Epidemiology and demographic patterns of cardiovascular diseases and neoplasms deaths in Western Europe: a 1990-2019 analysis.

OBJECTIVES: Cardiovascular diseases (CVDs) and neoplasms have been considered as public health concerns worldwide. This study aimed to estimate the epidemiological patterns of death burden on CVDs and neoplasms and its attributable risk factors in Western Europe from 1990 to 2019 to discuss the potential causes of the disparities. STUDY DESIGN AND METHODS: We collected data on CVDs and neoplasms deaths in 24 Western European countries from the Global Burden of Disease Study. We analyzed patterns by age, sex, country, and associated risk factors. The results include percentages of total deaths, age-standardized death rates per 100,000 population, and uncertainty intervals (UIs). Time trends were assessed using annual percent change. RESULTS: In 2019, CVDs and neoplasms accounted for 33.54% and 30.15% of Western Europe's total deaths, with age-standardized death rates of 128.05 (95% UI: 135.37, 113.02) and 137.51 (95% UI: 142.54, 128.01) per 100,000. Over 1990-2019, CVDs rates decreased by 54.97%, and neoplasms rates decreased by 19.54%. Top CVDs subtypes were ischemic heart disease and stroke; top cancers for neoplasms were lung and colorectal. Highest CVD death burdens were in Finland, Greece, Austria; neoplasm burdens in Monaco, San Marino, Andorra. The major risk factors were metabolic (CVDs) and behavioral (neoplasms). Gender differences revealed higher CVDs death burden in males, while neoplasms burden varied by risk factors and age groups. CONCLUSION: In 2019, CVDs and neoplasms posed significant health risks in Western Europe, with variations in death burdens and risk factors across genders, age groups, and countries. Future interventions should target vulnerable groups to lessen the impact of CVDs and neoplasms in the region.

Rates, determinants and success of implementing deprescribing in people with type 2 diabetes: A scoping review.

BACKGROUND: Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. AIMS: To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose-, blood pressure- or lipid-lowering medications in people with diabetes. METHODS: A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. RESULTS: Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA1c levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose-lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA1c . CONCLUSIONS: Deprescribing of glucose-lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure- and lipid-lowering medications in people with diabetes are needed.

Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding.

BACKGROUND: A recent study suggested that early-life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma. OBJECTIVE: This study aims to assess the association between prenatal antibiotic use and asthma in preschool children using data from the prescription database IADB.nl. To assess the influence of potential confounding, we conducted both a case-sibling and a case-control study and compared the results. METHODS: We conducted a case-sibling study in which 1228 children with asthma were compared to 1228 siblings without asthma, using data from the prescription database IADB.nl. In addition, a case-control study was conducted. Asthma in preschool children was defined as ≥ 3 prescriptions for anti-asthma medication within a year before the fifth birthday. Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs). RESULTS: In both the case-sibling and case-control analysis, the use of antibiotics in the third trimester of pregnancy was associated with an increased risk of asthma in preschool children (aOR 1.37; 95% CI 1.02-1.83 and aOR 1.40; 95% CI 1.15-1.47). Time-trend analyses showed that results were not influenced by a time trend in antibiotic exposure. A significant association between exposure to antibiotics in any trimester of pregnancy and the development of asthma in preschool children was observed in the case-control analysis only (aOR 1.46; 95% CI 1.34-1.59). CONCLUSION: Antibiotic use in the third trimester of pregnancy was associated with a small increased risk of asthma in preschool children. This association was robust to time-invariant confounding or exposure time trends, further supporting the important role for early-life intestinal microbiota in the development of childhood asthma.

Identification of Dutch children diagnosed with atopic diseases using prescription data: a validation study.

PURPOSE: The aim of this study is to validate medication proxies for the identification of children diagnosed with atopic disorders that can be applied in various types of epidemiological research. METHODS: Records of 7439 children, aged between 0 and 10 years, in the period 2001 until 2010, were retrieved from the Registration Network Groningen database, a general practitioners database in the north-eastern part of the Netherlands. The sensitivity and positive predictive value (PPV) of 22 medication proxies for the identification of children diagnosed with atopic disorders (asthma, atopic dermatitis, and allergic rhinitis) were computed using the registered diagnoses as gold standards. In addition, different capture periods (1 year, half year, and length of study period) for the detection of prescriptions were tested for all the medication proxies. RESULTS: The highest PPV (0.84, 95 % CI 0.81-0.87) in combination with a sufficient sensitivity value (0.54, 95 % CI 0.50-0.57) for the identification of children diagnosed with asthma was yielded for the medication proxy, ≥2 prescriptions for anti-asthma medication within 1 year, including 1 inhaled steroid. PPV and sensitivity were even higher in the age group 6-10 years. The proxies designed for the identification of children diagnosed with atopic dermatitis and allergic rhinitis yielded only high PPVs (≥0.75) in combination with low sensitivity values (≤0.22). Altering the capture period for the detection of prescriptions to half a year or the length of the study period only affected sensitivity values. CONCLUSION: Children diagnosed with asthma can be identified reliably with a range of medication proxies. The use of prescription data for the identification of children diagnosed with atopic dermatitis and allergic rhinitis is questionable.

An explorative study of school performance and antipsychotic medication.

BACKGROUND: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. METHODS: A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. RESULTS: In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p < 0.05). Scores of early starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). CONCLUSION: This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry.

Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the metabolite/mother compound ratio. Genotypes were assessed by the CYP2D6 *3 and *4 alleles. Results: Data was available from 81 patients (41 nortriptyline, 40 venlafaxine) with a mean age of 72 years. No phenoconversion from poor metabolizers (PM) to extensive metabolizers (EM), or vice versa, was found. However, we did find phenoconversion from PM to intermediate metabolizers (IM), IM to EM, or vice versa in 36% of observations. Among nortriptyline users, patients with a PM or IM genotype had more supra-therapeutic blood levels, although this did not reach statistical significance. In exploratory analyses we found men were more likely (RR: 2.4; 95% CI: 1.14-5.07) to display phenoconversion from an IM genotype to EM phenotype. In addition, compared to non-PMs, PMs were found to have higher risk (RR: 1.56; 95% CI: 1.03-2.37) on non-response, although this was only significant when response was measured on the Hamilton Rating Scale for Depression and not on the Montgomery Åsberg Depression Rating Scale. Conclusion: Patients phenoconversed, but we did not observe phenoconversion from PM to EM or vice versa. Genotype information could be used as a valuable tool, in addition to therapeutic drug monitoring, to prevent supratherapeutic drug levels of nortriptyline or venlafaxine in elderly patients with a PM genotype.

Prescribing patterns, adherence and LDL-cholesterol response of type 2 diabetes patients initiating statin on low-dose versus standard-dose treatment: a descriptive study.

AIMS: The aim of this study was to describe and compare treatment modifications and discontinuation, adherence levels and response to treatment in patients with type 2 diabetes initiating on low-dose vs. standard-dose statin treatment. METHODS: A 2-year follow-up cohort study was performed using data from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database in patients with type 2 diabetes initiating statin treatment between January 2007 and December 2012. First, we determined whether there were differences in treatment modifications and discontinuation after statin initiation between patients starting on a low-dose vs. standard-dose. Second, we looked at differences in adherence and LDL-cholesterol response after 2 years follow-up between these groups. RESULTS: Around 22% of patients initiated statin treatment on a dose lower than recommended. More than half of them remained on a low dose during a 2-year follow-up period, whereas less than 15% received a dose increase. Of the patients initiating on standard-dose, also more than half remained on the same treatment during this period, whereas 8% received a dose decrease without subsequent increase. Over 25% of patients starting on low-dose or standard-dose treatment discontinued treatment, often within the first 180 days after initiation or after a first treatment change. Patients on low-dose treatment had lower adherence levels and were less likely to have adequate LDL-cholesterol response compared with patients on standard-dose after 2 years follow-up. CONCLUSIONS: Current patterns of statin treatment in patients with type 2 diabetes are suboptimal, with discontinuation, inadequate adherence levels and lack of treatment intensification seen in those who had inadequate LDL-cholesterol response after 2 years of follow-up. Patients starting on low-dose had more treatment modifications, discontinuation and adherence problems as compared with those starting on standard-dose treatment, which calls for a closer look at the rationale of starting patients on low-dose statin treatment.

Predictors of response in initial users of metformin and sulphonylurea derivatives: a systematic review.

AIM: To provide an overview of factors predicting metformin and sulphonylurea treatment response. BACKGROUND: A large variability between individuals in treatment response to metformin and sulphonylurea derivatives exists. Understanding which factors determine response to these drugs may pave the way for more individualized therapy. METHODS: We conducted a systematic search in the MEDLINE, Cochrane and EMBASE databases, between 2003 and 2012 for articles assessing demographic and clinical prediction factors of treatment response in initial users of metformin or sulphonylurea. A literature search of articles referenced within the studies identified was also performed. Treatment response was defined as change in HbA1c level, reaching target HbA1c levels or time to treatment change. Studies were assessed on quality, sample size and type of analysis. Results were summarized by tabulating positive, null and negative associations observed for included predictors. RESULTS: A total of 10 articles (six trial reports and four cohort studies) were obtained, including three of sufficient quality. For metformin, baseline HbA1c , older age, lower BMI and shorter disease duration were found to be predictors of better treatment response in at least three studies of sufficient quality. For sulphonylurea derivatives, baseline HbA1c and shorter duration were identified as predictors of better treatment response in at least two studies of sufficient quality. Race, smoking status, lipid levels, blood pressure, kidney function and comorbidities were not significantly associated with treatment response. CONCLUSIONS: Several demographic and clinical factors were identified as possible predictors of response to metformin and sulphonylurea, but the number of studies with sufficient quality was small. Generally, early treatment seems important for achieving better glycaemic outcomes.

2012/13 influenza vaccine effectiveness against hospitalised influenza A(H1N1)pdm09, A(H3N2) and B: estimates from a European network of hospitals.

While influenza vaccines aim to decrease the incidence of severe influenza among high-risk groups, evidence of influenza vaccine effectiveness (IVE) among the influenza vaccine target population is sparse. We conducted a multicentre test-negative case-control study to estimate IVE against hospitalised laboratory-confirmed influenza in the target population in 18 hospitals in France, Italy, Lithuania and the Navarre and Valencia regions in Spain. All hospitalised patients aged ≥18 years, belonging to the target population presenting with influenza-like illness symptom onset within seven days were swabbed. Patients positive by reverse transcription polymerase chain reaction for influenza virus were cases and those negative were controls. Using logistic regression, we calculated IVE for each influenza virus subtype and adjusted it for month of symptom onset, study site, age and chronic conditions. Of the 1,972 patients included, 116 were positive for influenza A(H1N1)pdm09, 58 for A(H3N2) and 232 for influenza B. Adjusted IVE was 21.3% (95% confidence interval (CI): -25.2 to 50.6; n=1,628), 61.8% (95% CI: 26.8 to 80.0; n=557) and 43.1% (95% CI: 21.2 to 58.9; n=1,526) against influenza A(H1N1) pdm09, A(H3N2) and B respectively. Our results suggest that the 2012/13 IVE was moderate against influenza A(H3N2) and B and low against influenza A(H1N1) pdm09.

Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort study.

BACKGROUND: Recent studies reported increased risks for the development of asthma in children after prenatal exposure to acid-suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases. METHODS: Using the prescription database IADB.nl, we conducted a cohort study amongst 33 536 children in the Netherlands, with a maximum follow-up of 8 years. Maternal exposure was defined as ≥1 dispensed prescription for proton pump inhibitors (PPIs) and/or Histamine 2-antagonists (H2As) during pregnancy. Children were considered to have a drug-treated allergic disease if they received either ≥2 prescriptions for dermal (atopic dermatitis), inhaled (asthma) or nasal (allergic rhinitis) steroids within a 12-month period. Clustered Cox proportional hazard regression was used to estimate crude and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). RESULTS: The aHR for the development of any allergic disease was 1.37 (95% CI: 1.14-1.66) for children exposed to PPIs or H2As. Prenatal exposure to PPIs and/or H2As was associated with atopic dermatitis, asthma and allergic rhinitis with aHRs of 1.32 (95% CI 1.06-1.64), 1.57 (95% CI 1.20-2.05) and 2.40 (95% CI 1.42-4.04), respectively. The aHR for the development of two or more (aHR 2.13 95% CI: 1.43-3.19) and three allergic diseases (aHR 5.18 95% CI: 2.16-12.42) were even more elevated after prenatal exposure to PPIs or H2As. CONCLUSION: Prenatal exposure to PPIs and H2As appeared associated with an increased risk for the development of atopic dermatitis, asthma and allergic rhinitis in the offspring, especially with the development of multiple allergic diseases. Because our study has limitations inherent to observational studies, prospective studies are now warranted to confirm our findings.

Predictors of influenza in the adult population during seasonal and A(H1N1)pdm09 pandemic influenza periods.

We aimed to assess whether the characteristics of influenza-like illness (ILI) cases in the general population were similar during the seasonal and pandemic A(H1N1)pdm09 influenza periods. We conducted a study using a general population database, which included demographic (sex, age) and clinical (underlying medical conditions, influenza vaccination status) information on more than 80 000 subjects. We assessed the most important predictors of ILI during each season by using multiple logistic regression. We descriptively compared whether they were similar during different seasons. The model, including all demographic and clinical characteristics, showed that age ⩾60 years decreased the odds for ILI by 52% and 81% during the seasonal and A(H1N1)pdm09 pandemic periods, respectively. Being vaccinated decreased the odds of ILI for seasonal influenza by 32%, while suffering from the comorbidities other than lung or cardiovascular diseases doubled the odds of ILI during the A(H1N1)pdm09 pandemic.

Determination of venlafaxine and O-desmethylvenlafaxine in dried blood spots for TDM purposes, using LC-MS/MS.

Dried blood spot (DBS) sampling and quantitative analyses of many current therapeutic drug monitoring (TDM)-guided drugs are advantageous because of the minimal invasive sampling strategy. Here, a fast and robust LC-MS/MS method was developed and analytically validated for simultaneous determination of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV) in DBS. Six-millimeter circles were punched out from DBS collected on Whatman DMPK-C paper, and the DBS was extracted with acetonitrile/methanol at 1:3. The total run time was 4.8 min. The assay was linear in the range of 20-1,000 µg/L for both VEN and ODV. Assay accuracy and precision was well within limits of acceptance (LLOQ = 20 µg/L). Normal hematocrit concentrations (0.30-0.50) did not influence the results neither did a normal spot volume (40-80 µL). Punch position at the perimeter instead of the center of the blood spot gave a bias ranging from 2.4 to 10.4%. Correlation between plasma and spiked DBS samples was high. The concentrations found in spiked DBS samples were higher than those in plasma, indicating that a conversion factor for translation of DBS to plasma values is needed. This analytically validated method is suitable for determination of VEN and ODV in DBS and applicable for TDM. The method will be used for TDM of VEN in the Dutch CYSCE multicenter trial (NCT01778907).

Did introduction of pneumococcal vaccines in the Netherlands decrease the need for respiratory antibiotics in children? Analysis of 2002 to 2013 data.

To estimate the effect of the introduction of the 7- and 10-valentpneumococcal vaccines in 2006 and 2011, respectively in the Netherlands, we assessed respiratory antibiotic use in one to nine year-old children between 2002 and 2013. Seasonal autoregressive integrated moving-average models were applied to estimate the percentage reduction in respiratory antibiotic use. When compared with the pre-vaccination period, the proportion of respiratory antibiotic prescriptions fell by 4.94% (95% CI: 4.63 to 5.26) and 9.02% (95% CI: 2.83 to 14.82) after the introduction of the 7-valent vaccine in children aged three and four years, respectively. After the introduction of the 10-valent vaccine, we observed a reduction of 13.04% (95% CI: 2.76 to 22.23), 20.31% (95% CI: 13.50 to 26.58), 16.92% (95% CI: 3.07 to 28.80), 22.34% (95% CI: 3.73 to 37.35), 23.75% (95% CI: 2.37 to 40.44) in two, three, four, six and seven year-old children, respectively. Thus, our results indicate a reduction in respiratory antibiotic prescriptions in young children after introduction of the pneumococcal vaccines. As only children in our study population aged one and two years born after March 2011 had received the 10-valent vaccine, the effects of the 10-valent vaccine in children aged three to nine years likely reflect the effects of the 7-valent vaccine and herd immunity.

The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis.

The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.

Hospital-based cluster randomised controlled trial to assess effects of a multi-faceted programme on influenza vaccine coverage among hospital healthcare workers and nosocomial influenza in the Netherlands, 2009 to 2011.

Nosocomial influenza is a large burden in hospitals. Despite recommendations from the World Health Organization to vaccinate healthcare workers against influenza, vaccine uptake remains low in most European countries. We performed a pragmatic cluster randomised controlled trial in order to assess the effects of implementing a multi-faceted influenza immunisation programme on vaccine coverage in hospital healthcare workers (HCWs) and on in-patient morbidity. We included hospital HCWs of three intervention and three control University Medical Centers (UMCs), and 3,367 patients. An implementation programme was offered to the intervention UMCs to assess the effects on both vaccine uptake among hospital staff and patient morbidity. In 2009/10, the coverage of seasonal, the first and second dose of pandemic influenza vaccine as well as seasonal vaccine in 2010/11 was higher in intervention UMCs than control UMCs (all p<0.05). At the internal medicine departments of the intervention group with higher vaccine coverage compared to the control group, nosocomial influenza and/or pneumonia was recorded in 3.9% and 9.7% of patients of intervention and control UMCs, respectively (p=0.015). Though potential bias could not be completely ruled out, an increase in vaccine coverage was associated with decreased patient in-hospital morbidity from influenza and/or pneumonia.

Routine screening for Coxiella burnetii infection during pregnancy: a clustered randomised controlled trial during an outbreak, the Netherlands, 2010.

Between 2007 and 2010, the Netherlands experienced one of the largest outbreaks of Q fever. Since asymptomatic Coxiella burnetii infection has been associated with maternal and obstetric complications, evidence about the effectiveness of routine screening during pregnancy in outbreak areas is needed. We performed a clustered randomised controlled trial during the Dutch outbreak, in which 55 midwife centres were randomised to recruit pregnant women for an intervention or control strategy. In both groups a serum sample was taken between 20 and 32 weeks of gestation. In the intervention group (n=536), the samples were analysed immediately by indirect immunofluorescence assay for the presence of IgM and IgG (phase I/II) and treatment was given during pregnancy in case of an acute or chronic infection. In the control group (n=693), sera were frozen for analysis after delivery. In both groups 15% were seropositive. In the intervention group 2.2% of the women were seropositive and had an obstetric complication, compared with 1.4% in the control group (Odds ratio: 1.54 (95% confidence interval 0.60-3.96)). During a large Q fever outbreak, routine C. burnetii screening starting at 20 weeks of gestation was not associated with a relevant reduction in obstetric complications and should therefore not be recommended.

Metabolic syndrome in adults with autistic traits: associated psychological, behavioral, and biological factors in females and males - a PharmLines initiative.

Background: While cardiovascular diseases is highly prevalent and an important cause of mortality in autistic adults, knowledge on their increased cardiovascular risk is limited. Hence, this study aimed to investigate psychological, behavioral, and physical factors associated with metabolic syndrome (MetS) in adults with autistic traits. Methods: In total, 17,705 adults from the Lifelines Cohort were included and categorized using Autism Spectrum Quotient-10 sum-scores. The quartiles with highest (HQ-traits-group females: n = 2,635; males: n = 1803) and lowest levels of autistic traits (LQ-traits-group, n = idem) were analyzed. Using multivariable logistic regression, the associations between MetS and (self-reported and interviewed) psychological, behavioral, and physically measured factors in these stratified groups were investigated. Results: Among females, MetS was more common in the HQ-traits-group than in the LQ-traits-group (10.0% versus 7.5%, p < 0.01), while this was not the case among males (HQ-traits-group 13.8% versus LQ-traits-group 13.1%, p = 0.52). In both the female and male HQ-traits-group, the presence of MetS was associated with poorer self-reported health, less daily physical activity, and altered leukocyte counts. Conclusion: These findings underline the relevance of adequate cardiovascular prevention in adults with higher levels of autistic traits. Future research could gain more insight into the relationship between cardiovascular risk and autistic traits in females, and into tailored cardiovascular prevention.

Screening for Coxiella burnetii infection during pregnancy: pros and cons according to the Wilson and Jungner criteria.

In Europe the incidence of human Q fever has dramatically increased over the previous years. Untreated infections with Coxiella burnetii, the causal agent of Q fever, have been associated with both obstetric and maternal complications. The majority of pregnant women with a C. burnetii infection remain asymptomatic, hence screening could be of value to prevent unwanted outcomes in this high-risk group. We applied the updated Wilson and Jungner criteria to review the evidence for routine screening for C. burnetii infection during pregnancy. Since much uncertainty remains about the incidence, clinical consequences, diagnostics and treatment of C. burnetii infection during pregnancy, routine screening for C. burnetii infection during pregnancy should not be recommended. Rigorous studies to assess the effectiveness of C. burnetii screening are warranted.

In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39 weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67-1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

Antibiotic therapy for acute Q fever in The Netherlands in 2007 and 2008 and its relation to hospitalization.

Data about the effectiveness of different antibiotic regimens for the treatment of acute Q fever from clinical studies is scarce. We analysed the antibiotic treatment regimens of acute Q fever patients in 2007 and 2008 in The Netherlands and assessed whether hospitalization after a minimum of 2 days antibiotic therapy was related to the initial antibiotic therapy. Clinical data on antibiotic treatment and risk factors of acute Q fever patients were obtained from general practitioner medical records and self-reported by patients. For the 438 study patients, doxycycline was the most commonly prescribed initial antibiotic in both study years. After adjustments for confounding factors, doxycycline (200 mg/day), moxifloxacin, as well as other possibly effective antibiotics [including other new fluoroquinolones and doxycycline (100 mg/day)] showed significant lower risks for hospitalization compared to ß-lactam antibiotics and azithromycin (reference group), with the lowest risk for doxycycline (200 mg/day) (odds ratio 0·04, 95% confidence interval 0·01-0·22). These data support current guidelines that recommend doxycycline as the first choice antibiotic for treating acute Q fever.