Earlier diagnosis of peripheral neuropathy in primary care: A call to action.

Peripheral neuropathy (PN) often remains undiagnosed (~80%). Earlier diagnosis of PN may reduce morbidity and enable earlier risk factor reduction to limit disease progression. Diabetic peripheral neuropathy (DPN) is the most common PN and the 10 g monofilament is endorsed as an inexpensive and easily performed test for DPN. However, it only detects patients with advanced neuropathy at high risk of foot ulceration. There are many validated questionnaires to diagnose PN, but they can be time-consuming and have complex scoring systems. Primary care physicians (PCPs) have busy clinics and lack access to a readily available screening method to diagnose PN. They would prefer a short, simple, and accurate tool to screen for PN. Involving the patient in the screening process would not only reduce the time a physician requires to make a diagnosis but would also empower the patient. Following an expert meeting of diabetologists and neurologists from the Middle East, South East Asia and Latin America, a consensus was formulated to help improve the diagnosis of PN in primary care using a simple tool for patients to screen themselves for PN followed by a consultation with the physician to confirm the diagnosis.

Healthcare Challenges in the Management of Primary Aldosteronism in Southeast Asia.

OBJECTIVE: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited healthcare access. Hence, we aimed to assess the availability and affordability of healthcare resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. DESIGN: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries. RESULTS: Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin-ratio is performed in all countries, confirmatory testing is routinely performed in only six countries due to lack of facilities and local assays, and cost constraint. Assays are only locally available in four countries, and some centers have a test turnaround time exceeding three weeks. In seven countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In six countries, the cost of AVS and adrenalectomy combined is >30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable. CONCLUSION: Large populations currently do not have access to the healthcare resources required for the optimal management of PA. Greater efforts are required to improve healthcare access and affordability. Future guideline revisions for PA may need to consider these limitations.

Incidence and trends of ophthalmic cancer in Singapore: Data from Singapore Cancer Registry.

INTRODUCTION: Limited data are available on the incidence of primary ophthalmic cancers worldwide. We describe the incidence and trends of primary ophthalmic cancers in Singapore. METHODS: Data on ophthalmic cancers diagnosed in Singapore from 1996 to 2016 were retrieved from the Singapore Cancer Registry for analysis. All were histologically proven primary ophthalmic cancers. Calculations of incidence and age-specific frequency of ophthalmic malignancy were made. RESULTS: A total of 297 cases were included, with males constituting 59.9%. The race distribution was 78.5% Chinese, 16.5% Malay, 3.7% Indians and 1.3% others. There was an overall increase in ophthalmic malignancies. The mean age of onset was 47.4 years. The most common cancers were retinoblastoma (93.3%) in patients younger than 15 years, and lymphoma (71.3%) in patients aged 15 years and older. There has been an increase in lymphomas from 16.7% in 1968-1995 to 71.3% in 1996-2016 in those aged 15 years and older. The most common types of ophthalmic cancer according to location are lymphoma of the orbit, conjunctiva, cornea and lacrimal gland; retinoblastoma of the retina; and malignant melanoma of the choroid and ciliary body. CONCLUSION: Our study reported the incidence and trends of ophthalmic cancer in the Singapore population and showed an overall increase in ophthalmic malignancies in Singapore from 1996-2016. A substantial increase in lymphomas over the last 2 decades was noted. The data could aid clinicians, epidemiologists and policymakers in implementing strategies to address trends in ophthalmic cancers and spur aetiological research to improve quality of life in patients with such cancers.

Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.

The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.

Ketogenic diets, not for everyone.

BACKGROUND: The adoption of low-carbohydrate diets can lead to weight loss in many patients. However, these now widespread diets also have the potential to exacerbate hypercholesterolemia. OBJECTIVE: The objective of this study is to display the potentially harmful effects of the ketogenic diet on cholesterol levels in patients with or without underlying hyperlipidemia. METHODS: We describe 5 patients who developed marked increases in plasma cholesterol on ketogenic diets and assessed whether they had a well-described underlying genetic hyperlipidemia. RESULTS: Three out of 5 patients had extraordinary increases of blood cholesterol levels to over 500 mg/dL. The other 2 patients more than doubled their low-density lipoprotein cholesterol levels on a ketogenic diet. One patient had an APOE E2/E2 genotype. A higher burden of common genetic polymorphisms was found in 2 patients, with no major mutations found. No potential genetic cause was seen in a fourth patient, and the fifth patient had no genetic testing. Three patients, including the one who was most hypercholesterolemic, had a marked reduction in cholesterol after reverting to a more liberal diet. One refused to change his diet but had a satisfactory low-density lipoprotein cholesterol reduction on ezetimibe. CONCLUSION: These cases should serve as a caution that high-fat low-carbohydrate diets have the potential to exacerbate or cause hypercholesterolemia in patients with or without underlying genetic hyperlipidemia.

Reliability of Graders and Comparison with an Automated Algorithm for Vertical Cup-Disc Ratio Grading in Fundus Photographs.

INTRODUCTION: We aimed to investigate the intergrader and intragrader reliability of human graders and an automated algorithm for vertical cup-disc ratio (CDR) grading in colour fundus photographs. MATERIALS AND METHODS: Two-hundred fundus photographs were selected from a database of 3000 photographs of patients screened at a tertiary ophthalmology referral centre. The graders included glaucoma specialists (n = 3), general ophthalmologists (n = 2), optometrists (n = 2), family physicians (n = 2) and a novel automated algorithm (AA). In total, 2 rounds of CDR grading were held for each grader on 2 different dates, with the photographs presented in random order. The CDR values were graded as 0.1-1.0 or ungradable. The grading results of the 2 senior glaucoma specialists were used as the reference benchmarks for comparison. RESULTS: The intraclass correlation coefficient values ranged from 0.37-0.74 and 0.47-0.97 for intergrader and intragrader reliability, respectively. There was no significant correlation between the human graders' level of reliability and their years of experience in grading CDR (P = 0.91). The area under the curve (AUC) value of the AA was 0.847 (comparable to AUC value of 0.876 for the glaucoma specialist). Bland Altman plots demonstrated that the AA's performance was at least comparable to a glaucoma specialist. CONCLUSION: The results suggest that AA is comparable to and may have more consistent performance than human graders in CDR grading of fundus photographs. This may have potential application as a screening tool to help detect asymptomatic glaucoma-suspect patients in the community.

Metastatic Follicular Thyroid Carcinoma as a Cause of Low Serum Thyroxine with a Normal Thyroid Stimulating Hormone Level.

Thyroid function is usually normal in differentiated thyroid carcinoma. We describe a case of a female patient who had metastatic follicular thyroid carcinoma (FTC) to the spine and lungs, who was clinically euthyroid but had very low free tetraiodothyronine (fT4) and normal thyroid stimulating hormone (TSH). Free triiodothyronine (fT3) and total T3 (TT3) were normal. Levothyroxine treatment increased fT4 marginally but caused a two- to three-fold rise in fT3 and TT3 along with suppressed TSH. This is likely due to hyperconversion of T4 to T3 from elevation in D2 deiodinase activity in the tumor. This phenomenon has been reported to occur in about 20% of metastatic FTC.

Preliminary evidence that acute stress moderates basal testosterone's association with retaliatory behavior.

A contribution to a special issue on Hormones and Human Competition. Testosterone is theorized to increase retaliation after social provocation. However, empirical evidence in support of these theories is mixed. The present research investigated whether acute stress causally suppresses testosterone's association with retaliation. We also explored sex differences in behavioral responses to acute stress. Thirty-nine participants (51.28% male) were randomly assigned to a high- or low-stress condition. Then participants engaged in 20 one-shot rounds of the ultimatum game, which was used to assess retaliatory behavioral responses to unfair treatment. Participants provided two saliva samples to measure testosterone and cortisol concentrations - one sample before the stress manipulation, and the second after the ultimatum game (20minutes post-stressor). Results revealed a positive association between basal testosterone and retaliation in the low-stress condition, but not in the high-stress condition. Further, cortisol concentrations increased in the high- compared to the low-stress condition, and these cortisol changes moderated the association between basal testosterone and retaliation. The associations between basal testosterone and retaliation under varying levels of stress were similar in men and women. However, there was a sex difference in behavioral responses to the stress manipulation that was independent of testosterone. In women, the high-stress condition reduced retaliation compared to the low-stress condition, whereas in men the opposite pattern emerged. Collectively, this study (i) provides preliminary evidence that experimentally manipulated stress blocks basal testosterone's association with retaliation, and (ii) reveals a sex difference in retaliation under varying levels of stress. Discussion focuses on mechanisms, limitations, and the need for follow-up studies with larger sample sizes.

A practical approach to secondary osteoporosis - Case studies in Asia.

Osteoporosis is a major health disease that is increasing in Asia especially given the rapidly aging population in many of the countries. A major aim of the management of osteoporosis is to prevent the next fracture from happening and its attendant morbidity and possible mortality. A failure to identify a possible secondary cause of osteoporosis might lead to suboptimal benefits of treatment or possibly treatment failure. This article aims to use a series of cases in order to best illustrate the approach to the screening of secondary causes of osteoporosis and highlight learning points from each case with a slant towards the management of patients in Asia, focusing on the East and South East Asia (SEA).

Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism.

CONTEXT: The accurate distinction between unilateral and bilateral adrenal disease in patients with primary aldosteronism (PA) guides surgical management. Adrenal venous sampling (AVS), the criterion standard localization procedure, is not readily available at many centers throughout the world. OBJECTIVE: The objective of the study was to determine factors most consistent with surgically curable PA. DESIGN: This was a retrospective observational study. SETTING: The study was conducted at the Mayo Clinic (Rochester, Minnesota), a tertiary referral center. PATIENTS: All patients who underwent unilateral adrenalectomy for treatment of PA between January 1993 and December 2011 participated in the study. INTERVENTION: The intervention in the study was unilateral adrenalectomy. MAIN OUTCOME MEASURES: Variables associated with the prediction of unilateral disease were measured. RESULTS: Over 19 years, 263 patients underwent unilateral adrenalectomy for the treatment of PA. Long-term postoperative follow-up was obtained in 143 patients (54.4%). The overall effective cure rate of PA was 95.5% in those patients sent for adrenalectomy for presumptive unilateral disease. In patients with cured PA, defined as the resolution of autonomous aldosterone secretion, hypertension was cured in 53 (41.7%) and improved in 59 (46.5%) patients. PA was not cured with unilateral adrenalectomy in six patients (4.2%). Adrenal imaging and AVS were concordant to the surgically documented side in 58.6% and 97.1% of the patients, respectively. Although there was no statistically significant difference in mean age between the inaccurate vs the accurate adrenal imaging group, we found that the minimum age in the former was 35.1 years. CONCLUSIONS: Using adrenal imaging and AVS, the effective surgical cure rate for PA was 95.5%. Although the overall accuracy of computed tomography and magnetic resonance imaging in detecting unilateral adrenal disease was poor at 58.6%, adrenal imaging performed well in those patients younger than 35 years of age.

Dynamics of the job search process: developing and testing a mediated moderation model.

Taking a self-regulatory perspective, we develop a mediated moderation model explaining how within-person changes in job search efficacy and chronic regulatory focus interactively affect the number of job interview offers and whether job search effort mediates the cross-level interactive effects. A sample of 184 graduating college students provided monthly reports of their job search activities over a period of 8 months. Findings supported the hypothesized relationships. Specifically, at the within-person level, job search efficacy was positively related with the number of interview offers for job seekers with strong prevention focus and negatively related with the number of interview offers for job seekers with strong promotion focus. Results show that job search effort mediated the moderated relationships. Findings enhance understandings of the complex self-regulatory processes underlying job search.

Coexisting primary hyperparathyroidism and sarcoidosis cause increased angiotensin-converting enzyme and decreased parathyroid hormone and phosphate levels.

CONTEXT: Primary hyperparathyroidism (PHPT) and sarcoidosis may separately contribute to abnormal calcium and phosphate metabolism via different mechanisms, and their coexistence is infrequently reported. OBJECTIVE: We sought to characterize a group of 50 patients with coexisting PHPT and sarcoidosis in our institution to evaluate their clinical and laboratory characteristics. DESIGN AND SETTING: This was a retrospective observational study of patients with both disorders at our institution between January 1980 and December 2011. OUTCOME: A cohort of 50 patients was identified, with mean ± SD age 59.6 ± 13.9 years and 86% women. Serum calcium in the cohort was 11.1 ± 1.1 mg/dL, phosphate was 3.3 ± 0.6 mg/dL, and PTH was 76 ± 42 pg/mL. Serum 25-hydroxyvitamin D was 25 ± 9 ng/mL, and serum 1,25-dihydroxyvitamin D was 51 ± 20 pg/mL; 24-hour urine calcium was 275 ± 211 mg. In subjects with sarcoidosis, serum angiotensin-converting enzyme (ACE) was 47.2 ± 37.4 U/L. Sarcoidosis was diagnosed first in 50% of patients, PHPT was diagnosed first in 16% of patients, and sarcoidosis and PHPT were both diagnosed within 6 months of each other in 30% of patients. The interval between the 2 diagnoses when sarcoidosis was diagnosed first was 15.5 ± 12.4 years and was 5.5 ± 6.0 years when PHPT was diagnosed first. Patients with PHPT who had active sarcoidosis had higher serum ACE levels (60.9 ± 38.1 vs 20.2 ± 14.0 U/L, P <.0001), lower PTH levels (60 ± 24 vs 96 ± 41 pg/mL, P = .01), and lower phosphate levels (2.7 ± 0.6 vs 3.2 ± 0.5 mg/dL, P = .02). CONCLUSIONS: Fifty patients with coexisting PHPT and sarcoidosis are described, with patients with PHPT coexisting with clinically active sarcoidosis having increased serum ACE levels and decreased serum PTH and phosphate levels compared with those with inactive sarcoidosis.

Declining incidence of eyelid cancers in Singapore over 13 years: population-based data from 1996 to 2008.

PURPOSE: To describe the epidemiology and trends in eyelid malignancies in Singapore from 1996 to 2008. METHODS: The Singapore Cancer Registry has been collecting epidemiological data of all cancers seen in Singapore since 1968. Data of all eyelid cancers from 1996 to 2008 were retrieved for analysis. The age-standardised incidence rates and age-specific incidence rates were calculated with the direct method, using the 2000 world population as a standard. RESULTS: There were a total of 160 male patients (48%) and 173 female patients (52%). The median age at diagnosis was 66 years (range 31-95) for male subjects and 67 years (35-99) for female subjects. The average annual age-standardised incidence rate of all eyelid cancers over the 13 years was 5.0 per million. A significant decrease in rates from 6.6 per million in the 1996-1998 period to 3.9 per million in the 2005-2008 period with an annual percentage change of 3.6% (95% CI -6.5 to 0.7%; p=0.02) was noted for women. The most common cancer was basal cell carcinoma (82%), followed by sebaceous gland carcinoma (11%) and squamous cell carcinoma (4%). CONCLUSIONS: The annual age-standardised incidence rates for male and female residents showed a steady decline over the last 13 years. These data suggest that factors related to sun protection have resulted in reduced eyelid cancers over time and provide a basis for such public health programmes elsewhere.

New therapeutic targets for osteoporosis: beyond denosumab.

Treatments for osteoporosis over the last few decades have largely focused on antiresorptive agents that effectively prevent bone loss. Beginning with hormone therapy, a variety of new potent antiresorptive agents were developed, including oral and intravenous bisphosphonates, raloxifene and other selective estrogen receptor modulators, nasal spray calcitonin, and denosumab. Teriparatide and PTH 1-84 are the only approved anabolic agents to date that primarily build new bone density. A variety of new biologic agents that focus on molecular targets important for the stimulation of new bone formation are being developed. Cathepsin K inhibitors appear to have mixed antiresorptive and anabolic actions because they inhibit one of the major osteoclast digestive enzymes without suppressing bone formation, thereby leading to anabolic effects on bone. New biologic agents in clinical trials include anti-sclerostin and anti-dickkopf antibodies that stimulate the Wnt/ß-catenin pathway in osteoblasts, leading to new bone formation. These new agents will effectively stimulate new bone formation by different mechanisms, leading to improved bone mineral density and reduced fractures.

Lost sleep and cyberloafing: Evidence from the laboratory and a daylight saving time quasi-experiment.

The Internet is a powerful tool that has changed the way people work. However, the ubiquity of the Internet has led to a new workplace threat to productivity-cyberloafing. Building on the ego depletion model of self-regulation, we examine how lost and low-quality sleep influence employee cyberloafing behaviors and how individual differences in conscientiousness moderate these effects. We also demonstrate that the shift to Daylight Saving Time (DST) results in a dramatic increase in cyberloafing behavior at the national level. We first tested the DST-cyberloafing relation through a national quasi-experiment, then directly tested the relation between sleep and cyberloafing in a closely controlled laboratory setting. We discuss the implications of our findings for theory, practice, and future research.

Caring for underserved patients through neighborhood health screening: outcomes of a longitudinal, interprofessional, student-run home visit program in Singapore.

PURPOSE: Service learning, an effective vehicle for teaching undergraduate public health while providing underserved communities with medical care, is not well established in Asia. The authors evaluated a service learning program, Neighborhood Health Screening (NHS), in Singapore. METHOD: Medical and nursing undergraduate students provided in-home medical services to patients in a low-income neighborhood (January-June 2010). The authors assessed student-reported pedagogical effectiveness in nine domains, asked students for qualitative feedback on their experiences, assessed patients' satisfaction with NHS, and tracked clinical outcomes. RESULTS: Of the 240 medical and 34 nursing students who participated, 222 (93%) and 34 (100%), respectively, completed the questionnaire; 136 of the medical students (57%) also provided qualitative feedback. Most students felt NHS was beneficial across all domains. Male medical students were less likely to report increased understanding of deficiencies in the health care system and long-term management of chronic disease; preclinical students were more likely to report improvements in comprehending ethical issues, critical thinking and action skills, and gaining and applying knowledge. Qualitative feedback supported quantitative findings. Patients were satisfied with NHS: 266 (75%) agreed that NHS improved their health, and 301 (85%) felt NHS provided sufficient time to address their issues. After a single year, amongst patients with known hypertension, treatment increased from 63% to 93% (P < .001), and blood pressure control amongst those who were on treatment improved from 42% to 79% (P < .001). CONCLUSIONS: Service learning can make an important contribution to medical teaching and patient care in Asia.

Testing a social-cognitive model of moral behavior: the interactive influence of situations and moral identity centrality.

This article proposes and tests a social-cognitive framework for examining the joint influence of situational factors and the centrality of moral identity on moral intentions and behaviors. The authors hypothesized that if a situational factor increases the current accessibility of moral identity within the working self-concept, then it strengthens the motivation to act morally. In contrast, if a situational factor decreases the current accessibility of moral identity, then it weakens the motivation to act morally. The authors also expected the influence of situational factors to vary depending on the extent to which moral identity was central to a person's overall self-conception. Hypotheses derived from the framework were tested in 4 studies. The studies used recalling and reading a list of the Ten Commandments (Study 1), writing a story using morally laden terms (Study 4), and the presence of performance-based financial incentives (Studies 2 and 3) as situational factors. Participants' willingness to initiate a cause-related marketing program (Study 1), lie to a job candidate during a salary negotiation (Studies 2 and 3), and contribute to a public good (Study 4) were examined. Results provide strong support for the proposed framework.

Lactate levels in Asian patients with type 2 diabetes mellitus on metformin and its association with dose of metformin and renal function.

AIM: Our aims are to discover the average fasting plasma lactate level (FPL) in Asian patients with type 2 diabetes mellitus on metformin, with or without renal impairment and whether FPL is associated with the total daily dose of metformin (Tmet) and the degree of renal impairment in these patients. METHODS: We conducted an observational cross-sectional study of Asian patients with type 2 diabetes, using measurements of FPL levels and glomerular filtration rate (GFR) calculated, using the abbreviated modification of diet in renal disease (MDRD) formula. The association between FPL, Tmet, GFR and other potential predictors was analysed. RESULTS: A total of 97 subjects were recruited from our diabetes centre between July 2005 and February 2006. Sixty (61.9%) of the subjects were males; 69 (71.1%) Chinese, 21 (21.6%) Malays and 6 (6.2%) Indians. The mean (SD) age was 58.8 years (10.7) and the mean body mass index was 27.1 kg/m(2) (5.3). The mean FPL was 1.8 mmol/l (0.9) with 20 (20.6%) of subjects having an FPL beyond the upper limit of our reference range of 2.2 mmol/l. The mean FPL (two SE) of subjects with Tmet of < or = 1000, 1001-2000 and > 2000 mg were 1.7 mmol/l (0.2), 1.6 mmol/l (0.2) and 2.1 mmol/l (0.5) respectively, (p = 0.119). The mean FPL of subjects with GFR of < 60, 60-90 and > 90 ml/min/1.73 m(2) was 1.7 mmol/l (0.3), 1.8 mmol/l (0.3) and 1.8 mmol/l (0.4) respectively, p = 0.757. Among the potential predictors analysed, aspartate transaminase (p = 0.001) was found to be significantly associated with FPL. CONCLUSIONS: Our study shows no correlation between Tmet and GFR with FPL in Asian type 2 diabetic patients on metformin.

Does parental job insecurity matter? Money anxiety, money motives, and work motivation.

A structural model focusing on the spillover effect of parental perceived job insecurity on money anxiety was developed and tested. The crossover effect of parents' money anxiety on their children's money anxiety, money motives, and motivation to work was also examined. Data were collected from a sample of undergraduates and their parents. Results of structural equation modeling analyses supported a spillover effect of paternal perceived job insecurity on paternal money anxiety. However, maternal perceived job insecurity was not significantly associated with maternal money anxiety. Results also supported a crossover effect of parental money anxiety on youths' money anxiety. Youths' money anxiety was significantly related to youths' negative money motives. In turn, youths' negative money motives were associated with their intrinsic motivation to work. Implications of the findings are discussed.

Managing HIV at the workplace: An empirical study of HIV and HR managers in Singapore.

Drawing from previous research on individual differences, AIDS, and concerns for face, the author developed and tested a model examining the predictors (knowledge of AIDS transmission, level of homophobia, and concern for face) of AIDS fear and its organizational outcomes (perceived organizational consequences of hiring people living with HIV and attitudes toward disclosure of HIV-related information at the workplace). Data were collected using mail survey. Structural equation modeling was used to examine the relationships among these variables for 160 human resource managers. All of the hypothesized relationships were empirically supported. Implications of the research findings for human resource practices are discussed.