Association between primary hyperparathyroidism and cardiovascular outcomes: A systematic review and meta-analysis.

BACKGROUND: Excess parathyroid hormone (PTH) is associated with an increased risk of cardiovascular disease (CVD). PURPOSE: We aimed to evaluate the correlation between primary hyperparathyroidism (PHPT) and CVD or cardiovascular (CV) death. DATA SOURCES: Comprehensive searches of PubMed, Embase and ClinicalTrials.gov until May 20, 2023 with the following keywords: "primary hyperparathyroidism," "cardiovascular disease," and "mortality." STUDY SELECTIONS: Cohort studies and randomized controlled trials comparing PHPT patients to the general population and those who had received parathyroidectomy (PTX) to those who did not. DATA EXTRACTION: Three investigators independently extracted data and assessed study quality. DATA SYNTHESIS: Eleven cohort studies and one randomized controlled trial were identified, including 264,227 PHPT patients with or without PTX, and the average age reported in the studies was 62 years. PHPT was associated with a higher risk of total death (RR 1.39 [95 % confidence interval (CI) 1.23-1.57) and CV death (RR 1.61 [95 % CI 1.47-1.78]) than the general population. However, there was no significant difference in CVD risk between patients with PHPT and the general population (RR 1.73 [95 % CI 0.87-3.47]). When compared to patients without PTX, PTX had a lower risk of CV death (RR 0.75 [95 % CI 0.71-0.80]), total death (RR 0.64 [95 % CI 0.60-0.70]) and CVD (RR 0.92 [95 % CI 0.90-0.94]). LIMITATION: High heterogeneity among the included articles, and most of them were retrospective and older studies. CONCLUSIONS: PHPT was associated with higher risk of total death and CV death while PTX was associated with lower risk of total death, CV death, and CVD.

ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. METHODS AND RESULTS: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. CONCLUSIONS: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

The Effect of Mobile eHealth Education to Improve Knowledge, Skills, Self-Care, and Mobile eHealth Literacies Among Patients With Diabetes: Development and Evaluation Study.

BACKGROUND: The promotion of mobile health (mHealth) and eHealth technologies as tools for managing chronic diseases, particularly diabetes mellitus, is on the rise. Nevertheless, individuals with diabetes frequently face a literacy gap that hinders their ability to fully leverage the benefits offered by these resources. Enhancing technology literacy to facilitate the adoption of mobile eHealth services poses a significant challenge in numerous countries. OBJECTIVE: This study aims to develop an educational mobile eHealth literacy (eHL) program for patients with diabetes and to evaluate its effect on patients' outcomes. METHODS: This study designed a mobile eHL education program comprising 2 modules specifically tailored for individuals with type 2 diabetes (T2D). These modules focused on guiding participants through the process of effectively navigating reliable health websites and utilizing diabetes-related apps. Using a pre- and posttest experimental design, the study featured an intervention group and a control group. Participants were recruited from 3 outpatient departments in hospitals, and assessments were conducted both before and after the intervention, along with a follow-up measure at the 3-month mark. The evaluation encompassed sociodemographic characteristics, computer and internet proficiency, mobile app usage, mobile eHL, and patient outcomes such as self-care behaviors and glycated hemoglobin (HbA1c) levels. RESULTS: The analysis included a total of 132 eligible participants. Significant differences were observed in the mean scores of knowledge (P<.001) and skills (P<.001) related to computers, the web, and mobile devices at the initiation of the study and after the intervention. During the 3-month follow-up, the findings indicated a significant improvement in mobile eHL (t114=3.391, P=.001) and mHealth literacy (mHL, a subconcept of mobile eHL; t114=3.801, P<.001) within the intervention group, whereas no such improvement was observed in the control group. The chi-square values from the McNemar test underscored that individuals with uncontrolled diabetes (HbA1c≥7%) in the intervention group exhibited more improvement compared with the control group. The generalized estimating equations model unveiled a significant difference in the change of general mHL in the intervention group (ß=1.91, P=.047) and self-care behavior in the control group from T0 to T2 (ß=-8.21, P=.015). Despite being small, the effect sizes for mobile eHL (d=0.49) and HbA1c (d=0.33) in the intervention group were greater than those in the control group (d=0.14 and d=0.16, respectively). CONCLUSIONS: The implementation of a mobile eHL education intervention demonstrates a positive influence on the familiarity of patients with T2D regarding health technology, leading to favorable glycemic outcomes. While additional studies are warranted for a more comprehensive understanding, this program emerges as a promising solution for enhancing patients' uptake of digital health technology.

A Clinicopathological Analysis of Asian Patients with Adrenocortical Carcinoma: A Single-Center Experience.

BACKGROUND: There is limited information regarding the immunohistochemistry stain and its prognostic role in adrenocortical carcinoma (ACC), and few studies focus on Asian patients. Our study aims to identify the correlation between immunohistochemistry staining and the prognosis of ACC in Asian patients. METHODS: We searched the database of a single center in Taiwan for cases with a pathological diagnosis of ACC in the past 25 years. We collected patient data on age, sex, initial presentation, staging, metastatic site, and survival duration. Immunohistochemical studies using antibodies to CDK4, ATRX, beta-catenin, Ki-67, SSTR2, and p53 were performed. Survival analysis was performed using the log-rank test, the Cox proportional hazards model and bootstrapping with 5000 samplings. RESULTS: Fourteen patients were identified, and the median age was 49.5 (range 1-70) years. There were eight male and six female patients. Four patients presented with Cushing's syndrome, and half were diagnosed with stage IV ACC at presentation. Only three patients survived (21%). The median survival time was 15.5 (range 0.67-244) months. SSTR2 expression score > 50 (log-rank test: p = 0.009) and Ki-67 > 50% (log-rank test: p = 0.017) were associated with mortality. However, after adjusting for stage, the bootstrapping analysis demonstrated that Ki-67 [B 2.04, p = 0.004], Beta-catenin [B 2.19, p = 0.009], ATRX [B 1.48, p = 0.026], P53 [B 1.58, p = 0.027], SSTR2 [B 1.58, p = 0.015] and SSTR2 expression score [B 0.03, p < 0.001] were all significantly associated with mortality. CONCLUSIONS: After adjusting for stage, Ki-67 > 50%, Beta-catenin, ATRX, P53, SSTR2 and SSTR2 expression score > 50 were associated with mortality in Asian patients with ACC.

Association between thyroid cancer and cardiovascular disease: A meta-analysis.

Objective: To determine the association between thyroid cancer and coronary artery disease, atrial fibrillation, cerebrovascular disease, and cardiovascular disease mortality. Methods: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to September 22, 2022. Keywords included "thyroid cancer", "atrial fibrillation", "coronary artery disease", "cerebrovascular disease", and "mortality". Primary outcomes included the incidence of coronary artery disease, cerebrovascular disease, atrial fibrillation, and cardiovascular disease mortality among patients with thyroid cancer. Secondary outcomes included cardiovascular disease events among those with thyroid cancer that received or did not receive radioactive iodine or lenvatinib. Estimates were pooled using fixed- and random-effects meta-analysis. Results: A total of 771,220 patients who underwent thyroidectomy in 15 studies were included. Risk for cerebrovascular disease (risk ratio [RR] 1.15 [95% confidence interval (CI) 1.10-1.21]) and atrial fibrillation [RR 1.59 (95% CI: 1.45-1.73)] were significantly increased. Risk for coronary artery disease was significantly increased [RR 1.12 (95% CI: 1.08-1.17)] in the common effect model. Cardiovascular disease mortality associated with thyroid cancer was not significant [RR 0.93 (95% CI: 0.59-1.45)]. Radioactive iodine had a neutral effect on cardiovascular disease [RR 1.00 (95% CI: 0.87-1.16)], and there was no beneficial nor harmful effect among different RAI doses. Conclusions: Thyroid cancer was significantly associated with a higher risk for cerebrovascular disease and atrial fibrillation; however, the hazard risk was not different between patients with and without radioactive iodine treatment. Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health.

Comparison of two titration programmes for adding insulin detemir to oral antidiabetic drugs in patients with poorly controlled type 2 diabetes mellitus.

AIM: To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs). METHODS: In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events. RESULTS: At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol. CONCLUSION: Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Association between thyroid cancer and cardiovascular disease risk: a nationwide observation study.

Treatment with levothyroxine and radioiodine contribute alternative cardiovascular function in adults with thyroid cancer. The risks of long-term cardiovascular conditions among thyroid cancer patients is unknown. This study aimed to compare the incidence of coronary heart disease (CHD), ischemic stroke (IS), and atrial fibrillation (AF) among adults with thyroid cancer with that of the general population, especially when stratified by age (< 65 and ≥ 65 years old). This observational cohort study enrolled patients between January 1, 2011 and December 31, 2016 with a follow-up until December 31, 2018. This study analyzed the data of Taiwanese thyroid cancer patients registered on the National Taiwan Cancer Registry Database, with CHD and IS. SIR models were used to evaluate the association between thyroid cancer and CHD, IS, AF, and cardiovascular disease outcome, stratified by age and sex. SIR analyses were also conducted for both sexes, age groups (< 65, ≥ 65 years), and different follow-up years. After excluding 128 individuals (< 20 years or ≥ 85 years old) and with missing index data, 4274 eligible thyroid cancer patients without CHD history, 4343 patients without IS history, and 4247 patients without AF history were included for analysis. During the median follow-up of 3.5 (1.2) years among thyroid cancer patients, the observed number of new CHD events was 70; IS, 30; and AF, 20, respectively. The SIR was significantly higher for CHD (SIR, 1.57; 95% confidence interval [CI] 1.2-1.93) among thyroid cancer patients compared with the age- and sex-specific standardized population. However, the association between thyroid cancer and the risks of IS (SIR, 0.74; 95% CI 0.47-1), cardiovascular disease (SIR, 0.88; 95% CI 0.7-1.05), and atrial fibrillation (SIR, 0.74; 95% CI 0.42-1.06) were insignificant. Moreover, stratification by age < 65 or age ≥ 65 years old and by sex for CHD suggested that the diagnosis of thyroid cancer in the young may attenuate the CHD risk (SIR, 2.08; 95% CI 1.5-2.66), and the CVD risk was constant among both men (SIR, 1.63; 95% CI 1.03-2.24) and women (SIR, 1.53; 95% CI 1.06-1.99). The patients had persistent higher CHD risk for 5 years after cancer diagnosis. Thyroid cancer survivors have a substantial CHD risk, even at long-term follow-up, especially in those patients < 65 years old. Further research on the association between thyroid cancer and CHD risk is warranted.

Effect of empagliflozin versus linagliptin on body composition in Asian patients with type 2 diabetes treated with premixed insulin.

Insulin therapy often increases body weight and leads to visceral fat accumulation. Progression in diabetes is also associated with accelerated loss of muscle mass. Little is known about body composition changes in type 2 diabetes mellitus (T2DM) patients on insulin therapy who use sodium-glucose cotransporter-2 (SGLT2) inhibitors versus dipeptidyl peptidase-4 (DPP4) inhibitors. This study examined the effect of 25 mg of empagliflozin compared with 5 mg of linagliptin for 24 weeks on body weight and body composition in patients with T2DM on premixed insulin. Body composition was assessed with bioelectrical impedance analysis. The mean difference between the linagliptin and empagliflozin groups in terms of mean body weight change from baseline to 24 weeks was - 1.80 kg (95% CI - 2.57, - 1.03). Empagliflozin also significantly reduced muscle mass (- 1.39 kg, 95% CI - 2.49, - 0.29) and total body water (- 1.07 kg, 95% CI - 1.88, - 0.27) compared with linagliptin. Compared to linagliptin, empagliflozin decreased body fat mass more from baseline to week 24, but this was not significant (- 0.31 kg, 95% CI - 1.51, 0.90). Further research on insulin-treated T2DM patients is necessary to investigate the long-term effects of SGLT2 and DPP4 inhibitors on body composition, as well as their effects on muscle strength and physical function.Trial registration: ClinicalTrials.gov no. NCT03458715, registration date: March 8, 2018.

Predicting readmission due to severe hyperglycemia after a hyperglycemic crisis episode.

AIM: This study aimed to investigate the readmission pattern and risk factors for patients who experienced a hyperglycemic crisis. METHODS: Patients admitted to MacKay Memorial Hospital for diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar state (HHS) between January 2016 and April 2019 were studied. The timing of the first readmission for hyperglycemia and other causes was recorded. Kaplan-Meier analysis was used to compare patients with hyperglycemia and all-cause readmissions. Cox regression was used to identify independent predictors for hyperglycemia and all-cause readmission post-discharge. RESULTS: The study cohort included 410 patients, and 15.3 % and 46.3 % of them had hyperglycemia and all-cause readmissions, respectively. The DKA and HHS group showed a similar incidence for hyperglycemia, with the latter group showing a higher incidence of all-cause readmissions. The significant predictors of hyperglycemia readmissions included young age, smoking, hypoglycemia, higher effective osmolality, and hyperthyroidism in the DKA group and higher glycated hemoglobin level in the HHS group. CONCLUSIONS: Patients who experienced DKA and HHS had similar hyperglycemia readmission rates; however, predictors in the DKA group were not applicable to the HHS group. Designing different strategies for different types of hyperglycemic crisis is necessary for preventing readmission.

Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis.

AIMS: Diabetes is associated with increased risk of fracture. This study aims to evaluate the correlation between anti-diabetic agents and fracture risk in patients with type 2 diabetes. METHODS: Literature research was conducted using PubMed, Embase, and ClinicalTrials.gov. Search-term included "type 2 diabetes," "fracture," "randomized controlled trial," and seven kinds of anti-diabetic agents. Random-effect models established fractures in the follow-up period as the primary outcome. A network meta-analysis was performed to compare available treatments within a single Bayesian analytical framework. RESULTS: A total of 191,361 patients were included in 161 studies, with 2916 fractures. DPP-4i (risk ratio [RR] 1.76 [95 % confidence interval (CI) 1.21-2.55]), SGLT-2i (RR 1.5 [95 % CI 1.05-2.16]) and placebo (RR 1.44 [95 % CI 1.04-1.98]) increased fracture risk when compared to GLP1-RA. GLP1-RA (RR 0.5 [95 % CI 0.31-0.79]) and SU (RR 0.56 [95 % CI 0.41-0.77]) provided greater protection against fracture than TZD. DPP-4i increased fracture risk when compared to SU (RR 1.55 [95 % CI 1.08-2.22]), and was comparable in effect to TZD. CONCLUSIONS: GLP1-RA offered better protection against fracture than placebo. Insulin and SU had effects comparable with GLP1-RA. SU offered greater protection against fractures than TZD and DPP-4i. SGLT-2i increased risk of fracture when compared to GLP1-RA.

Mortality factors in recurrent parathyroid cancer: a pooled analysis.

INTRODUCTION: Parathyroid cancer is a rare disease with high recurrence rate. The prognostic factors for recurrent parathyroid cancer are yet to be ascertained. We aimed to establish the association between recurrent parathyroid cancer and previously reported prognostic factors. MATERIALS AND METHODS: We conducted a PubMed search using the keywords 'parathyroid cancer', 'parathyroid neoplasm', and 'hypercalcemia' during 1966-2019 and included 3272 articles. We focused on 73 patients with recurrent parathyroid cancer from 55 studies. We conducted a survival analysis using the Cox proportional hazards model with 95% confidence interval. RESULTS: For the 73 patients included in the analysis, the mean age (± standard deviation) was 44 ± 13.2 years, wherein 36 patients were women (49.3%). During the 5236 person-months at risk (mean follow-up 71.7 months, range 3-264), 38 patients died. The incidence of local recurrence, lymph-node metastasis, lung metastasis, and bone metastasis were 60.3, 12.3, 56.2, and 24.7, respectively. Bone metastasis, disease-free interval < 1 year, and total surgeries < 3 were significant prognostic factors in univariate analysis (log-rank test P = 0.0063, P = 0.0006, and P = 0.0056, respectively). In the multivariate-adjusted analysis, the mortality risk was significantly increased in patients with bone metastasis with a hazard ratio (HR) of 4.83 (95% CI 1.16-20.2; P = 0.03), disease-free interval <=1 year of 5.92 (95% CI 1.85-18.99; P = 0.003), and total surgeries <3 of 11.29 (95% CI 2.82-45.22; P = 0.001), considering these as possible predictive prognostic factors. CONCLUSION: Bone metastasis, duration of disease-free interval, and total number of surgeries predict survival in recurrent parathyroid cancer.

Comparison of four healthy lifestyle scores for predicting cardiovascular events in a national cohort study.

The protective effect of different healthy lifestyle scores for the risk of cardiovascular disease (CVD) was reported, although the comparisons of performance were lacking. We compared the performance measures of CVDs from different healthy lifestyle scores among Taiwanese adults. We conducted a nationwide prospective cohort study of 6042 participants (median age 43 years, 50.2% women) in Taiwan's Hypertensive, Hyperglycemia and Hyperlipidemia Survey, of whom 2002 were free of CVD at baseline. The simple and weighted the Mediterranean diet related healthy lifestyle (MHL) scores were defined as a combination of normal body mass index, Mediterranean diet, adequate physical activity, non-smokers, regular healthy drinking, and each dichotomous lifestyle factor. The World Cancer Research Fund and American Institute for Cancer Research cancer prevention recommended lifestyle and Life's Simple 7 following the guideline definition. The incidence of CVD among the four healthy lifestyle scores, each divided into four subgroups, was estimated. During a median 14.3 years follow-up period, 520 cases developed CVD. In the multivariate-adjusted Cox proportional hazard models, adherence to the highest category compared with the lowest one was associated with a lower incidence of CVD events, based on the simple (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.2-0.94) and weighted MHL scores (HR 0.44, 95% CI 0.28-0.68). Additionally, age played a role as a significant effect modifier for the protective effect of the healthy lifestyle scores for CVD risk. Specifically, the performance measures by integrated discriminative improvement showed a significant increase after adding the simple MHL score (integrated discriminative improvement: 0.51, 95% CI 0.16-0.86, P = 0.002) and weighted MHL score (integrated discriminative improvement: 0.38, 95% CI 0.01-0.74, P = 0.021). We demonstrated that the healthy lifestyle scores with an inverse association with CVD and reduced CVD risk were more likely for young adults than for old adults. Further studies to study the mechanism of the role of lifestyle on CVD prevention are warranted.

Effects of SGLT2 inhibitors on stroke and its subtypes in patients with type 2 diabetes: a systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effects in reducing major vascular events in several randomized controlled trials (RCTs). The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitors on the risk of stroke and its subtypes. All data from prospective RCTs up to 20 October 2020 involving SGLT2 inhibitors that reported stroke events as the primary endpoint or safety in subjects with type 2 diabetes were subjected to meta-analysis. Five eligible RCTs (EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE and VERTIS CV) involving 46,969 participants were included. Pooled analysis of the RCTs showed no significant effect of SGLT2 inhibitors on total stroke [risk ratio (RR) = 0.95; 95% confidence interval (CI) 0.79-1.13, P = 0.585]. Subgroup analysis indicated that SGLT2 inhibitors had no significant effect against fatal stroke, non-fatal stroke, ischemic stroke or transient ischemic attack. When only hemorrhagic stroke was included, SGLT2 inhibitors were associated with a significant 50% reduction compared with placebo (RR = 0.49, 95% CI 0.30-0.82, P = 0.007). This meta-analysis shows that SGLT2 inhibitors have a neutral effect on the risk of stroke and its subtypes but a potential protective effect against hemorrhagic stroke.

Risk associated with estimated glomerular filtration rate and albuminuria for PAD among patients with type 2 diabetes.

Chronic kidney disease (CKD) is significantly associated with peripheral arterial disease (PAD) in some studies, but data on the association of the risk of PAD across a broad range of kidney function in patients with type 2 diabetes are limited. Between October 17, 2013 and February 7, 2015, all consecutive outpatients with type 2 diabetes underwent ankle-brachial index (ABI) examination. We investigated the association of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) with the risk of PAD. A total of 1254 patients were cross-classified into 12 groups based on ACR category (normoalbuminuria, microalbuminuria and macroalbuminuria) and eGFR stage (≥90, 60-89, 30-59 and <30 mL/min/1.73 m2). Logistic regression analysis was used to investigate the association of eGFR and ACR with PAD. Within each ACR category, a lower eGFR stage was associated with PAD. Similarly, within each eGFR group, a higher ACR category was also associated with PAD. The OR for PAD was highest in patients with eGFR <30 mL/min/1.73 m2 and macroalbuminuria (OR 14.42, 95% CI 4.60 to 45.31) when compared with the reference group of subjects with eGFR ≥90 mL/min/1.73 m2 and normoalbuminuria. Our study found that cross-classification of eGFR with ACR revealed a more comprehensive association with risk of PAD than eGFR or ACR alone.

Hyperparathyroidism presenting as hyperemesis and acute pancreatitis in pregnancy: A case report.

RATIONALE: Nausea and vomiting are common in the early period of pregnancy and rarely seen as an overture to pancreatitis. PATIENT CONCERNS: Here, we describe a 31-year-old pregnant woman who presented with progressive nausea and vomiting followed by severe epigastric pain. Biochemical data and sonographic features confirmed the occurrence of acute pancreatitis. Accompanying electrolyte abnormalities included hypercalcemia and hypokalemia. Her condition stabilized following medical treatment, but hypercalcemia persisted despite intravenous fluids and furosemide administration. DIAGNOSES: A diagnosis of primary hyperparathyroidism was made based on the elevated parathyroid hormone level and urinary calcium-to-creatinine clearance ratio. INTERVENTIONS: Localization study with neck ultrasonography indicated left inferior parathyroid adenoma. She underwent parathyroidectomy successfully and made an uneventful recovery. OUTCOMES: At 37 weeks of gestation, she had a serum calcium level of 8.8 mg/dL and normal parathyroid hormone of 28.55 pg/mL. A healthy baby weighing 3180 g was delivered smoothly with no clinical nor biochemical evidence of hypocalcemia. LESSONS: Although primary hyperparathyroidism during pregnancy is usually asymptomatic, patients may present with atypical manifestations such as hyperemesis and pancreatitis. Proper diagnosis and timely intervention are crucial to minimizing potential hazards to both mother and fetus.

A 3D printed human upper respiratory tract model for particulate deposition profiling.

Pulmonary route is the main route of drug delivery for patients with asthma and chronic obstructive pulmonary diseases, offering several advantages over the oral route. Determining the amount of drug deposited onto various parts of the respiratory tract allows for a good correlation to clinical efficacy of inhalation drug devices. However, current in vitro cascade impactors measure only the aerodynamic particle size distribution, which does not truly represent the in vivo deposition pattern in human respiratory tract. In this study, a human upper respiratory tract model was fabricated using a 3D printer and subsequently characterized for its dimensional accuracy, surface finishing and air leaking. The effects of using a spacer and/or various airflow rates were also investigated. To assess this in vitro model, the deposition pattern of a model drug, namely, salbutamol sulphate, was tested. The resultant deposition pattern of salbutamol sulphate from a metered dose inhaler at 15 L per minute with the spacer, showed no significant difference from that of a published radiological in vivo study performed in adult humans. In addition, it was also found that the deposition pattern of salbutamol at 35 L per minute was comparable to the results of another published study in human. This in vitro model, showing reasonable in vitro-in vivo correlation, may provide opportunities for personalized medicine in special populations or disease states.

Relationships Between Mobile eHealth Literacy, Diabetes Self-care, and Glycemic Outcomes in Taiwanese Patients With Type 2 Diabetes: Cross-sectional Study.

BACKGROUND: Understanding how people with diabetes seek online health information and use health applications is important to ensure these electronic tools are successfully supporting patient self-care. Furthermore, identifying the relationship between patient mobile eHealth literacy (mobile eHL) and diabetes outcomes can have far-reaching utility, for example, in the design of targeted interventions to address mobile eHL limitations. However, only limited studies have explored the impact of mobile eHL in a population with diabetes. OBJECTIVE: This study aims to present data about online information-seeking behavior and mobile health (mHealth) app usage, investigate the factors related to mobile eHL in Taiwanese patients with type 2 diabetes, and flesh out the relationship between eHealth literacy (eHL), mobile health literacy (mHL), and health outcomes. METHODS: Subjects were recruited from January 2017 to December 2017 in the outpatient departments of 3 hospitals in Taiwan. A total of 249 Taiwanese patients with diabetes voluntarily completed a cross-sectional survey assessing sociodemographic characteristics; diabetes status; knowledge and skills of computers, the internet, and mobile apps; mobile eHL; and patient outcomes (self-care behaviors, self-rated health, HbA1c). Structural equation modeling analyses examined the model fit of mobile eHL scores and the interrelationships between latent constructs and observable variables. RESULTS: Of the 249 patients with diabetes, 67% (164/249) reported they had searched for online diabetes information. The participants with smartphones had owned them for an average of 6.5 years and used them for an average of 4.5 (SD 3.81) hours per day. Only 1.6% (4/249) of the patients used health apps. Some demographic factors affecting mobile eHL included age, education, and duration of type 2 diabetes. Mobile eHL was related to self-care behaviors as well as knowledge and skills of computers, the internet, and mobile technology, but only had a weak, indirect effect on self-rated health. The final model had adequate goodness-of-fit indexes: chi-square (83)=149.572, P<.001; comparative fit index (CFI)=0.925; root mean square of approximation (RMSEA)=0.057 (90% CI 004-006); chi-square/df=1.082. Mobile eHL had a weak, indirect effect on self-rated health through the variables of knowledge with skills. CONCLUSIONS: Our study reveals that although people with diabetes who rated their health conditions as moderate were confident in using mobile eHealth and technology, few adopted these tools in their daily lives. The study found that mobile eHL had a direct effect on self-care behavior as well as knowledge and skills of computers, the internet, and mobile technology, and had an indirect effect on health outcomes (glycemic control and self-rated health status). Information about this population's experiences and the role mobile eHL plays in them can spur necessary mobile eHealth patient education.

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.