Birth prevalence of achondroplasia: A systematic literature review and meta-analysis.

Achondroplasia is a genetic disorder that results in disproportionate short stature. The true prevalence of achondroplasia is unknown as estimates vary widely. This systematic literature review and meta-analysis was conducted to better estimate worldwide achondroplasia birth prevalence. PubMed, Embase, Scielo, and Google Scholar were searched, complemented by manual searching, for peer-reviewed articles published between 1950 and 2019. Eligible articles were identified by two independent researchers using predefined selection criteria. Birth prevalence estimates were extracted for analysis, and the quality of evidence was assessed. A meta-analysis using a quality effects approach based on the inverse variance fixed effect model was conducted. The search identified 955 unique articles, of which 52 were eligible and included. Based on the meta-analysis, the worldwide birth prevalence of achondroplasia was estimated to be 4.6 per 100,000. Substantial regional variation was observed with a considerably higher birth prevalence reported in North Africa and the Middle East compared to other regions, particularly Europe and the Americas. Higher birth prevalence was also reported in specialized care settings. Significant heterogeneity (Higgins I2 of 84.3) was present and some indication of publication bias was detected, based on visual asymmetry of the Doi plot with a Furuya-Kanamori index of 2.73. Analysis of pooled data from the current literature yields a worldwide achondroplasia birth prevalence of approximately 4.6 per 100,000, with considerable regional variation. Careful interpretation of these findings is advised as included studies are of broadly varying methodological quality.

Importance of feasibility assessments before implementing non-interventional pharmacoepidemiologic studies of vaccines: lessons learned and recommendations for future studies.

PURPOSE: Investigational and marketed vaccines are increasingly evaluated, and manufacturers are required to put in place mechanisms to monitor long-term benefit-risk profiles. However, generating such evidence in real-world settings remains challenging, especially when rare adverse events are assessed. Planning of an appropriate study design is key to conducting a valid study. The aim of this paper is to illustrate how feasibility assessments support the generation of robust pharmacoepidemiological data. METHODS: Following an initiative launched by the International Society for Pharmacoepidemiology in May 2014, a working group including members of the private and public sectors, was formed to assess the value of conducting feasibility assessments as a necessary step before embarking on larger-scale post-licensure studies. Based on five real-life examples of feasibility assessments, lessons learned and recommendations were issued by the working group to support scientific reasoning and decision making when designing pharmacoepidemiologic vaccine studies. RESULTS: The working group developed a toolbox to provide a pragmatic approach to conducting feasibility assessments. The toolbox contains two main components: the scientific feasibility and the operational feasibility. Both components comprise a series of specific questions aimed at overcoming methodological and operational challenges. CONCLUSIONS: A feasibility assessment should be formalized as a necessary step prior to the actual start of any pharmacoepidemiologic study. It should remain a technical evaluation and not a hypothesis testing. The feasibility assessment report may facilitate communication with regulatory agencies toward improving the quality of study protocols and supporting the endorsement of study objectives and methods addressing regulatory commitments. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Clinical Profile and Treatment in Hypereosinophilic Syndrome Variants: A Pragmatic Review.

BACKGROUND: Hypereosinophilic syndrome (HES) is a group of rare hematologic disorders leading to eosinophil-driven tissue damage and dysfunction. Better understanding of HES variants may facilitate improved patient management. OBJECTIVE: To describe disease characteristics, treatment, and outcomes of patients with idiopathic (I-HES), myeloproliferative (M-HES), lymphocytic (L-HES), and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) among HES case reports and aggregate data where available. METHODS: Relevant articles published between January 1, 2000, and March 20, 2020, were retrieved via PubMed; those reporting secondary, associated/reactive, overlap/single-organ, or familial HES were excluded. RESULTS: Of 188 articles included, 171 contained data on 347 separate HES cases (152 I-HES, 121 M-HES, 62 L-HES, 12 CEL-NOS). Based on individual data, mean age at diagnosis was 43 to 48 years for patients with all HES variants. Males accounted for 90% to 91% of M-HES/CEL-NOS and 55% to 65% of I-HES/L-HES cases. Cardiac symptoms were frequently observed for all HES variants (13%-22% of patients). Respiratory symptoms (I-HES), splenomegaly (M-HES and CEL-NOS), and skin conditions (L-HES) were also frequently observed. Bone marrow, heart, lung, spleen, liver, skin, and lymph nodes were commonly involved. Most patients with I-HES, L-HES, and CEL-NOS received corticosteroids (65%-85%), whereas most with M-HES received imatinib (81%); those with CEL-NOS also received interferon alpha (42%). CONCLUSIONS: Collective analysis of HES case reports supports and extends current understanding of HES variants, highlighting differences in signs and symptoms, organ involvement, and treatment approaches. Improved characterization of HES variants may facilitate the development of novel treatments.

The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey.

BACKGROUND: Varicella is a common childhood disease. Only 5% of first varicella-zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system. METHODS: An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses. RESULTS: The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X2 ; p = 0.964) between children with a recent (≤ 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode. CONCLUSIONS: This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases.

Rotavirus serotype G9 is associated with more-severe disease in Latin America.

The association between rotavirus serotypes and severity is not well established. Analysis of a clinical trial conducted in Latin America points at more-severe disease associated with serotype G9. Thus, demonstration of efficacy against G9 will be an important asset of any rotavirus vaccine to be introduced into a Latin American country or any country where G9 has been shown to be prevalent.

Rotavirus types in Europe and their significance for vaccination.

The degree of diversity of cocirculating human rotavirus wild-type strains is high. This article reviews the occurrence and frequency of rotavirus types in European children younger than 5 years of age during the past 10-15 years. To enable greater understanding of the overall epidemiologic situation, rotavirus types found in animals in Europe are described. In addition, rotavirus types occurring in children outside Europe are considered. Taken together, these data provide an essential background to the development of rotavirus vaccines. The different concepts of immunization with the 2 main rotavirus candidate vaccines are briefly discussed, and their potential impact on the epidemiology of cocirculating rotavirus wild-type viruses is considered. A case is made for comprehensive surveillance of cocirculating human rotavirus types in Europe after the implementation of rotavirus vaccination.

Intussusception among young children in Europe.

Intussusception, a potentially lethal condition with poorly understood etiology, is the most common cause of acute intestinal obstruction in children younger than 5 years old. In some cases, the condition has been associated with administration of the first licensed rotavirus vaccine, the reassortant rhesus-human tetravalent rotavirus vaccine (RRV-TV; RotaShield). No such association has to date been reported from large phase III safety trials with new rotavirus vaccines. As 2 new, live-attenuated oral rotavirus vaccines are currently under review for approval by the European Union regulatory authorities, a review of the clinical, etiologic and epidemiologic aspects of intussusception in Europe is urgently needed. We conducted a review of Medline literature, published from 1995 onwards on intussusception in the World Health Organization's European Region. The results are compared with data from previous reviews and other regions. The classic triad of intussusception symptoms (abdominal pain, abdominal mass, bloody stools) was present in 29-33% of patients according to the medical literature reviewed. Conservative treatment (barium, air or saline enema) was the rule (81% of cases), and few complications were observed during treatment. Treatment outcome was generally favorable, with recurrence occurring in approximately 1 in 10 patients, and only 1 death reported. Structural lead points were seen in 3% of patients; no other reliable data on the etiology of intussusception were found. The incidence of acute intussusception in young children in Europe, according to 6 heterogeneous hospital-based studies, ranged from 0.66 to 2.24 per 1000 children in inpatient departments and from 0.75 to 1.00 per 1000 children in emergency departments. Peak incidences were found in children 3-9 months of age. There are still gaps in our knowledge of intussusception with respect to its etiology and especially by which mechanisms RRV-TV might have caused it to occur. Data from regions outside Europe showed that rotavirus infection and disease are not associated with intussusception. As new rotavirus vaccines become available for use in Europe, postlicensure surveillance for intussusception is indicated and may be instrumental in further understanding the epidemiology of this condition and in further assessing the safety of future vaccines.

Review of predialysis education programs: a need for standardization.

To make an informed decision on renal replacement therapy, patients should receive education about dialysis options in a structured program covering all modalities. Many patients do not receive such education, and there is disparity in the information they receive. This review aims to compile evidence on effective components of predialysis education programs as related to modality choice and outcomes. PubMed MEDLINE, Cochrane Library, and Ovid searches (from January 1, 1995 to December 31, 2013) with the main search terms of "predialysis", "peritoneal dialysis", "home dialysis", "education", "information", and "decision" were performed. Of the 1,005 articles returned from the initial search, 110 were given full text reviews as they potentially met inclusion criteria (for example, they included adults or predialysis patients, or the details of an education program were reported). Only 29 out of the 110 studies met inclusion criteria. Ten out of 13 studies using a comparative design, showed an increase in home dialysis choice after predialysis education. Descriptions of the educational process varied and included individual and group education, multidisciplinary intervention, and varying duration and frequency of sessions. Problem-solving group sessions seem to be an effective component for enhancing the proportion of home dialysis choice. Evidence is lacking for many components, such as timing and staff competencies. There is a need for a standardized approach to evaluate the effect of predialysis educational interventions.

Risk of spontaneous abortion and other pregnancy outcomes in 15-25 year old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom.

BACKGROUND: We assessed the risk of spontaneous abortion (SA) after inadvertent exposure to HPV-16/18-vaccine during pregnancy using an observational cohort design. METHODS: The study population included women aged 15-25 years registered with the Clinical Practice Research Datalink General Practice OnLine Database in the United Kingdom (UK), who received at least one HPV-16/18-vaccine dose between 1st September 2008 and 30th June 2011. Exposed women had the first day of gestation between 30 days before and 45 days (90 days for the extended exposure period) after any HPV-16/18-vaccine dose. Non-exposed women had the first day of gestation 120 days-18 months after the last dose. SA defined as foetal loss between weeks 1 and 23 of gestation (UK definition). RESULTS: The frequency of SA was 11.6% (among 207 exposed) and 9.0% (632 non-exposed), women: hazard ratio (HR) adjusted for age at first day of gestation 1.30 (95% confidence interval: 0.79-2.12). Sensitivity analysis per number of doses administered (-30 to +45-day risk period) showed a HR for SA of 1.11 (0.64-1.91) for 18/178 women with one dose during the risk period versus 2.55 (1.09-5.93) in 6/29 women with two doses within a 4-5 weeks period. The proportion of pre-term/full-term/postterm deliveries, small/large for gestational age infants, and birth defects was not significantly different between exposed and non-exposed women. Results were consistent using a (United States) SA definition of foetal loss between weeks 1-19 and/or the extended risk period. CONCLUSION: There was no evidence of an increased risk of SA and other adverse pregnancy outcomes in young women inadvertently HPV-16/18-vaccinated around gestation. Nevertheless, women who are pregnant or trying to become pregnant are advised to postpone vaccination until completion of pregnancy.

The health care burden and societal impact of acute otitis media in seven European countries: results of an Internet survey.

This paper estimates medical resource use, direct costs, and productivity losses and costs (indirect costs) during episodes of acute otitis media (AOM) in young children. A 24-item Internet questionnaire was developed for parents in Belgium (Flanders), France, Germany, Italy, The Netherlands, Spain, and the United Kingdom (UK) to report health care resource use and productivity losses during the most recent episode of AOM in their child, younger than 5 years. The percentage who did not seek medical help for AOM was considerable in The Netherlands (28.3%) and the UK (19.7%). Antibiotic use was high, ranging from 60.8% (Germany) to 87.1% (Italy). Total costs per AOM episode ranged from €332.00 (The Netherlands) to €752.49 (UK). Losses in productivity accounted for 61% (France) to 83% (Germany) of the total costs. AOM poses a significant medical and economic burden to society.

School performance and social-emotional behavior of primary school children before and after a disaster.

OBJECTIVES: The purpose of this work was to evaluate the cognitive and social-emotional consequences in a general population of primary school children affected by the firework disaster in Enschede, The Netherlands, on May 13, 2000. The explosions caused tremendous damage in the surrounding neighborhood. Twenty-two people immediately died and >1000 were injured. METHODS: This retrospective study assessed school performance and social-emotional behavior before and up to 3 years after the disaster. Objectively measured school test results in spelling and arithmetic/mathematics and multi-informant social-emotional behavioral assessments were compared between exposed and nonexposed primary school children. Multivariate logistic-regression was used to assess the relationship between exposure and cognitive and social emotional functioning. RESULTS: On school performances, the children exposed to the disaster performed over a period of 3 years after the disaster as good as or better than classmates, controls, and a national reference population. Shortly after the disaster, exposed children even seemed to have better school test results than nonexposed children. Two to 3 years after the disaster, a significant effect of disaster exposure was found on social-emotional behavior. Problematic behavior was reported by teachers, parents, and the school doctor. CONCLUSIONS: This study demonstrates a limited influence of disaster exposure on school performance in primary school children. This study also shows that teachers and youth health care practitioners especially should be aware of children starting school several years after a disaster. Although very young at the time of a disaster (1-4 years of age), they may experience disaster-related problems.

Substandard factors in perinatal care in The Netherlands: a regional audit of perinatal deaths.

BACKGROUND: To determine: 1) whether substandard factors were present in cases of perinatal death, and to what extent another course of action might have resulted in a better outcome, and 2) whether there were differences in the frequency of substandard factors by level of care, particularly between midwives and gynecologists/obstetricians and between home and hospital births. METHODS: Population-based perinatal audit, with explicit evidence-based audit criteria. SETTING: The northern part of the province of South-Holland in The Netherlands. All levels of perinatal care (primary, secondary and tertiary care, and home and hospital births) were included. CASES: Three hundred and forty-two cases of perinatal mortality (24 weeks of pregnancy--28 days after birth). MAIN OUTCOME MEASURES: Scores by a Dutch and a European audit panel. Score 0: no substandard factors identified; score 1, 2 or 3: one or more substandard factors identified, which were unlikely (1), possibly (2) or probably (3) related to the perinatal death. RESULTS: In 25% of the perinatal deaths (95% Confidence Interval: 20-30%) a substandard factor was identified that according to the Dutch panel was possibly or probably related to the perinatal death. These were mainly maternal/social factors (10% of all perinatal deaths; most frequent substandard factor: smoking during pregnancy), and antenatal care factors (10% of all perinatal deaths; most frequent substandard factor: detection of intra-uterine growth retardation). We did not find statistically significant differences in scores between midwives and gynecologists/obstetricians or between home and hospital births. The European panel identified more substandard factors, but these were again equally distributed by level of care. CONCLUSIONS: Perinatal deaths might be partly preventable in The Netherlands. There is no evidence that the frequency of substandard factors is related to specific aspects of the perinatal care system in The Netherlands.