Guideline adherence of β-blocker initiating dose and its consequence in hospitalized patients with heart failure with reduced ejection fraction

Background: We aim to investigate the guideline adherence of β-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes.Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed.Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization.Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization

Visit-to-visit HbA_1c variability is associated with cardiovascular disease and microvascular complications in patients with newly diagnosed type 2 diabetes

OBJECTIVE To investigate the association between visit-to-visit HbA1c variability and cardiovascular events and microvascular complications in patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS This retrospective cohort study analyzed patients from Tayside and Fife in the Scottish Care Information–Diabetes Collaboration (SCI-DC) who were observable from the diagnosis of diabetes and had at least five HbA1c measurements before the outcomes were evaluated. We used the previously reported HbA1c variability score (HVS), calculated as the percentage of the number of changes in HbA1c >0.5% (5.5 mmol/mol) among all HbA1c measurements within an individual. The association between HVS and 10 outcomes was assessed using Cox proportional hazards models. RESULTS We included 13,111–19,883 patients in the analyses of each outcome. The patients with HVS >60% were associated with elevated risks of all outcomes compared with the lowest quintile (for example, hazard ratios and 95% CIs [HVS >80 to ≤100 vs. HVS ≥0 to ≤20]: 2.38 [1.61–3.53] for major adverse cardiovascular events, 2.4 [1.72–3.33] for all-cause mortality, 2.4 [1.13–5.11] for atherosclerotic cardiovascular death, 2.63 [1.81–3.84] for coronary artery disease, 2.04 [1.12–3.73] for ischemic stroke, 3.23 [1.76–5.93] for heart failure, 7.4 [3.84–14.27] for diabetic retinopathy, 3.07 [2.23–4.22] for diabetic peripheral neuropathy, 5.24 [2.61–10.49] for diabetic foot ulcer, and 3.49 [2.47–4.95] for new-onset chronic kidney disease). Four sensitivity analyses, including adjustment for time-weighted average HbA1c, confirmed the robustness of the results. CONCLUSIONS Our study shows that higher HbA1c variability is associated with increased risks of all-cause mortality, cardiovascular events, and microvascular complications of diabetes independently of high HbA1c

Case Report Fine needle aspiration cytology of a granular cell tumor arising in the thyroid gland: a case report and review of literature

Abstract: Granular cell tumor (GCT) is an uncommon tumor of soft tissue, and rarely occurs in thyroid. In this article, we report the FNAC results and pathological analysis of a 14-year-old female who presented with a painless mass in the right lobe of thyroid gland. A resection of the right lobe and isthmus of thyroid were applied after cells with abundant strong eosinophilic cytoplasma, indistinct border and inconspicuous nucleolus were found in the FNAC of the mass. Postoperative pathology and immunohistology helped diagnosis the lesion as thyroid GCT. Differential diagnosis from five diseases and cell types were performed and a review of all eleven papers reporting thyroid GCT was provided

The association between GAD1 gene polymorphisms and cerebral palsy in Chinese infants

Studies suggest that GAD1 gene was a functional candidate susceptibility gene for cerebral palsy (CP). In order to investigate the contribution of GAD1 gene to the etiology of CP in Chinese infants, we carried out a case-control association study between GAD1 gene and CP. In this study, 374 health controls and 392 infants with CP were recruited. Genomic DNA was extracted from venous blood and all three single nucleotide polymorphisms in GAD1 (rs3791874, rs3791862 and rs16858977) were genotyped by Sequenom’s MassARRAY system. There were no significant differences in allele or genotype frequencies between CP or mixed CP patients and controls at any of the three genetic polymorphisms. Through haplotype analysis we found that haplotype GG (rs3791862, rs16858977) frequency demonstrated significantly statistical difference between mixed CP patients and controls (p= 0.0371). Our positive findings of haplotype GG suggested that variation of GAD1 gene was an important risk factor for mixed CP.Предполагается, что ген GAD1 является функциональным кандидатом на роль гена подверженности церебральному параличу (ЦП). Для исследования вклада гена GAD1 в этиологию ЦП у китайских детей методом случай – контроль проведено исследование ассоциации между наличием гена GAD1 и ЦП. В исследовании были задействованы 374 здоровых ребенка (контроль) и 392 ребенка с ЦП. Геномную ДНК выделяли из венозной крови, и все три единичных нуклеотидных полиморфизма гена GAD1 (rs3791874, rs3791862 и rs16858977) были генотипированы в системе Sequenom MassARRAY. Ни для одного из трех генетических полиморфизмов не обнаружено существенных различий в частотах аллелей или генотипов между больными ЦП или смешанными больными ЦП и контролем. Анализ гаплотипов показал существенные статистические различия в частоте гаплотипа GG (rs3791862, rs16858977) у смешанных больных ЦП и контрольной группы (p = 0.0371). Позитивный результат по гаплотипу GG свидетельствует о том, что вариация гена GAD1 является важным фактором риска для смешанного ЦП

Circulating tissue factor-positive procoagulant microparticles in patients with type 1 diabetes

Aim: To investigate the count of circulating tissue factor-positive (TF+) procoagulant microparticles (MPs) in patients with type 1 diabetes mellitus (T1DM). Methods: This case-control study included patients with T1DM and age and sex-matched healthy volunteers. The counts of phosphatidylserine-positive (PS+) MPs and TF(+)PS(+)MPs and the subgroups derived from different cell types were measured in the peripheral blood sample of the two groups using multicolor flow cytometric assay. We compared the counts of each MP between groups as well as the ratio of the TF(+)PS(+)MPs and PS(+)MPs (TF(+)PS(+)MPs/PS(+)MPs). Results: We recruited 36 patients with T1DM and 36 matched healthy controls. Compared with healthy volunteers, PS(+)MPs, TF(+)PS(+)MPs and TF(+)PS(+)MPs/PS(+)MPs were elevated in patients with T1DM (PS(+)MPs: 1078.5 +/- 158.08 vs 686.84 +/- 122.04/mu L, P &lt;0.001; TF(+)PS(+)MPs: 202.10 +/- 47.47 vs 108.33 +/- 29.42/mu L, P &lt;0.001; and TF(+)PS(+)MPs/PS(+)MPs: 0.16 +/- 0.04 vs 0.19 +/- 0.05, P = 0.004), mostly derived from platelet, lymphocytes and endothelial cells. In the subgroup analysis, the counts of total and platelet TF(+)PS(+)MPs were increased in patients with diabetic retinopathy (DR) and with higher HbA1c, respectively. Conclusion: Circulating TF(+)PS(+)MPs and those derived from platelet, lymphocytes and endothelial cells were elevated in patients with T1DM.De tre första författarna delar förstaförfattarskapet.</p

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

OBJECTIVE To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. DESIGN Network meta-analysis. DATA SOURCES Medline, EMBASE, and Cochrane Library up to 31 December 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. MAIN OUTCOME MEASURES We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. RESULTS We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. CONCLUSIONS Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk

Glycated Haemoglobin A1c Variability Score Elicits Kidney Function Decline in Chinese People Living with Type 2 Diabetes

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m(2) per year on average; those with HVS > 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m(2) per year on average. Chinese adults with type 2 diabetes and HVS > 60% could experience a more rapid eGFR decline

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes : systematic review and meta-analysis of randomised and observational studies

Objectives To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Eligibility criteria Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Data collection and analysis Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Results Eligible studies included 43 trials (n=68 775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1 777 358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15 701 v 33/12 591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18 554 v 552/18 474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. Conclusions The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use