Multicenter study on the genetics of glomerular diseases among southeast and south Asians: Deciphering Diversities - Renal Asian Genetics Network (DRAGoN).

Multinational studies have reported monogenic etiologies in 25%-30% of children with steroid-resistant nephrotic syndrome. Such large studies are lacking in Asia. We established Deciphering Diversities: Renal Asian Genetics Network (DRAGoN) and aimed to describe the genetic and clinical spectrums in Asians. We prospectively studied a cohort of 183 probands with suspected genetic glomerulopathies from South and Southeast Asia, of whom 17% had positive family history. Using multi-gene panel sequencing, we detected pathogenic variants in 26 (14%) probands, of whom one-third had COL4A4 or COL4A5 variants (n = 9, 5%). Of those with COL4A5 defects, only 25% had features suggestive of Alport syndrome. Besides traditional predictors for genetic disease (positive family history and extrarenal malformations), we identified novel predictors, namely older age (6.2 vs. 2.4 years; p = 0.001), hematuria (OR 5.6; 95% CI 2.1-14.8; p < 0.001), and proteinuria in the absence of nephrotic syndrome (OR 4.6; 95% CI 1.8-11.8; p = 0.001) at first manifestation. Among patients who first presented with proteinuria without nephrotic syndrome, the genetic diagnostic rates were >60% when a second risk factor (positive family history or extrarenal manifestation) co-existed. The genetic spectrum of glomerulopathies appears different in Asia. Collagen IV genes may be included in sequencing panels even when suggestive clinical features are absent.

Risk factors associated with household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia.

AIM: Households are a significant venue for the transmission of SARS-CoV-2. We conducted a study to characterise the transmission dynamics and identify risk factors for household transmission of SARS-CoV-2 in Negeri Sembilan, Malaysia. METHODS: This retrospective observational study included 185 families of paediatric COVID-19 cases from 1 February 2020 to 31 December 2020. We identified the index case for each household and gathered the socio-demographic, epidemiological investigation results and risk factors for household transmission from medical case records. The secondary attack rate was calculated, and logistic regression analyses were used to identify risk factors associated with secondary household transmission of SARS-CoV-2. RESULTS: Of the 848 household contacts, 466 acquired secondary infections, resulting in a secondary attack rate of 55%. The median age of the secondary cases was 12 years. Female household contacts and household contacts who slept in the same room with the index case were significantly associated with increased risk for COVID-19. Other independent risk factors associated with higher transmission risk in the household included an index case who was symptomatic, a household index case aged greater than 18 years and a male household index case. CONCLUSIONS: High rates of household transmission of COVID-19 were found, indicating households were a major setting of transmission of SARS-CoV-2. Our data provide insight into the risk factors for household transmission of SARS-CoV-2 in Malaysia.

Clinical and epidemiological characteristics of children with COVID-19 in Negeri Sembilan, Malaysia.

OBJECTIVES: To describe the clinical and epidemiological characteristics of children with coronavirus disease 2019 (COVID-19) in the state of Negeri Sembilan, Malaysia in the setting of mandatory hospital isolation and quarantine for all confirmed cases. METHODS: A multi-centre, retrospective observational study was performed among children aged ≤12 years with laboratory-proven COVID-19 between 1 February and 31 December 2020. RESULTS: In total, 261 children (48.7% males, 51.3% females) were included in this study. The median age was 6 years [interquartile range (IQR) 3-10 years]. One hundred and fifty-one children (57.9%) were asymptomatic on presentation. Among the symptomatic cases, fever was the most common presenting symptom. Two hundred and forty-one (92.3%) cases were close contacts of infected household or extended family members. Twenty-one (8.4%) cases had abnormal radiological findings. All cases were discharged alive without requiring supplemental oxygen therapy or any specific treatment during hospitalization. The median duration of hospitalization was 7 days (IQR 6-10 days). One (2.1%) of the uninfected guardians accompanying a child in quarantine tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) upon discharge. CONCLUSIONS: COVID-19 in children was associated with mild symptoms and a good prognosis. Familial clustering was an important epidemiologic feature in the outbreak in Negeri Sembilan. The risk of transmission of SARS-CoV-2 from children to guardians in hospital isolation was minimal despite close proximity.

Vitamin D deficiency and insufficiency in Malaysian children with spina bifida.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To determine the prevalence and potential risk factors of vitamin D deficiency and insufficiency among Malaysian children with spina bifida. SETTING: Four Malaysian tertiary hospitals. METHODS: Children with spina bifida were assessed for potential demographic, disease severity and lifestyle risk factors for vitamin D deficiency and insufficiency. Blood for 25-hydroxy vitamin D (25(OH)D) was taken. Vitamin D deficiency was defined as 25(OH)D levels ≤ 37.5 nmol/L and insufficiency as 37.6-50 nmol/L. RESULTS: Eighty children aged 2-18 years (42 males) participated in the study. Vitamin D levels ranged from 14 to 105 nmol/L (mean 52.8, SD 19.1). Vitamin D deficiency was identified in 18 (22.5%) and insufficiency in 26 (32.5%) children. Logistic regression analysis showed that skin exposure to sunlight ≤ 21% body surface area (OR: 6.2, CI 1.7-22.9) and duration of sun exposure ≤ 35 min/day (OR: 4.0, CI 1.2-14.1) were significant risk factors for vitamin D deficiency and insufficiency, respectively. CONCLUSIONS: Over half (55%) of Malaysian children with spina bifida seen in urban tertiary hospitals have vitamin D insufficiency and deficiency. Lifestyle sun exposure behaviours were risk factors for vitamin D deficiency and insufficiency.

Interpreting systematic reviews: are we ready to make our own conclusions? A cross-sectional study.

BACKGROUND: Independent evaluation of clinical evidence is advocated in evidence-based medicine (EBM). However, authors' conclusions are often appealing for readers who look for quick messages. We assessed how well a group of Malaysian hospital practitioners and medical students derived their own conclusions from systematic reviews (SRs) and to what extent these were influenced by their prior beliefs and the direction of the study results. METHODS: We conducted two cross-sectional studies: one with hospital practitioners (n = 150) attending an EBM course in June 2008 in a tertiary hospital and one with final-year medical students (n = 35) in November 2008. We showed our participants four Cochrane SR abstracts without the authors' conclusions. For each article, the participants chose a conclusion from among six options comprising different combinations of the direction of effect and the strength of the evidence. We predetermined the single option that best reflected the actual authors' conclusions and labelled this as our best conclusion. We compared the participants' choices with our predetermined best conclusions. Two chosen reviews demonstrated that the intervention was beneficial ("positive"), and two others did not ("negative"). We also asked the participants their prior beliefs about the intervention. RESULTS: Overall, 60.3% correctly identified the direction of effect, and 30.1% chose the best conclusions, having identified both the direction of effect and the strength of evidence. More students (48.2%) than practitioners (22.2%) chose the best conclusions (P < 0.001). Fewer than one-half (47%) correctly identified the direction of effect against their prior beliefs. "Positive" SRs were more likely than "negative" SRs to change the participants' beliefs about the effect of the intervention (relative risk (RR) 1.8, 95% confidence interval 1.3 to 2.6) and "convert" those who were previously unsure by making them choose the appropriate direction of effect (RR 1.9, 95% confidence interval 1.3 to 2.8). CONCLUSIONS: The majority of our participants could not generate appropriate conclusions from SRs independently. Judicious direction from the authors' conclusions still appears crucial to guiding our health care practitioners in identifying appropriate messages from research. Authors, editors and reviewers should ensure that the conclusions of a paper accurately reflect the results. Similar studies should be conducted in other settings where awareness and application of EBM are different.

The place and barriers of evidence based practice: knowledge and perceptions of medical, nursing and allied health practitioners in malaysia.

BACKGROUND: Despite a recent increase in activities to promote evidence-based practice (EBP), it was unclear how Malaysian hospital practitioners received this new approach in medicine. This study examines their confidence and perceptions on EBP. FINDINGS: We conducted cross-sectional surveys using a self-administered questionnaire during two EBP training courses in two Malaysian hospitals in January and June 2007. Our subjects (n = 144) were doctors and nursing and allied health staff (NAH) participating in the EBP courses. Our questionnaire covered three domains: confidence and understanding (six items), attitude (five items) and barriers to practice (four items). We presented simple descriptive statistics, including the sum ratings and the proportions with different responses for each item, and compared different groups using Mann-Whitney U test for scaled ratings and Chi-square test for dichotomous responses.Ninety-two doctors and 52 NAH staff completed the surveys. Overall, doctors expressed slightly higher confidence on EBP compared to NAH staff. Out of a maximum sum rating of 27 over six items, doctors reported an average of 18.3 (SD 3.2) and NAH staff reported an average of 16.0 (SD 3.4), p = 0.002. Doctors were also more positive in their views on EBP. For example, 67.4% of doctors disagreed, but 61% of NAH staff agreed that "the importance of EBP in patient care is exaggerated", and 79.3% of doctors disagreed, but 46.2% of NAH staff agreed that "EBP is too tedious and impractical". Similar responses were observed for other items in the domain.Doctors and NAH staff shared similar concerns on barriers to evidence-based practice. The highest proportions considered poor facilities to access evidence a barrier (76% of doctors and 90% of NAH), followed by poor awareness of evidence (62% of doctors and 70% of NAH) and time constraints (63% of doctors and 68% of NAH), p = 0.09 for the combined rating of four items in the domain. CONCLUSIONS: The findings of our survey suggest a need for greater efforts in promoting EBP among Malaysian hospital practitioners especially for NAH staff. From the responses based on the barriers to EBP, improving facilities for accessing evidence and promoting more user-friendly resources to address time constraints appear to be the priorities.

A randomized, multicenter, open-label trial to determine peritonitis rate, product defect, and technique survival between ANDY-Disc and UltraBag in patients on CAPD.

BACKGROUND: With the various twin-bag systems available on the market, we decided to conduct a therapeutic equivalence study comparing ANDY-Disc (Fresenius Medical Care, Bad Homburg, Germany) with UltraBag (Baxter, Deerfield, IL) in patients on continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: This multicenter, open-label, parallel-group, randomized trial is designed to show the therapeutic equivalence of ANDY-Disc with UltraBag. All CAPD patients from the 6 participating centers who met inclusion/exclusion criteria were enrolled into the trial. They were randomly assigned and converted from the Y-disconnect system (Ultraset; Baxter) to the twin-bag systems. The primary outcome variable is peritonitis, and secondary outcome parameters are technique failure or product defect. RESULTS: From April 2002 to May 2003, a total of 270 patients were recruited for this study. Overall peritonitis rates were 22.9 patient-months/episode for ANDY-Disc and 35.0 patient-months/episode for UltraBag. The overall peritonitis rate for ANDY-Disc was 53% greater compared with UltraBag, but the 95% confidence interval overlaps the prespecified margin of equivalence. There were more product defects reported with ANDY-Disc; 236 product defects compared with 17 with UltraBag. The time series of the number of product defects and peritonitis count on the ANDY-Disc arm suggests a possible cause-and-effect relationship. CONCLUSION: Therapeutic equivalence of ANDY-Disc to UltraBag could not be established with respect to peritonitis. There is a trend toward greater risk for peritonitis on the Andy-Disc arm. There also is a suggestive cause-and-effect relation between the occurrence of product defect and peritonitis on the ANDY-Disc arm during the early part of the trial.