Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system

IntroductionMonoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021.MethodsAccording to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan.ResultsDuring Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12–0.53) and 0.10 (95% CI: 0.01–0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event.ConclusionsThe administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.     

Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Importance of human papillomavirus vaccination leaflets focusing on the safety profile targeted pediatricians in Japan

ObjectivesTo investigate the association between providing leaflets to support pediatricians in explaining the safety of the human papillomavirus (HPV) vaccine and mother’s decision to vaccinate their daughters in Japan.MethodsIn this cross-sectional study, we conducted a survey of mothers to evaluate the effect of leaflets that were created to support pediatricians in explaining the safety profile of the HPV vaccine. Mothers who provided consent for vaccination before receiving an explanation were excluded from the study. The primary outcome was the mother’s decision to vaccinate their daughters with the HPV vaccine after receiving an explanation from pediatricians using our leaflets.ResultsAmong 161 eligible mothers, 101 decided on HPV vaccination (decided group) and 60 did not (decided against group). There was no difference in the maternal background between the 2 groups. The decided group had a significantly more positive impression of the leaflets than the undecided group. In multivariable logistic regression analysis, a detailed explanation for possible adverse events and specific solutions to them was associated with the mother's decision to have their daughters vaccinated (odds ratio 2.35, 95% confidence interval 1.02–5.44), but not the pathology of cervical cancer and the HPV vaccination process.ConclusionLeaflets emphasizing an explanation of adverse events may contribute to mothers’ decision making for HPV vaccination.     

Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.     

滋肾育胎丸加减方预防ACA阳性者不良妊娠结局的效果及机制研究＊

目的 探讨滋肾育胎丸加减方预防抗磷脂抗体（ACA）阳性者不良妊娠结局的效果及机制研究。方法 选取2016年2月至2019年2月我院收治的89例ACA阳性，先兆性流产或有习惯性流产（RSA）史患者，将采用西医治疗的40例作为对照组，将采用西医联合滋肾育胎丸加减方治疗的49例作为观察组，比较两组中医证候疗效、中医证候积分、ACA-IgA、ACA-IgM、ACA-IgG、凝血指标［血小板聚集功能（PAF）、活化蛋白C（PC）、抗凝血酶（AT）、纤溶酶原激活抑制物-1（PAI-1）］、Th1/Th2细胞因子［干扰素γ（IFN-γ）、白介素-2（IL-2）、白介素-4（IL-4）、白介素-10（IL-10）］、妊娠结局、安全性。结果 治疗2周后检测ACA，观察组2例未降低，对照组11例未降低，观察组未降低患者占比低于对照组（P<0.05）；观察组总有效率100.00%高于对照组85.00%（P<0.05）；观察组治疗4周、7周后中医证候积分低于对照组（P<0.05）；观察组治疗4周、7周后ACA-IgA、ACA-IgM、ACA-IgG低于对照组（P<0.05）；观察组治疗4周、7周后PAF、PAI-1低于对照组，PC、AT高于对照组（P<0.05）；观察组治疗4周、7周后IFN-γ、IL-2低于对照组，IL-4、IL-10高于对照组（P<0.05）；观察组活产率95.92%高于对照组80.00%（P<0.05）；组间不良反应总发生率比较，差异无统计学意义（P>0.05）。结论 动态监测ACA对滋肾育胎丸加减方精准应用具有指导意义，指导滋肾育胎丸加减方通过调理脏腑、气血、经络功能，改善先兆性流产或有RSA史患者临床症状及凝血因子指标，降低ACA水平，并可改善患者免疫耐受功能，提高胎儿活产率，且安全性高。