Preventing Adverse Drug Reactions After Hospital Discharge (PADR-AD): Protocol for a randomised-controlled trial in older people

BackgroundAdverse drug reactions (ADRs) and adverse drug events (ADEs) in older people contribute to a significant proportion of hospital admissions and are common following discharge. Effective interventions are therefore required to combat the growing burden of preventable ADRs. The Prediction of Hospitalisation due to Adverse Drug Reactions in Elderly Community Dwelling Patients (PADR-EC) score is a validated risk score developed to assess the risk of ADRs in people aged 65 years and older and has the potential to be utilised as part of an intervention to reduce ADRs.ObjectivesThis trial was designed to investigate the effectiveness of an intervention to reduce ADR incidence in older people and to obtain further information about ADRs and ADEs in the 12–24 months following hospital discharge.MethodsThe study is an open-label randomised-controlled trial to be conducted at the Royal Hobart Hospital, a 500-bed public hospital in Tasmania, Australia. Community-dwelling patients aged 65 years and older with an unplanned overnight admission to a general medical ward will be recruited. Following admission, the PADR-EC ADR score will be calculated by a research pharmacist, with the risk communicated to clinicians and discussed with participants. Following discharge, nominated general practitioners and community pharmacists will receive the risk score and related medication management advice to guide their ongoing care of the patient. Follow-up with participants will occur at 3 and 12 and 18 and 24 months to identify ADRs and ADEs. The primary outcome is moderate-severe ADRs at 12 months post-discharge, and will be analysed using the cumulative incidence proportion, survival analysis and Poisson regression.SummaryIt is hypothesised that the trial will reduce ADRs and ADEs in the intervention population. The study will also provide valuable data on post-discharge ADRs and ADEs up to 24 months post-discharge.     

Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography

BackgroundInflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.MethodsCORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.ResultsThirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55–68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were ?74.9, ?74.2, and ?71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75–1.22, p ?= ?0.71), 1.31 (95% CI: 0.96–1.78, p ?= ?0.09), and 0.98 (95% CI: 0.78–1.22, p ?= ?0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44–1.07), 0.85 (0.56–1.29), and 0.57 (0.41–0.80), respectively.ConclusionsIn patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

童年期不良经历对个体健康影响的研究进展

童年期不良经历(ACEs)作为一项全球性的严峻公共卫生挑战,其对全生命周期的健康影响不容小觑。因此本文从心理健康、生理健康、性传播疾病及危险性行为、健康危险行为4个方面对ACEs的健康影响进行综述,为ACEs及其可能健康结局提供参考。     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

直肠癌新辅助放疗研究进展

在过去的近40年里，直肠癌的治疗方案逐渐标准化。大多数早期直肠癌患者仅通过手术即可得到充分的治疗。然而，相当比例的直肠癌患者处于局部进展期，此类患者需要行新辅助治疗。直肠癌的新辅助放射治疗已被证明能有效地降低患者术前肿瘤分期、改善患者生存以及降低直肠癌局部复发率等，随之而来的是患者放疗后出现的不同程度的放疗不良反应，但随着放射治疗规范化、放射治疗技术及设备的改进，放疗不良反应严重程度在逐渐降低。本文就新辅助放疗中的放疗方案的选择、放射治疗技术、放疗不良反应、放疗后的手术时间以及放疗后的观察与等待等问题的最新研究进展进行了系统性的综述，从而为临床直肠癌新辅助治疗提供有力依据。     

Impact of drug-eluting stent-associated coronary artery spasm on 3-year clinical outcomes: A propensity score matching analysis

BackgroundIt has been reported that significant endothelial dysfunction or clinically evident vasospasm can be associated with drug-eluting stents (DESs). However, the impact of DES associated coronary artery spasm (CAS) on long-term clinical outcomes has not been fully elucidated as compared with those of patients with vasospastic angina.MethodsA total of 2797 consecutive patients without significant coronary artery lesion (<70%), who underwent the Acetylcholine (Ach) provocation test, were enrolled between Nov 2004 and Oct 2010. DES-associated spasm was defined as significant CAS in proximal or distal to previously implanted DES site at follow-up angiography with Ach test. Patients were divided into two groups (DES-CAS; n = 108, CAS; n = 1878). For adjustment, propensity score matching (PSM) was done (C-statistics = 0.766, DES-CAS; n = 102, CAS; n = 102). SPSS 20 (Inc., Chicago, Illinois) was used to analyze this data.ResultsBaseline characteristics were worse in the DES-CAS group. After PSM, both baseline characteristics and the Ach test results were balanced except higher incidence of diffuse CAS and ECG change in the DES-CAS group. During Ach test, the incidence of diffuse spasm (93.1% vs. 81.3%, p = 0.012) and ST-T change (10.7% vs. 1.9%, p = 0.010) were higher in the DES-CAS group. At 3-year, before and after adjustment, the DES-CAS group showed a higher incidence of coronary revascularization (9.8% vs. 0.0%, p = 0.001), recurrent chest pain requiring follow up coronary angiography (CAG, 24.5% vs. 7.8%, p = 0.001) and major adverse cardiac events (MACEs, 9.8% vs. 0.9%, p < 0.005).ConclusionIn this study, DES associated CAS was associated with higher incidence of diffuse spasm, ST-T change and adverse 3-year clinical outcomes. Special caution should be exercised in this particular subset of patients.