OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.
SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
AIM: These post hoc analyses investigated the bleeding patterns in target joints.
METHODS: Patients randomized to 40 or 10 IU kg(-1) once weekly prophylaxis who had at least one target joint were included. Baseline demographics and disease-specific data were collected. Bleeding patterns were assessed, and an International Society on Thrombosis and Haemostasis (ISTH) definition of target joints was used.
RESULTS: A total of 67% and 8% of patients in the 40 and 10 IU kg(-1) arm, respectively, did not experience target joint bleeds during the paradigm(™) 2 trial. Twenty-four target joints were recorded in each prophylaxis arm at baseline. During the paradigm(™) 2 trial, no bleeds were reported in 17 (71%) and 7 (29%) target joints in the 40 and 10 IU kg(-1) arms respectively. All target joint bleeds in the 40 IU kg(-1) once weekly prophylaxis arm were controlled with a single injection of 40 IU kg(-1) nonacog beta pegol. By the latest ISTH definition, 90% and 58% of target joints in the 40 and 10 IU kg(-1) arms, respectively, were no longer considered target joints at the end of the paradigm(™) 2 trial. At the end of the paradigm(™) 4 extension trial, all target joints in the 40 IU kg(-1) arm were no longer considered target joints.
CONCLUSION: Routine prophylaxis with 40 IU kg(-1) once weekly nonacog beta pegol has the potential for effective management of target joint bleeds in haemophilia B patients.
METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.
RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.
CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
METHODS: This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA1c (%) after 26 weeks.
RESULTS: Change in HbA1c at Week 26 was IDegAspSimple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAspStepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAspSimple to IDegAspStepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAspStepwise [2.1 per patient years of exposure (PYE)] vs. IDegAspSimple (3.3 PYE) (estimated rate ratio IDegAspSimple /IDegAspStepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported.
CONCLUSIONS: In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAspSimple titration algorithm improved HbA1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.
DATA SOURCES: A systematic search using relevant keywords was conducted in PubMed-Medline, EMBASE, PsycINFO, CINAHL, Scopus, and The Cochrane Library.
INCLUSION CRITERIA: Randomized controlled trials (RCTs) that compared technology-based interventions with inactive controls in the treatment of moderate to severe dental anxiety were included.
RESULTS: A total of seven RCTs were included in the review. These studies investigated the effectiveness of video modeling, computerized cognitive behavioral therapy, virtual reality exposure therapy, and distraction with music and audiovisual video material. Six studies examining video modeling, computerized cognitive behavioral therapy, virtual reality exposure therapy, and distraction (audiovisual) showed significantly greater reductions in dental anxiety than inactive controls in both children and adults. None of the included studies followed Consolidated Standards of Reporting Trials guidelines completely or reported sufficient data, thereby precluding a possible meta-analysis. Four out of seven included studies were assessed to be at high risk of bias.
CONCLUSIONS: A limited number of studies supported the effectiveness of technology-based interventions in the treatment of dental anxiety in children and adults.
CLINICAL SIGNIFICANCE: The quality of the methods of studies on the effects of technology-based interventions allows only limited inferences on the effects of these interventions. However, within the limitations of the systematic review, the results converge to suggest that technology-based interventions may be useful as an adjunct to standard dental care. High-quality RCTs are needed to determine the (relative) effectiveness of these interventions.
PROSPERO REGISTRATION NUMBER: CRD42017064810.