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.     

Involvement of Patients and Medical Professionals in the Assessment of Relative Effectiveness: A Need for Closer Cooperation

ObjectivesInvolvement of patients and medical professionals in assessment of relative effectiveness (relative effectiveness assessment) contributes to an efficient and effective health technology assessment (HTA) process and supports acceptance and implementation of the outcome. This study aimed to analyze stakeholder involvement in assessing relative effectiveness and how the parties involved value this collaboration.MethodsThis is a document analysis of all drug assessments completed in 2019 (20) by the public HTA agency of The Netherlands, enriched with semistructured interviews with employees of the HTA agency (18) and representatives of patient (5) and medical (11) associations involved in these assessments. Data were analyzed, coded, and categorized.ResultsIn almost half of the assessments, there was no coordination with the medical associations at the start of the relative effectiveness assessment and no patient associations involved in this phase. During the assessment procedure, patient and medical associations were always asked to comment on the draft report. Nevertheless, the strict 5-day deadline that the HTA agency uses as a response period often hampered a proper response and involvement. According to interviewees of the HTA agency, this leads to a great diversity in the substantive quality of their input. Patient and medical associations indicated that the HTA agency relies too much on “paper knowledge,” which leads to a (perceived) lack of alignment with clinical practice.ConclusionsThe limited involvement results in a lack of coordination and mutual trust. Optimizing involvement of patients and medical professionals in HTA practice requires effort from all parties involved. Procedural adjustments and better coordination, especially at the start of the assessment, would probably improve cooperation.     

Vaccine effectiveness against onward transmission of SARS-CoV2-infection by variant of concern and time since vaccination,Belgian contact tracing, 2021

BackgroundDuring the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-‘variant of concern’ (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment.MethodsWe estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event.FindingsVET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0–50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72–64%) and especially of VEi (71–46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150–200 days after vaccination). We observed lower initial VEi in the age group 65–84 years (32% vs 46% in the age group 45–64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity.InterpretationVEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.     

昆虫抗菌肽抗炎活性及基于信号通路抗炎机制的研究进展

昆虫抗菌肽是昆虫为抵御外界病原微生物感染产生的免疫活性物质的总称,其优异的抗炎活性使其具有广阔的应用前景。综述了不同种类昆虫抗菌肽的抗炎活性及可能涉及的信号通路,介绍了昆虫抗菌肽临床研究现状,以期为昆虫抗菌肽的应用研究提供文献参考。     

氢氧化钙糊剂与根管内感染控制

感染控制对根管治疗的成功至关重要。尽管随着器械及设备的进步，对根管的清理及成形取得了很大的进展；然而，由于根管系统解剖结构错综复杂，使得获取清洁根管面临各种问题。例如：机械预备的宽度有限，不能彻底清理感染牙本质；冲洗技术的运用虽然可以去除根管器械预备后形成的玷污层，但对细菌内毒素的清除还是难以达到理想的效果，而残留的微生物、毒素等若得不到清除可能会在根尖周组织形成持续感染。因此，除外机械预备和冲洗，根管封药也是感染根管治疗过程中的重要步骤。氢氧化钙糊剂以其高效的抗菌作用在临床得到广泛使用。文章将对根管封药的必要性、氢氧化钙的作用机制及临床应用做一介绍。     

全腹腔镜、腹腔镜辅助与开腹胃癌根治术治疗Ⅱ、Ⅲ期胃癌的疗效对比

目的探讨全腹腔镜胃癌根治术（TLG）、腹腔镜辅助胃癌根治术（LAG）与传统开腹术（TOS）对Ⅱ、Ⅲ期胃癌的近期及远期疗效。 方法回顾性分析2013年1月至2016年6月陕西中医药大学附属医院行胃癌根治术的患者共136例，根据患者手术方式的不同分为TLG组（45例），LAG组（40例），TOS组（51例）。观察和比较3组患者手术时间、出血量、淋巴结清扫数、术后排气时间、住院时间、术后并发症发生情况，采用Kaplan-Meier法对患者术后5年远期疗效进行生存分析。 结果TLG组患者出血量、排气时间及住院时间低于TOS组及LAG组，LAG组患者手术时间高于TLG组及TOS组，差异均有统计学意义（P<0.05）；3组患者术后并发症发生率比较，差异无统计学意义。共129例获得随访，其中TLG组失访2例，LAG组2例，TOS组3例。TLG、LAG、TOS组平均无瘤生存时间为（53.4±2.1）个月（95%CI=50.45~58.22个月）、（54.3±2.0）个月（95%CI= 47.99~56.18个月）、（52.3±2.1）个月（95%CI=50.98~55.65个月），3组患者无瘤生存时间比较，差异无统计学意义（F=0.519，P=0.772）。 结论TLG术能够在保证患者术后疗效的同时，降低患者术中出血量、排气时间及术后住院时间，TLG术治疗Ⅱ、Ⅲ期胃癌安全可行，疗效显著，值得推广。     

Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.