Active surveillance of vaccine safety: a system to detect early signs of adverse events

BACKGROUND: There currently are no population-based systems in the United States to rapidly detect adverse events after newly introduced vaccines. To evaluate the feasibility of developing such systems, we used 5 years of data from 4 health maintenance organizations within the Centers for Disease Control and Prevention (CDC) Vaccine Safety Datalink. METHODS: Within every year, each week's vaccinated children were followed for 4 weeks, and rates of adverse events were compared with rates among children of similar ages before the introduction of the new vaccine. We assessed risks for intussusception after rotavirus vaccination and risks for fever, seizures, and other neurologic adverse events after the change from whole cell diphtheria-tetanus-pertussis (DTPw) to acellular DTP vaccine (DTPa). We used sequential probability ratio testing, adjusted for age, sex, calendar time, season, and HMO, and with a stopping value based on the probability of an adverse event under the null hypothesis and under a preset alternative hypothesis. RESULTS: We detected an increase in intussusception after 2589 vaccine doses of rotavirus vaccine, about the same time initial reports of intussusception were made to the Vaccine Adverse Events Reporting System. Decreases in risk for fever, seizures, and other abnormal neurologic events became detectable within 12 weeks, 42 weeks, and 18 months, respectively, after the change from DTPw to DTPa. CONCLUSIONS: We conclude that it is feasible to develop systems for rapid and routine population-based assessments of new vaccine safety.     

Embedding surveillance into clinical care to detect serious adverse events in pregnancy

Severe maternal complications in pregnancy in sub-Saharan Africa contribute to high maternal mortality and morbidity. Incidence data on severe maternal complications, life-threatening conditions, maternal deaths and birth outcomes are essential for clinical audit and to inform trial design of the types and frequency of expected severe adverse events (SAEs). However, such data are very limited, especially in sub-Saharan Africa. We set up standardized, systematic clinical surveillance embedded into routine clinical care in a rural county hospital in Kenya. Pregnant women and newborns are systematically assessed and investigated. Data are reported using a standardized Maternal Admission Record that forms both the hospital's clinical record and the data collection tool. Integrating clinical surveillance with routine clinical care is feasible and should be expanded in sub-Saharan Africa, both for improving clinical practice and as a basis for intervention studies to reduce maternal and newborn mortality and morbidity where rates are highest.     

Same-day administration of depot-medroxyprogesterone acetate injection: a retrospective chart review

A chart review of clients administered depot-medroxyprogesterone acetate (DMPA) injection in September of 2000 was performed to assess implementation of a same-day injection administration protocol irregardless of menstrual cycle day. Women were classified into one of the three categories: (1) routine injection (injection given as specified by the package label), (2) same-day start injection (no injection for more than 6 months, did not meet labeled criteria for administration and received an injection the day of the visit) or (3) same-day restart injection (injection given within 6 months prior to receiving an injection at the visit despite being late for their injection). Of the 228 women receiving an injection, 104 (46%) had a nonroutine same-day injection, meaning almost half of the women receiving a contraceptive injection would have had to return for another visit if this protocol had not been in place. Among these women administered a same-day injection, 23 (22%) were also dispensed emergency contraception. Only 1 of the 104 women was subsequently identified to have become pregnant. Other pregnancies are presented to illustrate the importance of adherence to pregnancy testing at the time of injection and revisit, and the need for backup contraception. Using a same-day injection protocol, women can have increased access to injection contraception, and proper adherence to a protocol can assure few pregnancies.     

Acupuncture-related adverse events: a systematic review of the Chinese literature

Objective

To systematically review the Chinese-language literature on acupuncture-related adverse events.

Methods

We searched three Chinese databases (the Chinese Biomedical Literature Database, 1980–2009; the Chinese Journal Full-Text Database, 1980–2009; and the Weipu Journal Database, 1989–2009) to identify Chinese-language articles about the safety of traditional needle acupuncture. Case reports, case series, surveys and other observational studies were included if they reported factual data, but review articles, translations and clinical trials were excluded.

Findings

The inclusion criteria were met by 115 articles (98 case reports and 17 case series) that in total reported on 479 cases of adverse events after acupuncture. Fourteen patients died. Acupuncture-related adverse events were classified into three categories: traumatic, infectious and “other”. The most frequent adverse events were pneumothorax, fainting, subarachnoid haemorrhage and infection, while the most serious ones were cardiovascular injuries, subarachnoid haemorrhage, pneumothorax and recurrent cerebral haemorrhage.

Conclusion

Many acupuncture-related adverse events, most of them owing to improper technique, have been described in the published Chinese literature. Efforts should be made to find effective ways of monitoring and minimizing the risks related to acupuncture.     

Case record review of adverse events: a new approach

Objectives: To redesign the existing clinical review form (RF2) used in previous retrospective case record review studies in order to clarify the review process and provide a more powerful analysis of adverse events; and then to ask clinicians to pilot and evaluate the new modular review form (MRF2). The review form is divided into five sections, each with a defined purpose, providing a modular structure.

Design: Design and testing of the MRF2 on a sample of medical and nursing records, and evaluation of the reviewers' responses regarding the new review form.

Setting: Hospital based teams from eight countries.

Results: The modular review form was reported to be comprehensive, well structured, and clear. Most of the reviewers agreed with the positive statements regarding the review form. Overall, the modular structure was thought to be helpful. Several modifications have been made to the final version to take account of criticisms and suggestions.

Conclusions: The full potential of case record review has yet to be explored. The benefits of this review form include a modular format which enables reviewers or project leaders to select the focus of their review based on resources and the purpose of the review, and to identify contributory factors which indicate areas for improvement and prevention. The training of reviewers is of vital importance for record review. Record review remains one of the primary methods for assessing the incidence of adverse events and the new format is suitable for both prospective and retrospective review.

     

No-fault compensation following adverse events attributed to vaccination: a review of international programmes

Programmes that provide no-fault compensation for an adverse event following vaccination have been implemented in 19 countries worldwide, the first in Germany in 1961 and the most recent in Hungary in 2005. We performed a review of these programmes and determined elements that were common to all of them: administration and funding, eligibility, process and decision-making, standard of proof, elements of compensation and litigation rights. Most programmes were administered by state or national governments except in Finland and Sweden where they are coordinated by pharmaceutical manufacturers. Although funding is usually from Treasury, Taiwan (China) and the United States of America impose a tax on vaccine doses distributed. Decisions on compensation are made using established criteria or assessed on a case-by-case basis, while the standard of proof required is usually less than that required for court cases. Benefits provided by programmes include medical costs, disability pensions and benefits for noneconomic loss and death. Most countries allow claimants to seek legal damages through the courts or a compensation scheme payout but not both. We conclude that a variety of programmes, based on ethical principles, have been successful and financially viable in developed countries throughout the world. We believe there is a strong argument for widespread implementation of these programmes in other developed countries.     

Computers and clinical judgment: the role of physician networks

In order to study the relationship between physician networks and utilization of a computer-based hospital information system (HIS), blockmodel analysis and multidimensional scaling were used to analyze and spatially represent the network of professional relations among 24 physicians in a private group practice. A blockmodel analysis of patient referrals, consultations, discussions, and on-call coverage identified four groups of physicians who share common locations and perform similar roles within the network. Investigation of the shared attributes of these groups supports this relational structure. The results suggest that the center-periphery model of diffusion of new ideas among professionals may be too simplistic. Instead, the communication network may involve multiple central cohesive subgroups of physicians who differentially initiate patient referrals and consultations with physicians in other subgroups. Network location was found to have a significant effect on the adoption and utilization of the HIS independently of background and practice characteristics of physicians. The results also suggest that adoption of an innovation and its implementation or utilization may involve separate processes that need to be differentiated in future research.     

Emergency department utilization among deaf and hard-of-hearing patients: A retrospective chart review

BackgroundDeaf and hard-of-hearing (DHH) patients are an underserved priority population. Existing, although contextually limited, findings indicate that DHH patients are more likely to use the emergency department (ED) than non-DHH patients. However, little attention has been given to the differences in ED utilization by patients’ language modalities.ObjectiveWe hypothesized that DHH ASL-users and DHH English speakers would have higher rates of ED utilization in the past 36 months than non-DHH English speakers.MethodsWe used a retrospective chart review design using data from a large academic medical center in the southeastern United States. In total, 277 DHH ASL-users, 1000 DHH English speakers, and 1000 non-DHH English speakers were included. We used logistic regression and zero-inflated modeling to assess relations between patient segment and ED utilization in the past 12- and 36-months. We describe primary ED visit diagnosis codes using AHRQ Clinical Classifications Software.ResultsDHH ASL users and DHH English speakers had higher adjusted odds ratios of using the ED in the past 36-months than non-DHH English speakers (aORs = 1.790 and 1.644, respectively). Both DHH ASL users and DHH English speakers had a higher frequency of ED visits among patients who used the ED in the past 36-months (61.0% and 70.1%, respectively). The most common principal diagnosis code was for abdominal pain, with DHH English speakers making up over half of all abdominal pain encounters.ConclusionsDHH ASL users and DHH English speakers are at higher risk of using the ED compared to non-DHH English speakers. We call for additional attention on DHH patients in health services and ED utilization research.     

Annual trends in adverse events following mumps vaccination in Japan: A retrospective study

BackgroundIn Japan, a monovalent mumps vaccine is provided on a voluntary basis. Due to public concerns over post-vaccination aseptic meningitis, the vaccination coverage is not high enough. The present study investigated the incidence of adverse events, including aseptic meningitis, after Torii strain–derived mumps vaccination.MethodsThis retrospective, observational study used data collected by a vaccine manufacturer regarding adverse events following mumps vaccinations at medical institutions between 1992 and 2018. In addition, the number of Torii strain–derived mumps vaccines shipped each year was obtained. The incidence (per 100,000 doses) and 95% confidence intervals (CIs) were calculated for all adverse events and each adverse event, categorized as aseptic meningitis, encephalitis, mumps, mumps complications, and others.ResultsDuring the study period, 8,262,121 mumps vaccine doses were shipped, and 688 subjects reported adverse events. The incidence for all adverse events (per 100,000 doses) was 8.33, and the incidence was 4.19 for aseptic meningitis, 0.33 for encephalitis, 0.80 for mumps, 0.25 for mumps complications, and 3.78 for others. The incidence of aseptic meningitis (per 100,000 doses) was 7.90 (95% CI: 5.61–10.18) between 1998 and 2000 but declined by half, to 3.91 (2.46–5.36), between 2001 and 2003. The most recent incidence (per 100,000 doses) of aseptic meningitis, for the period 2016 to 2018, was 2.78 (1.94–3.62).ConclusionThe incidence of post-vaccination aseptic meningitis has declined significantly since 2001, and the incidence has remained stable at fewer than 3 cases per 100,000 doses since 2010. Multiple factors might have contributed to the decline in aseptic meningitis incidence, including (i) lowered misclassification of aseptic meningitis resulting from echovirus infection; (ii) changes in the vaccine manufacturing process in 2000; and (iii) publication in 2008 of the recommendation for vaccination of children at 1 year of age.     

Frequency and characteristics associated with opportunistic salpingectomy at cesarean delivery: A retrospective chart review

ObjectivesTo identify the frequency and characteristics associated with total salpingectomy (TS) versus occlusion or partial salpingectomy (PS) at the time of cesarean delivery.Study designWe performed a retrospective chart review of cesarean deliveries with a concurrent permanent contraception procedure, from July 1, 2014 to June 30, 2019 at 2 hospitals (community hospital and tertiary care academic center) within a single healthcare system. We assessed the proportion of TS versus PS at cesarean, and secondarily compared operative times between the 2 procedures.ResultsWe identified 2110 procedures during the 5-year period. Surgeons performed TS in 302 (14%, 95% confidence interval [CI] 13%–16%) cases, and the annual rate varied from 14% to 18% over the study period (p = 0.14). Factors associated with increased likelihood of TS rather than PS included public insurance/self-pay (adjusted odds ratio, aOR 2.8, 95% CI 2.0–4.1), delivery at the community hospital (aOR 4.8, 95% CI 3.0–7.7), parity of 5 or more (aOR 2.2, 95% CI 1.1–4.4), and presence of an obstetrician/gynecologist for cesarean delivery (aOR 2.9, 95% CI 1.6–5.4). The total operative time for TS and PS differed at the academic center (90 vs 68 minutes, p < 0.001) but not at the community hospital (55 vs 54 minutes, p = 0.5).ConclusionsThis study highlights provider and institutional characteristics associated with TS compared to PS at the time of cesarean delivery, which may inform future programs aimed at increasing utilization of TS at cesarean delivery.ImplicationsAccess to TS at the time of cesarean delivery may provide pregnant women with a very effective permanent contraception method at a convenient time of concurrent cesarean. This study identifies patient factors that may influence access to TS as part of obstetrical care.     

A super-combo-drug test to detect adverse drug events and drug interactions from electronic health records in the era of polypharmacy

Pharmacoinformatics research has experienced a great deal of successes in detecting drug-induced adverse events (AEs) using large-scale health record databases. In the era of polypharmacy, pharmacoinformatics faces many new challenges, and two significant challenges are to detect high-order drug interactions and to handle strongly correlated drugs. In this article, we propose a super-combo-drug test (SupCD-T) to address the aforementioned two challenges. SupCD-T detects drug interactions by identifying optimal drug combinations with increased AE risks. In addition, SupCD-T increases the statistical powers to detect single-drug effects by combining strongly correlated drugs. Although SupCD-T does not distinguish single-drug effects from their combination effects, it is noticeably more powerful in selecting an individual drug effect in the multiple regression analysis, where confounding justification between two correlated drugs reduces the power in testing the individual drug effects on AEs. Our simulation studies demonstrate that SupCD-T has generally better power comparing with the multiple regression analysis. In addition, SupCD-T is able to select meaningful drug combinations (eg, highly coprescribed drugs). Using electronic health record database, we illustrate the utility of SupCD-T and discover a number of drug combinations that have increased risk in myopathy. Some novel drug combinations have not yet been investigated and reported in the pharmacology research.     

Safety and immunogenicity of HepB-CpG in women with documented pregnancies post-vaccination: A retrospective chart review

BackgroundThere are currently no published data on the use of HepB-CpG (HEPLISAV-B®) during pregnancy or in women with documented pregnancies in the post-vaccination period. We aimed to evaluate data from the clinical development program of HepB-CpG in women who became pregnant during study participation and follow up.MethodsWe identified all study participants in the HepB-CpG pivotal pre-licensure clinical trials that had documented pregnancies during study follow up. We measured immunogenicity among study participants in the HepB-CpG (Heplisav-B®) arm compared to the HepB-alum (Engerix-B®) arm of the studies by comparing seroprotection rates (SPRs; anti-HBs ≥ 10 mIU/mL) and geometric mean concentrations (GMCs) of anti-HBs, obtained with FDA approved anti-HBsAg antibody assays at prespecified time points up to 28 weeks of follow up. Pregnancy outcomes were ascertained by chart review of extracted medical records of study participants.ResultsWe identified 40 documented pregnancies in the HepB-CpG arm and 19 documented pregnancies in the HepB-alum arm. Among subjects with documentation of seroprotection rates, 97.2% (95% CI 85.5–99.9) were seroprotected in the HepB-CpG arm and 66.7% (95% CI 41.0–86.7) were seroprotected in the HepB-alum arm. In the HepB-CpG arm, thirty-six study participants from the pivotal trials had reported pregnancy outcomes, the majority, 21/36 (58%) had a healthy term delivery, with 3/36 (8%) with spontaneous abortions, 1/36 (3%) congenital anomaly, and 2/36 (6%) had preterm birth. In the HepB-alum arm, 10/17 (59%) had healthy term deliveries, with 2/17 (12%) had spontaneous abortions and 1/17 (6%) had congenital anomaly.ConclusionsThese limited data suggest that HepB-CpG is immunogenic in women who become pregnant after vaccination, and pregnancy outcomes appear to be similar to women who received HepB-alum prior to pregnancy. These results need to be further verified with larger prospective studies with HBV vaccine administration during pregnancy.     

The vaccine data link in Nha Trang,Vietnam: a progress report on the implementation of a database to detect adverse events related to vaccinations

Real, perceived and unknown adverse events secondary to vaccinations are a source of concern for care providers of children. In the USA large linked databases have provided helpful information regarding the safety of vaccines. Very little prospectively collected data on vaccine safety is available from resource poor countries, but safety concerns may be even more relevant in such settings. Vaccine manufacturers do not have to pass the same rigorous safety standards as vaccine manufacturers in rich countries. Vaccines, which protect against cholera, Japanese encephalitis, rabies or typhoid fever are predominantly used in resource poor, tropical countries and frequently do not undergo vigorous post marketing surveillance. New vaccines specifically suited for resource poor countries are sometimes marketed without the scrutiny of vigilant, independent regulatory authorities.We describe here the design and implementation of a large linked database for a semi-rural province in central Vietnam. The design overcomes several problems inherent in data bases of medical events and vaccinations in developing countries. Assigning a permanent identification (ID) number to each resident avoids the ambiguities of ID numbers based on the address. The distribution and use of medical identification cards with a permanent ID number assists in the unambiguous identification of vaccinees and patients. Medical records of all admissions are coded according to International Classification of Diseases (ICD-10) and transcribed into a computer system. Because these processes are novel the data collected by the study will be validated. Project staff will check records on vaccinations and hospital admissions through household visits at regular intervals. Data describing vaccinations and medical events are linked to the data collected by the project staff in a computer system. Based on the validation of the data we hope to optimize this model. Once we find the model working it is planned export this vaccine data safety link to other settings of similar economic status.     

医疗器械不良事件的防范

分析了医疗器械产品从研发、生产、流通到应用各阶段存在的风险因素,提出了相应的风险防范措施。