Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations

Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.     

The relative risk of noncervical high-risk human papillomavirus-related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3: A population-based study

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long-lasting increased risk for noncervical high-risk human papillomavirus (hrHPV)-related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post-treatment. Cases of noncervical hrHPV-related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person-years of follow-up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV-related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow-up and prophylactic hrHPV vaccination are warranted.     

Tumor control of cervical lymph node metastases of unknown primary origin: the impact of the radiotherapy target volume

European Archives of Oto-Rhino-Laryngology - Debate on the extent of treatment of neck metastasis of cancer of unknown primary tumors (CUPs) is still ongoing. In two Dutch tertiary referral...     

The Evaluation of Daily Life Activities after Application of an Osseointegrated Prosthesis Fixation in a Bilateral Transfemoral Amputee: A Case Study

Individuals with a transfemoral amputation (TFA) may experience limitations in daily life due to reduced mobility and prosthesis-related problems. An osseointegrated prosthesis fixation (OPF) procedure in amputees might contribute to a solution for patients with short stumps or socket-related problems. To date, no study has specifically described the application of an OPF procedure in individuals with a TFA. This study evaluated the level of daily life activities of a 21-year old service member with a bilateral TFA and cerebral trauma. Due to a short stump length and coordination problems, an OPF procedure was deemed the most suitable option.The result of this procedure and the rehabilitation program showed an increased mobility and satisfaction as obtained by the assessment of life habits questionnaire (LIFE-H) and lower extremity functional scale. The participant was able to walk short distances and the Genium knee provided a stance position. Stair ambulation is impossible because of inadequate muscle capacity.In this specific case we conclude that the quality of life improved through the use of an OPF. However, OPF might not be the appropriate device for every individual with TFA, due to varying bone compositions, co-morbidities, and limited clinical experience and unknown long-term effects.     

How does cultural capital keep you thin? Exploring unique aspects of cultural class that link social advantage to lower body mass index

A widely used indicator for cultural class is strongly related to a lower body mass index (BMI): cultural capital measured as ‘highbrow' taste. This study’s objective was to theorise and measure aspects of cultural class that are more plausibly linked to low BMI, and subsequently explore their relevance. Building on Bourdieusian theory we derive four of those aspects: ‘refinement’ (valuing form and appearance over function and substance), ‘asceticism’ (self-imposed constraints), ‘diversity’ (appreciation of variety in and of itself) and ‘reflexivity’ (reflexive deliberation and internal dialogue). Using standardised interviews with 597 participants in the Dutch GLOBE study in 2016, we subsequently demonstrate: (i) newly developed survey items can reliably measure four aspects of cultural class: ‘asceticism’, ‘general refinement’, ‘food refinement’ and ‘reflexivity’ (Cronbach’s alphas between 0.67–0.77); (ii) embodied/objectified cultural capital (i.e. ‘highbrow’ taste) was positively associated with general refinement, food refinement and reflexivity, whereas institutionalised cultural capital (i.e. education) was positively associated with asceticism and reflexivity; (iii) asceticism, general refinement, reflexivity, but not food refinement, were associated with a lower BMI; (iv) asceticism, general refinement and reflexivity together accounted for 52% of the association between embodied/objectified cultural capital and BMI, and 38% of the association between institutionalised cultural capital and BMI.     

Neonatal herpes infections in The Netherlands in the period 2006–2011

Objective: To monitor the incidence of neonatal herpes in The Netherlands between 2006 and 2011, as well as the adherence to the rather conservative Dutch prevention policy.

Methods: Questionnaires were sent to all virology laboratories (n?=?44), gynaecology and paediatrics departments of all hospitals in The Netherlands (n?=?89). Questionnaires for the laboratories pertained to rates of proven cases of neonatal herpes; for the gynaecologists and paediatricians it pertained to rates of genital herpes during pregnancy and neonatal herpes, and their policy. For gynaecologists this concerned the risk of herpes simplex virus transmission in case of primary genital herpes during pregnancy or labour; for paediatricians it concerned the diagnostic policy in a neonate suspected of neonatal herpes.

Results: For the period 2006–2011 38 cases of neonatal herpes were reported, yielding an incidence of 4.7 per 100?000 births. The estimated annual number of pregnant women with primary or recurrent genital herpes was 278. Of the responding gynaecologists and paediatricians, only 59% and up to 39%, respectively, reported a policy in accordance with the national guideline.

Conclusions: The incidence of neonatal herpes in The Netherlands seems to have increased in the period 2006–2011. Combined with suboptimal guideline adherence this warrants strategies to improve awareness and subsequent adherence.