Exploring the Implementation of Shared Decision-Making Involving Health Coaches for Diabetes and Hypertension Self-Management: Qualitative Study.

BACKGROUND: An emerging focus on person-centered care has prompted the need to understand how shared decision-making (SDM) and health coaching could support self-management of diabetes and hypertension. OBJECTIVE: This study aims to explore preferences for the scope of involvement of health coaches and health care professionals (HCPs) in SDM and the factors that may influence optimal implementation of SDM from the perspectives of patients and HCPs. METHODS: We conducted focus group discussions with 39 patients with diabetes and hypertension and 45 HCPs involved in their care. The main topics discussed included the roles of health coaches and HCPs in self-management, views toward health coaching and SDM, and factors that should be considered for optimal implementation of SDM that involves health coaches. All focus group discussions were audio recorded, transcribed verbatim, and analyzed using thematic analysis. RESULTS: Participants agreed that the main responsibility of HCPs should be identifying the patient's stage of change and medication education, while health coaches should focus on lifestyle education, monitoring, and motivational conversation. The health coach was seen to be more effective in engaging patients in lifestyle education and designing goal management plans as health coaches have more time available to spend with patients. The importance of a health coach's personal attributes (eg, sufficient knowledge of both medical and psychosocial management of disease conditions) and credentials (eg, openness, patience, and empathy) was commonly emphasized. Participants viewed that addressing the following five elements would be necessary for the optimal implementation of SDM: (1) target population (newly diagnosed and less stable patients), (2) commitment of all stakeholders (discrepancy on targeted times and modality), (3) continuity of care (familiar faces), (4) philosophy of care (person-centered communication), and (5) faces of legitimacy (physician as the ultimate authority). CONCLUSIONS: The findings shed light on the appropriate roles of health coaches vis-à-vis HCPs in SDM as perceived by patients and HCPs. Findings from this study also contribute to the understanding of SDM on self-management strategies for patients with diabetes and hypertension and highlight potential opportunities for integrating health coaches into the routine care process.

Empowering patients with comorbid diabetes and hypertension through a multi-component intervention of mobile app, health coaching and shared decision-making: Protocol for an effectiveness-implementation of randomised controlled trial.

INTRODUCTION: Diabetes and hypertension are prevalent and costly to the health system. We have developed a mobile app (EMPOWER app) which enables remote monitoring and education through personalised nudges. We aim to study the effectiveness of a multi-component intervention comprising the EMPOWER mobile app with health coaching and shared decision-making for diabetes and hypertension. METHODS: We will conduct a two-arm, open-label, pragmatic randomised controlled trial (RCT). Participants with comorbid diabetes and hypertension enrolled from public primary care clinics will be randomised to either intervention or control in a 1:1 ratio. The intervention group participants will have access to health coaching with shared decision-making interventions in addition to the EMPOWER app and their usual primary care. The control group participants will continue to receive usual primary care and will neither receive the EMPOWER app nor health coaching and shared decision-making interventions. Our primary outcome is change in HbA1c level over 9 months. Secondary outcomes include change in systolic blood pressure, quality of life, patient activation, medication adherence, physical activity level, diet, and healthcare cost (direct and indirect) over 9 months. DISCUSSION: Our trial will provide key insights into clinical- and cost-effectiveness of a multi-component intervention comprising EMPOWER mobile app, health coaching and shared decision-making in diabetes and hypertension management. This trial will also offer evidence on cost-effective and sustainable methods for promoting behavioural changes among patients with comorbid diabetes and hypertension. TRIAL REGISTRATION: This study was registered on clintrials.gov on August 3, 2022, with the trial registration number: NCT05486390.

Performance of a multigene genomic classifier and clinical parameters in predicting malignancy in a Southeast Asian cohort of patients with cytologically indeterminate thyroid nodules.

BACKGROUND: Most thyroid nodules are benign. It is important to determine the likelihood of malignancy in such nodules to avoid unnecessary surgery. The primary objective of this study was to characterize the genetic landscape and the performance of a multigene genomic classifier in fine-needle aspiration (FNA) biopsies of cytologically indeterminate thyroid nodules in a Southeast Asian cohort. The secondary objective was to assess the predictive contribution of clinical characteristics to thyroid malignancy. METHODS: This prospective, multicenter, blinded study included 132 patients with 134 nodules. Molecular testing (MT) with ThyroSeq v3 was performed on clinical or ex-vivo FNA samples. Centralized pathology review also was performed. RESULTS: Of 134 nodules, consisting of 61% Bethesda category III, 20% category IV, and 19% category V cytology, and 56% were histologically malignant. ThyroSeq yielded negative results in 37.3% of all FNA samples and in 42% of Bethesda category III-IV cytology nodules. Most positive samples had RAS-like (41.7%), followed by BRAF-like (22.6%), and high-risk (17.9%) alterations. Compared with North American patients, the authors observed a higher proportion of RAS-like mutations, specifically NRAS, in Bethesda categories III and IV and more BRAF-like mutations in Bethesda category III. The test had sensitivity, specificity, negative predictive value, and positive predictive value of 89.6%, 73.7%, 84.0%, and 82.1%, respectively. The risk of malignancy was predicted by positive MT and high-suspicion ultrasound characteristics according to American Thyroid Association criteria. CONCLUSIONS: Even in the current Southeast Asian cohort with nodules that had a high pretest cancer probability, MT could lead to potential avoidance of diagnostic surgery in 42% of patients with Bethesda category III-IV nodules. MT positivity was a stronger predictor of malignancy than clinical parameters.

Economic Evaluation of Novel Models of Care for Patients With Acute Medical Problems.

Importance: During COVID-19, Singapore simultaneously experienced a dengue outbreak, and acute hospitals were under pressure to lower bed occupancy rates. This led to new models of care to treat patients with acute, low-severity medical conditions either at home, in a hospital-at-home (HaH) model, or in a clinic-style setting sited at the emergency department in an ambulatory care team (ACT) model, but a reliable cost analysis for these models is lacking. Objective: To compare personnel costs of HaH and ACT with inpatient care. Design, Setting, and Participants: In this economic evaluation study, time-driven activity-based costing was used to compare the personnel cost of inpatient care with treating dengue via HaH and treating chest pain via ACT. Participants were patients with nonsevere dengue and chest pain unrelated to a coronary event admitted via the emergency department to the internal medicine service of a tertiary hospital in Singapore. Exposures: HaH for dengue and ACT for chest pain. Main Outcomes and Measures: A process map was created for the patient journey for a typical patient with each condition. The amount of time personnel spent on delivering care was estimated and the cost per minute determined based on their wages in 2022. The total cost of care was calculated by multiplying the time spent by the per-minute cost of the personnel resource and summing all costs. Results: Compared with inpatient care, HaH used 50% less nursing time (418 minutes, 95% uncertainty interval [UI], 370 to 465 minutes) but 80% more medical time (303 minutes, 95% UI, 270 to 338 minutes) per case of dengue. If implemented nationally, HaH would save an estimated 56 828 SGD per year (95% UI, -169 497 to 281 412 SGD [US $41 856; 95% UI, -$124 839 to $207 268]). The probability that HaH is cost saving was 69.2%. Compared with inpatient care, ACT used 15% less nursing time (296 minutes, 95% UI, 257 to 335 minutes) and 50% less medical time (57 minutes, 95% UI, 46 to 69 minutes) per case of chest pain. If implemented nationally, ACT would save an estimated 1 561 185 SGD per year (95% UI, 1 040 666 to 2 086 518 SGD [US $1 149 862; 95% UI, $766 483 to $1 536 786]). The probability that ACT is cost saving was 100%. Conclusions and Relevance: This economic evaluation found that the HaH and ACT models decreased the overall personnel cost of care. Reorganizing hospital resources may help hospitals reap the benefits of reduced hospital-acquired infections, improved patient recovery, and reduced hospital bed occupancy rates.

Personal Goals, Barriers to Self-Management and Desired mHealth Application Features to Improve Self-Care in Multi-Ethnic Asian Patients with Type 2 Diabetes: A Qualitative Study.

(1) Introduction: The ubiquity of mobile phones suggests the potential of mobile health applications to reach patients with type 2 diabetes and engage them to improve self-care. This study aimed to explore personal goals, barriers to self-management and desired mobile health application features to improve self-care among multi-ethnic Asian patients with type 2 diabetes. (2) Methods: We conducted semi-structured interviews with patients with type 2 diabetes (n = 29). Patients were recruited from a multi-disciplinary center for diabetes and metabolism in Singapore, using a purposive sampling strategy. Various visual materials, collated from existing mobile health application features, were used to facilitate the discussion. Interviews were transcribed verbatim and thematically analyzed. (3) Results: A total of 29 patients participated in 11 focus group discussions or one-on-one interviews. Personal goals for self-management were centered around short-term outcome expectancy, such as better glucose control and a reduced number of medications. Self-management was hampered by competing priorities and limited healthy food options when at work, while a lack of tailored advice from healthcare providers further diminished competence. The desired mobile health app features to improve self-care behaviors included quantifiable goal-setting, personalized nudges based on tracked data, built-in resources from credible sources, in-app social support through virtual interaction with peers and healthcare providers, technology-driven novel data logging and user-defined nudges. (4) Conclusions: We identified a set of app features that may foster motivation to engage in lifestyle modification for patients with T2DM. The findings serve to inform the design of artificial intelligence-enabled mobile health application intervention aimed at improving diabetes self-care.

EMPOWERing Patients With Diabetes Using Profiling and Targeted Feedbacks Delivered Through Smartphone App and Wearable (EMPOWER): Protocol for a Randomized Controlled Trial on Effectiveness and Implementation.

Introduction: Type 2 diabetes mellitus (T2DM) poses huge burden and cost on the healthcare system. Mobile health (mHealth) interventions that incorporate wearables may be able to improve diabetes self-management. The aim of this randomized controlled trial (RCT) is to investigate the clinical and cost-effectiveness of personalized educational and behavioral interventions delivered through an EMPOWER mobile application (app) among patients with T2DM. Methods: This is a parallel two-arm randomized controlled trial (RCT). Patients with T2DM recruited from primary care will be randomly allocated in a 1:1 ratio to either intervention or control group. The intervention group will receive personalized educational and behavioral interventions through the EMPOWER app in addition to their usual clinical care. The control group will receive the usual clinical care for their T2DM but will not have access to the EMPOWER app. Our primary outcome is patient activation score at 12 months. Secondary outcomes will include HbA1c, physical activity level and diet throughout 12 months; quality of life (QoL), medication adherence, direct healthcare cost and indirect healthcare cost at 6 and 12 months. Discussion: This RCT will provide valuable insights into the effectiveness and implementation of personalized educational and behavioral interventions delivered through mobile application in T2DM management. Findings from this study can help to achieve sustainable and cost-effective behavioral change in patients with T2DM, and this can be potentially scaled to other chronic diseases such as hypertension and dyslipidemia.

Genetic interaction mapping highlights key roles of the Tol-Pal complex.

The conserved Tol-Pal trans-envelope complex is important for outer membrane (OM) stability and cell division in Gram-negative bacteria. It is proposed to mediate OM constriction during cell division via cell wall tethering. Yet, recent studies suggest the complex has additional roles in OM lipid homeostasis and septal wall separation. How Tol-Pal facilitates all these processes is unclear. To gain insights into its function(s), we applied transposon-insertion sequencing, and report here a detailed network of genetic interactions with the tol-pal locus in Escherichia coli. We found one positive and > 20 negative strong interactions based on fitness. Disrupting osmoregulated-periplasmic glucan biosynthesis restores fitness and OM barrier function, but not proper division, in tol-pal mutants. In contrast, deleting genes involved in OM homeostasis and cell wall remodeling causes synthetic growth defects in strains lacking Tol-Pal, especially exacerbating OM barrier and/or division phenotypes. Notably, the ΔtolA mutant having additional defects in OM protein assembly (ΔbamB) exhibited severe division phenotypes, even when single mutants divided normally; this highlights the possibility for OM phenotypes to indirectly impact cell division. Overall, our work underscores the intricate nature of Tol-Pal function, and reinforces its key roles in cell wall-OM tethering, cell wall remodeling, and in particular, OM homeostasis.

Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.

The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment. However, even in one of the best studied organisms, Escherichia coli, there remain gaps in our understanding of how the synthesis of the successive layers of the cell envelope are coordinated during growth and cell division. Here, we used a whole-genome phenotypic screen to identify mutants with a defective cell envelope. We report that loss of yhcB, a conserved gene of unknown function, results in loss of envelope stability, increased cell permeability and dysregulated control of cell size. Using whole genome transposon mutagenesis strategies, we report the comprehensive genetic interaction network of yhcB, revealing all genes with a synthetic negative and a synthetic positive relationship. These genes include those previously reported to have a role in cell envelope biogenesis. Surprisingly, we identified genes previously annotated as essential that became non-essential in a ΔyhcB background. Subsequent analyses suggest that YhcB functions at the junction of several envelope biosynthetic pathways coordinating the spatiotemporal growth of the cell, highlighting YhcB as an as yet unexplored antimicrobial target.

A Multiplex Thyroid-Specific Assay for Quantification of Circulating Thyroid Cell-Free RNA in Plasma of Thyroid Cancer Patients.

BACKGROUND: The standard of care for thyroid cancer management is thyroidectomy and adjuvant radioactive iodine (RAI). There is a paucity of clinical tool that quantifies residual thyroid volume reliably for precise adjuvant RAI dosing. Serum thyroglobulin (TG), tumour marker for thyroid cancer, takes 4 weeks for complete clearance due to its long half-life, and might be undetectable in 12% of structural disease patients. It detects recurrence with a sensitivity of 19-40%, mainly attributed to issue of TG antibody interference with TG immunometric assay. We hypothesise that the quantity of thyroid-specific cell-free RNA (cfRNA) is indicative of amount of thyroid tissues, and that during thyroid surgery, cfRNA levels decrease accordingly. METHODS: We identified 11 biologically significant and highly expressed thyroid-specific targets from Human Protein Atlas and literature. To assess for a fall in thyroid-specific cfRNA level, we recruited 16 patients undergoing thyroid surgery or RAI for malignant or benign thyroid disease, and tracked longitudinal trend of cfRNA. To assess the utility of cfRNA in detecting metastatic thyroid cancer, cfRNA of 11 patients at intermediate to high risk of recurrence was measured during surveillance and at time of clinical recurrence. RESULTS: The multiplex assay was capable of amplifying and quantifying multiple thyroid-specific genes in a single reaction. The selected targets were amplified successfully from RNA extracted directly from the thyroid (positive control), indicating that they were highly expressed within thyroid tissue. These cfRNAs were present in plasma, in amounts quantifiable using qRT-PCR. Four cfRNA transcripts (TPO, GFRA2, IVD, TG) fell post-treatment in more than 50% of cohort. The thyroid peroxidase (TPO) cfRNA fell post-therapy in 63% of cohort by 80%, as early as 1 day post-treatment, supporting the potential role as early indicator of remnant thyroid tissue volume. We demonstrated the clinical relevance of circulating TPO cfRNA by tracking temporal changes in setting of peri-treatment, recurrence, and TG Ab positive state. CONCLUSION: Using a multiplex pre-amplification approach, the TPO cfRNA was a potential biomarker that can track residual thyroid mass. It can be further optimised for quantification of thyroid volume to guide RAI doses and for detection of thyroid cancer recurrence.

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.

Persistent Anxiety Is Associated with Higher Glycemia Post-Transition to Adult Services in Asian Young Adults with Diabetes.

BACKGROUND: There is little longitudinal information on psychological burden and metabolic outcomes in young adults with diabetes (YAD) in Asia. We aimed to evaluate the association between psychological status and glycemia at baseline and 2 years following transition in a cohort of YAD in Singapore. METHODS: Subjects with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), aged 17 to 25 years, were recruited from the YAD clinic in Singapore General Hospital. The Hospital Anxiety and Depression and Problem Areas for Diabetes scales were administered at transition (baseline) and at 18 to 24 months. Glycosylated hemoglobin (HbA1c) assessed during routine visits was tracked longitudinally. RESULTS: A total of 98 T1DM (74.8%) and 33 T2DM (25.2%) subjects were recruited between January 2011 and November 2017. At baseline, mean HbA1c was 8.6%±1.7%. Only 26.0% achieved HbA1c of ≤7.5% and 16.8% achieved HbA1c of <7%. At baseline, prevalence of anxiety was 29.8%. At 24 months, 14.1% had persistent anxiety. Those with persistent anxiety had the highest mean HbA1c, particularly at 6 months (persistently anxious vs. persistently non-anxious: 9.9%±1.2% vs. 8.2%±1.9%, P=0.009). At baseline, 9.2% of subjects had depression. This group also had poorer glycemia at baseline (HbA1c of depressed vs non-depressed: 9.6%±2.1% vs. 8.5%±1.6%, P=0.04), which persisted up to 24 months. CONCLUSION: The majority of YAD in Singapore have suboptimal glycemia. Psychological distress is a critical harbinger of poorer metabolic outcomes.

Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function in Escherichia coli tol-pal mutants.

The outer membrane (OM) is an essential component of the Gram-negative bacterial envelope that protects the cells against external threats. To maintain a functional OM, cells require distinct mechanisms to ensure balance of proteins and lipids in the membrane. Mutations in OM biogenesis and/or homeostasis pathways often result in permeability defects, but how molecular changes in the OM affect barrier function is unclear. Here, we seek potential mechanism(s) that can alleviate permeability defects in Escherichia coli cells lacking the Tol-Pal complex, which accumulate excess PLs in the OM. We identify mutations in enterobacterial common antigen (ECA) biosynthesis that re-establish OM barrier function against large hydrophilic molecules, yet did not restore lipid homeostasis. Furthermore, we demonstrate that build-up of biosynthetic intermediates, but not loss of ECA itself, contributes to the rescue. This suppression of OM phenotypes is unrelated to known effects that accumulation of ECA intermediates have on the cell wall. Finally, we reveal that an unusual diacylglycerol pyrophosphoryl-linked lipid species also accumulates in ECA mutants, and might play a role in the rescue phenotype. Our work provides insights into how OM barrier function can be restored independent of lipid homeostasis, and highlights previously unappreciated effects of ECA-related species in OM biology.

Epidemiologic Characteristics of Multimorbidity and Sociodemographic Factors Associated With Multimorbidity in a Rapidly Aging Asian Country.

Importance: Multimorbidity is a growing health care problem in aging societies and is strongly associated with epidemiologic characteristics and sociodemographic factors. Knowledge of these associations is important for the design of effective preventive and management strategies. Objectives: To determine the association between multimorbidity and sociodemographic factors (age, socioeconomic status [SES], sex, and race/ethnicity) and the association between mental health diseases and physical diseases, as well as their implications for the types and costs of health care use. Design, Setting, and Participants: This population-based cross-sectional study used deidentified Singapore Eastern Regional Health System data collected between January 1, 2012, and December 31, 2016. Patients who were alive as of January 1, 2016, and residing in the Regional Health System region in 2016 (N = 1 181 024) were included. Patients who had no year of birth records (n = 573), were born in 2017 (n = 93), or died before January 1, 2016 (n = 47 322), were excluded. Main Outcomes and Measures: Multimorbidity, age, sex, SES, mental health, race/ethnicity, and health care use. Results: In the study population of 1 181 024 individuals, the mean (SD) age was 39.6 (22.1) years, 51.2% were women, 70.1% were Chinese, 7.1% were Indian, 13.5% were Malayan, and 9.3% were other races/ethnicities. Multimorbidity, present in 26.2% of the population, was more prevalent in female (26.8%; 95% CI, 26.7%-26.9%) than in male (25.6%; 95% CI, 25.5%-25.7%) patients and among patients with low SES (41.6%) than those with high SES (20.1%). Mental health diseases were significantly more prevalent among individuals with low SES (5.2%; 95% CI, 5.1%-5.2%) than high SES (2.1%; 95% CI, 2.0%-2.1%; P < .001). The 3 most prevalent disease combinations were chronic kidney disease and hypertension, chronic kidney disease and lipid disorders, and hypertension and lipid disorders. Although chronic kidney disease, hypertension, lipid disorders, and type 1 and/or type 2 diabetes-related diseases had a low cost per capita, the large number of patients with these conditions caused the overall proportion of the cost incurred by health care use to be more than twice that incurred in other diseases. Conclusions and Relevance: These findings emphasize the association between multimorbidity and sociodemographic factors such as increasing age, lower SES, female sex, and increasing number of mental disorders. Health care policies need to take sociodemographic factors into account when tackling multimorbidity in a population.

The Efficacy and Safety of High-Intensity Focused Ultrasound (HIFU) Therapy for Benign Thyroid Nodules-A Single Center Experience from Singapore.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a recent noninvasive technique of treating thyroid nodules. Our study aims to investigate the efficacy and safety of HIFU in treating benign thyroid nodules. METHODS: This is a retrospective analysis of consecutive patients who underwent HIFU of benign thyroid nodules at our institution from July 2017-2018. All procedures were performed by a single surgeon. Patients were evaluated immediately post-procedure, and at subsequent intervals of 1 week, 1 month, 3 months, and 6 months. The primary endpoint was thyroid nodule volume reduction at 6 months posttreatment. Secondary endpoints were post-procedure local complications. RESULTS: Ten patients with 13 thyroid nodules were included. The median follow-up period was 426 days (range 238-573). Mean maximum diameter reduced from 2.6 cm (±0.8) pretreatment to 1.4 cm (±0.7, P < 0.05) 6 months posttreatment. Mean nodule volume reduced from 5.2 cm3 (±4.2) pretreatment to 1.5 cm3 (±1.3, P = 0.01) 6 months posttreatment. Mean volume reduction ratio (VRR) at 6 months posttreatment was 63.2% (±22.5, P < 0.05), with volume reduction of ≥50% in 10 of 13 (76.9%) nodules. Two nodules (15.4%) showed size increases from 4 months posttreatment. No patients experienced local skin burns or hematomas. Mean pain scores were 1.5 (±1.2) immediate post-procedure, 0.8 (±1.5) at 1 week, and 0.6 (±1.2) at 1 month post-procedure, respectively, with no reports of pain beyond 1 month. Only two (20.0%) patients had early, temporary posttreatment voice hoarseness. CONCLUSION: Our study shows HIFU ablation to be efficacious and safe-with significant thyroid nodule volume reductions, and no significant or prolonged local complications.

Predictors of thyroxine replacement following hemithyroidectomy in a south east Asian cohort.

BACKGROUND: Thyroxine replacement following a hemithyroidectomy is not commonly discussed during consent for the procedure as the risk of hypothyroidism is perceived to be low. METHODS: Retrospective review of 901 patients who underwent hemithyroidectomy at a tertiary referral institution during the period January 2000 to December 2015. The main outcome studied was the overall incidence of hypothyroidism and the associated risk factors. RESULTS: Hypothyroidism developed in 123 (13%) patients and 94 patients (10%) required hormone supplementation over a mean follow up of 21 months (range 1-168 months). Preoperative TSH of more than 2.5 was seen in 38 of 123 (31%) of patients. Presence of diffuse thyroiditis was the only independent risk factor on multivariate analysis (P = 0.002) found to be associated with the development of hypothyroidism. CONCLUSION: After thyroid lobectomy, approximately one in 10 patients requiring thyroid hormone treatment for hypothyroidism. Presence of diffuse thyroiditis is a significant risk factor for hypothyroidism.

Predictors of survival outcome following radical gastrectomy for gastric cancer.

BACKGROUND: Radical surgery with adjuvant therapy is now the standard treatment for locally advanced gastric cancer. However, the best regimen for adjuvant therapy remains controversial. We aim to determine the predictors of survival outcome of gastric cancer patients who underwent curative surgery with or without adjuvant therapy in our institution. METHODS: All patients who received surgery for gastric cancer from years 2000 to 2015 were studied using a prospective gastric cancer database at the National University Hospital, Singapore. RESULTS: A total of 405 patients underwent radical gastrectomy with curative intent. Seventy-eight percent received extended lymphadenectomy (≥D1). R0 resection was achieved in 377 patients (93%) with 30-day mortality rate of 1.7%. There was no significant difference in the complication rate between D1 and extended lymphadenectomy group. One hundred and forty-five patients (36%) received adjuvant therapy. With a median follow-up of 5.9 years, the 5-year disease-free survival for stage I to IV patients were 78%, 58%, 27% and 9%, respectively. Among the 141 patients with known recurrences, the first site of recurrence was 38% distant, 24% locoregional, 20% peritoneal and the rest were multiple sites. Stage of disease, adjuvant therapy, extent of lymphadenectomy, post-operative complication and approach of surgery were independent risk factors for long-term survival. CONCLUSIONS: Stage of disease, adjuvant therapy, extent of lymphadenectomy, post-operative complication and approach of surgery are significant predictors for long-term survival. Adequate and safe surgery to allow adjuvant therapy should be the goal of all surgeons for our gastric cancer patients.

Subclassification of Bethesda Atypical and Follicular Neoplasm Categories According to Nuclear and Architectural Atypia Improves Discrimination of Thyroid Malignancy Risk.

BACKGROUND: Although The Bethesda System for Reporting Thyroid Cytopathology has provided clinicians with a standardized classification scheme for the diagnosis of thyroid fine-needle aspiration cytology (FNAC) specimens, the indeterminate categories of Bethesda III (B3)-atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)-and Bethesda IV (B4)-follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)-continue to pose challenges with regards to ideal diagnostic and therapeutic management. Having previously demonstrated the presence of nuclear atypia as a high-risk subgroup in B3, the objective of this study was to evaluate the malignancy rates in the B4 subgroup with nuclear atypia. METHODS: A retrospective review of all thyroid FNACs diagnosed as B4 (FN/SFN) between 2008 and 2015 was conducted at a tertiary referral center in Singapore. Data on patient demographics, sonographic features, and final histological diagnosis were collected. This was compared to data from a previous analysis on all nodules diagnosed as B3 (AUS/FLUS) over a similar period. RESULTS: A total of 137/309 (44.3%) and 88/111 (79.3%) FNACs diagnosed as B3 and B4, respectively, underwent surgical excision yielding final histopathological diagnoses. The malignancy rate of B4 was 31/88 (35.2%) compared to B3, which was 37/137 (27.0%). Subclassification based on the presence of architectural versus nuclear atypia showed significantly higher malignancy rates in B4 nodules with nuclear atypia (21.8% vs. 57.6%; p < 0.01). These findings corroborate previous results within the B3 category (malignancy rate of 14.7% vs. 36.8%; p < 0.01). The only sonographic features predictive of malignancy were the presence of macrocalcifications in B4 compared to irregularity of margins in B3. CONCLUSION: The presence of nuclear atypia identifies subgroups with significant differential malignancy risks within both the B3 and B4 categories. This supports the notion that subclassification is a useful risk stratification tool that can guide diagnostic and therapeutic management of indeterminate thyroid nodules with heterogenous risk profiles.

Psychometric validation of the Hypoglycemia Fear Survey-II (HFS-II) in Singapore.

OBJECTIVE: We conducted a cross-sectional study to adapt and validate the Hypoglycemia Fear Survey-II (HFS-II) for use in Singapore among persons with type 1 and 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: A total of 144 patients with type 1 or 2 diabetes on insulin therapy for at least a year completed the HFS-II between September and December 2013 in the Diabetes Center at Singapore General Hospital. We examined the validity (content, concurrent and discriminant validity, and construct validity) and reliability (internal consistency and test-retest reliability) of the instrument. Content validity was established using cognitive interviews. Construct validity was assessed using confirmatory factor analysis (CFA) followed by exploratory factor analysis (EFA) after the hypothesized two-factor structure was not confirmed by CFA. Measures of anxiety (Generalized Anxiety Disorder-7 (GAD-7)) and depression (Patient Health Questionnaire-9 (PHQ-9)) were used to establish concurrent validity; history of severe hypoglycemia and status of glycemic control were used to establish discriminant validity. Internal consistency was measured by Cronbach's α; test-retest reliability was measured by intracluster correlation coefficient (ICC). RESULTS: Scores of the adapted HFS-II had moderate positive correlations with measures of anxiety and depression scores (ranxiety=0.41, p<0.01; rdepression=0.37, p<0.01). Patients with a recent history of severe hypoglycemia had higher HFS-II scores than those without (mean difference=9, p<0.01). Patients with poor glycemic control had higher HFS-II scores than those with good control (p<0.05). The original two-factor structure was not confirmed in our sample. EFA results suggested a three-factor solution with the original Behavior subscale splitting into two dimensions. The adapted HFS-II displayed good internal consistency (Cronbach's α=0.93) and test-retest reliability (ICC=0.75). CONCLUSIONS: The adapted HFS-II has good content, concurrent and discriminant validity, and reliability, but its constructvalidity was not proven with the Behavior subscale turning out to be non-unidimensional.

A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore.

BACKGROUND: Impaired awareness of hypoglycaemia (IAH) predisposes affected patients to severe hypoglycaemia. There are few data on prevalence of IAH in adults with insulin-treated type 2 diabetes in Asia. We aim to ascertain the prevalence of IAH among insulin-treated patients with type 2 diabetes in an outpatient clinic in a tertiary care centre in Singapore. METHODS: A total of 374 patients with insulin-treated type 2 diabetes attending the outpatient diabetes clinic in a tertiary referral centre in Singapore were recruited over a 4-month period. Participants completed a questionnaire to document baseline characteristics and assess their hypoglycaemia awareness status, using a combination of the Clarke, Gold and Pedersen-Bjergaard methods. RESULTS: Using the Clarke, Gold and Pedersen-Bjergaard methods, prevalence of IAH in our cohort was 9.6%, 13.4% and 33.2% respectively. Overall, 7.2% of participants suffered from severe hypoglycaemia in the preceding year. The IAH group had more episodes of severe hypoglycaemia across all three methods, compared with the normal awareness group (p < 0.01). There were no significant differences in mean HbA1c, duration of diabetes and insulin treatment between the IAH and normal awareness groups. CONCLUSIONS: IAH is prevalent in adults with insulin-treated type 2 diabetes in Asia, and is associated with significantly increased risk of severe hypoglycaemia.