Immunogenicity and safety of a 2-dose hepatitis B vaccine,HBsAg/CpG 1018, in persons with diabetes mellitus aged 60–70 years

BackgroundHepatitis B virus (HBV) remains a major public health issue, although it is a vaccine-preventable disease. Adults with diabetes are at greater risk of contracting HBV than the general population. Commonly used 3-dose HBV vaccines have reduced immunogenicity in older individuals and in those with diabetes mellitus.MethodsIn this post hoc analysis of a phase 3 clinical trial, participants with type 2 diabetes mellitus aged 60–70 years received either 2-dose HBsAg/CpG 1018 (HEPLISAV-B®, n = 327) at 0 and 4 weeks and placebo at 24 weeks or 3-dose HBsAg/alum (Engerix-B®, n = 153) at 0, 4, and 24 weeks. Immunogenicity, including seroprotection rate (SPR) at week 28, and safety were assessed by subgroup (sex, body mass index, and smoking status). SPR was defined as antibody against hepatitis B surface antigen serum concentration ≥10 mIU/mL.ResultsThe SPR at week 28 was significantly higher with HBsAg/CpG 1018 (85.8% [235/274]) than with HBsAg/alum (58.5% [76/130]) in the per-protocol analysis, for an overall difference of 27.3% (95% CI, 18.0–36.8). SPRs with HBsAg/CpG 1018 were consistently markedly higher compared with HBsAg/alum, regardless of sex, body mass index, or smoking status. Adverse events and deaths were comparable between groups.ConclusionsTwo-dose HBsAg/CpG 1018 provides a higher level of seroprotection against HBV than does a 3-dose vaccine (HBsAg/alum) with a similar safety profile in patients aged 60–70 years with type 2 diabetes mellitus.Study identifier: NCT02117934.     

Cost-benefit analysis of a national influenza vaccination program in preventing hospitalisation costs in Australian adults aged 50–64 years old

IntroductionInfluenza causes a significant burden among Australian adults aged 50–64, however, vaccine coverage rates remain suboptimal. The National Immunisation Program (NIP) currently funds influenza vaccinations in this age group only for those at high risk of influenza complications.AimsThe main aim of this study was to determine whether a strategy of expanding the government-funded vaccination program to all adults 50–64 in preventing influenza-related hospitalisations will be cost beneficial to the government.MethodsA cost-benefit analysis from a governmental perspective was performed using parameters informed by publicly available databases and published literature. Costs included cost of vaccinations and general practitioner consultation while benefits included the savings from averted respiratory and acute myocardial infarction (AMI) hospitalisations.ResultsIn the base-case scenario, the proposed policy would prevent 314 influenza/pneumonia, 388 other respiratory and 1482 AMI hospitalisations in a year. The government would save $8.03 million with an incremental benefit-cost ratio of 1.40. Most savings were due to averted AMI hospitalisations. In alternative scenarios cost savings ranged from saving of $31.4 million to additional cost to the government of $15.4 million, with sensitive variation in vaccine administration practices (through general practitioner or pharmacists) and vaccine effectiveness estimates.DiscussionExtension of the NIP to include adults 50–64 years of age is likely to be cost beneficial to the government, although this finding is sensitive to vaccine administration cost, which varies if provided through general practitioners or pharmacists; and to variation in vaccine effectiveness. An increased role of pharmacists in immunisation programs would likely result in cost savings in an expanded adult immunisation program.     

Current state of biologic pharmacovigilance in the European Union: improvements are needed

Introduction: Pharmacovigilance is essential to monitoring the safety profiles of authorized medicines. Compared with small-molecule drugs, biological drugs are more complex, more susceptible to structural variability due to manufacturing processes, and have the potential to induce immune-related reactions, underscoring the importance of safety monitoring for these products. Although highly similar to reference products, biosimilars are not expected to be structurally identical. For these reasons, proper reporting of potential adverse drug reactions (ADRs) using distinguishable names and batch numbers is essential for accurate tracing of all biological drugs. To address the need for robust pharmacovigilance, the European Parliament and Council of the European Union provided legislation regarding pharmacovigilance of biologics in 2010.

Areas covered: This narrative review examines the current state of pharmacovigilance for biologics in the European Union (EU) and discusses relevant information on pharmacovigilance of biosimilars, the current EU pharmacovigilance system, and areas that could be improved.

Expert opinion: Although steps have been taken to improve pharmacovigilance of biologics in the EU, several enhancements can still be made, including additional training for healthcare professionals on ADR reporting, the use of 2D barcodes that enhance traceability, and an open discussion of potentially missed opportunities in the pharmacovigilance of biosimilars.     

Factors that facilitate reporting of adverse drug reactions by pharmacists in Saudi Arabia

Objectives: Adverse drug reactions (ADRs) are a pervasive global problem, and its management is integral to patient safety and healthcare quality. Pharmacists play a pivotal role in monitoring and reporting ADRs, which has a direct impact on patient care. The aim of this study was to identify potential factors that facilitate pharmacists in community and hospital settings to report ADRs.

Methods: A cross-sectional, online survey using a validated questionnaire was administered to pharmacists working in community and hospital pharmacies in Saudi Arabia.

Results: 1,717 community and 153 hospital pharmacists participated in this study. Only 10.2% and 26.8% of community and hospital pharmacists, respectively, admitted ever reporting an ADR. The most reported factors that may facilitate ADRs reporting have included ongoing improvements in therapeutic knowledge about ADRs, attending educational programs with continuous medical education credits, the seriousness of the experienced ADRs and accessibility to patients’ medical profile. The impact of peers by seeing colleagues reporting ADRs and ADRs due to herbal or traditional medicine were the least important factors reported by pharmacists.

Conclusion: The study identified factors that can effectively address the under-reporting of ADRs by pharmacists. A multi-stakeholder, multi-pronged approach of ADR reporting is needed to develop greater awareness of this issue among pharmacists.     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

某社区2019年第二类疫苗接种疑似预防接种异常反应监测结果

目的了解某社区第二类疫苗接种及疑似预防接种异常反应(AEFI)情况。方法通过查询疫苗出入库系统和中国免疫规划信息管理系统,对2019年该社区第二类疫苗使用及AEFI报告情况进行分析。结果2019年,该社区接种门诊共接种第二类疫苗21种7449剂,接种数最多的是13价肺炎疫苗(784剂)。接种数居前6位的依次为13价肺炎疫苗、ACYW135群流脑多糖疫苗、轮状病毒疫苗、百白破-IPV-HIB五联疫苗、手足口EV71疫苗、九价人乳头瘤疫苗。累计报告AEFI病例94例,发生率为1.26%;一般反应占96.81%,异常反应占3.19%。报告AEFI疫苗共12种,报告发生率居前6位的分别为13价肺炎疫苗、百白破-IPV-HIB五联疫苗、百白破-IPV-HIB四联疫苗、手足口EV71疫苗、九价HPV疫苗、AC结合流脑疫苗。结论第二类疫苗品种接种量均有所增加,AEFI报告发生率有所波动,需加强监测。     

Acute total hip arthroplasty for older patients with acetabular fractures: A meta-analysis

ObjectiveMultiple treatment options for acetabular fractures in geriatric patients exist. However, no large-scale studies have reported the outcomes of acute total hip arthroplasty (THA) in this patient population. We systematically evaluated all available evidence to characterize clinical outcomes, complications, and revisions of acute THA for acetabular fractures in geriatric patients.MethodsMeta-analysis of 21 studies of 430 acetabular fractures with mean follow-up of 44 months (range, 17−97 months). Two independent researchers searched and evaluated the databases of Ovid, Embase, and United States National Library of Medicine using a Boolean search string up to December 2019. Population demographics and complications, including presence of heterotopic ossification (HO), dislocation, infection, revision rate, neurological deficits, and venous thromboembolic event (VTE), were recorded and analyzed.ResultsWeighted mean Harris Hip Score was 83.3 points, and 20% of the patients had reported complications. The most common complication was HO, with a rate of 19.5%. Brooker grade III and IV HO rates were lower at 6.8%. Hip dislocation occurred at a rate of 6.1%, 4.1% of patients developed VTE, deep infection occurred in 3.8%, and neurological complications occurred in 1.9%. Although the revision rate was described in most studies, we were unable to perform a survival analysis because the time to each revision was described in only a few studies. The revision rate was 4.3%.ConclusionsAcute THA is a viable option for treatment of acetabular fracture and can result in acceptable clinical outcomes and survivorship rates in older patients but with an associated complication rate of approximately 20%. Considering the limited treatment options, THA might be a viable alternative for appropriately selected patients.     

Investigating the association of receipt of seasonal influenza vaccine with occurrence of anesthesia/paresthesia and severe headaches,Canada 2012/13–2016/17, the Canadian Vaccine Safety Network

BackgroundConcern about adverse events following immunization is frequently cited by both those who receive or decline vaccines. Neurological adverse events are especially concerning.ObjectivesOur aim was to detect associations between seasonal influenza vaccination and the occurrence of severe anesthesia/paresthesia or severe headaches.MethodsData were analyzed from the Canadian National Vaccine Safety network. Events occuring on days 0–7 were self-reported and prevented daily activity, led to school or work absenteeism, or required medical attention. Controls were the previous year’s vaccinees; events in controls were collected prior to the start of the influenza vaccination program of each year (2012/13 through 2016/17). Multivariable logistic regression was used to determine the association between seasonal influenza vaccination and the occurrence of anesthesia/paresthesia or severe headaches.ResultsThe total sample was 107,565 for investigating anesthesia/paresthesia and 97,420 for investigating severe headaches. Anesthesia/paresthesia was reported by 104/107,565 (0.10%) participants; 63/69,129 (0.09%) vaccinees and 41/38,436 (0.11%) controls (adjusted odds ratio (aOR) = 0.89; 95% CI = 0.60, 1.32). Severe headaches were reported by 1361/97,420 (1.40%) participants; 907/61,463 (1.48%) vaccinees and 454/35,957 (1.26%) controls (aOR = 1.21; 95% CI = 1.08, 1.36). No specific vaccine product was associated with severe headaches.ConclusionsOur study found no association between severe anesthesia/paresthesia and seasonal influenza vaccination. While there was an association with severe headaches as an adverse event following influenza vaccination, the rates of these events are similar to rates reported from clinical trials and are not a cause for additional concern.