The Qualitative Assessment of Two Translated Dutch Spirituality Scales for Children.

PURPOSE: This article describes the translation and qualitative assessment and small scale validation of two spirituality scales designed for children from English to Dutch and includes the translation and validation process and the results of the two most commonly used and best validated measurement instruments for spirituality in children: the Feeling Good, Living Life scale (FGLL) by Fisher (2004, 2009) and the Spirituality Sensitivity Scale for Children by Stoyles et al. (2012). DESIGN AND METHODS: The translation process was designed according to Beaton et al. (2000) and both the translation and the validation process followed the instructions of the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN, 2018). The qualitative validation was done by a three-step test-interview eliciting the face validity of both questionnaires. RESULTS AND CONCLUSIONS: The results show that both instruments were reliably translated, are face valid with some minor alterations and structurally validated overall in the small-scale pilot. PRACTICE IMPLICATIONS: More attention from healthcare professionals and educators should be directed at using spiritual measuring instrument to develop the spiritual vocabulary of children. A larger study is needed to also confirm the cultural validity of the translated scales.

Results of plate fixation for humerus fractures in a large single-center cohort.

INTRODUCTION: This study aims to describe the results of plate fixation in one of the largest single-center cohorts that employs plate fixation as the golden standard. Additionally, risk factors related to a negative outcome were identified. MATERIALS AND METHODS: This was a retrospective cohort study of all patients treated for a humeral shaft fracture in a level-one trauma center between January 2010 and December 2017 with a mean follow-up of 1 year. RESULTS: Plate fixation was performed in 102 patients with a humeral shaft fracture. The mean age was 50 (SD 20) years with 54.9% (n = 56) being male. Forty-eight percent (n = 48) had an AO type-A, 34.3% (n = 35) type-B, and 18.7% (n = 19) type-C fracture. Deep surgical site infections and non-union occurred in 1% (n = 1) and 3.9% (n = 4) of patients, respectively. Revision of the implant was performed in 15.7% (n = 16) mainly due to implant-related complaints. Only one patient developed radial nerve palsy after surgery. The median duration to radiological fracture healing and full-weight bearing was 18 (range 7-65) weeks and 14 (range 6-56) weeks, respectively. Risk factors for negative outcome included higher age, osteoporosis, open and higher AO class fractures, performing surgery during out-office hours, and the use of LCP 3.5-mm plate and an anterolateral approach. CONCLUSION: Plate fixation for humeral shaft fractures has low risks of complications. It should be emphasized that the complications can be further minimized with a greater surgical expertise and by refraining from performing a surgery during out-office hours.

Field and laboratory findings following the large-scale use of intermediate type infectious bursal disease vaccines in Denmark.

Following a period of clinical outbreaks of very virulent infectious bursal disease virus (vvIBDV) in Denmark, the histological bursal lesion score (HBLS) was used on a national scale to screen broiler flocks vaccinated with intermediate IBD vaccines for lesions indicative of IBDV challenge. High lesion scores were detected in a high percentage of healthy and well performing flocks despite the lack of other indications of the presence of vvIBDV. RT-PCR and subsequent sequencing showed the frequent presence of H253Q and H253N IBDV strains that were genetically close to the sequence of the intermediate vaccines with a relative risk ratio of 13.0 (P < 0.0001) in intermediate vaccine A or B vaccinated flocks compared to unvaccinated flocks. The relevance of these H253Q and H253N strains was tested under experimental conditions using a protocol derived from the European Pharmacopoeia for safety of live IBD vaccines. The results confirmed the higher pathogenicity for the bursa of these strains compared to intermediate vaccines as well as the negative effect on antibody response to a Newcastle disease (ND) vaccination performed at the peak of the bursa damage. The efficacy of the ND vaccination was still 100% showing that the H253N and H253Q IBDV strains would be considered as safe vaccine viruses. In conclusion, the use of the HBLS to screen commercial broiler flocks vaccinated with intermediate IBD vaccines for the presence of vvIBDV does not seem to be a reliable method due to the frequent occurrence of H253N and H253Q strains in those flocks. For screening of IBD vaccinated flocks for the presence of vvIBDV or other field strains, the RT-PCR with subsequent sequencing seems to be most suitable.

Drug-drug interactions in pediatric oncology patients.

BACKGROUND: Drug-drug interactions (DDIs) can negatively affect pharmacotherapy. However, pediatric DDI studies are scarce. We undertook an exploratory study to investigate prevalence and clinical relevance of DDIs between cytostatic and noncytostatic drugs in outpatient pediatric oncology patients. PROCEDURE: After informed consent and inclusion, the following information was collected: currently prescribed noncytostatic and cytostatic drugs, comorbidities, and use of over-the-counter (OTC) drugs, complementary and alternative medicines (CAMs), and dietary supplements. All medication was screened for DDIs according to two databases: Micromedex® Solutions and the Dutch drug database G-Standard. The researcher presented DDIs with an associated potential for adverse outcome and a proposal for intervention to three independent experts. If the experts considered a DDI to be potentially clinically relevant and requiring intervention, the physician was notified. RESULTS: Seventy-three patients were included (median age 8.9 years). A total of 67 different DDIs were counted (66 in Micromedex® Solutions, 14 in G-Standard, and 13 DDIs in both databases). The medication reviews resulted in 35 interventions related to 11 different DDIs. The majority of DDIs concerned noncytostatic drugs (25/35) and one third occurred between cytostatic and noncytostatic drugs (10/35). The use of QTc-interval-prolonging drugs resulted in one intervention. The use of OTC drugs, CAM, or dietary supplements did not lead to DDIs. CONCLUSIONS: This study resulted in a selection of 11 potentially clinically relevant DDIs for 73 outpatients in our pediatric oncology department. Interventions were formulated in close collaboration between physicians and clinical pharmacists. Future research should focus on assessing DDIs concerning QTc-interval prolongation.

The Role of Spirituality in Lifestyle Changing Among Patients with Chronic Cardiovascular Diseases: A Literature Review of Qualitative Studies.

Chronic cardiovascular diseases (CVD) are diseases with marked morbidity. Patients are often advised to change their lifestyle to prevent complications and impairment of their diseases. Compliance, however, is influenced by multiple factors. Initial studies show that spirituality is an important aspect in health behavior and lifestyle changing, but to health professionals like nurses this is unknown. The aim of this review is to investigate and synthesize evidence about the role of spirituality in lifestyle changing in patients with chronic CVD. A comprehensive search was conducted in electronic databases Academic Search Premier, E-journals, Medline and PubMed, published between the years 2000-2015. After selection based on pre-set inclusion criteria, studies were retrieved and evaluated on quality using the criteria of the QOREC. Twelve studies with a qualitative empirical design and mixed methods were included. This review shows that spirituality, is related to the self-management of patients with chronic diseases. For instance, lifestyle changes are experienced as a continuous inner battle. Religion gives strength, but is also experienced as a struggle. Feelings of guilt and becoming a victim influence patients' experience. For effectively advising patients with CVD on lifestyle changes, nurses cannot ignore this factor but further investigation is required.

Vertex Corrections for Positive-Definite Spectral Functions of Simple Metals.

We present a systematic study of vertex corrections in a homogeneous electron gas at metallic densities. The vertex diagrams are built using a recently proposed positive-definite diagrammatic expansion for the spectral function. The vertex function not only provides corrections to the well known plasmon and particle-hole scatterings, but also gives rise to new physical processes such as the generation of two plasmon excitations or the decay of the one-particle state into a two-particle-one-hole state. By an efficient Monte Carlo momentum integration we are able to show that the additional scattering channels are responsible for a reduction of the bandwidth, the appearance of a secondary plasmon satellite below the Fermi level, and a substantial redistribution of spectral weights. The feasibility of the approach for first-principles band-structure calculations is also discussed.

Drug-drug interactions in patients treated for cancer: a prospective study on clinical interventions.

BACKGROUND: Drug-drug interactions (DDIs) are of major concern in oncology, since cancer patients typically take many concomitant medications. Retrospective studies have been conducted to determine the prevalence of DDIs. However, prospective studies on DDIs needing interventions in cancer patients have not yet been carried out. Therefore, a prospective study was designed to identify DDIs leading to interventions among ambulatory cancer patients receiving anticancer treatment. PATIENTS AND METHODS: Patients starting with a new treatment regimen with i.v. or oral anticancer medication were asked to participate. The patients' medication was checked for DDIs by using drug interaction software. An expert team of clinical pharmacologists evaluated the relevance of these identified DDIs. If a DDI was qualified as potentially clinically relevant, an intervention was proposed to the treating (hemato)oncologist. Several variables were studied as determinants for performing an intervention. Descriptive statistics and uni- and multivariate logistic regression analyses were carried out. RESULTS: In this study, 302 patients were included. A total of 603 DDIs were identified by the drug interaction software and judged by the expert team. Of all 603 DDIs, 120 DDIs were considered potentially clinically relevant. These 120 DDIs, present in a total of 81 patients, resulted in a clinical intervention already executed by the (hemato)oncologist in 39 patients (13%), while an additional intervention was proposed by a clinical pharmacologist in 42 patients (14%). The number of comorbidities and the number of 'over-the-counter' drugs were identified as determinants. CONCLUSIONS: Clinical interventions on DDIs are frequently required among patients starting with anticancer therapy. Structured screening for these potentially clinically relevant DDIs, by (hemato)oncologists in close collaborations with clinical pharmacologists, should take place before the start and during anticancer treatment. CLINICAL TRIALS NUMBER: This study was registered at the Dutch Trial Registry under number NTR3760.

Pick-up and drop transfer of diamond nanosheets.

Nanocrystalline diamond (NCD) is a promising material for electronic and mechanical micro- and nanodevices. Here we introduce a versatile pick-up and drop technique that makes it possible to investigate the electrical, optical and mechanical properties of as-grown NCD films. Using this technique, NCD nanosheets, as thin as 55 nm, can be picked-up from a growth substrate and positioned on another substrate. As a proof of concept, electronic devices and mechanical resonators are fabricated and their properties are characterized. In addition, the versatility of the method is further explored by transferring NCD nanosheets onto an optical fiber, which allows measuring its optical absorption. Finally, we show that NCD nanosheets can also be transferred onto two-dimensional crystals, such as MoS2, to fabricate heterostructures. Pick-up and drop transfer enables the fabrication of a variety of NCD-based devices without requiring lithography or wet processing.

Comparing the effectiveness and costs of Bevacizumab to Ranibizumab in patients with Diabetic Macular Edema: a randomized clinical trial (the BRDME study).

BACKGROUND: The effectiveness of ranibizumab in the treatment of diabetic macular edema has been proven with large clinical trials. For bevacizumab only two clinical trials have been published and a head-to-head comparison is lacking to date. However, if proved non-inferior to ranibizumab, use of the off-label bevacizumab could reduce costs enormously without a loss in visual acuity. A cost-effectiveness study has been designed to substantiate this hypothesis. AIM: To compare the effectiveness and costs of 1.25 mg of bevacizumab to 0.5 mg ranibizumab given as monthly intravitreal injections during 6 months in patients with diabetic macular edema. It is hypothesized that bevacizumab is non-inferior to ranibizumab regarding its effectiveness. DESIGN: This is a randomized, controlled, double masked, clinical trial in 246 patients in seven academic trial centres in The Netherlands. OUTCOMES: The primary outcome measure is the change in best-corrected visual acuity (BCVA) in the study eye from baseline to month 6. Secondary outcomes are the proportions of patients with a gain or loss of 15 letters or more or a BCVA of 20/40 or more at 6 months, the change in leakage on fluorescein angiography and the change in foveal thickness by optical coherence tomography at 6 months, the number of adverse events in 6 months, and the costs per quality adjusted life-year of the two treatments.

Prevalence of unrecognized benign paroxysmal positional vertigo in older patients.

Dizziness is a relatively common complaint which occurs more often with increasing age. Benign paroxysmal positional vertigo (BPPV) is an important cause which can easily be treated but is frequently not recognized by professionals. The aim of this study was to assess the prevalence of unrecognized BPPV in older patients. Patients ≥70 years of age (n = 989) indicated whether they experienced dizziness, and if so whether the symptoms were typical for BPPV. If affirmed, a diagnostic maneuver was performed. Positive patients were treated at once. All suspected patients completed quality of life questionnaires and were followed for 3 and 6 months. Positive BPPV patients were compared with negative (but suspected) patients. Almost one quarter of the patients (226 patients, 23 %) suffered from dizziness, among whom 101 were suspected of BPPV. Less than half (n = 45) underwent the diagnostic maneuver, of whom 13 (29 %) were positive for BPPV. At follow-up, one patient developed BPPV, leading to a total of 14 positive patients (overall prevalence 1.4 %). BPPV positive patients did not differ from BPPV negative patients. Among a large group of older patients, one quarter experiences dizziness, and 1.4 % has definite BPPV.

DNA methylation analysis in self-sampled brush material as a triage test in hrHPV-positive women.

BACKGROUND: Primary high-risk human papillomavirus (hrHPV) testing in cervical cancer screening shows relatively low specificity, which makes triage testing necessary. In this study, DNA methylation analysis was compared with cytology for triage testing in hrHPV-positive women. Moreover, feasibility of DNA methylation analysis directly on brush-based self-sampled specimens was assessed. METHODS: Non-responding women from population-based screening were invited to self-collect a cervico-vaginal specimen for hrHPV testing; hrHPV-positive women were referred to a physician for triage liquid-based cytology. DNA methylation analysis was performed on 128 hrHPV-positive physician-collected triage samples and 50 matched brush self-samples with QMSP for C13ORF18, EPB41L3, JAM3 and TERT. RESULTS: In physician-taken triage material, DNA methylation analysis of JAM3 showed the highest combined specificity (88%) and sensitivity (82%) for detection of CIN3+, whereas cytology showed a specificity of 48% and a sensitivity of 91%. Out of 39 women with abnormal cytology and normal histology (false-positive by cytology), 87% were negative for JAM3 and 90% for C13ORF18 methylation. Agreement between DNA methylation analysis performed directly on the matched self-sampled material and physician-taken samples was 88% for JAM3 (κ=0.75, P<0.001) and 90% for C13ORF18 (κ=0.77; P<0.001). CONCLUSIONS: DNA methylation analysis as a triage test in hrHPV-positive women is an attractive alternative to cytology. Furthermore, DNA methylation is feasible directly on brush-based self-samplers and showed good correlation with matched physician-taken samples. Direct molecular triage on self-collected specimens could optimise the screening program, especially for non-responders, as this would eliminate the need for an additional physician-taken scraping for triage testing.

Ultra-nonlocality in density functional theory for photo-emission spectroscopy.

We derive an exact expression for the photocurrent of photo-emission spectroscopy using time-dependent current density functional theory (TDCDFT). This expression is given as an integral over the Kohn-Sham spectral function renormalized by effective potentials that depend on the exchange-correlation kernel of current density functional theory. We analyze in detail the physical content of this expression by making a connection between the density-functional expression and the diagrammatic expansion of the photocurrent within many-body perturbation theory. We further demonstrate that the density functional expression does not provide us with information on the kinetic energy distribution of the photo-electrons. Such information can, in principle, be obtained from TDCDFT by exactly modeling the experiment in which the photocurrent is split into energy contributions by means of an external electromagnetic field outside the sample, as is done in standard detectors. We find, however, that this procedure produces very nonlocal correlations between the exchange-correlation fields in the sample and the detector.

Applying a cost-based pricing model for innovative cancer treatments subject to indication expansion: A case study for pembrolizumab and daratumumab.

BACKGROUND: Expanding the indication of already approved immuno-oncology drugs presents treatment opportunities for patients but also strains healthcare systems. Cost-based pricing models are discussed as a possibility for cost containment. This study focuses on two drugs, pembrolizumab (Keytruda) and daratumumab (Darzalex), to explore the potential effect of indication broadening on the estimated price when using the cost-based pricing (CBP) model proposed by Uyl-de Groot and Löwenberg (2018). METHODS: The model was used to calculate cumulative yearly prices, cumulative prices per indication, and non-cumulative indication-based prices using inputs such as research and development (R&D) costs, manufacturing costs, eligible patient population, and a profit margin. A deterministic stepwise analysis and scenario analysis were conducted to examine how sensitive the estimated price is to the different input assumptions. RESULTS: The yearly cumulative cost-based prices (CBPs) ranged from €52 to €885 for pembrolizumab per vial and €823 to €31,941 for daratumumab per vial. Prices were higher in initial years or indications due to smaller patient populations, decreased over time or after additional indications. Sensitivity analysis showed that the number of eligible patients had the most significant impact on the estimated price. In the scenario analysis the profit margin contributed most to a higher CBPs for both drugs. Lower estimates resulted from assumed lower R&D costs. DISCUSSION: The estimated CBPs are consistently lower than Dutch list prices for pembrolizumab (€2,861), mainly resulting from larger patient populations in registered indications. However, daratumumab's list prices fall within the range of modeled CBPs depending on the year or indication (€4,766). Both CBPs decrease over time or with additional indications. The number of eligible patients and initial R&D costs have the most significant influence on the CBPs. These findings contribute to the ongoing discussions on pharmaceutical pricing, especially concerning cancer drugs with expanding indications.

Prevalence of potential drug-drug interactions in cancer patients treated with oral anticancer drugs.

BACKGROUND: Potential drug-drug interactions (PDDIs) in patients with cancer are common, but have not previously been quantified for oral anticancer treatment. We assessed the prevalence and seriousness of potential PDDIs among ambulatory cancer patients on oral anticancer treatment. METHODS: A search was conducted in a computer-based medication prescription system for dispensing oral anticancer drugs to outpatients in three Dutch centres. Potential drug-drug interactions were identified using electronic (Drug Interaction Fact software) and manual screening methods (peer-reviewed reports). RESULTS: In the 898 patients included in the study, 1359 PDDIs were identified in 426 patients (46%, 95% confidence interval (CI)=42-50%). In 143 patients (16%), a major PDDI was identified. The drug classes most frequently involved in a major PDDI were coumarins and opioids. The majority of cases concerned central nervous system interactions, PDDIs that can cause gastrointestinal toxicity and prolongation of QT intervals. In multivariate analysis, concomitant use of more drugs (odds ratio (OR)=1.66, 95% CI=1.54-1.78, P<0001) and genito-urinary cancer (OR=0.25, 95% CI=0.12-0.52, P<0001) were risk factors. CONCLUSION: Potential drug-drug interactions are very common among cancer patients on oral cancer therapy. Physicians and pharmacists should be more aware of these potential interactions.

Natural occupation numbers: when do they vanish?

The non-vanishing of the natural orbital (NO) occupation numbers of the one-particle density matrix of many-body systems has important consequences for the existence of a density matrix-potential mapping for nonlocal potentials in reduced density matrix functional theory and for the validity of the extended Koopmans' theorem. On the basis of Weyl's theorem we give a connection between the differentiability properties of the ground state wavefunction and the rate at which the natural occupations approach zero when ordered as a descending series. We show, in particular, that the presence of a Coulomb cusp in the wavefunction leads, in general, to a power law decay of the natural occupations, whereas infinitely differentiable wavefunctions typically have natural occupations that decay exponentially. We analyze for a number of explicit examples of two-particle systems that in case the wavefunction is non-analytic at its spatial diagonal (for instance, due to the presence of a Coulomb cusp) the natural orbital occupations are non-vanishing. We further derive a more general criterium for the non-vanishing of NO occupations for two-particle wavefunctions with a certain separability structure. On the basis of this criterium we show that for a two-particle system of harmonically confined electrons with a Coulombic interaction (the so-called Hookium) the natural orbital occupations never vanish.

Dizziness impairs health-related quality of life.

PURPOSE: Relatively little is known about the level of impairment in patients with dizziness. RESEARCH QUESTION: How much does dizziness impair the quality of life of patients referred to a multidisciplinary dizziness unit? PATIENTS AND METHODS: All 2,252 patients completed the Dutch version of the Dizziness Handicap Inventory (DHI-D; score 0-100 with higher scores representing more impairment). The results were classified into three categories: mild, moderate, and severe impairment. The three domains in the DHI representing physical, functional, and emotional aspects of dizziness were compared, as well as DHI scores of men versus women, between diagnoses, and the relationship between DHI and age. RESULTS: A total of 2,242 patients (64% women, mean age 54 years) completed the DHI with a mean score of 40.6. Almost 70% of patients had moderate or severe complaints. The handicap perceived by patients was primarily caused by physical and functional factors and less by emotional factors. Female patients and patients with hyperventilation syndrome and/or anxiety disorder had significantly higher DHI scores on all subscales. There was an S-shaped relationship between DHI score and age, and older patients reported more impairment. CONCLUSION: Dizziness has considerable impact on health-related quality of life of dizzy patients.

Long-term follow-up of patients with displaced scapular fractures managed surgically and non-operatively.

INTRODUCTION: Controversy remains on which patients with displaced scapula fractures benefit from surgery. This retrospective cohort study aims to compare and describe long-term patient-reported outcomes of patients with displaced scapula fractures treated both surgically and conservatively. METHODS: This study included patients with intra- and extra-articular scapula fractures, treated between 2010 and 2020 in a Swiss level 1 trauma centre. The decision to operate was based on standardized criteria for fracture displacement. Patients with isolated Bankart lesions (Ideberg 1) and process fractures (AO type 14-A) were excluded. Primary outcomes were functional patient reported measures (DASH score) and quality of life (EQ5D score). Secondary outcomes were complications, radiological union, satisfaction with treatment, pain and range of motion. RESULTS: Out of 486 cases, 74 patients had displaced scapula fractures. Forty patients were treated surgically and 34 were treated conservatively. Significantly more patients with intra-articular fractures and high-energy trauma were treated surgically. Fifty percent returned the questionnaires after a mean follow-up of 47 months (± SD 36). The mean DASH score of this group was 12 (SD 15.6), with a mean of 14.7 (SD 15.9) in the surgery group and 9.8 (SD 14.6) in the non-operative group (p = 0.7). Multivariate analysis did not show statistically significant correlating factors. No significant differences in quality of life were observed. Patients rated their treatment with a mean of 8.6/10 (SD 1.8). Among surgically treated patients, 19 underwent a deltoid sparing procedure with significant shorter time to union than those that underwent deltoid release (23 vs. 49 weeks, p<0.01). Complications occurred in 3/28 surgically treated patients and all three required a reoperation. CONCLUSION: In this cohort, functional results after conservative and surgical treatment were similar, despite more complex fractures and more intra-articular fractures being treated surgically. Osteosynthesis of both intra- and extra-articular scapula fractures is safe and leads to good functional results, furthermore, new minimal invasive techniques may lead to faster bone healing and return to work and sports.

Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method.

BACKGROUND: In cancer patients, drug interactions may intensify adverse events or reduce antitumour effects. We assessed the prevalence of potential drug interactions (PDIs) among ambulatory cancer patients on i.v. treatment using an advanced screening method. PATIENTS AND METHODS: Data on drugs used for comorbidities, anticancer agents, over-the-counter (OTC) drugs, and comorbidities were collected by means of a structured interview among the patients and review of medical charts. PDIs were identified using electronic (Drug Interaction Facts software, version 4.0) and manual screening methods (peer-reviewed reports). RESULTS: In this study, 278 patients were enrolled. We identified 348 PDIs. Of all patients, 161 (58%) had at least one PDI. Of all PDIs, 34% was classified as major and 60% as moderate. Coumarins, quinolones, antiepileptics, and hydrochlorothiazide were frequently part of a PDI. Interactions that potentially cause QT interval prolongation, gastrointestinal toxicity, and central nervous system depression were also common. In multivariate analysis, an increasing number of drugs [odds ratio (OR) = 1.4, confidence interval (CI) 1.23-1.52; P < 0.001] and the use of an OTC drug (OR = 0.56, CI 0.32-0.97; P = 0.045) were risk factors. CONCLUSIONS: PDIs are common in patients treated for an (haemato-) oncological disease. Screening for potential interactions should take place routinely before administering chemotherapy.