基于COSMIN指南对癌症患者支持性照护需求量表的系统评价

背景国内外用于评估癌症患者支持性照护需求的量表较多，但有关此类量表质量的标准化评价研究及不同量表间的横向比较研究较为缺乏，也少有研究者对此类量表的测量特性进行系统的整合与评价。目的评价中文版癌症患者支持性照护需求量表的测量学性能及研究的方法学质量。方法2021年4月检索中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库、中国生物医学文献数据库、PubMed、EmBase、Web of Science、CINAHL Complete数据库，获取有关中文版癌症患者支持性照护需求量表测量学性能评价的研究，检索时限均为建库至2021年3月30日。由两位研究者独立筛选文献、提取资料后，采用健康测量工具遴选标准（COSMIN）系统综述指南，在对量表的测量特性及研究的方法学质量进行评价的基础上，综合评定中文版癌症患者支持性照护需求评估量表各测量特性的证据等级，并形成对于量表的最终推荐意见。采用描述分析法对评价结果进行汇总、分析。结果共纳入15项研究，涉及8个中文版癌症患者支持性照护需求评估量表〔癌症患者支持性照护需求简明问卷中文版（SCNS-SF34）、中文版支持性照护需求筛查工具（SCNS-ST9-C）、癌症患者综合需求评估量表（CNAT）、癌症需求简明问卷（CNQ-SF）、中文版癌症患者未满足需求量表（CaSUN-C）、癌症患者未满足需求简明量表（SF-SUNS）、晚期癌症患者需求评估问卷（ACNQ-41）、晚期癌症患者需求评估表简表（ACNQ-29）〕。就量表的测量特性质量而言，除ACNQ-29的内容效度为"未提及"外，其余7个量表的内容效度均为"不确定"；除CaSUN-C、SF-SUNS的结构效度为"充分"外，其余6个量表的结构效度均为"不确定"；SCNS-SF34、CNQ-SF、CaSUN-C、SF-SUNS的内部一致性为"充分"，ACNQ-41的内部一致性为"不充分"，其余3个量表的内部一致性为"不确定"；CNAT、CNQ-SF、ACNQ-29的假设检验为"未提及"，CaSUN-C、SF-SUNS、ACNQ-41的假设检验为"不确定"，SCNS-SF34、SCNS-ST9-C的假设检验为"充分"；除ACNQ-41的稳定性为"不充分"，SCNS-ST9-C、ACNQ-29的稳定性为"未提及"外，其余5个量表的稳定性均为"充分"；仅SCNS-SF34的跨文化效度为"充分"，其余7个量表的跨文化效度均为"未提及"。8个量表的推荐等级均为B级。结论SCNS-SF34的测量特性得到了最为全面的评价，其具有较好的信效度，且临床应用可行性高，可暂时被推荐使用，但上述结论仍有待更多高质量证据加以支撑。     

Immunogenicity of two doses of BNT162b2 and mRNA-1273 vaccines for solid cancer patients on treatment with or without a previous SARS-CoV-2 infection

Previous studies on the immunogenicity of SARS-CoV-2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single-institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA-1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS-CoV-2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty-one cancer patients had a previous exposure to SARS-CoV-2. Cancer patients previously exposed to the virus had significantly higher median levels of anti-S1 and anti-RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti-S1: P < .0001; anti-RBD: P = .0045), comorbidities (anti-S1: P = .0274; anti-RBD: P = .0048) and the use of G-CSF (anti-S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS-CoV-2 significantly enhanced the response to vaccination (anti-S1: P < .0001; anti-RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS-CoV-2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.     

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.     

Home Use Guidance for Aerosol-Generating Procedures During the Coronavirus Disease 2019 Pandemic

From the early days of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were concerns that nebulizers used for the treatment of respiratory diseases as aerosol-generating devices could enhance the transmission of SARS-CoV-2. However, given the absence of any compelling data showing that nebulized treatments increase the risk of SARS-CoV-2 infection, it is unnecessary for community-dwelling patients with respiratory diseases to alter their current therapies, including nebulized treatments, to prevent symptom exacerbations. Maintaining current inhaled therapies also minimizes the risk of hospitalization and hospital-acquired infection of SARS-CoV-2.     

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.     

Dose optimization with population pharmacokinetics of ritonavir-boosted lopinavir for Thai people living with HIV with and without active tuberculosis

BackgroundPrior to dolutegravir availability, ritonavir-boosted lopinavir (LPV/r) was an alternative recommendation when first-line drugs could not be used. A high concentration of protease inhibitors was observed in the Thai people living with HIV (PLWH). Thus, dose reduction of LPV/r may be possible. However, the pharmacokinetics and dose optimization of LPV/r have never been investigated. This study aimed to develop a population pharmacokinetic model of LPV/r and provide dosage optimization in Thai PLWH.MethodsLPV and RTV trough concentrations from Thai PLWH were combined with intensive data. The data were analyzed by the nonlinear mixed-effects modeling approach. The influence of RTV concentration on LPV oral clearance (CL/F) was investigated.ResultsRifampicin (RIF) use increased LPV and RTV CL/F by 2.16-fold and 1.99-fold, respectively. The reduced dose of 300/75 and 200/150 mg twice daily provided a comparable percentage of patients achieving LPV target trough concentration to the standard dose for PI-naïve patients. For HIV/TB co-infected patients receiving RIF who could not tolerate the recommended dose, the reduced dose of 600/150 mg twice daily was recommended.ConclusionThe population pharmacokinetic model was developed by integrating the interaction between LPV and RTV. The reduced LPV/r dosage offers sufficient LPV exposure for Thai PLWH.     

Correlation between cow’s milk protein allergy and otitis media: a systematic review

ObjectivesTo review the evidence pertaining to the association between cow’s milk protein allergy and recurrent acute otitis media and otitis media with effusion.MethodsThe CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched.ResultsFour studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow’s milk protein allergy, 10.7% of cow’s milk protein allergy in 242 children who underwent ENT procedures, 40% of cow’s milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow’s milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p < 0.1).ConclusionConsidering the characteristics and methodological variations of the identified studies, it is not possible to state that there is reliable evidence of an association between cow’s milk protein allergy and otitis media.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.     

信息化随访干预措施对HBV感染患者依从性影响分析

目的通过信息化随访方式干预慢性乙型病毒性肝炎患者,对比分析其对患者疾病及用药依从性影响。方法收集2014年10月至2017年10月惠州市第六人民医院门诊及住院部诊断为慢性乙型病毒性肝炎、乙肝肝硬化患者,剔除不符合纳入条件患者,共纳入符合条件患者264例,有42例合并肝硬化。对纳入患者采取分层随机抽样方法进行分组,最终微信+电话随访组87例,电话随访组88例,对照组89例。随访并对比三组在2年后肝功能、肝硬化人数及停用恩替卡韦时间等不同差异。结果随访年后三组在失访人数上差异存在统计学意义,其中A组与B组2年后两组在ALT(Z=-3.218,P=0.02)、AST(Z=-2.749,P=0.03)、Alb(Z=1.746,P=0.04)、乙肝病毒DNA(Z=-3.231,P=0.02)指标差异具有统计学意义,而TBil、FIB-4指数、APRI、γ-GT指标差异无统计学意义。A组与C组2年后对比结果显示,两组在ALT(Z=-11.089,P<0.001)、AST(Z=-9.247,P=0.01)、TBil(Z=-7.623,P=0.01)、APRI(Z=-4.834,P=0.01)、γ-GT(Z=-2.867,P=0.03)、Alb(Z=3.187,P=0.02)、乙肝病毒DNA(Z=-10.078,P<0.001)指标差异具有统计学意义,而FIB-4指数指标差异无统计学意义。B组与C组2年后两组对比结果显示,两组在ALT(Z=-1.275,P=0.04)、AST(Z=-2.045,P=0.03)、TBil(Z=-3.762,P=0.02)、APRI(Z=-1.461,P=0.04)、γ-GT(Z=-2.254,P=0.03)、乙肝病毒DNA(Z=-1.782,P=0.04)指标差异具有统计学意义,而Alb、FIB-4指数指标差异无统计学意义。随访2年后A组肝硬化人数为12人,B组为16人,C组为24人。A组与B组(χ²=0.945,P=0.408)、B组与C组肝硬化人数(χ²=2.741,P=0.103)差异无统计学意义,而A、C两组肝硬化人数差异有统计学意义(χ²=6.843,P=0.013)。在2年时间内,A组有15例患者暂停使用恩替卡韦,B组有28例,C组有61例,三组停用恩替卡韦人数差异有统计学意义(χ²=25.061,P<0.001),通过Kaplan-meier分析,结果显示A组使用恩替卡韦时间长于B组(83.0%vs 68.5%,χ²=5.754,P=0.016)及C组(83.0%vs 33.7%,χ²=61.601,P<0.001),而B组使用时间长于C组(63.5%vs 33.7%,χ²=32.451,P<0.001)。结论通过对患者强化信息化干预,可以使患者服用抗乙肝病毒药物依从性提高,降低患者肝功能异常发生及肝硬化发病率。