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Fulltext Angiotensin-converting enzyme gene polymophism in adult primary focal segmental glomerulosclerosis

Mohd R, Wahab ZA, Cader R, Gafor HA, Radzi AM, Shah SA, et al.

J Clin Med Res, 2014 Aug;6(4):245-51.
PMID: 24883149 DOI: 10.14740/jocmr1550w

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) accounts for a third of biopsy-proven primary glomerulonephritis in Malaysia. Pediatric studies have found the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene to be associated with renal disease progression. The aim of this study was to determine the prevalence of the ACE (I/D) genotypes in adult primary FSGS and its association with renal outcome on follow-up.
METHODS: Prospective observational study involving primary FSGS patients was conducted. Biochemical and urine tests at the time of study were compared to the time of the diagnosis and disease progression analyzed. ACE gene polymorphism was identified using polymerase chain reaction amplification technique and categorized into II, ID and DD genotypes.
RESULTS: Forty-five patients with a median follow-up of 3.8 years (interquartile range: 1.8 - 5.6) were recruited. The commonest genotype was II (n = 23, 51.1%) followed by ID (n = 19, 42.2%) and DD (n = 3, 6.7%). The baseline characteristics were comparable between the II and non-II groups at diagnosis and at study recruitment except that the median urine protein-creatinine index was significantly lower in the II group compared to the non-II group (0.02 vs. 0.04 g/mmol (P = 0.03). Regardless of genotypes, all parameters of renal outcome improved after treatment.
CONCLUSION: The II followed by ID genotypes were the predominant ACE gene alleles in our FSGS. Although the D allele has been reported to have a negative impact on renal outcome, treatment appeared to be more important than genotype in preserving renal function in this cohort.
Fulltext The effect of calcium with or without calcitriol supplementation on renal function in patients with hypovitaminosis d and chronic kidney disease

Mustafar R, Mohd R, Ahmad Miswan N, Cader R, Gafor HA, Mohamad M, et al.

Nephrourol Mon, 2014 Jan;6(1):e13381.
PMID: 24719814 DOI: 10.5812/numonthly.13381

Hypovitaminosis D (serum 25-OHD < 30 ng/mL) is common in patients with chronic kidney disease (CKD). Vitamin D is believed to involve in the regulation of renin-angiotensin system and may be renoprotective.
Fulltext The effects of calcitriol with calcium carbonate supplementation on inflammatory biomarkers in chronic kidney disease patients' with low vitamin D

Mustafar RB, Mohd R, Miswan NA, Bain A, Cader R, Gafor AH, et al.

Cent Eur J Immunol, 2014;39(2):236-42.
PMID: 26155130 DOI: 10.5114/ceji.2014.43729

Chronic kidney disease (CKD) patients' are at risk of low vitamin D and chronic inflammation. We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum; interleukin-6 (IL-6), interleukin-10 (IL-10) and highly sensitive C-reactive protein (hs-CRP).
Assessment of fluid status in CAPD patients using the body composition monitor

Cader RA, Gafor HA, Mohd R, Kong NC, Ibrahim S, Wan Hassan WH, et al.

J Clin Nurs, 2013 Mar;22(5-6):741-8.
PMID: 23039369 DOI: 10.1111/j.1365-2702.2012.04298.x

To assess the degree of overhydration in our peritoneal dialysis patients and to examine the factors contributing to overhydration.
Assessment of body fluid status in hemodialysis patients using the body composition monitor measurement technique

Mamat R, Kong NC, Ba'in A, Shah SA, Cader R, Wong V, et al.

J Clin Nurs, 2012 Oct;21(19-20):2879-85.
PMID: 22646855 DOI: 10.1111/j.1365-2702.2012.04091.x

The main objective of the study was to correlate the target dry weight in haemodialysis (HD) patients as assessed clinically by nephrologists to those measured by the Body Composition Monitor (BCM - Fresenius) machine. The second objective was to compare pre and postdialysis changes of extracellular fluid and clinical parameters.
Immunoadsorption and plasmapheresis are equally efficacious as adjunctive therapies for severe lupus nephritis

Loo CY, Mohamed Said MS, Mohd R, Abdul Gafor AH, Saidin R, Halim NA, et al.

Transfus Apher Sci, 2010 Dec;43(3):335-40.
PMID: 21051293 DOI: 10.1016/j.transci.2010.10.003

This was a prospective randomized controlled trial to evaluate the effects of immunoadsorption (IA) versus conventional PP (PP) as adjunctive therapy in the treatment of severe lupus nephritis (LN). Of 28 patients with biopsy-proven severe LN (ISN/RPS classes III or IV ± V), 14 underwent 36 sessions of PP and the other 41 sessions of IA in addition to our center's standard LN treatment protocol. Three patients in the PP group and 2 in the IA group experienced a transient, marked drop in platelets with the second session. Except for a higher pre treatment mean SLEDAI score in the PP group 17.4 ± 2.0 vs. 13.5 ± 4.8; p = 0.009 and a serum creatinine of 163 ± 7.9 vs. 81.7 ± 10.2; p = 0.33, there were no other baseline differences. Some differences did exist between the two therapies in the immediate post-treatment phase, at 1 and 3 months. Three in IA relapsed, none of PP in third months, whereas two patients relapsed in the PP and none of IA cohorts at 6 months. However, most of these parameters did not differ by 6 months. The pre- and post-therapy SLEDAI scores remained different 12.4 ± 4.5 vs. 9 ± 4; p = 0.04 at 1 month, and at 3 month 13.5 ± 4.7 vs. 7.7 ± 1.1; p = 0.012 but not at 6 months. We conclude that IA and PP were equally well tolerated and efficacious as adjunctive therapy for severe LN.
Fulltext Role of febuxostat in retarding progression of diabetic kidney disease with asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial

Mukri MNA, Kong WY, Mustafar R, Shaharir SS, Shah SA, Abdul Gafor AH, et al.

EXCLI J, 2018;17:563-575.
PMID: 30108461 DOI: 10.17179/excli2018-1256

Introduction: Hyperuricemia is associated with chronic kidney disease (CKD) progression and poor cardiovascular outcomes. We studied the effect of febuxostat on estimated glomerular filtration rate (eGFR), proteinuria and monitored the safety profile of the medication.
Material and Methods: This is a prospective open-label, randomized study in CKD stage 3 and 4 patients with diabetic nephropathy and asymptomatic hyperuricemia. Patients were randomized into febuxostat 40 mg daily and no treatment group using block randomization method and were followed up for 6 months. Their usual care for diabetes mellitus, hypertension and dyslipidemia were continued in the study. Blood and urine investigations were monitored at baseline, 3 months and 6 months.
Results: The eGFR in febuxostat group was stabilized at 6 months with no significant reduction [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there was a significant reduction of the eGFR in no treatment group from 28.2 (IQR 17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c (glycosylated hemoglobin) was significantly increased in febuxostat group from 7.2 ± 0.5 % at baseline to 7.6 ± 1.4 at 6 months (p value 0.04) but no significant change of HbA1c in the no treatment group. Proteinuria level was unchanged in both groups. The commonest adverse event was joint pain.
Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic nephropathy and this effect was beyond glycemic control. Increment of HbA1c level in febuxostat group needs further larger trials.
Study site: Chronic kidney disease clinic, Hospital Canselor Tuanku Muhriz, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
Fulltext Risk factors for symptomatic Avascular Necrosis (AVN) in a multi-ethnic Systemic Lupus Erythematosus (SLE) cohort

Shaharir SS, Chua SH, Mohd R, Mustafar R, Noh MM, Shahril NS, et al.

PLoS One, 2021;16(3):e0248845.
PMID: 33739994 DOI: 10.1371/journal.pone.0248845

Avascular necrosis of bone (AVN) is increasingly being recognized as a complication of SLE and causes significant disability due to pain and mobility limitations. We studied the prevalence and factors associated with avascular necrosis (AVN) in a multiethnic SLE cohort. SLE patients who visited the outpatient clinic from October 2017 to April 2019 were considered eligible. Their medical records were reviewed to identify patients who developed symptomatic AVN, as confirmed by either magnetic resonance imaging or plain radiography. Subsequently, their SLE disease characteristics and treatment were compared with the characteristics of patients who did not have AVN. Multivariable logistic regression analyses were performed to determine the independent factors associated with AVN among the multiethnic SLE cohort. A total of 390 patients were recruited, and the majority of them were females (92.6%); the patients were predominantly of Malay ethnicity (59.5%), followed by Chinese (35.9%) and Indian (4.6%). The prevalence of symptomatic AVN was 14.1%, and the mean age of AVN diagnosis was 37.6 ± 14.4 years. Both univariate and multivariable logistic regression analyses revealed that a longer disease duration, high LDL-C (low density lipoprotein cholesterol), positive anti-cardiolipin (aCL) IgG and anti-dsDNA results, a history of an oral prednisolone dose of more than 30 mg daily for at least 4 weeks and osteoporotic fractures were significantly associated with AVN. On the other hand, hydroxychloroquin (HCQ), mycophenolate mofetil (MMF) and bisphosphonate use were associated with a lower risk of AVN. No associations with ethnicity were found. In conclusion, several modifiable risk factors were found to be associated with AVN, and these factors may be used to identify patients who are at high risk of developing such complications. The potential protective effects of HCQ, MMF and bisphosphonates warrant additional studies.
Cefepime Induced Encephalopathy in a Non-dialysis Dependent Chronic Kidney Disease Patient: A Case Report

Muniandy G, Kamaruzaman L, Jan TH, Mohd R, Neesam MT, Fong Voon K, et al.

Acta Med Indones, 2023 Jan;55(1):78-82.
PMID: 36999269

Cefepime is a frequently used fourth-generation cephalosporin antibiotic for a wide variety of infections. Toxic levels of this drug can cause neurological complications. The most common neurological adverse event of cefepime is headache and lightheadedness. Here, we presented a case of cefepime induced encephalopathy in a 57-year-old female patient with acute on chronic kidney disease. With an accurate diagnosis that requires a high index of clinical suspicion, prompt management was instituted. She had full resolution of symptoms following discontinuation of the medication and also emergent dialysis.
Supporting family doctors to address elder abuse: a quasi-experimental study in Malaysia

Mohd Mydin FH, Othman S, Choo WY, Hairi NNM, Hairi FM, Syed Karim SN, et al.

J Elder Abuse Negl, 2021 04 25;33(2):151-167.
PMID: 33899705 DOI: 10.1080/08946566.2021.1919272

This quasi-experimental study examined the effect of Supporting Family Doctors to Address Elder Abuse (SAFE) educational intervention among family doctors practicing at public primary care clinics in Malaysia. SAFE is an intensive, multimodal, locally tailored, and culturally sensitive face-to-face educational intervention on elder abuse. A significant mean score improvement of knowledge [Baseline: 5.33 (SD:1.33) to 6-month post-intervention: 6.45 (SD: 1.35); p<0.001] and perceived behavioral control [Baseline: 50.83 (SD: 8.87) to six-month post-intervention: 56.16 (SD: 9.56); p<0.001] observed in the intervention group compared to the control group. No significant difference in attitude, subjective norm, and practice scores between the two groups over time. SAFE educational intervention for family doctors was effective to improve but not sustainable knowledge and perceived behavioral control toward elder abuse identification and management. We recommend SAFE educational intervention as part of the continuous medical education for family doctors supplemented with a change in organization and national policy.
Retinal changes and cardiac biomarker assessment in relation to chronic kidney disease: a single centre study

Mustafar R, Hishamuddin KAM, Mohd R, Kamaruzaman L, Halim WHWA, Hsien YM, et al.

BMC Nephrol, 2023 Nov 13;24(1):338.
PMID: 37957551 DOI: 10.1186/s12882-023-03386-w

BACKGROUND: The prevalence of chronic kidney disease (CKD) is rising in Malaysia. Early detection is necessary to prevent disease progression, especially in terms of cardiovascular (CV) risk, the main cause of death in end-stage renal disease (ESRD). Retinal changes have proven to be a good predictor of CKD whereas cardiac biomarkers are useful in cardiovascular risk stratification. We aimed to demonstrate the correlation between retinal changes and cardiac biomarkers with CKD.
METHODS: This single-centre cross-sectional study was conducted among patients with CKD stages 3, 4, and 5 (not on dialysis) from the Nephrology Clinic, Universiti Kebangsaan Malaysia Medical Centre. A total of 84 patients were recruited with an even distribution across all three stages. They underwent fundus photography where images were analysed for vessel calibre (central retinal venular equivalent (CRVE), central retinal arterial equivalent (CRAE), and tortuosity indices. Optical coherence tomography was used to measure macular volume. Blood samples were sent for laboratory measurement of high-sensitivity C-reactive protein (hs-CRP) and asymmetric dimethylarginine (ADMA). These parameters were analysed in relation to CKD.
RESULTS: The mean age was 58.8 ± 11.7 years, with 52.4% male and 47.6% female patients. Among them, 64.3% were diabetics. Retinal vessel tortuosity (r = -0.220, p-value = 0.044) had a negative correlation with the estimated glomerular filtration rate (eGFR). CRVE showed a positive correlation with proteinuria (r = 0.342, p = 0.001) but negative correlation with eGFR (r = -0.236, p = 0.031). Hs-CRP positively correlated with proteinuria (r = 0.313, p = 0.04) and negatively correlated with eGFR (r = -0.370, p = 0.001). Diabetic patients had a higher CRVE compared to non-diabetic patients (p = 0.02). History of ischaemic heart disease was associated with a smaller macula volume (p = 0.038). Male gender (r2 = 0.066, p = 0.031) and HbA1c had a positive influence (r2 = 0.066, p = 0.047) on retinal vessel tortuosity. There was a positive influence of age (r2 = 0.183, p = 0.012) and hs-CRP (r2 = 0.183, p = 0.045) on CRVE. As for macula volume, it negatively correlated with diabetes (r2 = 0.015, p = 0.040) and positively correlated with smoking (r2 = 0.015, p = 0.012).
CONCLUSION: Our study showed that eGFR value affects retinal vessel tortuosity, CRVE and hs-CRP. These parameters bear potential to be used as non-invasive tools in assessing CKD. However, only macula volume may be associated with CVD risk among the CKD population.
Fulltext Full Genome Characterization of Human Influenza A/H3N2 Isolates from Asian Countries Reveals a Rare Amantadine Resistance-Conferring Mutation and Novel PB1-F2 Polymorphisms

Zaraket H, Kondo H, Hibino A, Yagami R, Odagiri T, Takemae N, et al.

Front Microbiol, 2016;7:262.
PMID: 27014195 DOI: 10.3389/fmicb.2016.00262

Influenza A viruses evolve at a high rate requiring continuous monitoring to maintain the efficacy of vaccines and antiviral drugs. We performed next generation sequencing analysis of 100 influenza A/H3N2 isolates collected in four Asian countries (Japan, Lebanon, Myanmar, and Vietnam) during 2012-2015. Phylogenetic analysis revealed several reassortment events leading to the circulation of multiple clades within the same season. This was particularly evident during the 2013 and 2013/2014 seasons. Importantly, our data showed that certain lineages appeared to be fitter and were able to persist into the following season. The majority of A/H3N2 viruses continued to harbor the M2-S31N mutation conferring amantadine-resistance. In addition, an S31D mutation in the M2-protein, conferring a similar level of resistance as the S31N mutation, was detected in three isolates obtained in Japan during the 2014/2015 season. None of the isolates possessed the NA-H274Y mutation conferring oseltamivir-resistance, though a few isolates were found to contain mutations at the catalytic residue 151 (D151A/G/N or V) of the NA protein. These variations did not alter the susceptibility to neuraminidase inhibitors and were not detected in the original clinical specimens, suggesting that they had been acquired during their passage in MDCK cells. Novel polymorphisms were detected in the PB1-F2 open-reading frame resulting in truncations in the protein of 24-34 aminoacids in length. Thus, this study has demonstrated the utility of monitoring the full genome of influenza viruses to allow the detection of the potentially fittest lineages. This enhances our ability to predict the strain(s) most likely to persist into the following seasons and predict the potential degree of vaccine match or mismatch with the seasonal influenza season for that year. This will enable the public health and clinical teams to prepare for any related healthcare burden, depending on whether the vaccine match is predicted to be good or poor for that season.
Clinical recognition of elder maltreatment and intention to report among primary care doctors

Mohd Mydin FH, Othman S, Choo WY, Hairi NNM, Hairi FM, Syed Karim SN, et al.

J Elder Abuse Negl, 2020 02 21;32(1):72-83.
PMID: 32085693 DOI: 10.1080/08946566.2020.1731640

This study aimed to determine the primary care doctors' ability to recognize elder maltreatment and their intentions to report on such conditions. About 358 primary care doctors participated in this study. Outcomes were assessed using a validated five context-relevant clinical vignettes. Primary care doctor's recognition of sexual abuse was highest (91.0%); while the lowest (70.2%) in case signifying physical abuse. Despite being able to ascertain elder maltreatment, the intention to report the event is generally low even for cases exemplifying physical abuse, emotional abuse and neglect. However, intentions to report cases of sexual and financial abuse are 86.9% and 73.5% respectively. Findings highlighted the uncertainties of primary care doctors in distinguishing the clinical findings of non-accidental injuries and injuries due to acts of maltreatment. This provides support for educational intervention and guidelines or policies to improve the knowledge and skills of primary care doctors to intervene in elder maltreatment.

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