Maternal Sociodemographic Factors Are Associated with Methylphenidate Initiation in Children in the Netherlands: A Population-Based Study.

Multiple factors may contribute to the decision to initiate methylphenidate treatment in children such as maternal sociodemographic factors of which relatively little is known. The objective was to investigate the association between these factors and methylphenidate initiation. The study population included 4243 children from the Generation R Study in the Netherlands. Maternal sociodemographic characteristics were tested as determinants of methylphenidate initiation through a time-dependent Cox regression analysis. Subsequently, we stratified by mother-reported ADHD symptoms (present in 4.2% of the study population). When ADHD symptoms were absent, we found that girls (adjusted HR 0.25, 95%CI 0.16-0.39) and children born to a mother with a non-western ethnicity (compared to Dutch-Caucasian) (adjusted HR 0.42, 95%CI 015-0.68) were less likely to receive methylphenidate. They were more likely to receive methylphenidate when their mother completed a low (adjusted HR 2.29, 95%CI 1.10-4.77) or secondary (adjusted HR 1.71, 95%CI 1.16-2.54) education. In conclusion, boys and children born to a mother of Dutch-Caucasian ethnicity were more likely to receive methylphenidate, irrespective of the presence of ADHD symptoms.

The concordance between self-reported medication use and pharmacy records in pregnant women.

PURPOSE: Several studies have been conducted to assess determinants affecting the performance or accuracy of self-reports. These studies are often not focused on pregnant women, or medical records were used as a data source where it is unclear if medications have been dispensed. Therefore, our objective was to evaluate the concordance between self-reported medication data and pharmacy records among pregnant women and its determinants. METHODS: We conducted a population-based cohort study within the Generation R study, in 2637 pregnant women. The concordance between self-reported medication data and pharmacy records was calculated for different therapeutic classes using Yule's Y. We evaluated a number of variables as determinant of discordance between both sources through univariate and multivariate logistic regression analysis. RESULTS: The concordance between self-reports and pharmacy records was moderate to good for medications used for chronic conditions, such as selective serotonin reuptake inhibitors or anti-asthmatic medications (0.88 and 0.68, respectively). Medications that are used occasionally, such as antibiotics, had a lower concordance (0.51). Women with a Turkish or other non-Western background were more likely to demonstrate discordance between pharmacy records and self-reported data compared with women with a Dutch background (Turkish: odds ratio, 1.63; 95% confidence interval, 1.16-2.29; other non-Western: odds ratio, 1.33; 95% confidence interval, 1.03-1.71). CONCLUSIONS: Further research is needed to assess how the cultural or ethnic differences may affect the concordance or discordance between both medication sources. The results of this study showed that the use of multiple sources is needed to have a good estimation of the medication use during pregnancy.

Antidepressants and heart-rate variability in older adults: a population-based study.

BACKGROUND: Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study. METHOD: In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991-2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs. RESULTS: We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes. CONCLUSION: TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.

Women have a higher risk of hospital admission associated with hyponatremia than men while using diuretics.

Background: Hyponatremia is a common electrolyte disturbance and known adverse drug reaction of diuretics. Women tend to be more susceptible for diuretic associated hyponatremia. The aim of this study was to find more evidence whether women have a higher risk of diuretic associated hyponatremia than men measured at hospital admission for specific diuretic groups and whether there is a sex difference in risk of severity of hyponatremia. Methods: All patients using a diuretic and admitted for any reason to Tergooi MC and Haga Teaching hospital in the Netherlands between the 1st of January 2017 and the 31st of December 2021, with recorded sodium levels at admission were included in this study. Cases were defined as patients with a sodium level <135 mmol/L, while control patients had a sodium level ≥135 mmol/L at admission. Logistic regression analysis was used to calculate odds ratios (OR) with 95% CIs for women versus men and adjusted for potential confounding covariables (age, body mass index, potassium serum level, systolic and diastolic blood pressure, estimated glomerular filtration rate, number of diuretics, comedications and comorbidities). Stratified analyses were conducted for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists), and adjusted for dose. Furthermore, stratified analyses were performed by severity of hyponatremia (severe: <125 mmol/L), mild: 125-134 mmol/L). Results: A total of 2,506 patients (50.0% women) were included, of which 516 had hyponatremia at admission (20.6%, 56.2% women). Women had a statistically significantly higher risk for hyponatremia at admission than men (OR 1.37; 95% CI 1.12-1.66) and after adjustment for potential risk factors (ORadj 1.55; 95% CI 1.22-1.98). Stratified analyses showed increased odds ratios for thiazides (ORadj 1.35; 95% CI 1.00-1.83) and loop diuretics (ORadj 1.62; 95% CI 1.19-2.19) among women. Use of aldosterone antagonists was also increased but not statistically significant (ORadj 1.15; 95% CI 0.73-1.81). Women had a statistically higher risk to develop mild and severe hyponatremia than men (ORadj 1.36; 95% CI 1.10-1.68 and ORadj 1.96; 95%CI 1.04-3.68, respectively). Conclusion: Women have a higher risk of a hospital admission associated with hyponatremia while using diuretics than men. Further research is necessary to provide sex-specific recommendations.

Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy.

Several statins are substrates for the multidrug resistance-associated protein 2 transporter, encoded by the ABCC2 gene. We analyzed in the Rotterdam Study whether the common polymorphisms -24C>T, 1249G>A and 3972C>T in the ABCC2 gene were associated with a dose decrease or switch to another cholesterol-lowering drug in simvastatin and atorvastatin users. These events could indicate an adverse effect or a too strong reduction in cholesterol level. We identified 1014 simvastatin and atorvastatin users during the period 1 January 1991 to 1 January 2010. Associations between genetic variation and the risk of these events were analyzed using Cox proportional hazards modelling. The ABCC2 -24C>T genotype (HR 1.32 95% CI 1.04-1.69) and the H12 haplotype versus the H2 haplotype (HR 1.49; 95% CI 1.06-2.09) were associated with these events in simvastatin users. A similar but not significant association was found in atorvastatin users. To conclude, genetic variation in the ABCC2 gene is associated with these events in simvastatin users.

The effect of thiazide and loop diuretics on urinary levels of free deoxypyridinoline: an osteoclastic bone-resorption marker.

WHAT IS KNOWN AND OBJECTIVE: Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link between adjacent collagen chains to provide structural rigidity. Our aim was to investigate the association between use of thiazides and loop diuretics and urinary levels FDP. METHODS: In this follow-up study, data were obtained from the Rotterdam Study, a large population-based prospective cohort study. For a subset of 658 participants, urinary levels of FDP were measured at baseline. Linear regression analysis was performed to assess the association between the use of thiazides and loop diuretics and the urinary levels of FDP. RESULTS: In women, current use of loop diuretics for less than 42 days was associated with an increased level of urinary FDP (+3·43 nmol deoxypyridinoline per mmol urinary creatinine; 95% CI 1·85; 5·02) compared with no use. However, use for a period of more than 42 days was not associated with an increased level of FDP, nor was past use of loop diuretics. For thiazide diuretics, no statistically significant associations were found. WHAT IS NEW AND CONCLUSION: In women, short-term use of loop diuretics is associated with an increased level of FDP, reflecting increased bone resorption by osteoclasts. As the difference disappears with longer term use, the clinical significance is unclear and the value of FDP as a biomarker in this setting is not established. The molecular mechanism for the observed differences in bone fracture rates with use of diuretics remains unclear.

Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study.

AIMS/HYPOTHESIS: Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. METHODS: Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a cohort of incident users of insulin, the association between insulin glargine and other insulin analogues, respectively, and cancer was analysed in comparison with human insulin using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. The first hospital admission with a primary diagnosis of cancer was considered as the main outcome; secondary analyses were performed with specific cancers as outcomes. RESULTS: Of the 19,337 incident insulin users enrolled, 878 developed cancer. Use of insulin glargine was associated with a lower risk of malignancies in general in comparison with human insulin (HR 0.75, 95% CI 0.71, 0.80). In contrast, an increased risk was found for breast cancer (HR 1.58, 95% CI 1.22, 2.05). Dose-response relationships could not be identified. CONCLUSION/INTERPRETATION: Users of insulin glargine and users of other insulin analogues had a lower risk of cancer in general than those using human insulin. Both associations might be a consequence of residual confounding, lack of adherence or competing risk. However, as in previous studies, we demonstrated an increased risk of breast cancer in users of insulin glargine in comparison with users of human insulin.

Home-based intravenous treatment with reslizumab for severe asthma in the Netherlands - An evaluation.

The anti-IL-5 biologic reslizumab for the treatment of severe eosinophilic asthma is administered intravenously. In the current study home administration of intravenous reslizumab was evaluated in 24 patients included between 2019 (July) and 2020 (July). This is the first study to show that intravenous reslizumab can be administered safely and successfully in an outpatient setting. Notably, not all patients prefer home administration and severe asthma patients may have different needs when it comes to choosing treatment at home or in the hospital.

Real-World Metastatic Renal Cell Carcinoma Treatment Patterns and Clinical Outcomes in The Netherlands.

The number of treatment options for patients with metastatic renal cell carcinoma (mRCC) has significantly grown in the last 15 years. Although randomized controlled trials are fundamental in investigating mRCC treatment efficacy, their external validity can be limited. Therefore, the efficacy of the different treatment options should also be evaluated in clinical practice. We performed a chart review of electronic health records using text mining software to study the current treatment patterns and outcomes. mRCC patients from two large hospitals in the Netherlands, starting treatment between January 2015 and May 2020, were included. Data were collected from electronic health records using a validated text mining tool. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method. Most frequent first-line treatments were pazopanib (n = 70), sunitinib (n = 34), and nivolumab with ipilimumab (n = 28). The overall median PFS values for first-line treatment were 15.7 months (95% confidence interval [95%CI], 8.8-20.7), 16.3 months (95%CI, 9.3-not estimable [NE]) for pazopanib, and 6.9 months (95% CI, 4.4-NE) for sunitinib. The overall median OS values were 33.4 months (95%CI, 28.1-50.9 months), 39.3 months (95%CI, 29.5-NE) for pazopanib, and 28.1 months (95%CI, 7.0-NE) for sunitinib. For nivolumab with ipilimumab, median PFS and median OS were not reached. Of the patients who finished first- and second-line treatments, 64 and 62% received follow-up treatments, respectively. With most patients starting on pazopanib and sunitinib, these real-world treatment outcomes were most likely better than in pivotal trials, which may be due to extensive follow-up treatments.

Reporting of sex-specific outcomes in trials of interventions for cardiovascular disease: Has there been progress?

In the past decade, the leading international cardiology societies have released statements that emphasize the importance of sex-specific reporting of the findings of clinical trials in cardiovascular research. To find out whether this has led to improvement, we compared sex-specific reporting of efficacy and safety outcomes for trials of cardiovascular drug interventions presented at the major clinical trials sessions of the European Society of Cardiology (ESC), American Heart Association (AHA) and the American College of Cardiology (ACC) before and after publication of these statements. We found that sex-specific efficacy and safety outcomes of the most influential cardiovascular intervention trials are still not systematically presented.

Sex differences associated with adverse drug reactions resulting in hospital admissions.

BACKGROUND: Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5-1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. METHODS: ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged ≥ 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. RESULTS: A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. CONCLUSIONS: There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.

Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus.

The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin. Incident metformin users in the Rotterdam Study, whose HbA1c measurements were available, were identified. Associations between 11 tagging single nucleotide polymorphisms in the SLC22A1 gene and change in the HbA1c level were analyzed. A total of 102 incident metformin users were included in this study sample. Except for the rs622342 A>C polymorphism, no significant differences in metformin response were observed. For each minor C allele at rs622342, the reduction in HbA1c levels was 0.28% less (95% CI 0.09-0.47, P=0.005). After Bonferroni correction, the P-value was 0.050. To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus.

Vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam Study.

OBJECTIVE: Besides effects on hemostasis, vitamin K-dependent proteins play a role in bone mineralization and arterial calcification. We investigated the association between the VKORC1 1173C>T polymorphism and calcification of the aortic far wall in a large population-based cohort. METHODS AND RESULTS: Aortic calcification was diagnosed by radiographic detection of calcified deposits in the abdominal aorta. In all cohort members for whom DNA was available, the C1173T SNP of VKORC1 (rs9934438) was determined. With multivariable logistic regression analysis the association between this polymorphism and the risk of aortic calcification was calculated, adjusted for potential confounders. The T allele frequency of the VKORC1 1173C>T polymorphism was 38.8%. 1185 (37.2%) persons were homozygous CC, 1529 (48,0%) were heterozygous CT and 473 (14.8%) were homozygous TT. Persons with at least one T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender. CONCLUSIONS: The T-allele of the VKORC1 1173C>T polymorphism was associated with a significantly higher risk of aortic calcification in Whites.

Failure of a new antivenom to treat Echis ocellatus snake bite in rural Ghana: the importance of quality surveillance.

This study compares two antivenoms used to treat Echis ocellatus snake bite patients at Mathias Hospital, Yeji, central Ghana. FAV-Afrique antivenom (Aventis Pasteur) was given to 278 patients during 2001--2003, whilst Asna Antivenom C (Bharat Serum and Vaccines Ltd) was used in 2004 to treat 66 patients. The two groups had comparable patient attributes, time from snake bite to treatment and staff adherence to the tested treatment protocol. The antivenom C group required more repeat doses and twice the amount of antivenom to treat coagulopathy. Of greater concern, the antivenom C mortality rate was 12.1%, a marked rise from the 1.8% rate in the earlier FAV-Afrique antivenom group. In this study, antivenom C was ineffective as treatment for West African E. ocellatus snake venom. This illustrates the absolute need for regional pilot tests to assess the effectiveness of a new antivenom against local snake venoms before its sole and general distribution in a region is initiated.

Filled prescriptions of age-related contraindicated drugs in children: a one-year nationwide cohort study in the Netherlands.

Background Children are still prescribed age contraindicated drugs, but information about the number and type of these drugs dispensed for children in the Netherlands is limited. Objective To determine the incidence and prevalence of contraindicated drugs that were dispensed for the use by children. Setting The study was conducted in the Netherlands with routinely collected data from 95% of all community pharmacies. Method We performed a one-year nationwide observational study where all patients aged 17 years or younger who have received at least one prescription in 2016 were included. Contraindicated drugs were selected, according to the 5th level of ATC code, using different information sources. Main outcome measure The proportion of (newly) contraindicated drugs that were dispensed to children. Results In total, 3.9% of all children received at least one drug that was contraindicated for their age. The highest percentage of contraindicated drugs that was dispensed, was observed in patients aged 1-2 years and 13-17 years (7.0 and 5.7%, respectively) and the percentage of contraindicated drugs that were dispensed was higher in female than in male patients (4.3 and 3.6%, respectively; p value < 0.001). Conclusion The results of this study show that a substantial percentage of children received a drug that was conta-indicated for their age, and it happes more in female than in male patients. Furthermore, the information about this type of contraindications is limited and inconsistent.

Angiotensin converting enzyme inhibitor associated cough: a population-based case-control study.

The objectives of this study were to determine the risk for coughing as an adverse reaction to angiotensin converting enzyme (ACE) inhibitors under everyday circumstances in a large population and to study whether this adverse effect is more common in women. A population-based case-control study was used. The study was set in the practices of 161 Dutch general practitioners (GPs), in which all consultations, morbidity, mortality, medical interventions and prescriptions were registered during 4 consecutive 3-month periods in 4 consecutive groups of 40-41 GPs. The subjects were 2436 patients with incident coughing and up to 3 controls per case were obtained (total group: 7348 controls), matched for GP and a contemporary consultation in the same 3 months. All cases and controls were 20 years or older and had no notification of respiratory infections, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the 3-month period. The results showed that cases were 3.6 times as likely as controls to have been exposed to ACE inhibitors (95% CI: 2.4-5.5) but after adjustment for potential confounders the odds ratio was 2.5 (95% CI: 1.6-3.9). The crude odds ratio for males was 2.7 (95% CI: 1.4-5.1) and for females 4.2 (95% CI: 2.4-7.5). The adjusted odds ratio for males was 1.8 (95% CI: 0.9-3.5) and for females 2.7 (95% CI: 1.5-4.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Protocol and monitoring to improve snake bite outcomes in rural Ghana.

A study was conducted in Mathias Hospital, Yeji, an area of Ghana, where snake bite cases are an important cause of morbidity and mortality, with a case fatality rate of 11% (8/72). Case management difficulties included uncertainty about the assessment of the severity of envenoming, the dosage of antivenom, and the response to treatment. An intervention with several components was introduced: development of a treatment protocol, staff training, monitoring of compliance and patient education. During a 33-month post-intervention period there was excellent protocol compliance, fewer snake bite complications, and a fall in mortality rate to 1.3% (3/238) compared with a 15-month baseline review. There was a 50% increase in snake bite admissions and fewer delays. To improve snake bite outcomes in comparable settings, particularly if inexperienced staff are involved in care, we recommend a similar quality assurance project, involving case review and use of a treatment protocol with monitoring of compliance to sustain an improved approach.

Malaria prophylaxis and the reduction of anemia at childbirth.

OBJECTIVES: To assess the effect of introducing chloroquine prophylaxis during pregnancy on prevalence of anemia (<10.9 g/dl) at childbirth and perinatal outcome. METHODS: Observational study in a rural district hospital in Ghana, which compared 2803 women who received chloroquine prophylaxis during pregnancy with 3084 historical controls, who had not received prophylaxis during pregnancy. Main outcome measures were hemoglobin level at childbirth, perinatal mortality and birth weight. RESULTS: Mean hemoglobin level before childbirth increased from 10.7 g/dl (S.D.=1.0 g/dl) to 11.0 g/dl (S.D.=0.9 g/dl). Prevalence of anemia decreased from 29.4 to 13.3% (OR=0.4 and 95% CI=0.3-0.4). Prevalence of moderately severe anemia (<9.0 g/dl) decreased from 4.4 to 3.3% (OR=0.7, 95% CI=0.6-0.97). Perinatal mortality and low birth weight (<2500 g) remained unchanged. CONCLUSIONS: Routine chloroquine prophylaxis in pregnancy is useful in reducing anemia at childbirth in malaria-endemic regions. Fetal outcome did not improve with chloroquine prophylaxis in this study.

An outbreak of mumps in the Province of León Spain 1995-1996.

In Spain mumps vaccine is given at the age of 15 months together with measles and rubella vaccines since 1982. Increased numbers of cases and outbreaks of mumps appeared in several autonomous communities in 1995. An outbreak of mumps in the province of.

An outbreak of mumps in the Province of Leon Spain 1995-1996.

In Spain mumps vaccine is given at the age of 15 months together with measles and rubella vaccines since 1982. Increased numbers of cases and outbreaks of mumps appeared in several autonomous communities in 1995. An outbreak of mumps in the province of -