Printed educational materials: effects on professional practice and healthcare outcomes.

BACKGROUND: Printed educational materials are widely used dissemination strategies to improve the quality of healthcare professionals' practice and patient health outcomes. Traditionally they are presented in paper formats such as monographs, publication in peer-reviewed journals and clinical guidelines. This is the fourth update of the review. OBJECTIVES: To assess the effect of printed educational materials (PEMs) on the practice of healthcare professionals and patient health outcomes. To explore the influence of some of the characteristics of the printed educational materials (e.g. source, content, format) on their effect on healthcare professionals' practice and patient health outcomes. SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), HealthStar, CINAHL, ERIC, CAB Abstracts, Global Health, and EPOC Register from their inception to 6 February 2019. We checked the reference lists of all included studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised trials (RTs), controlled before-after studies (CBAs) and interrupted time series studies (ITSs) that evaluated the impact of PEMs on healthcare professionals' practice or patient health outcomes. We included three types of comparisons: (1) PEM versus no intervention, (2) PEM versus single intervention, (3) multifaceted intervention where PEM is included versus multifaceted intervention without PEM. Any objective measure of professional practice (e.g. prescriptions for a particular drug), or patient health outcomes (e.g. blood pressure) were included. DATA COLLECTION AND ANALYSIS: Two reviewers undertook data extraction independently. Disagreements were resolved by discussion. For analyses, we grouped the included studies according to study design, type of outcome and type of comparison. For controlled trials, we reported the median effect size for each outcome within each study, the median effect size across outcomes for each study and the median of these effect sizes across studies. Where data were available, we re-analysed the ITS studies by converting all data to a monthly basis and estimating the effect size from the change in the slope of the regression line between before and after implementation of the PEM. We reported median changes in slope for each outcome, for each study, and then across studies. We standardised all changes in slopes by their standard error, allowing comparisons and combination of different outcomes. We categorised each PEM according to potential effects modifiers related to the source of the PEMs, the channel used for their delivery, their content, and their format. We assessed the risks of bias of all the included studies. MAIN RESULTS: We included 84 studies: 32 RTs, two CBAs and 50 ITS studies. Of the 32 RTs, 19 were cluster RTs that used various units of randomisation, such as practices, health centres, towns, or areas. The majority of the included studies (82/84) compared the effectiveness of PEMs to no intervention. Based on the RTs that provided moderate-certainty evidence, we found that PEMs distributed to healthcare professionals probably improve their practice, as measured with dichotomous variables, compared to no intervention (median absolute risk difference (ARD): 0.04; interquartile range (IQR): 0.01 to 0.09; 3,963 healthcare professionals randomised within 3073 units). We could not confirm this finding using the evidence gathered from continuous variables (standardised mean difference (SMD): 0.11; IQR: -0.16 to 0.52; 1631 healthcare professionals randomised within 1373 units ), from the ITS studies (standardised median change in slope = 0.69; 35 studies), or from the CBA study because the certainty of this evidence was very low. We also found, based on RTs that provided moderate-certainty evidence, that PEMs distributed to healthcare professionals probably make little or no difference to patient health as measured using dichotomous variables, compared to no intervention (ARD: 0.02; IQR: -0.005 to 0.09; 935,015 patients randomised within 959 units). The evidence gathered from continuous variables (SMD: 0.05; IQR: -0.12 to 0.09; 6,737 patients randomised within 594 units) or from ITS study results (standardised median change in slope = 1.12; 8 studies) do not strengthen these findings because the certainty of this evidence was very low. Two studies (a randomised trial and a CBA) compared a paper-based version to a computerised version of the same PEM. From the RT that provided evidence of low certainty, we found that PEM in computerised versions may make little or no difference to professionals' practice compared to PEM in printed versions (ARD: -0.02; IQR: -0.03 to 0.00; 139 healthcare professionals randomised individually). This finding was not strengthened by the CBA study that provided very low certainty evidence (SMD: 0.44; 32 healthcare professionals). The data gathered did not allow us to conclude which PEM characteristics influenced their effectiveness. The methodological quality of the included studies was variable. Half of the included RTs were at risk of selection bias. Most of the ITS studies were conducted retrospectively, without prespecifying the expected effect of the intervention, or acknowledging the presence of a secular trend. AUTHORS' CONCLUSIONS: The results of this review suggest that, when used alone and compared to no intervention, PEMs may slightly improve healthcare professionals' practice outcomes and patient health outcomes. The effectiveness of PEMs compared to other interventions, or of PEMs as part of a multifaceted intervention, is uncertain.

Fracture Risk in Dialysis and Kidney Transplanted Patients: A Systematic Review.

Chronic kidney disease is associated with an increased risk of fracture and cardiovascular mortality. The risk of fracture in hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) patients is higher when compared with the general population. However, there exists a knowledge gap concerning which group has the highest risk of fracture. We aimed to compare the risk of fracture in HD, PD, and KT populations. We conducted a systematic review of observational studies evaluating the risk of fracture in HD, PD, or KT patients. Eligible studies were searched using MEDLINE, Embase, Web of Science, and Cochrane Library from their inception to January 2016, and in grey literature. Incidences (cumulative and rate) of fracture were described together using the median, according to fracture sites, the data source (administrative database or cohort and clinical registry), and fracture diagnosis method. Prevalence estimates were described separately. We included 47 studies evaluating the risk of fracture in HD, PD, and KT populations. In administrative database studies, incidence of hip fracture in HD (median 11.45 per 1000 person-years [p-y]), range: 9.3 to 13.6 was higher than in KT (median 2.6 per 1000 p-y; range 1.5 to 3.8) or in PD (median 5.2 per 1000 p-y; range 4.1 to 6.3). In dialysis (HD+PD), three studies reported a higher incidence of hip fracture than in KT. Prevalent vertebral fracture (assessed by X-rays or questionnaire) reported in HD was in a similar range as that reported in KT. Incidence of overall fracture was similar in HD and KT, from administrative databases studies, but lower in HD compared with KT, from cohorts or clinical registry studies. This systematic review suggests an important difference in fracture risk between HD, PD, and KT population, which vary according to the diagnosis method for fracture identification. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Disease-causing mutations of RhoGDIα induce Rac1 hyperactivation in podocytes.

Nephrotic syndrome (NS) describes a group of kidney disorders in which there is injury to podocyte cells, specialized cells within the kidney's glomerular filtration barrier, allowing proteins to leak into the urine. Three mutations in ARHGDIA, which encodes Rho GDP dissociation inhibitor α (GDIα), have been reported in patients with heritable NS and encode the following amino acid changes: ΔD185, R120X, and G173V. To investigate the impact of these mutations on podocyte function, endogenous GDIα was knocked-down in cultured podocytes by shRNA and then the cells were re-transfected with wild-type or mutant GDIα constructs. Among the 3 prototypical Rho-GTPases, Rac1 was markedly hyperactivated in podocytes with any of the 3 mutant forms of GDIα while the activation of RhoA and Cdc42 was modest and variable. All three mutant GDIα proteins resulted in slow podocyte motility, suggesting that podocytes are sensitive to the relative balance of Rho-GTPase activity. In ΔD185 podocytes, both random and directional movements were impaired and kymograph analysis of the leading edge showed increased protrusion and retraction of leading edge (phase switching). The mutant podocytes also showed impaired actin polymerization, smaller cell size, and increased cellular projections. In the developing kidney, GDIα expression increased as podocytes matured. Conversely, active Rac1 was detected only in immature, but not in mature, podocytes. The results indicate that GDIα has a critical role in suppressing Rac1 activity in mature podocytes, to prevent podocyte injury and nephrotic syndrome.

ARHGDIA: a novel gene implicated in nephrotic syndrome.

BACKGROUND: Congenital nephrotic syndrome arises from a defect in the glomerular filtration barrier that permits the unrestricted passage of protein across the barrier, resulting in proteinuria, hypoalbuminaemia, and severe oedema. While most cases are due to mutations in one of five genes, in up to 15% of cases, a genetic cause is not identified. We investigated two sisters with a presumed recessive form of congenital nephrotic syndrome. METHODS AND RESULTS: Whole exome sequencing identified five genes with diallelic mutations that were shared by the sisters, and Sanger sequencing revealed that ARHGDIA that encodes Rho GDP (guanosine diphosphate) dissociation inhibitor α (RhoGDIα, OMIM 601925) was the most likely candidate. Mice with targeted inactivation of ARHGDIA are known to develop severe proteinuria and nephrotic syndrome, therefore this gene was pursued in functional studies. The sisters harbour a homozygous in-frame deletion that is predicted to remove a highly conserved aspartic acid residue within the interface where the protein, RhoGDIα, interacts with the Rho family of small GTPases (c.553_555del(p.Asp185del)). Rho-GTPases are critical regulators of the actin cytoskeleton and when bound to RhoGDIα, they are sequestered in an inactive, cytosolic pool. In the mouse kidney, RhoGDIα was highly expressed in podocytes, a critical cell within the glomerular filtration barrier. When transfected in HEK293T cells, the mutant RhoGDIα was unable to bind to the Rho-GTPases, RhoA, Rac1, and Cdc42, unlike the wild-type construct. When RhoGDIα was knocked down in podocytes, RhoA, Rac1, and Cdc42 were hyperactivated and podocyte motility was impaired. The proband's fibroblasts demonstrated mislocalisation of RhoGDIα to the nucleus, hyperactivation of the three Rho-GTPases, and impaired cell motility, suggesting that the in-frame deletion leads to a loss of function. CONCLUSIONS: Mutations in ARHGDIA need to be considered in the aetiology of heritable forms of nephrotic syndrome.