Adult ; Aged ; Antimalarials ; therapeutic use ; Female ; Humans ; Immune Reconstitution Inflammatory Syndrome ; drug therapy ; JC Virus ; immunology ; Leukoencephalopathy, Progressive Multifocal ; drug therapy ; Male ; Mefloquine ; therapeutic use ; Middle Aged ; Treatment Outcome

Background & Objective: Modulation of cortical excitability by low frequency repetitive transcranial magnetic stimulation (rTMS) has demonstrated therapeutic use in epilepsy. This study aimed to evaluate the efficacy of low-frequency rTMS on refractory epilepsy in a group of Malaysian subjects. Methods: Nine patients with refractory epilepsy completed the study. All patients received 10 sessions of 1Hz rTMS (1000 pulses per session) at 90% of resting motor threshold. Outcome measures included seizure frequency, Symptom Checklist-90 (SCL-90), Beck Depression Inventory II (BDI II) and Quality of Life in Epilepsy-31 (QOLIE-31). Responders were defined as having ≥ 50% seizure reduction. Results: The mean age was 33.8 years (SD 11.7), with 4 male. Three patients had mesial temporal sclerosis (MTS); 4 with focal cortical dysplasia (FCD) and two lesion-negative. Three patients achieved >50% seizure reduction at 8 weeks post-treatment, with 2 of them had improvement in the number of IED. All of the responders had FCD. The responders were younger (mean 24.7 vs. 38.3 years old), had shorter duration of illness (mean 15.7 vs. 30.5 years) and had less frequent seizure frequency prior to treatment (mean 5.5 vs. 10.8 attacks per week), as compared to the non-responders. Six patients had improvement in BDI-II scores, two in QOLIE-31 and four in SCL-90 post treatment, irrespective of seizure control. The mean scores in BDI-II improved significantly with treatment (p<0.01). Conclusion: rTMS is a potentially promising treatment for epilepsy, esp
Transcranial Magnetic Stimulation ; Epilepsy

INTRODUCTIONHigh workload volumes in a Cytogenetics laboratory can lead to long result turn-around times (TAT). This study aimed to improve laboratory efficiency by adopting Lean Management System initiatives to increase productivity through the elimination of wastes. This study examined if the prerequisite 20-cell analysis was sufficient for a conclusive result or if additional cell workup was necessary to ascertain the presence of a previous chromosome abnormality among cases on follow-up, or when a single abnormal cell was encountered during the analysis to determine the presence of a clone.

MATERIALS AND METHODSThe karyotype results of cases that had additional workup were retrieved from among 8040 bone marrow cases of various haematological disorders performed between June 2003 and June 2008.

RESULTSOf 8040 cases analysed, 2915 cases (36.3%) had additional cell workup. Only 49 cases (1.7%) led to the establishment of a clone. The majority of these cases could have been resolved without the additional workup, especially if fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)-based assays had been utilised.

CONCLUSIONThis study shows that the additional workup procedure is redundant. The time saved by discontinuing the workup procedure can be used to analyse other cases, leading to increased laboratory efficiency and a faster TAT without compromise to patient care. The practice of additional workup over and above the 20- cell analysis should be dispensed with as little benefit was derived for the amount of additional manpower expended. FISH or PCR-based assays should be utilised to elucidate a case further.

Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; Bone Marrow Cells ; Cytogenetics ; Efficiency ; Efficiency, Organizational ; Female ; Hematologic Diseases ; diagnosis ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; instrumentation ; methods ; Karyotyping ; instrumentation ; methods ; Male ; Polymerase Chain Reaction

INTRODUCTIONThis study investigated the effect of an access-enhanced intervention on hypertension screening and management, as well as on health behaviours among newly diagnosed hypertensives, in a multi-ethnic low socioeconomic status (SES) community. Factors associated with hypertension screening, treatment, and control in the community were also determined.

MATERIALS AND METHODSThe study involved all residents aged ≥40 years in 2 public rental housing precincts (low SES), between 2009 and 2011, who were followed-up prospectively for 1 year after a 6-month community-based intervention comprising a 3-month access-enhanced screening component and a 3-month follow-up (outreach) component. Blood pressure was measured at baseline and follow-up. Multivariate Cox regression determined predictors of hypertension management at follow-up.

RESULTSThe follow-up rate was 80.9% (467/577). At baseline, 60.4% (282/467) were hypertensive; 53.5% (151/282) were untreated; 54.2% (71/131) uncontrolled. One year later, postintervention, 51.6% (78/151) of untreated hypertensives were treated; combined with treated hypertensives previously uncontrolled, 53.0% (79/149) achieved control. Older age independently predicted treatment (adjusted relative risk, aRR = 1.98, CI, 1.08 to 3.65); majority ethnicity (aRR = 1.76, CI, 1.05 to 2.96), employment (aRR = 1.85, CI, 1.26 to 2.80) and newly treated hypertension (aRR=1.52, CI, 1.01 to 2.32) predicted control. A total of 52.4% (97/185) were irregularly screened at baseline; at follow-up 61.9% (60/97) were regularly screened. Cost and misperceptions were common barriers to screening and treatment. Newly diagnosed hypertensives were also less likely to go for additional cardiovascular screening (aRR = 0.54, CI, 0.29 to 0.99).

CONCLUSIONAn access-enhanced intervention had some success in improving hypertension management within low SES communities; however, it was less successful in improving cardiovascular risk management, especially in encouraging lifestyle changes and additional cardiovascular screening amongst newly diagnosed hypertensives.

Adult ; Age Factors ; Aged ; Antihypertensive Agents ; therapeutic use ; Asian Continental Ancestry Group ; statistics & numerical data ; Diet, Sodium-Restricted ; methods ; Exercise Therapy ; methods ; Female ; Health Services Accessibility ; statistics & numerical data ; Humans ; Hypertension ; diagnosis ; ethnology ; therapy ; Male ; Mass Screening ; Middle Aged ; Multivariate Analysis ; Patient Compliance ; ethnology ; statistics & numerical data ; Patient Dropouts ; statistics & numerical data ; Poverty ; statistics & numerical data ; Proportional Hazards Models ; Prospective Studies ; Risk Reduction Behavior ; Singapore ; Smoking Cessation ; methods ; Social Class ; Treatment Outcome ; Weight Reduction Programs ; methods

Background/Aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients. Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks. Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1–2, and no linvencorvir-related serious adverse events were reported. Conclusions 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.