Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

The role of National Immunization Technical Advisory Groups (NITAG) in strengthening health system governance: Lessons from three middle-income countries—Argentina,Jordan, and South Africa (2017–2018)

IntroductionToward the Global Vaccine Action Plan 2020 goal, almost 90% of countries have established a National Immunization Technical Advisory Group (NITAG). However, little is known about NITAG's contributions to governance.MethodsIn 2017–2018, a two-step, qualitative retrospective study was conducted. Jordan (JO), Argentina (AR), and South Africa (SA) were selected owing to government-financed NITAGs from middle-income countries (MICs), geographic diversity, and a vaccine introduction with NITAG support. Country case studies were developed, collecting data through desk review and face-to-face key informant interviews (KIIs) from Ministry of Health (MoH) and NITAG. Case studies were analyzed together, to assess governance applying the European Observatory on Health Systems and Policies framework focusing on transparency, accountability, participation, integrity, and policy capacity (TAPIC).ResultsDocument review and 53 KII (22 AR, 20 SA, 11 JO) showed NITAGs played a pivotal role as advisors promoting a culture of evidence-informed policies. NITAGs strengthened governance, although practices varied among countries. Meetings were conducted behind-closed-doors, participation restricted to members, only in one country agendas, and recommendations were public (AR). To increase participation, policy capacity, and transparency, countries considered adding experts in communications, advocacy, and economics. AR and SA contemplated including community members. NITAGs functioned autonomously from the government, with no established internal or external monitoring or supervision. NITAG meeting minutes allowed the review of integrity, adherence to terms of reference, standard operating procedures, and conflict of interest (CoI). For the most part, NITAGs abided by their mandates. Significant issues were related to the level of MoH support and oversight of CoI declaration and documentation.ConclusionsSystematically implementing governance approaches could improve processes, better tailor policies, and implementation. The long-term survival and resilience of NITAGs in these countries showed they play a significant role in strengthening governance. Lessons learned could be useful to those promoting country-driven evidence-informed decision-making.     

Nerve ultrasound reference data in children from two to seven years

ObjectiveWe examined selected peripheral and spinal nerves of children aged between two and seven years.MethodHigh resolution ultrasound was performed in 116 children (2–7 years of age) at 19 predefined landmarks of median, ulnar, tibial, fibular, sural and radial nerves, the vagus as well as cervical spinal nerve 5 and 6. Further, side-to-side measuring and grey-scale analysis was done at selected nerve sites.ResultsNerves of children were on average smaller than those of adults. Nerve growth correlates significantly with age in all nerves, the mean values were similar in the age of two to four years and five to seven years. Body mass index (BMI) and gender showed moderate effect at some nerve sites, however not uniformly in all. A side-to-side difference of up to 30% in median, and up to 20% in tibial nerve can occur in healthy individuals. Grey-scale analysis for echointensity has been performed in median, ulnar and tibial nerves.ConclusionNerve size increases with age, BMI and gender have moderate effect. A side-to-side-difference of up to 30% can exist.SignificanceReference values of nerve cross-sectional area, side-to-side-difference and echo intensity are necessary to detect nerve pathology in children as well as in adults.     

Easy Words: Reference Resolution in a Malevolent Referent World

This article describes early stages in the acquisition of a first vocabulary by infants and young children. It distinguishes two major stages, the first of which operates by a stand‐alone word‐to‐world pairing procedure and the second of which, using the evidence so acquired, builds a domain‐specific syntax‐sensitive structure‐to‐world pairing procedure. As we show, the first stage of learning is slow, restricted in character, and to some extent errorful, whereas the second procedure is determinative, rapid, and essentially errorless. Our central claim here is that the early, referentially based learning procedure succeeds at all because it is reined in by attention‐focusing properties of word‐to‐world timing and related indicants of referential intent.     

对血清蛋白白球比值参考范围的修改及其临床应用

目的探讨血清蛋白白球比值(A／G)的参考范围和A／G在计算过程中产生的误差对临床应用的影响。方法①选取健康查体人员统计其A／G参考范围；②从理论上分析A／G计算误差的存在。结果①以统计结果的2s置信区间作为A／G的参考范围是1.1～2.2；②A／G计算值的误差会远大于相应总蛋白和白蛋白的测定误差。结论A／G较合适的参考范围为1.1～2.2,并且在临床应用中仍可根据实际情况降低其范围的下限。     

Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases. Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis. Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients; metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous and metachronous cases. Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases. Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining candidates for surgery and in selecting surgical procedure.     

Hygiene in Operationsabteilungen – Empfehlungen des Nationalen Referenzzentrums für Krankenhaushygiene

Zusammenfassung. Viele Hygienema?nahmen in Operationsabteilungen sind durch wissenschaftliche Untersuchungen nicht belegt. Die in dieser Arbeit vom Nationalen Referenzzentrum für Krankenhaushygiene, das 1996 vom Bundesgesundheitsministerium eingerichtet wurde, zusammengestellten Empfehlungen stützen sich auf die Ergebnisse wissenschaftlicher Untersuchungen und trennen so die unbedingt notwendigen von den weniger bzw. nicht sinnvollen Ma?nahmen.

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Summary. Many hygienic procedures performed in operation units are not supported by scientific investigations. The following recommendations by the National Reference Center for Hospital Epidemiology, founded by the German Ministry of Health in 1996, are based on the scientific literature and separate necessary from less necessary and unnecessary procedures.

     

Myocardial sestamibi single-photon emission tomography: Variations in reference values with gender, age and rest versus stress?

Reference data files support the evaluation of myocardial perfusion single-photon emission tomography (SPET). The aim of this study was to create a large reference data base for technetium-99m sestamibi SPET, age and gender matched to the general patient population. One hundred and twenty-eight healthy volunteers (76 males and 52 females) with a likelihood of coronary artery disease of less than 5% underwent rest and maximal exercise^99mTc-sestamibi SPET with a 2-day protocol and 180° elliptical rotation. The normalized activity values of^99mTc-sestamibi in the inferior wall differed significantly between men and women. Age variations were found for men in the anterior wall. Normalized activity values in all four walls were strikingly similar during rest and stress. Our results suggest that the use of reference files in^99mTc-sestamibi SPET requires a gender- and, for males, possibly an age-matched reference population. Different reference files at rest and during stress might not be necessary.