RESUMO
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.
Assuntos
Infecções Meningocócicas , Vacinas Meningocócicas , Adolescente , Anticorpos Antibacterianos , Estudos Transversais , Humanos , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/efeitos adversos , Países Baixos/epidemiologia , Vacinação/efeitos adversos , Vacinas ConjugadasRESUMO
UNLABELLED: Since the introduction of the bivalent human papilloma virus (HPV) vaccine in the Netherlands, migraine has been reported as a notable event in the passive safety surveillance system. Research on the association between HPV vaccination and migraine is needed. Therefore, potential migraine cases in 2008-2010 were selected from a group of general practitioners and linked to the vaccination registry. Data were analysed in three ways: (i) incidences of migraine postvaccination (2009/2010) were compared to pre-vaccination incidences (2008); (ii) in a cohort, incidence rates of migraine in vaccinated and unvaccinated girls were compared and (iii) in a self-controlled case series analysis, the relative incidence of migraine in potentially high-risk periods was compared to non-high-risk periods. Incidence rates of migraine for 12- to 16-year-old girls and boys postvaccination were slightly higher than pre-vaccination incidence rates. Incidence rate ratios (IRRs) for vaccinated compared to unvaccinated girls were not statistically significantly higher. Furthermore, the RR for migraine in the high-risk period of 6 weeks following each dose versus non-high-risk period was 4.3 (95% confidence interval (CI) 0.69-26.6) for certain migraine. CONCLUSION: Using different methods, no statistically significant association between HPV vaccination and incident migraine was found. However, the number of cases was low; to definitively exclude the risk, an increased sample size is needed.
Assuntos
Transtornos de Enxaqueca/etiologia , Vacinas contra Papillomavirus/efeitos adversos , Vacinação/efeitos adversos , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Países Baixos , Infecções por Papillomavirus/prevenção & controleRESUMO
BACKGROUND: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. METHODS: A retrospective cohort study (1996-2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. RESULTS: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2-7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3-5) in 1996-2004 to 9/100,000 py in 2007/8 (95% CI, 6-16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). CONCLUSIONS: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.
Assuntos
Esclerose Múltipla/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Retrospectivos , Distribuição por SexoRESUMO
INTRODUCTION: 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. METHODS: In this retrospective cohort study conducted in the Integrated Primary Care Information database, we investigated the occurrence of chronic fatigue syndrome (CFS), fatigue ≥6â¯months and 3-6â¯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 ≥6â¯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 12â¯months after each dose was defined. RESULTS: 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 ≥6â¯m: 7.3 (1.8-29.0) and 19.4 (16.1-23.4); certain fatigue 3-6â¯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). CONCLUSIONS: Fatigue ≥6â¯m and 3-6â¯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 ≥6â¯m in the high-risk period.
Assuntos
Fadiga/etiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Criança , Feminino , Humanos , Infecções por Papillomavirus/imunologia , Fatores de Risco , Vacinação/efeitos adversosRESUMO
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.
Assuntos
Efeitos Psicossociais da Doença , Complicações Parasitárias na Gravidez/epidemiologia , Toxoplasmose Congênita/epidemiologia , Feminino , Humanos , Incidência , Países Baixos/epidemiologia , Gravidez , Complicações Parasitárias na Gravidez/mortalidade , Toxoplasmose Congênita/mortalidadeRESUMO
OBJECTIVE: To determine the adverse reactions to the combined vaccine against diptheria, acellular pertussis, tetanus, poliomyelitis and Haemophilus Infuenzae type B (DTP-IPV-Hib) before and after the introduction of an acellular pertussis component. DESIGN: Descriptive. METHOD: Safety surveillance of the Dutch National Vaccination Programme is performed by the National Institute for Public Health and Environment (RIVM). It is based on an enhanced passive reporting system and complemented by targeted survey-based studies. The data obtained were analysed. RESULTS: The passive surveillance system showed a large increase in reports in 2004, probably linked to increased media attention on the efficacy and safety of the whole-cell DTP-IPV-Hib vaccine. The Health Council recommended transitioning to the use of a DTP-IPV-Hib vaccine with an acellular pertussis component, which was implemented in January 2005. The number of reports dropped sharply in 2005 to a level below that of 2002-2003. Results of a survey study on adverse events following DTP-IPV-Hib vaccination that began in late 2003 and continued in 2005 confirmed the wide coverage ofthe enhanced passive surveillance system and revealed low rates of underreporting of rare adverse events, such as collapse and convulsions. CONCLUSION: This study confirms the data from the passive surveillance system, which show that the newly introduced acellular DTP-IPV-Hib vaccine is associated with fewer adverse events than the whole-cell vaccine that was used previously.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Vacinas contra Difteria, Tétano e Coqueluche Acelular/normas , Vacina contra Coqueluche/efeitos adversos , Vacinação/normas , Vacinas Combinadas/efeitos adversos , Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Humanos , Países Baixos , Vacina contra Coqueluche/imunologia , Vacina Antipólio de Vírus Inativado , Vigilância da População , Fatores de Risco , Segurança , Vacinas Combinadas/imunologiaRESUMO
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.
Assuntos
Anticoncepcionais Orais/efeitos adversos , Acidente Vascular Cerebral/genética , Trombofilia/complicações , Adulto , Isquemia Encefálica , Estudos de Casos e Controles , Fator V , Feminino , Heterozigoto , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombofilia/epidemiologia , Trombofilia/genéticaRESUMO
With regard to oral contraceptives, much research has concentrated on venous thrombosis and on the coronary and cerebral forms of atherosclerotic disease, while peripheral arterial disease (PAD) has received little attention. In this case-control study, we assessed oral contraceptive use and the risk of PAD in young women using a population-based case-control study. The women were 18-49 years of age, and had been admitted to a collaborating hospital between January 1990 and October 1995, and had a diagnosis of PAD. Participants were patients with PAD (n = 152), and control women (n = 925), identified by random digit dialing. The diagnosis of PAD was based almost exclusively on intra-arterial angiography. Patients and control subjects filled out the same structured questionnaire, which included questions on medical history, cardiovascular risk factors, and contraceptive use. The adjusted odds ratio for PAD in women using any type of oral contraceptives vs. no use, was 3.8 (95% CI 2.4-5.8). When first generation oral contraceptive use was compared with no use, the odds ratio was 8.7 (95% CI 3.6-21.3). For second and third generation oral contraceptives, the adjusted odds ratios (compared with non-users) were 2.6 (95% CI 1.4-4.9) and 3.0 (95% CI 1.4-6.6), respectively. This is the first study on oral contraceptive use and PAD in humans. All types of oral contraceptives were associated with an increased risk of PAD.
Assuntos
Anticoncepcionais Orais/efeitos adversos , Doenças Vasculares Periféricas/induzido quimicamente , Adulto , Arteriopatias Oclusivas/induzido quimicamente , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Razão de Chances , Progestinas/efeitos adversos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Compared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis especially in women with the factor V Leiden mutation. To find an explanation for these risk differences we investigated the effects of desogestrel- and levonorgestrel-containing oral contraceptives as well as their progestagens separately on the coagulation system in the absence or presence of the factor V Leiden mutation. In a single center, double blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of 2 menstrual cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. In plasmas of the participating women fragment 1+2, factor V, VII, VIII, IX, X and XI were determined. Both combined oral contraceptives induced a decrease in factor V, whereas the levels of all other coagulant parameters increased. However, in women without the factor V Leiden mutation the effects of desogestrel-containing preparations were significantly different compared to levonorgestrel-containing oral contraceptives for factor V (-8.0; 95% CI -13.4 to -2.6), factor VII (26.8; 95% CI 15.5 to 38.0) and factor IX (-9.6; 95% CI -16.2 to -3.2). When these women used progestagen-only pills, a differential effect between desogestrel and levonorgestrel was only found for factor IX (-6.5; 95% CI -11.4 to -1.5). In carriers of the factor V Leiden mutation desogestrel-containing oral contraceptives induced more pronounced changes in factor V (-14.2; 95% CI -22.4 to -6.0) and factor VII (36.1; 95% CI 19.7 to 52.6) compared to levonorgestrel-containing oral contraceptives. Comparing desogestrel- and levonorgestrel-only, only for factor V a differential effect was found in these women (-9.5; 95% CI -18.3 to -0.6). It appears that desogestrel-containing oral contraceptives have a more pronounced effect on the coagulation system than levonorgestrel-containing oral contraceptives which may be explained by a less effective compensation of the thrombotic effect of ethinylestradiol by desogestrel.
Assuntos
Resistência à Proteína C Ativada/genética , Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea/efeitos dos fármacos , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Hormonais/efeitos adversos , Desogestrel/efeitos adversos , Etinilestradiol/efeitos adversos , Fator V/genética , Levanogestrel/efeitos adversos , Trombofilia/induzido quimicamente , Resistência à Proteína C Ativada/sangue , Adulto , Anticoncepcionais Orais Combinados/farmacologia , Anticoncepcionais Orais Hormonais/farmacologia , Desogestrel/administração & dosagem , Desogestrel/farmacologia , Método Duplo-Cego , Etinilestradiol/administração & dosagem , Etinilestradiol/farmacologia , Fator IX/análise , Fator V/análise , Fator VII/análise , Feminino , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/farmacologia , Fragmentos de Peptídeos/análise , Protrombina/análise , Trombofilia/sangue , Trombofilia/genéticaRESUMO
In a cohort of 12,239 women aged 50-69, who participated in a population-based breast cancer screening project (DOM-project) in Utrecht, The Netherlands, as well as being coded for micro-calcifications indicative of breast cancer, the mammograms were also coded for arterial calcifications. This allowed for a secondary analysis of associations between breast arterial calcification (BAC) and the occurrence of arteriosclerosis-associated morbidity (ie diabetes, hypertension, albuminuria, stroke, thrombosis and myocardial infarction). Arterial calcifications were seen on screening mammograms in 9.1% of the women. Significant relations were found between BAC and albuminuria [Relative risk (RR) 2.7; 95% CI 1.0-7.0], BAC and hypertension (RR 1.1; 95% CI 1.0-1.3), transient ischaemic attack (TIA)/stroke (RR 1.4; 95% CI 1.1-1.8), thrombosis (RR 1.5; 95% CI 1.0-2.2) and myocardial infarction (RR 1.8; 95% CI 1.1-2.9). In addition BAC were associated with diabetes in the oldest age-group (RR 1.7; 95% CI 1.2-2.4). All relations were adjusted for age, smoking, parity and Quetelet index. The results of the present study show that BAC as detected on breast cancer screening mammograms are associated with disorders related to increased or accelerated arterio-sclerosis. Where increased parity is associated with a decrease in breast cancer risk, parity increases the occurrence of BAC. The present study suggests that breast-cancer screening mammograms may allow for the early detection of enhanced cardiovascular disease risk among otherwise healthy women.
Assuntos
Arteriosclerose/diagnóstico por imagem , Neoplasias da Mama/prevenção & controle , Mama/irrigação sanguínea , Calcinose/diagnóstico por imagem , Mamografia , Programas de Rastreamento , Doenças Vasculares/diagnóstico por imagem , Idoso , Arteriosclerose/complicações , Calcinose/complicações , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Paridade , Fatores de Risco , Doenças Vasculares/complicaçõesRESUMO
Third-generation oral contraceptives (OC) have been associated with an increased risk of venous thrombosis compared with second-generation OC. To find an explanation for this increased risk, the effect of a second- and third-generation OC and of the progestagens used in these pills on several fibrinolytic parameters was studied in the absence or presence of the factor V Leiden mutation. In a single-center, double-blind trial, 51 women without and 35 women with the factor V Leiden mutation were randomized to either a second-generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third-generation (30 microg ethinylestradiol/150 microg desogestrel) oral contraceptive. After two menstrual cycles of use and a wash-out period of two cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. D-Dimers, thrombin-activatable fibrinolysis inhibitor (TAFI) and the clot lysis time in the absence (LYSmin) or the presence (LYSplus) of a blocking anti-factor XI antibody were determined in plasmas of the participating women, and the mean difference in changes between the OC were calculated. Both combined OC induced increased plasma levels of D-dimers and TAFI, and induced a prolongation of LYSplus, whereas LYSmin hardly changed. Virtually no changes in fibrinolytic parameters were observed for the progestagen-only preparations. No differential effects between levonorgestrel- and desogestrel-containing OC were found in women without factor V Leiden. Women with the mutation on levonorgestrel-containing OC showed an increased LYSplus compared with desogestrel containing OC (3.9; 95% confidence interval, 0.1-7.7). When using progestagen-only preparations, no differential effect on the fibrinolytic parameters were found, except for non-carriers on levonorgestrel who showed a reduced LYSmin compared with non-carriers on desogestrel (-4.0; 95% confidence interval, -7.8 to -0.2). In conclusion, the effect of oral contraceptives on fibrinolytic parameters is largely independent of the type of progestagen. The increased fibrinolytic activity during OC use appears to be induced by the estrogen component and may be counteracted by increased TAFI activation. This may result in an enhanced downregulation of fibrinolysis.
Assuntos
Resistência à Proteína C Ativada/sangue , Anticoncepcionais Orais Hormonais/farmacologia , Desogestrel/farmacologia , Etinilestradiol/farmacologia , Fator V/análise , Fibrinólise/efeitos dos fármacos , Levanogestrel/farmacologia , Trombofilia/induzido quimicamente , Resistência à Proteína C Ativada/genética , Adulto , Carboxipeptidase B2/análise , Anticoncepcionais Orais Hormonais/efeitos adversos , Anticoncepcionais Orais Hormonais/classificação , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Método Duplo-Cego , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Trombofilia/sangue , Trombofilia/etiologiaRESUMO
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.
Assuntos
Anticoncepcionais Orais Sintéticos/efeitos adversos , Congêneres da Progesterona/efeitos adversos , Trombose Venosa/induzido quimicamente , Adulto , Viés , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Medição de Risco , Fatores de Risco , Tromboembolia/induzido quimicamenteRESUMO
The selection of a valid control group is important in case control studies and has therefore generated a fair amount of discussion in the epidemiologic literature. The proposal of the study usually determines the type of control group that should be selected. It is possible to select population controls, hospital controls, friends or relatives of patients or a variant of these. Each method has specific advantages and disadvantages. Random-digit dialing can be used to select population controls by telephone. This method is a valuable alternative when no registry exists.
Assuntos
Estudos de Casos e Controles , Projetos de Pesquisa/normas , Viés de Seleção , Métodos Epidemiológicos , Humanos , Reprodutibilidade dos TestesRESUMO
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.
Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Vacinação/efeitos adversos , Adolescente , Sistemas de Notificação de Reações Adversas a Medicamentos , Relação Dose-Resposta a Droga , Feminino , Humanos , Internet , Países Baixos , Vacinas contra Papillomavirus/administração & dosagem , Inquéritos e Questionários , Vacinação/estatística & dados numéricosRESUMO
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.
Assuntos
Ataxia Cerebelar/etiologia , Vacina contra Varicela/efeitos adversos , Varicela/complicações , Vacinação/efeitos adversos , Ataxia Cerebelar/induzido quimicamente , Ataxia Cerebelar/epidemiologia , Criança , Pré-Escolar , Feminino , Herpesvirus Humano 3/imunologia , Hospitalização , Humanos , Programas de Imunização , Incidência , Lactente , Masculino , Países Baixos/epidemiologia , Vigilância da População , Estudos ProspectivosRESUMO
The aim of the study was to assess the incidence and severity of local reactions and systemic events among 4-year-old children receiving a fifth dose of diphtheria-tetanus-inactivated poliovirus (dT-IPV) and acellular pertussis (aP) vaccines. Of 810 children, 483 had no adverse events following immunization. Of the reported local reactions of 281 children, pain was the most frequent (n=246). Eighty-one children developed redness, and 54, swelling. Pain, reduced use of the arm, redness, and swelling occurred significantly more often at the dT-IPV injection site than at the aP injection site (p<0.05). Local reactions were mainly mild and transient. Among the 104 reported systemic events, fever was the most frequent (n=42). In general, the vaccinations for the 4-year-olds are well tolerated.
Assuntos
Toxoide Diftérico/efeitos adversos , Imunização Secundária/efeitos adversos , Vacina contra Coqueluche/efeitos adversos , Vacina Antipólio de Vírus Inativado/efeitos adversos , Toxoide Tetânico/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Países Baixos , Vacinas Acelulares/efeitos adversos , Vacinas Combinadas/efeitos adversosRESUMO
OBJECTIVES: The effect of a second and third generation oral contraceptive and of the progestagens used in these pills on lipid metabolism was studied in the absence or presence of the factor V Leiden mutation. DESIGN: A single centre, double blind randomized trial. SETTING: University Medical Centre. SUBJECTS: A total of 51 women without and 35 women with the factor V Leiden mutation. INTERVENTIONS: A second generation (30 microg ethinylestradiol/150 microg levonorgestrel) or a third generation (30 microg ethinylestradiol/l 50 microg desogestrel) oral contraceptive. After two cycles of use and a wash-out period of two cycles, the participants received the corresponding progestagen-only preparation containing 150 microg levonorgestrel or 150 microg desogestrel. MAIN OUTCOME MEASURES: Mean difference in changes between the treatment groups on total cholesterol, HDL, LDL, triglycerides and total/HDL cholesterol ratio. RESULTS: Compared with levonorgestrel, desogestrel-containing oral contraceptives caused in women without the factor V Leiden mutation significant changes in HDL (0.43; 95% confidence interval [CI] 0.25-0.61), LDL (-0.55; 95% CI -0.90 to -0.20), triglycerides (0.19; 95% CI 0.06-0.32) and total/ HDL cholesterol ratio (-0.87; 95% CI -1.21 to -0.53). When the progestagen-only preparations were used, differential changes were found for HDL (0.16; 95% CI 0.03-0.29), LDL (-0.31; 95% CI - 0.56 to -0.05) and total/HDL cholesterol ratio (-0.55; 95% CI -0.84 to -0.26). Desogestrel-only caused changes opposite to those of desogestrel-containing oral contraceptives. For cholesterol and triglycerides, this effect was also found for levonorgestrel-only in comparison with levonorgestrel-combined oral contraceptives. Levonorgestrel appeared to induce the effect on HDL. Almost all results were similar for women with the factor V Leiden mutation. CONCLUSION: It appears that desogestrel counteracts the effects of oestrogens to a lesser extent than levonorgestrel. Desogestrel-containing oral contraceptives have therefore a more favourable influence on cholesterol metabolism in comparison with levonorgestrel-containing oral contraceptives.
Assuntos
Anticoncepcionais Orais Sintéticos/farmacologia , Fator V/efeitos dos fármacos , Fator V/genética , Metabolismo dos Lipídeos , Lipídeos/genética , Mutação Puntual/efeitos dos fármacos , Mutação Puntual/genética , Congêneres da Progesterona/farmacologia , Adolescente , Adulto , Colesterol/sangue , Desogestrel/farmacologia , Método Duplo-Cego , Etinilestradiol/farmacologia , Feminino , Humanos , Levanogestrel/farmacologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/efeitos dos fármacos , Triglicerídeos/sangueRESUMO
A nested lung cancer case-control study was carried out using 397 12 h urine samples originally collected from a cohort of over 26,000 women aged 40-64 at entry who were then followed for up to 15 years. The urine samples from active smokers were first identified using a simple qualitative method and their total nicotine metabolites/creatinine ratios then determined by automated colorimetric methods. The results obtained demonstrated the capacity of nicotine metabolite estimations in a single 12 h sample of urine to predict the subsequent risk of lung cancer. The risk of lung cancer among the biochemically proven active smokers during this period was 7.8 times that of the non-smokers, suggesting that the dose-response relationship between smoking and lung cancer is no less step in women than in men. The smoking-related risk of adenocarcinoma was less than that of other lung carcinomas. It is suggested that this biochemical epidemiology approach to exploring the relationship between smoking and lung cancer could profitably be applied to the study of other smoking-related diseases.
Assuntos
Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/urina , Nicotina/urina , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Creatinina/urina , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fumar/urinaRESUMO
OBJECTIVE: To determine whether breast size as reflected in cup size is independently associated with Wolfe's mammographic patterns. DESIGN: Univariate and multivariate associations between the waist/hip ratio (WHR), body mass index (BMI), cup size, age, parity, age at menarche menopausal status and Wolfe's mammographic parenchymal patterns were determined by (multiple) linear logistic regression. SETTING: Population based mammographic breast cancer screening project. SUBJECTS: 7819 women between 39 to 52 years of age. RESULTS: The univariate analysis demonstrated that women in the lowest tertile with respect to BMI and WHR when compared to women in the upper tertile were significantly more likely to display the high risk P2, Dy breast patterns. Cup size showed a similar inverse relation with the P2, Dy patterns. When age, WHR and BMI are entered together in the multivariate model the relation between cup size and the P2 Dy patterns is no longer significant in the upper tertile. CONCLUSION: Breast size is not a major independent determinant of the high risk P2, Dy parenchymal breast patterns when the WHR and BMI are taken into account.
Assuntos
Neoplasias da Mama/epidemiologia , Mama/anatomia & histologia , Adulto , Fatores Etários , Constituição Corporal , Índice de Massa Corporal , Feminino , Humanos , Mamografia , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
In a cohort of women aged 40-64 at entry, 12 h urine samples were obtained at the beginning of a follow-up period of up to 15 years in which incident cases of lung cancer were registered as well as deaths from lung cancer. In this cohort a nested case-control study (n = 397) was carried out by measuring urinary cotinine. The method for quantitation of cotinine was sensitive enough to study lung cancer risk not only in active smokers but also in passive smokers. The results seem to indicate that cotinine estimations in single 12 h samples of urine are enough to predict lung cancer risk. Relative risk rose with increasing levels of nicotine intake already in the range associated with passive smoking. The smoking-related risk of adenocarcinoma was much less than that of other lung carcinomas.