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.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.

Precision diagnosis is the keystone of clinical medicine. In East Asians, classical type 1 diabetes is uncommon in patients with youngonset diabetes diagnosed before age of 40, in whom a family history, obesity, and beta-cell and kidney dysfunction are key features. Young-onset diabetes affects one in five Asian adults with diabetes in clinic settings; however, it is often misclassified, resulting in delayed or non-targeted treatment. Complex aetiologies, long disease duration, aggressive clinical course, and a lack of evidence-based guidelines have contributed to variable care standards and premature death in these young patients. The high burden of comorbidities, notably mental illness, highlights the numerous knowledge gaps related to this silent killer. The majority of adult patients with youngonset diabetes are managed as part of a heterogeneous population of patients with various ages of diagnosis. A multidisciplinary care team led by physicians with special interest in young-onset diabetes will help improve the precision of diagnosis and address their physical, mental, and behavioral health. To this end, payors, planners, and providers need to align and re-design the practice environment to gather data systematically during routine practice to elucidate the multicausality of young-onset diabetes, treat to multiple targets, and improve outcomes in these vulnerable individuals.

INTRODUCTION: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic breast condition that can cause repeated abscesses or mass formation in bilateral breasts. The condition can severely impact the quality of life of affected women. This study aims to evaluate effective treatment modalities, as well as understand the demographics and clinical presentation of patients with IGM. METHODS: An 11-year retrospective review was performed of patients diagnosed with IGM from 1 January 2008 to 31 December 2018 at a tertiary breast unit. RESULTS: A total of 77 patients were included in the study. The median age at presentation was 36 years old. IGM presented most commonly as a breast lump (98.1%). The median number of flares was 2 (1-12). Of the 77 patients, 68.8% (53) were treated with antibiotics, 50.6% (39) with steroids, and 44.2% (34) underwent surgery, in the course of their IGM treatment. Forty-five (59.2%) of the 76 patients with IGM required a multimodal treatment approach to achieve remission. There was no significant difference in the number of flares no matter the initial treatment ( CONCLUSION IGM is a clinical diagnosis. It is a rare, relapsing breast inflammatory condition that affects young females with no superior treatment modality. Smoking is associated with higher number of flares of IGM and should be discouraged in IGM patients.
Adult ; Anti-Bacterial Agents/therapeutic use* ; Female ; Granulomatous Mastitis/therapy* ; Humans ; Quality of Life ; Retrospective Studies ; Treatment Outcome

INTRODUCTION: Advanced breast cancer (ABC) remains common in Singapore. In 2019, 22.1% of breast cancer patients presented with ABC in our institution. Despite increasing affluence and the advent of national mammographic screening, the incidence of ABC has not changed significantly. This suggests inherent differences in women who present late. We aim to explore the socio-economic background, knowledge and attitudes of women who present with ABC. METHODS: Between December 2013 and July 2015, 100 patients who presented consecutively with ABC in a tertiary institution in Singapore were recruited to participate in an interviewer-led questionnaire exploring psychosocial and economic issues. RESULTS: Among the 100 patients, 63 and 37 presented with stages 3 and 4 breast cancer respectively. Median age was 57 (27-86), 52% had at least secondary education, 53% had no formal employment and 71% were married; 88% were aware of breast cancer symptoms, 82% were aware that mammography can help detect cancer, 82% believed that current treatment modality for breast cancer is effective, 96% had never undergone a mammography and 52.9% felt mammograms were unnecessary. A total of 64% presented symptomatic from the breast tumour, with a median duration of 3 months. Many of the patients were aware of breast cancer symptoms and the utility of mammography. However, a group of patients did not comply with screening. This may be due to poor understanding about breast screening and detection in its asymptomatic phase. CONCLUSION Further public education to improve understanding of breast cancer and screening mammography may help to improve rates for earlier detection of breast cancer.