficacy of replacement therapy, making it very difficult to control the bleeding. People with inhibitors continue to have significantly higher risks of morbidity and mortality, with considerable treatment costs. Given the wide 'off-label' use of rituximab for treating people with hemophilia and inhibitors, its efficacy and safety need to be evaluated. To assess the efficacy and safety of rituximab for treating inhibitors in people with inherited severe hemophilia A or B. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, complied from electronic database searches and handsearching of journals and conference abstract books. We searched the reference lists of relevant articles and reviews and also searched for ongoing or unpublished studies.Date of last search: 27 January 2015. Randomized controlled trials and controlled clinical trials investigating the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. No randomized controlled trials matching the selection criteria were eligible for inclusion. No randomized controlled trials on rituximab for treating inhibitors in people with hemophilia were identified. We were unable to identify any relevant trials on the efficacy and safety of rituximab for treating inhibitors in people with hemophilia. The research evidence available is from case reports and case series. Randomized controlled trials are needed to evaluate the efficacy and safety of rituximab for this condition. However, prior to the publication of any possible future randomized controlled trials, meta-analysis of case reports and case series may provide some evidence.

Sapropterin dihydrochloride for phenylketonuria.

Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria. This is an update of a previously published Cochrane Review. To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria. We identifiedrelevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 11 August 2014.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 4 September 2014We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials. Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency. Two authors independently assessed trials and extracted outcome data. Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group. There is evidence of short-term benefit from using sapropterin in some people with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.

Interventions for treating intrahepatic cholestasis in people with sickle cell disease.

Sickle cell disease is the most common hemoglobinopathy occurring worldwide and sickle cell intrahepatic cholestasis is a complication long recognized in this population. Cholestatic liver diseases are characterized by impaired formation or excretion (or both) of bile from the liver. There is a need to assess the clinical benefits and harms of the interventions used to treat intrahepatic cholestasis in people with sickle cell disease. To assess the benefits and harms of the interventions for treating intrahepatic cholestasis in people with sickle cell disease. We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 7 July 2014) and the WHO International Clinical Trials Registry Platform Search Portal (7 July 2014).Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 10 October 2014. We searched for published or unpublished randomised controlled trials. Each author intended to independently extract data and assess the risk of bias of the trials by standard Cochrane Collaboration methodologies; however, no trials were included in the review. There were no randomised controlled trials identified. This Cochrane Review did not identify any randomised controlled trials assessing interventions for treating intrahepatic cholestasis in people with sickle cell disease. Randomised controlled trials are needed to establish the optimum treatment for this condition.

Embolisation for pulmonary arteriovenous malformation.

Pulmonary arteriovenous malformations are abnormal direct connections between the pulmonary artery and pulmonary vein which result in a right-to-left shunt. They are associated with substantial morbidity and mortality mainly from the effects of paradoxical emboli. Potential complications include stroke, cerebral abscess, pulmonary haemorrhage and hypoxaemia. Embolisation is an endovascular intervention based on the occlusion of the feeding arteries the pulmonary arteriovenous malformations thus eliminating the abnormal right-to-left-shunting. To determine the efficacy and safety of embolisation in patients with pulmonary arteriovenous malformations including a comparison with surgical resection and different embolisation devices. We searched the Cystic Fibrosis and Genetic Disorders Group's Trials Register; date of last search: 31 March 2014.We also searched the following databases: the Australian New Zealand Clinical Trials Registry; ClinicalTrials.gov; International Standard Randomised Controlled Trial Number Register; International Clinical Trials Registry Platform Search Portal (last searched 1 July 2014).We checked cross-references and searched references from review articles. Trials in which individuals with pulmonary arteriovenous malformations were randomly allocated to embolisation compared to no treatment, surgical resection or embolisation using a different embolisation device. Studies identified for potential inclusion were independently assessed for eligibility by two authors, with excluded studies further checked by a third author. No trials were identified for inclusion in the review and hence no analysis was performed. There were no randomised controlled trials included in the review; one ongoing trial has been identified which may be eligible for inclusion in the future. There is no evidence from randomised controlled trials for embolisation of pulmonary arteriovenous malformations. However, randomised controlled trials are not always feasible on ethical grounds. Accumulated data from observational studies suggest that embolisation reduces morbidity. A standardised approach to reporting with long-term follow-up through registry studies can help to strengthen the evidence for embolisation in the absence of randomised controlled trials.

The role of simulation in continuing medical education for acute care physicians: a systematic review.

We systematically reviewed the effectiveness of simulation-based education, targeting independently practicing qualified physicians in acute care specialties. We also describe how simulation is used for performance assessment in this population. Data source included: DataMEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL Database of Controlled Trials, and National Health Service Economic Evaluation Database. The last date of search was January 31, 2013. All original research describing simulation-based education for independently practicing physicians in anesthesiology, critical care, and emergency medicine was reviewed. Data analysis was performed in duplicate with further review by a third author in cases of disagreement until consensus was reached. Data extraction was focused on effectiveness according to Kirkpatrick's model. For simulation-based performance assessment, tool characteristics and sources of validity evidence were also collated. Of 39 studies identified, 30 studies focused on the effectiveness of simulation-based education and nine studies evaluated the validity of simulation-based assessment. Thirteen studies (30%) targeted the lower levels of Kirkpatrick's hierarchy with reliance on self-reporting. Simulation was unanimously described as a positive learning experience with perceived impact on clinical practice. Of the 17 remaining studies, 10 used a single group or "no intervention comparison group" design. The majority (n = 17; 44%) were able to demonstrate both immediate and sustained improvements in educational outcomes. Nine studies reported the psychometric properties of simulation-based performance assessment as their sole objective. These predominantly recruited independent practitioners as a convenience sample to establish whether the tool could discriminate between experienced and inexperienced operators and concentrated on a single aspect of validity evidence. Simulation is perceived as a positive learning experience with limited evidence to support improved learning. Future research should focus on the optimal modality and frequency of exposure, quality of assessment tools and on the impact of simulation-based education beyond the individuals toward improved patient care.

Vitamin E supplementation in people with cystic fibrosis.

People with cystic fibrosis are at an increased risk of fat-soluble vitamin deficiency including vitamin E. Vitamin E deficiency can cause a host of conditions such as haemolytic anaemia, cerebellar ataxia and cognitive difficulties. Vitamin E supplementation is widely recommended in cystic fibrosis and aims to ameliorate this deficiency. To determine the effects of any level of vitamin E supplementation on the frequency of vitamin E deficiency disorders in people with cystic fibrosis. We searched the Cochrane Group's Cystic Fibrosis Trials Register and also searched international trial registers for any ongoing clinical trials that were not identified during our register search.Date of last search of the Register: 10 February 2014. Date of last search of international trial registers: 30 August 2014. Randomised controlled trials and quasi-randomised controlled trials comparing any preparation of vitamin E supplementation to placebo or no supplement, regardless of dosage or duration. Two authors extracted outcome data from each study (published information) and assessed the risk of bias of each included study. Four studies with a total of 141 participants were included in the review, two of these were in children (aged six months to 14.5 years), and the other two did not specify participants' age. All studies used different formulations and doses of vitamin E for various durations of treatment (10 days to six months). Two studies compared the supplementation of fat-soluble as well as water-soluble formulations to no supplementation in different arms of the same study. A third study compared a water-soluble formulation to a placebo; and in the fourth study a fat-soluble formulation of vitamin E was assessed against placebo.At one month, three months and six months, water-soluble vitamin E significantly improved serum vitamin E levels compared with control: at one month, two studies, mean difference 17.66 (95% confidence interval 10.59 to 24.74); at three months, one study, mean difference 11.61 (95% confidence interval 4.77 to 18.45); and at six months, one study, mean difference 19.74 (95% confidence interval 13.48 to 26.00). At one month fat-soluble vitamin E significantly improved serum vitamin E levels compared with control: one month, two studies, mean difference 13.59 (95% CI 9.52 to 17.66). The findings at three months were imprecise; one study; mean difference 6.40 (95% CI -1.45 to 14.25).None of the studies report the review's primary outcomes of vitamin E total lipid ratio or the incidence of vitamin E-specific deficiency disorders, or the secondary outcomes lung function or quality of life. Only one study, comparing water-soluble vitamin E with placebo, reported the secondary outcome of growth and nutritional status (weight), but the results are uncertain due to imprecision around the effect estimate.There was limited detail about randomisation and blinding in the included studies which compromises the quality of the evidence base for the review. The heterogeneous mix of the formulations with differing biovailabilities among these studies also limits the generalisability of the data to the wider cystic fibrosis population. Vitamin E supplementation led to an improvement in vitamin E levels in people with cystic fibrosis, although the studies may have been at risk of bias. No data on other outcomes of interest were available to allow conclusions about any other benefits of this therapy.In future, larger studies are needed, especially in people already being treated with enteric-coated pancreatic enzymes and supplemented with vitamin E, to look at more specific outcome measures such as vitamin E status, lung function and nutritional status. Future studies could also look at the optimal dose of vitamin E required to achieve maximal clinical effectiveness.

Antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis.

Nontuberculous mycobacteria are mycobacteria, other than those in the Mycobacterium tuberculosis complex, and are commonly found in the environment. Nontuberculous mycobacteria species (most commonly Mycobacterium avium complex and Mycobacterium abscessus) are isolated from the respiratory tract of approximately 5% to 20% of individuals with cystic fibrosis; they can cause lung disease in people with cystic fibrosis leading to more a rapid decline in lung function and even death in certain circumstances. Although there are guidelines for the antimicrobial treatment of nontuberculous mycobacteria lung disease, these recommendations are not specific for people with cystic fibrosis and it is not clear which antibiotic regimen may be the most effective in the treatment of these patients. The objective of our review was to compare antibiotic treatment to no antibiotic treatment, or to compare different combinations of antibiotic treatment, for nontuberculous mycobacteria lung infections in people with cystic fibrosis. The primary objective was to assess the effect of treatment on lung function and pulmonary exacerbations and to quantify adverse events. The secondary objectives were to assess treatment effects on the amount of bacteria in the sputum, quality of life, mortality, nutritional parameters, hospitalizations and use of oral antibiotics. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search: 13 November 2014.We also searched a register of ongoing trials and the reference lists of relevant articles and reviews. Date of last search: 24 September 2014. Any randomized controlled trials comparing nontuberculous mycobacteria antibiotics to no antibiotic treatment, as well as one nontuberculous mycobacteria antibiotic regimen compared to another nontuberculous mycobacteria antibiotic regimen, in individuals with cystic fibrosis. Data were not collected because no completed trials were identified by the searches. No completed trials were identified by the searches, but one ongoing trial was identified, which may be eligible for inclusion in this review when completed. This review did not find any evidence for the effectiveness of different antimicrobial treatment for nontuberculous mycobacteria lung disease in people with cystic fibrosis. Until such evidence becomes available, it is reasonable for clinicians to follow the American Thoracic Society guidelines for the diagnosis and treatment of nodular or bronchiectatic pulmonary disease due to Mycobacterium avium complex or Mycobacterium abscessus in patients with cystic fibrosis.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) in terms of reducing the risk of joint damage, improving physical function and improving quality of life. This Cochrane review is an update of a review of the treatment of RA with certolizumab pegol that was first published in 2011. To assess the clinical benefits and harms of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 5), MEDLINE, EMBASE, Scopus, TOXLINE, Web of Knowledge; websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA); reference lists of articles; and searched http/clinicaltrials.gov. The searches were updated from 2009 (date of last search for the original review) to 5 June 2014. Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult patients with active RA despite current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. Two authors independently assessed search results, trial quality and extracted data. Disagreements were resolved by discussion or referral to a third author. Eleven trials were included in this update. Ten (4324 patients) were included in the pooled analysis for benefits, five more than previously, and 10 (3711 patients) in the pooled analysis for harms, four more trials (1930 patients) than previously. The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously (sc). In phase III trials, the control was placebo plus MTX in five trials and placebo in four trials. The risk of bias of the included studies was assessed as low but there may have been a risk of attrition bias.Statistically significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol every other week, in 1) American College of Rheumatology (ACR) 50% improvement: 27% absolute improvement (95% CI 20% to 33%), NNT of 4 (95% CI 3 to 8), risk ratio (RR) 3.80 (95% CI 2.42 to 5.95); 2) the Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%), NNT of 6 (95% CI 5 to 8), mean difference (MD) - 0.35 (95% CI -0.43 to -0.26) (scale 0 to 3); 3) Disease Activity Score (DAS) remission improvement: absolute improvement 11% (95% CI 8% to 15%), NNT of 9 (95% CI 4 to 20), RR 8.47 (95% CI 4.15-17.28); and 4) radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%), NNT of 6 (95% CI 4 to 10), MD -0.67 (95% CI -0.96 to -0.38) (scale 0 to 230). Serious adverse events were statistically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 4% (95% CI 2% to 6%), NNTH of 32 (95% CI 17 to 88), Peto odds ratio (OR) 1.77 (95% CI 1.27 to 2.46). There was a statistically significant increase in all withdrawals in the placebo groups (for all doses and all follow-ups) with an absolute rate difference of -34% (95% CI -18% to -50%), NNTH of 4 (95% CI 3 to 5), NNTH of 4 (95% CI 3 to 5), RR 0.42 (95% CI 0.36 to 0.50); and there was a statistically significant increase in all withdrawals due to adverse events in the certolizumab groups (for all doses and all follow-up) with an absolute rate difference of 2% (95% CI 1% to 3%), NNTH of 55 (95% CI 27 to 238), Peto OR 1.66 (95% CI 1.15 to 2.37).The risk of bias was low and the quality of evidence was downgraded to moderate because of high rates of dropouts (> 20%) in most of the trials. We did not find any problems with inconsistency, indirectness, imprecision or publication bias. The results and conclusions did not change from the previous review. There is moderate-level evidence from randomised controlled trials that certolizumab pegol alone or combined with methotrexate is beneficial in the treatment of RA. Adverse events were more frequent with active treatment. We found a potential risk of serious adverse events.

Topical corticosteroids for treating phimosis in boys.

Until recently, phimosis has been treated surgically by circumcision or prepuceplasty; however, recent reports of non-invasive treatment using topical corticosteroids applied for four to eight weeks have been favourable. The efficacy and safety of topical corticosteroids for treating phimosis in boys has not been previously systematically reviewed. We aimed to 1) compare the effectiveness of the use of topical corticosteroid ointment applied to the distal stenotic portion of the prepuce in the resolution of phimosis in boys compared with the use of placebo or no treatment, and 2) determine the rate of partial resolution (improvement) of phimosis, rate of re-stenosis after initial resolution or improvement of phimosis, and the rate of adverse events of topical corticosteroid treatment in boys with phimosis. We searched the Cochrane Renal Group's Specialised Register through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Date of last search: 16 June 2014. We included all randomised controlled trials (RCTs) that compared use of any topical corticosteroid ointment with placebo ointment or no treatment for boys with phimosis. Two authors independently assessed titles, abstracts and the full-text of eligible studies, extracted data relating to the review's primary and secondary outcomes, and assessed studies' risk of bias. Statistical analyses were performed using the random-effects model and results were expressed as risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). We contacted authors of primary articles asking for details of study design and specific outcome data. We included 12 studies that enrolled 1395 boys in this review. We found that both types of corticosteroids investigated and treatment duration varied among studies.Compared with placebo, corticosteroids significantly increased complete or partial clinical resolution of phimosis (12 studies, 1395 participants: RR 2.45, 95% CI 1.84 to 3.26). Our analysis of studies that compared different types of corticosteroids found that these therapies also significantly increased complete clinical resolution of phimosis (8 studies, 858 participants: RR 3.42, 95% CI 2.08 to 5.62). Although nine studies (978 participants) reported that assessment of adverse effects were planned in the study design, these outcomes were not reported.Overall, we found that inadequate reporting made assessing risk of bias challenging in many of the included studies.Selection bias, performance and detection bias was unclear in the majority of the included studies: two studies had adequate sequence generation, none reported allocation concealment; two studies had adequate blinding of participants and personnel and one had high risk of bias; one study blinded outcome assessors. Attrition bias was low in 8/12 studies and reporting bias was unclear in 11 studies and high in one study. Topical corticosteroids offer an effective alternative for treating phimosis in boys. Although sub optimal reporting among the included studies meant that the size of the effect remains uncertain, corticosteroids appear to be a safe, less invasive first-line treatment option before undertaking surgery to correct phimosis in boys.

Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage kidney disease.

Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis.This is an update of a review first published in 2000. This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. We searched the Cochrane Renal Group's Specialised Register through contact with the Trials Search Co-ordinator. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. Date of last search: 22 October 2013. Randomised controlled trials (RCTs) or quasi-RCTs comparing double bag, Y-set and standard peritoneal dialysis (PD) exchange systems in patients with end-stage kidney disease. Data were abstracted by a single investigator onto a standard form and analysed by Review Manager. Analysis was by a random effects model and results were expressed as risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Twelve eligible trials with a total of 991 randomised patients were identified. Despite the large total number of patients, few trials covered the same interventions, small numbers of patients were enrolled in each trial and the methodological quality was suboptimal. Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) in preventing peritonitis in PD. Disconnect systems should be the preferred exchange systems in CAPD.

Surgery for weight loss in adults.

Surgery for weight loss in adults.