Intensification with Dipeptidylpeptidase-4 Inhibitor, Insulin, or Thiazolidinediones and risks of all-cause mortality, cardiovascular diseases and severe hypoglycemia in patients on metformin-sulfonylurea dual therapy: A retrospective study

Background: Although patients with type 2 diabetes mellitus (T2DM) may fail to achieve adequate hemoglobin A1c (HbA1c) control despite metformin-sulfonylurea (Met-SU) dual therapy, a third-line glucose-lowering medication—including dipeptidyl peptidase-4 inhibitor (DPP4i), insulin, or thiazolidinedione (TZD)—can be added to achieve this. However, treatment effects of intensification with the medications on the risk of severe hypoglycemia (SH), cardiovascular disease (CVD), and all-cause mortality are uncertain. Study aim was to compare the risks of all-cause mortality, CVD, and SH among patients with T2DM on Met-SU dual therapy intensified with DPP4i, insulin, or TZD. Methods and findings: We analyzed a retrospective cohort data of 17,293 patients with T2DM who were free from CVD and on Met-SU dual therapy and who were intensified with DPP4i (n = 8,248), insulin (n = 6,395), or TZD (n = 2,650) from 2006 to 2017. Propensity-score weighting was used to balance out baseline covariates across groups. Hazard ratios (HRs) for all-cause mortality, CVD, and SH were assessed using Cox proportional hazard models. Mean age of all patients was 58.56 ± 11.41 years. All baseline covariates achieved a balance across the 3 groups. Over a mean follow-up period of 34 months with 49,299 person-years, cumulative incidences of all-cause mortality, SH, and CVD were 0.061, 0.119, and 0.074, respectively. Patients intensified with insulin had higher risk of all-cause mortality (HR = 2.648, 95% confidence interval [CI] 2.367–2.963, p < 0.001; 2.352, 95% CI 2.123–2.605, p < 0.001) than those intensified with TZD and DPP4i, respectively. Insulin users had the greatest risk of SH (HR = 1.198, 95% CI 1.071–1.340, p = 0.002; 1.496, 95% CI 1.342–1.668, p < 0.001) compared with TZD and DPP4i users, respectively. Comparing between TZDs and DPP4i, TZDs were associated with a higher risk of SH (HR = 1.249, 95% CI 1.099–1.419, p < 0.001) but not all-cause mortality (HR = 0.888, 95% CI 0.776–1.016, p = 0.084) or CVD (HR = 1.005, 95% CI 0.915–1.104, p = 0.925). Limitations of this study included the lack of data regarding lifestyle, drug adherence, time-varying factors, patients’ motivation, and cost considerations. A limited duration of patients intensifying with TZD might also weaken the strength of study results. Conclusions: Our results indicated that, for patients with T2DM who are on Met-SU dual therapy, the addition of DPP4i was a preferred third-line medication among 3 options, with the lowest risks of mortality and SH and posing no increased risk for CVD events when compared to insulin and TZD. Intensification with insulin had the greatest risk of mortality and SH events

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. METHODS: Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.published_or_final_versio

Associations between usual glycated haemoglobin A1c and Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A 10‐year Diabetes cohort study

Aims: The long‐term effect of glycated haemoglobin A1c(HbA1c) level on cardiovascular disease(CVD) risks among patients with type 2 diabetes remains controversial. The aim of this study was to investigate their associations. / Materials and methods: This retrospective cohort study conducted in Hong Kong selected patients aged 45‐84 years old with type 2 diabetes mellitus and without CVD in primary care clinics within 2008‐2010. The usual HbA1c measurement was calculated using a mixed effects model to minimize regression dilution bias. The association between usual HbA1c and CVD risk was assessed by Cox regression with adjustment of baseline covariates. Subgroup analyses by patient characteristics were also conducted. / Results: After a median follow‐up period of 8.4years (1.4 million person‐years), 174,028 patients with 34,074 CVD events were observed. Curvilinear association was found between the usual HbA1c and total CVD, stroke, heart failure and CVD mortality risk. No significant difference was found among patients with usual HbA1c7%(53mmol/mol) was 21% (HR: 1.21; 95%C.I. (Confidence Interval): 1.18‐1.23). Similar pattern was identified in patient's subgroups analysis, but the effect of usual HbA1c in younger patients were more prominent than the others. / Conclusions: Increment in usual HbA1c level >7.0% (53mmol/mol) was associated with elevated CVD risk, but no difference was found in population with usual HbA1c<7.0% (53mmol/mol) irrespective of the patients' characteristics. For the CVD prevention, a strict adherence of HbA1c <7% (53 mmol/mol) should apply to patients with younger age

Post-Covid-19-vaccination adverse events and healthcare utilization among individuals with or without previous SARS-CoV-2 infection

Background: Post-marketing pharmacovigilance data are scant on the safety of Covid-19 vaccines among people with previous SARS-CoV-2 infection compared with ordinary vaccine recipients. We compared the post-vaccination adverse events of special interests (AESI), accident and emergency room (A&E) visit, and hospitalization between these two groups. Methods: We conducted a retrospective cohort study using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. Results: In total, 3922 vaccine recipients with previous SARS‑CoV‑2 infection and 1,137,583 vaccine recipients without previous SARS‑CoV‑2 infection were included. No significant association was observed between previous SARS‑CoV‑2 infection and AESI or hospitalization. Previous SARS‑CoV‑2 infection was significantly associated with a lower risk of A&E visit (CoronaVac: hazard ratios [HR] = 0.56, 95% confidence intervals [CI]: 0.32–0.99; Comirnaty: HR = 0.62, 95% CI: 0.47–0.82). Conclusion: No safety signal of Covid-19 vaccination was detected from the comparison between vaccine recipients with previous SARS-CoV-2 infection and those without infection

The phenomenon of micronutrient deficiency among children in China: a systematic review of the literature

Objective: The present study aimed to review the literature on micronutrient deficiency and other factors influencing a deficiency status among children living in China. Design: A systematic review was performed to analyse the literature. Setting: Studies were identified through a search of PubMed and secondary references. Subjects: Children living in China aged less than 18 years. Results: Sixty-one articles were included. The prevalence of vitamin A deficiency decreased to approximately 10 % in 1995–2009. It increased with age but no significant difference was found between genders. The prevalence of thiamin and vitamin B12 deficiency was 10·5 % in Yunnan and 4·5 % in Chongqing provinces, respectively. Higher vitamin D deficiency rates were seen in spring and winter. The incidence of bleeding due to vitamin K deficiency was 3·3 % in 1998–2001 and more prevalent in rural areas. Both iodine deficiency and excess iodine intake were observed. Goitre rates were reported in Tibet, Jiangxi, Gansu and Hong Kong (3·5–46 %). Anaemia rates ranged from 20 % to 40 % in 2007–2011. High Se deficiency rates were found in Tibet, Shaanxi and Jiangsu. High Zn deficiency rates were also found (50–70 %) in 1995–2006. Few studies reported Ca deficiency rates (19·6–34·3 %). The degrees of deficiency for vitamin A, vitamin B12, Fe and Zn were more substantial in rural areas compared with urban areas. Conclusions: The prevalence of micronutrient deficiency rates varied. Socio-economic status, environmental factors and the Chinese diet may influence micronutrient deficiency. Public health policies should consider implementing programmes of supplementation, food fortification and nutrition education to address these deficiencies among Chinese children.link_to_subscribed_fulltex

Early results of a safety and feasibility clinical trial of a novel single-port flexible robot for transoral robotic surgery

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Age-specific associations between Systolic Blood Pressure and Cardiovascular Disease: A 10-years diabetes cohort study

Abstract: Background The relationship between systolic blood pressure (SBP) and cardiovascular disease (CVD) among patients with diabetes mellitus remains unclear. The study aimed to explore age‐specific associations between SBP and CVD. Methods and Results: A population‐based retrospective cohort study was conducted on 180 492 Chinese adults with type 2 diabetes mellitus in 2008–2010, with follow‐up to 2017. Age‐specific associations (<50, 50–59, 60–69, and 70–79 years) between the average SBP in the previous 2 years and CVD risk were assessed by adjusted Cox proportional hazards regression with age‐specific regression dilution ratios and patient characteristics stratified by subgroups. During a median follow‐up of 9.3 years (1.5 million person‐years), 32 545 patients developed a CVD, with an incidence rate of 23.4 per 1000 person‐years. A positive and log‐linear association between SBP and CVD risk was observed among the 4 age groups without evidence of a threshold down to 120 mm Hg, but the magnitude of SBP effect on CVD attenuated with increased age. The CVD risk in the age group <50 years was ≈22% higher than the age group 70 to 79 years (hazard ratio [HR], 1.33 [95% CI, 1.26–1.41] versus HR, 1.09 [95% CI, 1.07–1.11]). Each 10‐mm Hg higher SBP was associated with 12% (HR, 1.12 [95% CI, 1.10–1.13]), 11% (HR, 1.11 [95% CI, 1.10–1.13]), and 20% (HR, 1.20 [95% CI, 1.17–1.22]) higher risk of all composite CVD events, individual CVD, and CVD mortality, respectively. Conclusions: There is a significant log‐linear relationship between baseline SBP and the risk of CVD among patients with diabetes mellitus in China. The risk increases from an SBP of 120 mm Hg onward. Age influences this relationship significantly, with younger patients (<50 years) having a greater risk of CVD for a similar rise in SBP as compared with those who are older. These findings suggest that differential target blood pressures stratified by age maybe usefu

Effectiveness of BNT162b2 after extending the primary series dosing interval in children and adolescents aged 5–17

Extended intervals between the first and second doses of mRNA Covid-19 vaccines may reduce the risk of myocarditis in children and adolescents. However, vaccine effectiveness after this extension remains unclear. To examine this potential variable effectiveness, we conducted a population-based nested case-control study of children and adolescents aged 5–17 years who had received two doses of BNT162b2 in Hong Kong. From January 1 to August 15, 2022, 5396 Covid-19 cases and 202 Covid-19 related hospitalizations were identified and matched with 21,577 and 808 controls, respectively. For vaccine recipients with extended intervals [≥28 days, adjusted odds ratio 0.718, 95% Confidence Interval: 0.619, 0.833] there was a 29.2%-reduced risk of Covid-19 infection compared to those with regular intervals (21–27 days). If the threshold was set at eight weeks, the risk reduction was estimated at 43.5% (aOR 0.565, 95% CI: 0.456, 0.700). In conclusion, longer dosing intervals for children and adolescents should be considered

The effectiveness and safety of mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines among individuals with chronic kidney diseases

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to individuals with underlying chronic kidney disease (CKD). People with CKD are immunocompromised and therefore result in poorer outcomes including increased risk of hospitalization and mortality after COVID-19.1 Despite the availability of COVID-19 vaccines, current data on the vaccine efficacy in individuals with CKD are limited to surrogate endpoints such as antibody titers. As a result, a dedicated study is required to evaluate the effectiveness and safety of COVID-19 vaccines for the CKD population