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Purpose: Type 2 diabetes requires patients to make lifestyle changes and perform daily self-care. To determine at what stages patients may need particular self-management support, we examined (1) whether patients’ performance of self-care related to their diabetes duration, and (2) whether illness characteristics (treatment and complications) and diabetes-related distress influenced this relationship. Methods: Cross-sectional data from 590 type 2 diabetes patients were analysed through linear and logistic regression analysis. Self-care behaviours were assessed by the revised Summary of Diabetes Self-Care Activities (SDSCA) measure. Diabetes duration (model 1), treatment and complications (model 2), and distress, as assessed by the Problem Areas In Diabetes (PAID) scale (model 3), were stepwise included. Sociodemographic characteristics were added to all models to account for confounding. Results: Patients with a longer history of diabetes were less physically active, but monitored their blood glucose levels more frequently than more recently diagnosed patients. These relationships were mediated by the presence of complications and the use of insulin, with lower levels of physical activity being found among patients with macrovascular complications and higher frequencies of glucose monitoring among patients on insulin. All predictors together explained maximally 5% of the variance in self-care, except for glucose monitoring (37%) and smoking (11%). Conclusion: Type 2 diabetes patients’ self-care activity changes over the course of illness. To provide tailored self-management support, diabetes care providers should take into account patients’ phase of illness, including their treatment and complications, as well as their personal characteristics and distress level.

The Integrated Multimorbidity Care Model (IMCM), developed by the Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS), proposes a set of 16 multidimensional components (i.e., recommendations) to improve the care of persons with multimorbidity in Europe. This study aimed at analyzing the potential applicability of the IMCM. We followed a qualitative approach that comprised two phases: (1) The design of a case study based on empirical clinical data, which consisted of a hypothetical woman with multimorbidity, type 2 diabetes mellitus, mental health, and associated social problems, and (2) the creation of a consensus group to gather the opinions of a multidisciplinary group of experts and consider the potential applicability of the IMCM to our case study. Experts described how care should be delivered to this patient according to each model component, suggested the use of specific rating scales and tools to assess her needs in a comprehensive and regular way, and pointed our crucial health and social resources to improve her care process. Experts also highlighted patient-centered, integrated and tailored care as one of the keystones of quality healthcare. Our results suggest that the IMCM is applicable in complex patients with multimorbidity.

Deze rapportage beschrijft de wensen en eisen voor het toekomstige BART! participatiesysteem. Dit rapport vormt onderdeel van het iteratieve ontwerpproces waarin behoeftenonderzoek, ontwerp, ontwikkeling en beproeving achtereenvolgens plaatsvindt in nauwe samenwerking met de beoogde eindgebruikers.

Aims: Lidocaine is used to treat neonatal seizures refractory to other anticonvulsants. It is effective, but also associated with cardiac toxicity. Previous studies have reported on the pharmacokinetics of lidocaine in preterm and term neonates and proposed a dosing regimen for effective and safe lidocaine use. The objective of this study was to evaluate the previously developed pharmacokinetic models and dosing regimen. As a secondary objective, lidocaine effectiveness and safety were assessed. Methods: Data from preterm neonates and (near-)term neonates with and without therapeutic hypothermia receiving lidocaine were included. Pharmacokinetic analyses were performed using non-linear mixed effects modelling. Simulations were performed to evaluate the proposed dosing regimen. Lidocaine was considered effective if no additional anticonvulsant was required and safe if no cardiac adverse events occurred. Results: Data were available for 159 neonates; 50 (31.4%) preterm and 109 term neonates, of whom 49 (30.8%) were treated with therapeutic hypothermia. Lidocaine clearance increased with postmenstrual age by 0.69%/day (95% confidence interval 0.54–0.84%). During therapeutic hypothermia (33.5°C), lidocaine clearance was reduced by 21.8% (7.26%/°C, 95% confidence interval 1.63–11.2%) compared to normothermia (36.5°C). Simulations demonstrated that the proposed dosing regimen leads to adequate average lidocaine plasma concentrations. Effectiveness and safety were assessed in 92 neonates. Overall effectiveness was 53.3% (49/92) and 56.5% (13/23) for neonates receiving the proposed dosing regimen. No cardiac toxicity was observed. Conclusion: Lidocaine pharmacokinetics was adequately described across the entire neonatal age range. With the proposed dosing regimen, lidocaine can provide effective and safe treatment for neonatal seizures.

Background: Phenobarbital and midazolam are commonly used drugs in (near-)term neonates treated with therapeutic hypothermia for hypoxic-ischaemic encephalopathy, for sedation, and/or as anti-epileptic drug. Phenobarbital is an inducer of cytochrome P450 (CYP) 3A, while midazolam is a CYP3A substrate. Therefore, co-treatment with phenobarbital might impact midazolam clearance. Objectives: To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines. Methods: Data were collected in the prospective multicentre PharmaCool study. In the present study, neonates treated with therapeutic hypothermia and receiving midazolam and/or phenobarbital were included. Plasma concentrations of phenobarbital and midazolam including its metabolites were determined in blood samples drawn on days 2–5 after birth. Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs. Results: Data were available from 113 (phenobarbital) and 118 (midazolam) neonates; 68 were treated with both medications. Only clearance of 1-hydroxy midazolam was influenced by hypothermia. Phenobarbital co-administration increased midazolam clearance by a factor 2.3 (95% CI 1.9–2.9, p < 0.05). Anticonvulsant effectiveness was 65.5% for phenobarbital and 37.1% for add-on midazolam. Conclusions: Therapeutic hypothermia does not influence clearance of phenobarbital or midazolam in (near-)term neonates with hypoxic-ischaemic encephalopathy. A phenobarbital dose of 30 mg/kg is advised to reach therapeutic concentrations. Phenobarbital co-administration significantly increased midazolam clearance. Should phenobarbital be substituted by non-CYP3A inducers as first-line anticonvulsant, a 50% lower midazolam maintenance dose might be appropriate to avoid excessive exposure during the first days after birth.

Objective: Evaluate the incidence of and risk factors for behavioural problems in twin-twin transfusion syndrome (TTTS) survivors treated with fetoscopic laser coagulation.Design: Observational cohort study.Setting: National referral center for fetal therapy, Leiden University Medical Center, The Netherlands.Patients: Behavioural outcome was assessed in 417 TTTS survivors, at the age of 2 years.Interventions: Parents completed the Child Behavior Checklist for their twins. Antenatal, neonatal and follow-up data including Bayley III and a neurological exam were recorded from the medical database.Main outcome measures: The incidence of and risk factors for behavioural problems.Results: 332 twin pregnancies (664 fetuses) were treated with fetoscopic laser for TTTS between 2008 and 2015. For 517 children eligible for follow-up, 417 (81%) Child Behavior Checklist questionnaires were completed. The study group was born at a mean gestational age of 32.8 weeks±3.2. Total behavioural problems within the borderline to clinical range were reported in 8% (95% CI 5.9 to 11.2) of survivors, compared with 10% in the general Dutch population (p=0.12). No difference between donors and recipients was detected (p=0.84). Internalising and externalising problems were reported in 9.4% (95% CI 6.9 to 12.6) and 11.5% (95% CI 8.8 to 15.0), respectively. Severe neurodevelopmental impairment was more frequent in the children with behavioural problems. High maternal educational level was associated with lower behavioural problem scores.Conclusion: Parents of twins treated with fetoscopic laser therapy for TTTS do not report more behavioural problems compared with general population norms. More behavioural problems are reported in children with severe neurodevelopmental impairment.

Objectives. Hepatitis B virus (HBV) was believed to have minimal impact on pregnancy outcomes apart from the risk of perinatal transmission. In more recent years, there have been reports of adverse associations, most consistently preterm birth (PTB), but this is in the context of high rates of caesarean section. The aim of this study was to explore the association of HBV on pregnancy outcomes in marginalized, low-income populations on the Myanmar-Thailand border. Methods. HBsAg positive (+) point of care rapid detection tests results were confirmed by immunoassays. Women with a confirmed HBsAg status, HIV- and syphilis-negative at first antenatal care screening, singleton fetus and known pregnancy outcome (Aug-2012 to Dec-2016) were included. Logistic regression analysis was used to evaluate associations between HBV group (controls HBsAg negative, HBsAg+/HBeAg-, or HBsAg+/HBeAg+) and pregnancy outcome and comorbidity. Results. Most women were tested, 15,046/15,114 (99.6%) for HBV. The inclusion criteria were not met for 4,089/15,046 (27.2%) women due mainly to unavailability of pregnancy outcome and nonconfirmation of HBsAg+. In evaluable women 687/11,025 (6.2%) were HBsAg+, with 476/11,025 (4.3%) HBsAg+/HBeAg- and 211/11,025 (1.9%) were HBsAg+/HBeAg+. The caesarean section rate was low at 522/8,963 (5.8%). No significant associations were observed between pregnancy comorbidities or adverse pregnancy outcomes and HBV status. Conclusions. The results highlight the disease burden of HBV in women on the Myanmar-Thailand border and support original reports of a lack of significant associations with HBsAg+ irrespective of HBeAg status, for comorbidity, and pregnancy outcomes in deliveries supervised by skilled birth attendants.

ObjectiveMorphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.Study designTerm and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008-2010 (SHIVER) and 2010-2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.Results244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C- 8.41%/°C, pConclusionsClearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.Trial registrationwww.trialregister.nl NTR2529.

Sociale media bieden veel nieuwe kansen en mogelijkheden. Kijk bijvoorbeeld naar al die initiatieven in buurten en wijken, waarin bewoners elkaar opzoeken en zich met elkaar verbinden. Ze willen samen werken aan een betere buurt. Hun sociale netwerken groeien en gedijen zonder enige overheidsbemoeienis. Ook het aantal toepassingen daarvoor groeit.

Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and >62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation.