► This method may be of high value when performing TDM and clinical pharmacokinetic research. ► This method is the first analytical assay on UPLC for all azoles used for the treatment of invasive ...fungal disease. ► This method is very rapid, sensitive and accurate. It has been externally validated.
A reversed phase ultra-performance liquid chromatography method was developed for the simultaneous quantitative determination of the systemically administered azoles voriconazole, posaconazole, isavuconazole, itraconazole and its metabolite hydroxy-itraconazole in plasma. The method involved a simple liquid–liquid extraction followed by ultra-performance liquid chromatography with an Acquity UPLC BEH Phenyl column and ultraviolet detection set at a wavelength of 260nm. The assay was validated over the concentration range of 0.050–10,000mg/l for all four azoles and one metabolite. The accuracies for the assay were 97–104%, inter- and intra-day coefficients of variation were <7.5% and extraction recoveries were 98% for voriconazole, posaconazole, isavuconazole and the internal standard (UK115794), and 79% and 88% for itraconazole and hydroxy-itraconazole respectively. This method proved to be simple, accurate, precise and fast and is currently in use in our laboratory for the quantitative analysis of these azoles for Therapeutic Drug Monitoring and pharmacokinetic research.
This meta-analytic review critically examines the effectiveness of workplace interventions targeting physical activity, dietary behaviour or both on weight outcomes. Data could be extracted from 22 ...studies published between 1980 and November 2009 for meta-analyses. The GRADE approach was used to determine the level of evidence for each pooled outcome measure. Results show moderate quality of evidence that workplace physical activity and dietary behaviour interventions significantly reduce body weight (nine studies; mean difference MD−1.19 kg 95% CI −1.64 to −0.74), body mass index (BMI) (11 studies; MD −0.34 kg m⁻²95% CI −0.46 to −0.22) and body fat percentage calculated from sum of skin-folds (three studies; MD −1.12% 95% CI −1.86 to −0.38). There is low quality of evidence that workplace physical activity interventions significantly reduce body weight and BMI. Effects on percentage body fat calculated from bioelectrical impedance or hydrostatic weighing, waist circumference, sum of skin-folds and waist-hip ratio could not be investigated properly because of a lack of studies. Subgroup analyses showed a greater reduction in body weight of physical activity and diet interventions containing an environmental component. As the clinical relevance of the pooled effects may be substantial on a population level, we recommend workplace physical activity and dietary behaviour interventions, in cluding an environment component, in order to prevent weight gain.
The restorative effect of sleep on waking brain activity remains poorly understood. Previous studies have compared overall neural network characteristics after normal sleep and sleep deprivation. To ...study whether sleep and sleep deprivation might differentially affect subsequent connectivity characteristics in different brain regions, we performed a within-subject study of resting state brain activity using the graph theory framework adapted for the individual electrode level.In balanced order, we obtained high-density resting state electroencephalography (EEG) in 8 healthy participants, during a day following normal sleep and during a day following total sleep deprivation. We computed topographical maps of graph theoretical parameters describing local clustering and path length characteristics from functional connectivity matrices, based on synchronization likelihood, in five different frequency bands. A non-parametric permutation analysis with cluster correction for multiple comparisons was applied to assess significance of topographical changes in clustering coefficient and path length.
Significant changes in graph theoretical parameters were only found on the scalp overlying the prefrontal cortex, where the clustering coefficient (local integration) decreased in the alpha frequency band and the path length (global integration) increased in the theta frequency band. These changes occurred regardless, and independent of, changes in power due to the sleep deprivation procedure.
The findings indicate that sleep deprivation most strongly affects the functional connectivity of prefrontal cortical areas. The findings extend those of previous studies, which showed sleep deprivation to predominantly affect functions mediated by the prefrontal cortex, such as working memory. Together, these findings suggest that the restorative effect of sleep is especially relevant for the maintenance of functional connectivity of prefrontal brain regions.
Background. This study explored the associations between various types of activities, their underlying physical components, and recurrent falling in community-dwelling older persons. Methods. This ...study included 1,329 community-dwelling persons (≥65 years) of the Longitudinal Aging Study Amsterdam (LASA). The time spent in walking, cycling, light and heavy household activities, and two sports was measured using the LASA Physical Activity Questionnaire (LAPAQ). Physical activity components included strength, intensity, mechanical strain, and turning. Time to second fall in a 6-month period was measured during 3 years with fall calendars. Cox proportional hazards models were adjusted for confounders and stratified for physical performance and sex in case of significant (p < .10) interaction. Results. During 3 years, 325 (24.5%) persons became recurrent fallers. In women, doing light (hazard ratios HRs = 0.40, 95% confidence intervals CIs = 0.20–0.79) or heavy household activities (HR = 0.63, CI = 0.44–0.79) was associated with a decreased risk of recurrent falling. In persons with good physical performance, doing sports (HR = 1.56, CI = 1.07–2.28), high intensity (HR > 1.75, CI = 1.09–3.16), and high mechanical strain (HR = 1.70, CI = 1.01–2.83) activities was associated with an increased risk of recurrent falling. Conclusions. The results suggest that the relationship between physical activity and recurrent falling differs per type of activity and is modified by physical performance. Doing household activities was associated with a decreased risk of recurrent falling in women. In physically fit older persons, doing sports or activities with high intensity or mechanical strain demands was associated with an increased risk of recurrent falling.
Current thinking on the development of molecular microbial characterisation techniques in public health focuses mainly on operational issues that need to be resolved before incorporation into daily ...practice can take place. Notwithstanding the importance of these operational challenges, it is also essential to formulate conditions under which such microbial characterisation methods can be used from an ethical perspective. The potential ability of molecular techniques to show relational patterns between individuals with more certainty brings a new sense of urgency to already difficult ethical issues associated with privacy, consent and a moral obligation to avoid spreading a disease. It is therefore important that professionals reflect on the ethical implications of using these techniques in outbreak management, in order to be able to formulate the conditions under which they may be applied in public health practice.
Objective This study aims to evaluate the effectiveness of a draft occupational health guideline, aimed at preventing weight gain, on employees' body weight-related outcomes, cardiovascular disease ...(CVD) risk factors, and quality of life. Methods In a cluster randomized controlled trial including 16 occupational physicians (OP) and 523 employees, guideline-based care was compared to usual care by OP between 2009—2011 in the Netherlands. Guideline-based care consisted of (i) providing advice to employers on how to assess and intervene on the obesogenic work environment, (ii) conducting five face-to-face behavioral change counseling sessions with employees to improve their lifestyles, and (iii) evaluating the outcome and maintaining sections i and ii. Data were collected at baseline and 6, 12, and 18-months follow-up. To evaluate the effects of the intervention, multilevel analyses were performed. Results No significant differences were found between the intervention and control group on waist circumference β 1.2 cm, 95% confidence interval (95% CI) -0.6—2.9, body weight (β 0.3 kg, 95% CI -1.0—1.6), body mass index (β 0.1 kg/m2, 95% CI -0.3—0.5), systolic blood pressure (β 1.7 mmHG, 95% CI -2.4—5.8), diastolic blood pressure (β 0.3 mmHG, 95% CI -1.0—0.6), cholesterol (β 0 mmol/l,95% CI -0.2—0.2), or quality of life indicators after 18-months follow-up. Stratified analyses showed an increase in waist circumference among men (β 2.5 cm, 95% CI 0.5—4.5) and obese intervention participants (β 2.7 cm, 95% CI 0.6—4.7) compared to control participants. Conclusion The draft occupational health guideline was not more effective than usual care. Therefore, the guideline in its current form cannot be recommended for implementation.
Hazelnut (Corylus avellana) allergy varies from rather mild oral allergy symptoms to potentially life-threatening anaphylaxis and exhibits geographic and age-related variations. Severity of symptoms ...depends on the sensitisation profile of the patient and can partially be predicted using 'component-resolved diagnosis'. In our region (young) children predominantly exhibit sensitisation to hazelnut storage proteins Cor a 9 and Cor a 11 that is unrelated to birch pollen allergy and is generally associated with a more severe clinical outcome on consumption on raw and processed hazelnut. In contrast, adults predominantly present with an oral allergy syndrome due to an extensive cross-reactivity between the labile Cor a 1.04 and Bet v 1, the major allergen from birch (Betula verrucosa) pollen. In the absence of a cure, avoidance remains the key measure of effective management, particularly in those patients presenting with a severe form.
Background
The heart rate variability‐derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool for the assessment of pain and discomfort in infants. Little is ...known about its performance in the early postoperative setting, where assessment of pain/discomfort is usually based on discontinuous observational scoring systems or personal experience of medical staff.
Aims
To investigate the performance of the NIPE as a measure of early postoperative pain and/or discomfort in infants.
Methods
The potential of the NIPE to detect pain/discomfort, as assessed by two clinical scoring systems (FLACC and COMFORT‐B scale), was investigated in postoperative infants (0–2 years).
Results
Receiver operating curve (ROC) analyses investigating the power of the NIPE to distinguish between comfort and pain/discomfort, revealed areas under the curve (AUC) of 0.77 for the FLACC, 0.81 for the COMFORT‐B score, and 0.77 for a combination of FLACC & COMFORT‐B. Logistic regression analysis provided initial evidence that the NIPE is an independent predictor of a FLACC score ≥4 and/or a COMFORT‐B score ≥17, though R2 values were below .2. NIPE values associated with a FLACC ≥4 (48 45–56), a COMFORT‐B score ≥17 (47 42–53), and a FLACC ≥4 & COMFORT‐B ≥17 (47 42–57) were lower than NIPE values associated with a FLACC <4 (60 53–68, 95% CI of difference −14 to −8, p < .0001), a COMFORT‐B score <17 (61 54–68, 95% CI of difference −16 to −10, p < .0001), and a FLACC <4 & COMFORT‐B score <17 (60 53–68, 95% CI of difference −15 to −8, p < .0001). We found no evidence of a predictive value of the NIPE regarding the occurrence of pain.
Conclusions
The NIPE detected pain and discomfort in infants after general anesthesia with reasonable areas under the ROC curve (±0.8), whereas it was not predictive of clinically detectable pain or discomfort.
High‐risk human papillomavirus (hrHPV) testing has a higher sensitivity but lower specificity than cytology for detection of high‐grade intraepithelial neoplasia (CIN). To avoid over‐referral to ...colposcopy and overtreatment, hrHPV‐positive women require triage testing and/or followup. A total of 25,658 women (30–60 years) enrolled in a population‐based cohort study had an adequate baseline Pap smear and hrHPV test. The end‐point was cumulative two‐year risk of CIN grade 3 or worse (CIN3+). In a post‐hoc analysis, fourteen triage/followup strategies for hrHPV‐positive women (n = 1,303) were evaluated for colposcopy referral rate, positive (PPV) and negative predictive value (NPV). Five strategies involved triage testing without a repeat test and nine strategies involved triage testing followed by one repeat testing. The tests were cytology, hrHPV, HPV16/18 genotyping and HPV16/18/31/33/45 genotyping. Results were adjusted for women in the cohort study who did not attend repeat testing. Of the strategies without repeat testing, combined cytology and HPV16/18/31/33/45 genotyping gave the highest NPV of 98.9% (95%CI 97.6–99.5%). The corresponding colposcopy referral rate was 58.1% (95%CI 55.4–60.8%). Eight of the nine strategies with retesting had an estimated NPV of at least 98%. Of those, cytology triage followed by cytology at 12 months had a markedly lower colposcopy referral rate of 33.4% (95%CI 30.2–36.7%) than the other strategies. The NPV of the latter strategy was 99.3% (95%CI 98.1–99.8%). Triage hrHPV‐positive women with cytology, followed by repeat cytology testing yielded a high NPV and modest colposcopy referral rate and appear to be the most feasible management strategy.
In this work, we bridge fundamental electromagnetics and chemical process engineering with the aim to develop tailor-made (microwave or high frequency radiowave) applicators for heating of micro- and ...small-structured process equipment. In this context, two simple configurations with well-defined single mode field patterns, namely a cylindrical and a rectangular cavity both containing a homogeneous cylindrical load were analyzed either analytically or numerically. We present design charts that illustrate how important operating, geometric and materials parameters relate with each other. It was found that load size, heating uniformity and desired frequency mutually constrain one another. The required cavity volume increases with increasing heating uniformity or with increasing load permittivity for a given heating uniformity requirement. At the popular frequency of 2.45
GHz the load is restricted to a small size, compared to the cavity size, in order to achieve high heating uniformity. Opting for lower resonance frequencies allows for bigger load volumes to be heated uniformly. Furthermore, we show that the relations found for the operating, structural and material properties on the basis of these simple configurations can provide design guidelines and first approximations for more realistic process equipment geometries.
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