Abstract Objective: To evaluate quantitatively articles that compared effects of second and third generation oral contraceptives on risk of venous thrombosis. Design: Meta-analysis. Studies: Cohort ...and case-control studies assessing risk of venous thromboembolism among women using oral contraceptives before October 1995. Main outcome measures: Pooled adjusted odds ratios calculated by a general variance based random effects method. When possible, two by two tables were extracted and combined by the Mantel-Haenszel method. Results: The overall adjusted odds ratio for third versus second generation oral contraceptives was 1.7 (95% confidence interval 1.4 to 2.0; seven studies). Similar risks were found when oral contraceptives containing desogestrel or gestodene were compared with those containing levonorgestrel. Among first time users, the odds ratio for third versus second generation preparations was 3.1 (2.0 to 4.6; four studies). The odds ratio was 2.5 (1.6 to 4.1; five studies) for short term users compared with 2.0 (1.4 to 2.7; five studies) for longer term users. The odds ratio was 1.3 (1.0 to 1.7) in studies funded by the pharmaceutical industry and 2.3 (1.7 to 3.2) in other studies. Differences in age and certainty of diagnosis of venous thrombosis did not affect the results. Conclusions: This meta-analysis supports the view that third generation oral contraceptives are associated with an increased risk of venous thrombosis compared with second generation oral contraceptives. The increase cannot be explained by several potential biases. What is already known on this topic Third generation oral contraceptives have been reported to increase the risk of venous thrombosis compared with second generation oral contraceptives The findings have been vigorously debated, with suggestions that the results can be explained by confounding or bias, or both. What this study adds Women taking third generation oral contraceptives have a 1.7-fold increased risk of venous thrombosis compared with those taking second generation oral contraceptives Risk is highest in first time users The biases were not large enough to account for the observed results
Abstract
Background
In 2018, meningococcal ACWY-TT vaccine (MenACWY-TT) was offered to adolescents in the Netherlands within the National Immunization Programme at 14 years of age. A questionnaire ...study assessed the tolerability of this vaccine.
Methods
Five thousand adolescents were invited to participate and to fill in two questionnaires about systemic events in the week before vaccination and local reactions and systemic events in the week after vaccination. Frequencies of local and systemic adverse events in the week after vaccination were calculated. Association between the occurrence of systemic symptoms in the week before and after the vaccination was tested by using generalized mixed models (GLMM).
Results
Of all adolescents, 139 returned one or both questionnaires. Any local reaction within 7 days after vaccination was reported by 55.6% of the adolescents. Pain (50%) and reduced use of the injected arm (21.3%) were most often reported. Any systemic event was reported by 67.6% of the participants, with myalgia as the most often reported event (37.0%). Compared with the week before vaccination, there were no increased odds of experiencing systemic symptoms in the week after vaccination (OR 0.95; 95%CI 0.40–2.27).
Conclusions
After vaccination with MenACWY-TT vaccine, most adolescents reported one or more adverse events, which were mostly mild and transient. Systemic symptoms were not reported more often in the week after compared to the week before vaccination. Unfortunately, due to a low response rate we were not able to detect the absolute elevated risks the sample size calculation was based on. However, despite limited data, our results are in line with results from prelicensure data, and indicate that MenACWY-TT vaccination is well tolerated in adolescents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral Contraceptives and the Risk of Myocardial Infarction Tanis, Bea C; van den Bosch, Maurice A.A.J; Kemmeren, Jeanet M ...
New England journal of medicine/The New England journal of medicine,
12/2001, Letnik:
345, Številka:
25
Journal Article
Recenzirano
Odprti dostop
Some studies have indicated that women who take oral contraceptives have an increased risk of myocardial infarction. This study focused specifically on second- and third-generation oral ...contraceptives. The risk of myocardial infarction was significantly increased by the use of second-generation pills; the findings regarding the use of third-generation pills were inconclusive but suggested that the risk was lower than that with second-generation pills.
The risk was increased with second-generation pills. It may be lower with third-generation pills.
The first report of coronary thrombosis associated with the use of oral contraceptives appeared in 1963.
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Later studies established the use of oral contraceptives as a risk factor for venous as well as arterial thrombosis.
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Various modifications were made in an attempt to lower these risks, including a reduction in the estrogen dose and changes in the progestagen compound. Oral contraceptives containing an estrogen and the progestagen desogestrel or gestodene, available since the 1980s, are associated with at least a doubling of the risk of venous thrombosis as compared with other combined oral contraceptives.
8
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12
It has been suggested . . .
In 2013, the Netherlands Pharmacovigilance Center Lareb published an overview of reports of long-lasting fatigue following bivalent HPV-vaccination (2vHPV). After an update of this overview in 2015, ...concerns regarding the safety of 2vHPV was picked up by the media, which led to further reports of long-lasting fatigue. Therefore, the Dutch National Institute for Public Health and the Environment (RIVM) investigated a possible association between HPV-vaccination and long-term fatigue.
In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6 months and 3–6 months in all girls born in 1991–2000 during the follow-up period January 1st 2007-December 31st 2014 (2007–2008 pre-vaccination and 2009–2014 post-vaccination). Patients with certain fatigue ≥6 m were asked for consent to link their primary care information with vaccination data. Incidence rates per 10,000 person years (PY) for 12–16-year-old girls were compared between pre- and post-HPV-vaccine era. A self-controlled case series (SCCS) analysis was performed using consenting vaccinated cases. A primary high-risk period of 12 months after each dose was defined.
The cohort consisted of 69,429 12–16-year-old girls accounting for 2758 PY pre-vaccination and 57,214 PY post-vaccination. Differences between pre- and post-vaccination incidences (CFS: 3.6 (95% CI 0.5–25.7)/10,000 PY and 0.9 (0.4–2.1); certain fatigue ≥6 m: 7.3 (1.8–29.0) and 19.4 (16.1–23.4); certain fatigue 3–6 m: 0.0 and 16.6 (13.6–20.3), respectively) were not statistically significant. SCCS analyses in 16 consenting vaccinated cases resulted in an age-adjusted RR of 0.62 (95%CI 0.07–5.49).
Fatigue ≥6 m and 3–6 m was frequently found among adolescent girls, but CFS was rarely diagnosed. No statistically significant increased incidence rates were found post-vaccination compared to similar age groups of girls pre-vaccination. The SCCS analysis included a low number of cases but revealed no elevated risk of certain fatigue ≥6 m in the high-risk period.
Disease Burden of Congenital Toxoplasmosis Havelaar, A. H.; Kemmeren, J. M.; Kortbeek, L. M.
Clinical infectious diseases,
06/2007, Letnik:
44, Številka:
11
Journal Article
Recenzirano
Although the outcomes of toxoplasmosis have been well documented, an integrated estimate of the impact of this infection on the health status of the population is not available. "Disability-adjusted ...life years" are the sum of years of life lost and years lived with disability, weighted for the severity of the illness. The estimated disease burden of congenital toxoplasmosis in The Netherlands is 620 (range, 220-1900) disability-adjusted life years per year, which is similar to that for salmonellosis and is mainly caused by fetal loss and chorioretinitis. However, there is considerable uncertainty in this estimate. Scenario analysis indicates that the true burden may be underestimated. In other countries, the disease burden is expected to vary with the incidence of congenital infection, but it may also depend on the health care system. In countries that actively screen for toxoplasmosis, such as France, there may be a lower burden of morbidity but a higher burden of mortality.
The identification of genes underlying human genetic disorders requires the combination of data related to cytogenetic localization, phenotypes and expression patterns, to generate a list of ...candidate genes. In the field of human genetics, it is normal to perform this combination analysis by hand. We report on GeneSeeker (http://www.cmbi.ru.nl/GeneSeeker/), a web server that gathers and combines data from a series of databases. All database searches are performed via the web interfaces provided with the original databases, guaranteeing that the most recent data are queried, and obviating data warehousing. GeneSeeker makes the same selection of candidate genes as the human geneticists would have performed, and thus reducing the time-consuming process to a few minutes. GeneSeeker is particularly well suited for syndromes in which the disease gene displays altered expression patterns in the affected tissue(s).
In 2009, human papillomavirus (HPV) vaccination was offered to girls born in 1993–1996 in a catch-up campaign, followed in 2010 by the implementation of the vaccination in the National Immunization ...Programme (NIP) for girls born in 1997. To monitor the tolerability of the 2009 catch-up campaign, we investigated the occurrence of adverse events within 7 days after vaccination with the bivalent HPV vaccine. A total of 6000 girls were asked to participate, including 1500 from each birth cohort from 1993 to 1996. One week after each of the required three successive doses, the participants received by e-mail a Web-based questionnaire focused on local reactions and systemic events. One or more questionnaires were returned by 4248 girls. Any local reaction was reported by 92.1% of the girls after the first dose, 79.4% after the second dose, and 83.3% after the third dose, and 91.7%, 78.7%, and 78.4% reported any systemic event after the three doses, respectively. Pain in the arm was the most frequently reported local reaction, of which 24.0%, 11.7%, and 14.7% was classified as pronounced. Myalgia was the most often reported systemic event. The proportion of local reactions and most systemic events was significantly lower after the second and third dose compared with the first dose (Odds ratio OR, 0.33–0.76). Older girls reported a higher proportion of adverse events than younger girls. After vaccination with the bivalent HPV vaccine, girls 13–16 years of age reported a high proportion of short-term adverse events. These are maximum estimates and not necessarily caused by the vaccination itself. Although, girls experienced HPV vaccination as painful, no serious or unexpected adverse events were reported. The results of this survey are being communicated to health care workers and the public.
The interpretation of genetic variants after genome-wide analysis is complex in heterogeneous disorders such as intellectual disability (ID). We investigate whether algorithms can be used to detect ...if a facial gestalt is present for three novel ID syndromes and if these techniques can help interpret variants of uncertain significance.
Facial features were extracted from photos of ID patients harboring a pathogenic variant in three novel ID genes (PACS1, PPM1D, and PHIP) using algorithms that model human facial dysmorphism, and facial recognition. The resulting features were combined into a hybrid model to compare the three cohorts against a background ID population.
We validated our model using images from 71 individuals with Koolen-de Vries syndrome, and then show that facial gestalts are present for individuals with a pathogenic variant in PACS1 (p = 8 × 10
), PPM1D (p = 4.65 × 10
), and PHIP (p = 6.3 × 10
). Moreover, two individuals with a de novo missense variant of uncertain significance in PHIP have significant similarity to the expected facial phenotype of PHIP patients (p < 1.52 × 10
).
Our results show that analysis of facial photos can be used to detect previously unknown facial gestalts for novel ID syndromes, which will facilitate both clinical and molecular diagnosis of rare and novel syndromes.
Abstract Aim Acute cerebellar ataxia (ACA, sudden onset of truncal ataxia and gait disturbances) usually follows a benign illness (25% varicella). It is also described after vaccination, like MMR and ...varicella zoster virus (VZV). We will establish incidence rates of (varicella related) ACA and assess the attributable risk of vaccination to ACA in the Netherlands. Method Data on ACA in children, following infections, like varicella, and vaccinations, obtained from prospective, active pediatric surveillance and passive surveillance on adverse events following immunizations (AEFI) were compared with hospitalization data for ataxia. Capture–recapture (CRC) method was used to estimate the burden of ACA in the Netherlands. Results 45 children with ACA were included (44 and 1 reported by pediatric and AEFI surveillance respectively, 30 were hospitalized). Chickenpox preceded ACA in 15 cases, one case followed MMR. Of the hospitalization reports, 13 fulfilled the criteria for ACA. Using CRC the estimated number of hospitalized ACA cases was 42. For varicella related ACA, this estimate was 10, resulting in an incidence rate of 0.7:100,000 (95%CI 0.52–0.94, all cases) and 0.17:100,000 (95%CI 0.09–0.31, varicella related cases) for children under 15 years of age. Conclusion The incidence rates were comparable with other studies. We found no association with MMR, but chickenpox was clearly related to ACA. According to age-specific seroprevalence data the incidence rate of ACA was 5:100,000 VZV infections for children up to 5 years, compared to an ACA-reporting rate of 0.15:100,000 doses VZV-vaccine. Therefore, uptake of VZV-vaccine in the immunization programme will diminish the incidence rate of ACA.
Background: The role of inherited prothrombotic conditions, including factor V Leiden (FV G1691A), prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T genotype, in the ...pathogenesis of ischemic stroke is not well established. The effects of these factors may be potentiated by the use of oral contraceptives, analogous to observations in venous thrombosis. Methods: Patients (n = 193) were women aged 20–49 years with ischemic stroke. Controls (n = 767) were women without arterial thrombosis stratified for age, calendar year of the index event, and residence. The relative risk of ischemic stroke was estimated with unconditional logistic regression, adjusted for stratification variables. Findings: Factor V Leiden and MTHFR 677TT were more common in patients than in controls odds ratio (OR): 1.8; 95% confidence interval (CI): 0.9–3.6 respectively OR: 1.5; 95% CI: 0.9–2.6. The frequency of prothrombin G20210A was similar in cases and controls. Carriers of FV Leiden using oral contraceptives had a 11.2‐fold (95% CI: 4.3–29.0) higher risk of ischemic stroke than women without either risk factor. Women with MTHFR 677TT using oral contraceptives had a 5.4‐fold (95% CI: 2.4–12.0) higher risk than women without these risk factors. Interpretation: These data suggest that carriers of FV Leiden or MTHFR 677TT who use oral contraceptives have an increased risk of ischemic stroke. When these findings are confirmed, a cost‐effectiveness analysis should indicate whether ischemic stroke could be prevented with genetic testing before the start of oral contraceptives.
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