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.     

Effect of chlorhexidine digluconate on antimicrobial activity,cell viability and physicochemical properties of three endodontic sealers

ObjectiveAssess the biological and physicochemical properties of AH Plus, BioRoot RCS and Pulp Canal Sealer (PCS) leachates with and without chlorhexidine (CHX).MethodsThe sealers were studied in no contact and 1-minute contact with CHX. For biological properties (antibacterial activity and cytotoxicity), leachates were formed in saline of freshly mixed, 1-, 7- and 28 days set sealers. The antibacterial properties of sealer leachates were investigated for planktonic and biofilm growth of E. faecalis, S. mutans, S.epidermidis and S.aureus. The 3-(4,5 dimethylthiazolyl-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate murine fibroblast cell viability after exposure to the leachates. The physical properties (water uptake, sorption, solubility, porosity, surface characteristics) of sealers and the pH of the immersion liquid (saline or distilled water) were also assessed over a 28-days period.ResultsCHX improved the antibacterial properties of the sealer leachates and reduced cell viability for all sealer leachates, except for freshly mixed PCS. BioRoot RCS leachates presented the highest antibacterial properties and cell viability with and without CHX contact. PCS was the material most affected by CHX in terms of physical properties, whereas for AH Plus, solubility was increased. CHX did not affect the physical properties of BioRoot RCS, except for solubility that was decreased. CHX contact did not change sealers’ alkalinity in distilled water whereas it increased it for AH Plus and BioRoot RCS in saline.SignificanceCHX improved the antibacterial efficacy of sealer leachates and either compromised or did not affect cell viability. CHX affected to various extent sealers’ physicochemical properties.     

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。     

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention

BackgroundPostherpetic neuralgia (PHN) occurs in 5–30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN.MethodsWe conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status.ResultsFrom 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent.ConclusionsOverall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.     

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis

BackgroundSerotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.MethodsWe performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.ResultsTwo published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2–75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed.ConclusionsCurrently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.     

一株海绵共附生真菌Fusarium equiseti SCSIO 41019的次级代谢产物及其抑菌活性研究

目的 研究海绵共附生真菌Fusarium equiseti SCSIO 41019的次级代谢产物及抑菌活性。方法 采用中压硅胶柱色谱、中压反相ODS柱色谱及高效液相色谱等方法对发酵产物进行分离和纯化，运用核磁数据及文献对比的方法鉴定化合物结构。采用滤纸片琼脂扩散法、改良肉汤稀释法评价化合物的抑菌活性。结果 从其大米发酵产物中分离并鉴定了8个化合物，分别为equisetin(1)、5'-epiequisetin(2)、lumichrome(3)、N-乙酰基色胺(4)、亚油酸(5)、methyl (4-hydroxyphenyl) acetate(6)、methyl (2-hydroxyphenyl) acetate(7)和graminin B(8)。化合物1、2和5对金黄色葡萄球菌(Staphylococcus aureus)和耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA)分别具有不同程度的抑制作用，最小抑菌浓度(minimal inhibitory concentration, MIC)为2.0~125μg/mL，其中化合物1的抑菌活性最强(MIC值分别为2.0和3.9μg/mL)。结论 从菌株Fusarium equiseti SCSIO 41019分离得到两个具良好抑菌活性的化合物(1~2)，为将其开发为耐甲氧西林金黄色葡萄球菌的先导化合物提供一定参考。