We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates. We report additional mutational events in 64 previously reported candidates (40 recessive), and these events support their candidacy. We report recessive forms of genes that were previously associated only with dominant disorders and that have phenotypes ranging from consistent with to conspicuously distinct from the known dominant phenotypes. We also report homozygous loss-of-function events that can inform the genetics of complex diseases. We were also able to deduce the likely causal variant in most couples who presented after the loss of one or more children, but we lack samples from those children. Although a similar pattern of mostly recessive causes was observed in the prenatal setting, the higher proportion of loss-of-function events in these cases was notable. The allelic series presented by the wealth of recessive variants greatly expanded the phenotypic expression of the respective genes. We also make important observations about dominant disorders; these observations include the pattern of de novo variants, the identification of 74 candidate dominant, disease-related genes, and the potential confirmation of 21 previously reported candidates. Finally, we describe the influence of a predominantly autosomal-recessive landscape on the clinical utility of rapid sequencing (Flash Exome). Our cohort's genotypic and phenotypic data represent a unique resource that can contribute to improved variant interpretation through data sharing.

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BackgroundIdiopathic nephrotic syndrome (INS) is a common pediatric disease. Minimal change disease (MCD) is the most common histopathological subtype and usually has good prognosis. However, in less common presentations, INS may have an unusual course that makes renal biopsy a necessity to identify its etiology. Immunoglobulin M (IgM) occasionally deposits in the mesangium and can be seen under immunofluorescence (IF). The role of IgM is controversial in MCD. It is likely associated with less favorable outcomes for MCD. This study aims to investigate the clinical significance of mesangial IgM deposits on the outcome of MCD in a pediatric population.MethodsIn this retrospective cohort study, we obtained native kidney biopsy samples from 192 children who were diagnosed with MCD from 2003 to 2014. The samples were divided into groups according to the histopathological deposition of IgM in biopsies under IF. The group for which biopsies showed IgM was labeled as IgM + IF (n = 77), and the group for which biopsies were without IgM was labeled as IgM-IF (n = 115). We reviewed hypertension, hematuria, and estimated glomerular filtration rate (eGFR) at the time of presentation to our institute; response to steroid therapy (remission, dependence, frequent relapses, and resistance) and response after adjuvant immunosuppressive therapy (complete remission, partial remission, frequent relapses, and no response) when indicated; development of chronic kidney disease (CKD) and end-stage renal disease during the course of the disease (ESRD).ResultsOur results showed that mesangial IgM deposition in MCD showed significant statistical association with hypertension at the time of presentation (P = .05). There was statistically significant association between the presence of IgM deposition and the development of steroid dependence (P = .05) and CKD during the course of the disease (P = .05).ConclusionsOur study showed that IgM deposition in MCD showed statistical association with hypertension by the time the patient presented to our institute, development of steroid dependence, and CKD. IgM may play a role in MCD. However, we recommend a prospective study to verify the role of IgM in MCD outcomes.

Background and objectivesThe objective of this research is to improve compliance of the medication reconciliation process at the time of patient admission in the Department of Pediatrics at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia using an innovative evidence-based approach.Materials and methodsMost of the recent efforts at our institution to revamp the medication reconciliation process have failed. Thus, we implemented an innovative evidence-based approach to improve the compliance of the reconciliation process at admission. This approach focused on the Department of Pediatrics at King Faisal Specialist Hospital and Research Centre (KFSH&RC). We established specific educational and monitoring programs that were run over a two-month period, from June to July 2015. The educational program consisted of focused hands-on daily interactive training sessions presented to a small group of residents, i.e., 5–6 residents per session, for a period of one week. One resident was identified as a ”Super-User” to provide ongoing support for the other residents involved in the process. A close monitoring process was also implemented, which included daily follow up and encouragement from three assigned consultants. In addition, periodic independent audit report results prepared by Healthcare Information Technology Affairs (HITA) were communicated to the Department of Pediatrics regarding physician compliance in the medication reconciliation process.ResultsPhysician compliance for admission medication reconciliation documentation in ICIS ranged from (0–15%) between the first quarter of 2012 and the first quarter 2015, we designated the official hospital audit for the first quarter of 2015 as a baseline audit report. Between the first quarter of 2012 and 2015, the physician compliance for admission medication reconciliation was ranged between 0 to 15% according to the official hospital audit. We implemented our initiative during the months of June and July 2015. During that time, there was a gradual improvement in the number of admission medication reconciliations reported by the independent audits of our general Pediatrics Ward (B1), which represents the majority of pediatric admissions. The 57% of 26 patients had medication reconciliation completed by the first report dated 16 June 2015. This percentage improved to 92% out of a total of 13 patients at the last report on 12 July 2015. This consistent improvement also occurred in other areas where pediatric patients were admitted including the B3-1 (from 88% to 90%), the NICU 1 (from 83% to 100%) and the NICU 2 (from 90% to 100%).ConclusionsBy structuring and implementing intensive educational and monitoring programs, a marked improvement in the compliance of medication reconciliation at the time of admission for the pediatric patient population was achieved. We believe that our department-based results would be generalizable if a similar hospital-wide programme was to be rigorously implemented.

Introduction Breaking bad ne ws to caregivers of children with (CKD) [I can’t comment in the box] Title says to breaking bad news to children but in here, breaking bad news to caregivers. Please clarify and edit accordingly. is an important role of nephrologists. In our practice there has been a thought about parental dissatisfaction from breaking bad news to CKD patients. Caregiver’s preferences on how to be told the bad news in CKD children has not been studied adequately. Our objective was to identify how much is the emotional and knowledge satisfaction of CKD caregivers and the relation of their socioeconomic and educational levels with their preferences in breaking bad news. Methods A questionnaire based study was conducted for caregivers of CKD children, in the outpatient clinics, and peritoneal dialysis and hemodialysis units at the King Faisal Specialist Hospital and Research Centre for three months. Results 83 questionnaires from caregivers of CKD patients age (1–14) years, mean age of 8.5 ± 3.9 years. (47.6%) were emotionally very satisfied, 29.5% were very satisfied about the knowledge they had. Conclusion Caregivers of CKD patients are satisfied emotionally more than the satisfaction about the amount of information they got. Different demographic data might affect their preferences in the way of receiving the bad news. The dissatisfaction suggesting that physicians’ communication skills needs improvement.