The levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the costs and non-inferiority of a strategy starting with the levonorgestrel intrauterine system (LNG-IUS) compared with endometrial ablation (EA) in the treatment of heavy menstrual bleeding (HMB). DESIGN: Cost-effectiveness analysis from a societal perspective alongside a multicentre randomised non-inferiority trial. SETTING: General practices and gynaecology departments in the Netherlands. POPULATION: In all, 270 women with HMB, aged ≥34 years old, without intracavitary pathology or wish for a future child. METHODS: Randomisation to a strategy starting with the LNG-IUS (n = 132) or EA (n = 138). The incremental cost-effectiveness ratio was estimated. MAIN OUTCOME MEASURES: Direct medical costs and (in)direct non-medical costs were calculated. The primary outcome was menstrual blood loss after 24 months, measured with the mean Pictorial Blood Assessment Chart (PBAC)-score (non-inferiority margin 25 points). A secondary outcome was successful blood loss reduction (PBAC-score ≤75 points). RESULTS: Total costs per patient were €2,285 in the LNG-IUS strategy and €3,465 in the EA strategy (difference: €1,180). At 24 months, mean PBAC-scores were 64.8 in the LNG-IUS group (n = 115) and 14.2 in the EA group (n = 132); difference 50.5 points (95% CI 4.3-96.7). In the LNG-IUS group, 87% of women had a PBAC-score ≤75 points versus 94% in the EA group (relative risk [RR] 0.93, 95% CI 0.85-1.01). The ICER was €23 (95% CI €5-111) per PBAC-point. CONCLUSIONS: A strategy starting with the LNG-IUS was cheaper than starting with EA, but non-inferiority could not be demonstrated. The LNG-IUS is reversible and less invasive and can be a cost-effective treatment option, depending on the success rate women are willing to accept. TWEETABLE ABSTRACT: Treatment of heavy menstrual bleeding starting with LNG-IUS is cheaper but slightly less effective than endometrial ablation.

[Behavioral phenotypes and recent developments in genetic technologies]. / Gedragsfenotypes en recente ontwikkelingen in het genetisch onderzoek.

BACKGROUND: Recent developments in genetic technologies make it possible to find a causative genetic defect in about 60% of patients diagnosed with neurodevelopmental disorders. A genetic etiology may provide insight into associated psychopathology, somatic comorbidity, course and direction for treatment.
AIM: To provide an overview of recent developments in genetic technologies, of genetic syndromes and their associated psychopathology. This is illustrated by describing two recently described syndromes.
METHOD: Clinical expertise combined with a search in Pubmed with the key words 'behavioural phenotype', 'intellectual disabilit*', 'next generation sequencing', 'exome' and 'genome'.
RESULTS: We provide an overview of developments in genetic technologies. A schematic overview of syndromes, which may present in clinical practice, is offered and completed with implications for treatment. Findings in recently reported syndromes are illustrated.
CONCLUSION: There is an increase in genetic diagnosis in patients with neurodevelopmental disorders. Knowledge about recent developments in genetics is helping psychiatrists to deal with considerations about referral for genetic diagnostics and putting a genetic syndrome in the context of psychiatric treatment.

Patient-reported health outcomes in long-term lung transplantation survivors: A prospective cohort study.

During the last three decades lung transplantation (LTx) has become a proven modality for increasing both survival and health-related quality of life (HRQoL) in patients with various end-stage lung diseases. Most previous studies have reported improved HRQoL shortly after LTx. With regard to long-term effects on HRQoL, however, the evidence is less solid. This prospective cohort study was started with 828 patients who were on the waiting list for LTx. Then, in a longitudinal follow-up, 370 post-LTx patients were evaluated annually for up to 15 years. For all wait-listed and follow-up patients, the following four HRQoL instruments were administered: State-Trait Anxiety Inventory, Zung Self-rating Depression Scale, Nottingham Health Profile, and a visual analogue scale. Cross-sectional and generalized estimating equation (GEE) analysis for repeated measures were performed to assess changes in HRQoL during follow-up. After LTx, patients showed improvement in all HRQoL domains except pain, which remained steady throughout the long-term follow-up. The level of anxiety and depressive symptoms decreased significantly and remained constant. In conclusion, this study showed that HRQoL improves after LTx and tends to remain relatively constant for the entire life span.

"Not getting worse" a qualitative study of patients perceptions of treatment goals in patients with heart failure.

BACKGROUND: Knowledge of patient reported outcomes helps to provide personalized care on a patient level, optimize care on a population level, and identify the most appropriate patient reported outcomes for clinical trials. To be able to provide personalized care to patients with HF, it is important to know which treatment goals patients with HF consider the most important. This is particularly useful for interventions aimed at improving symptoms, functional status, or health-related quality of life. AIM: The aim of this study was (1) to explore which treatment goals patients with heart failure (HF) perceive as important for their treatment and (2) to identify which treatment goals take priority over other treatment goals. METHODS: The study had a qualitative design and included one focus group interview with 6 patients with HF. Data were analyzed using qualitative content analysis. RESULTS: The overall theme of this study was found to be 'Not getting worse'. This theme was composed of 4 categories that described how the patients perceived the goals of treatment: to decrease symptoms, to improve physical function, to prevent readmission, and to live a normal life. None of the participants mentioned improved survival or being cured of their HF as a treatment goal. CONCLUSION: 'Not getting worse' was perceived as the treatment goal that matters to patients with HF and is in line with currently used endpoints for the evaluation of a treatment in a clinical trial. More research is necessary to develop endpoints that are consistent with the perception of patients, useful for clinical practice, and measurable.

Optimism and quality of life in patients with heart failure.

OBJECTIVES: Health-related quality of life (HR-QoL) of patients with heart failure (HF) is low despite the aim of HF treatment to improve HR-QoL. To date, most studies have focused on medical and physical factors in relation to HR-QoL, few data are available on the role of emotional factors such as dispositional optimism. This study examines the prevalence of optimism and pessimism in HF patients and investigates how optimism and pessimism are associated with different patient characteristics and HR-QoL. METHODS: Dispositional optimism was assessed in 86 HF patients (mean age 70 ± 9 years, 28% female, mean left ventricular ejection fraction 33%) with the Revised Life Orientation Test (LOT-R). HR-QoL was assessed with the Minnesota Living with Heart Failure Questionnaire and the EuroQol. RESULTS: The (mean ± SD) total score on the LOT-R was 14.6 ± 2.9 (theoretical range 0-24) and the scores on the subscales optimism and pessimism were 8.1 ± 1.9 and 5.5 ± 2.5, respectively. Higher age was related to more optimism (r = 0.22, p < 0.05), and optimism was associated with higher generic HR-QoL (B = 0.04, p < 0.05).Significance of resultsThe association found between optimism and generic HR-QoL of HF patients can lead to promising strategies to improve HF patients' HR-QoL, particularly because the literature has indicated that optimism is a modifiable condition.

Two-year effects and cost-effectiveness of pelvic floor muscle training in mild pelvic organ prolapse: a randomised controlled trial in primary care.

OBJECTIVE: To compare effects and cost-effectiveness of pelvic floor muscle training (PFMT) and watchful waiting in women with pelvic organ prolapse. DESIGN: Randomised controlled trial. SETTING: Dutch general practice. POPULATION: Women (≥55 years) with symptomatic mild prolapse, identified by screening. METHODS: Linear multilevel analysis. MAIN OUTCOME MEASURES: Primary outcome was change of pelvic floor symptoms (Pelvic-Floor-Distress-Inventory-20 [PFDI-20]) during 24 months. Secondary outcomes were condition-specific and general quality of life, costs, sexual functioning, prolapse stage, pelvic floor muscle function and women's perceived improvement of symptoms. RESULTS: PFMT (n = 145) resulted in a 12.2-point (95% CI 7.2-17.2, P < 0.001) greater improvement in PFDI-20 score during 24 months compared with watchful waiting (n = 142). Participants randomised to PFMT more often reported improved symptoms (43% versus 14% for watchful waiting). Direct medical costs per person were €330 for PFMT and €91 for watchful waiting but costs for absorbent pads were lower in the PFMT group (€40 versus €77). Other secondary outcomes did not differ between groups. Post-hoc subgroup analysis demonstrated that PFMT was more effective in women experiencing higher pelvic floor symptom distress at baseline. CONCLUSION: PFMT resulted in greater pelvic floor symptom improvement compared with watchful waiting. The difference was statistically significant, but below the presumed level of clinical relevance (15 points). PFMT more often led to women's perceived improvement of symptoms, lower absorbent pads costs, and was more effective in women experiencing higher pelvic floor symptom distress. Therefore, PFMT could be advised in women with bothersome symptoms of mild prolapse. TWEETABLE ABSTRACT: Pelvic floor muscle training can be effective in women with bothersome symptoms of mild prolapse.

Cost-effectiveness of a pro-active approach of urinary incontinence in women.

OBJECTIVE: To estimate the cost-effectiveness and cost-utility of actively encouraging older community-dwelling women with urinary incontinence to be diagnosed and treated. DESIGN: The study was designed as cost-effectiveness and cost-utility analyses alongside a cluster randomised controlled trial. Analyses were performed from a societal perspective. Direct medical and nonmedical costs were taken into account and valued according to the standard Dutch guidelines for economic evaluations. SETTING: Primary care. POPULATION: Study participants were 350 community-dwelling women 55 years or older with urinary incontinence. METHODS: Women in the intervention group were invited for diagnostic testing and treatment. The control group received usual care according to the Dutch guideline on urinary incontinence. Follow-up period was 12 months. MAIN OUTCOME MEASURES: Incontinence Impact Adjusted Life Years (IIALY), Quality Adjusted Life Years (QALY) and incremental costs calculated per IIALY and per QALY gained. RESULTS: Costs per extra life year without impact on daily life from urinary incontinence amounted to €5179 (95% CI -17 323 to 36 260). Costs per QALY amounted to €23 907 (95% CI -124 849 to 121 849). Assuming a ceiling ratio of €20 000, the probability that the intervention was cost-effective based on IIALYs was 91% and 46% based on QALYs. CONCLUSIONS: Improvements in severity of incontinence in older community-dwelling women can be achieved against reasonable costs, with an improvement of symptom-specific QALYs. Findings support an active role of primary care physicians towards women who hesitate to ask for help for urinary incontinence. TWEETABLE ABSTRACT: Encouraging women with urinary incontinence to be treated, improves symptoms and QOL against reasonable costs.

Cost-effectiveness of a carcinoembryonic antigen (CEA) based follow-up programme for colorectal cancer (the CEA Watch trial).

AIM: The study CEA Watch (Netherlands Trial Register 2182) has shown that an intensified follow-up schedule with more frequent carcinoembryonic antigen (CEA) measurements but fewer outpatient visits detects more curable recurrences compared with the usual follow-up protocol in colorectal cancer (CRC) patients. The aim of the study was to compare the cost and cost-effectiveness between various follow-up programmes. METHOD: In total, 3223 patients with stage I-III CRC were followed between October 2010 and October 2012. Direct medical costs were calculated per patient adding the costs for all visits, CEA measurements and imaging. Productivity losses and travel expenses were calculated using answers from questionnaires. The cost-effectiveness displayed the additional costs per additional patient with recurrent disease and used an incremental cost-effectiveness ratio (ICER) to compare them. RESULTS: The mean yearly cost per patient was €548 in the intensified protocol and €497 in the control protocol. The ICER was €94 (95% CI €76-€157) per cent; to detect one additional patient with a recurrence in the intervention protocol compared with the control protocol would require an additional €9400. For curable recurrences, the ICER was €607 (95% CI €5695-€5728). Annual patient-reported costs were €509 per year in the intervention protocol and €488 in the control protocol. CONCLUSION: The current study demonstrates that the direct medical and patient-reported cost of a newly introduced, safe and effective way of CRC follow-up was comparable to that of standard care. The ICER per curable recurrence was considered acceptably low.

Intraoperative administered tramadol reduces the need for piritramide in the immediate postoperative period in children undergoing adenotonsillectomy: A retrospective observational study.

PURPOSE: Adenotonsillectomy is a frequently performed procedure in pediatric day-case surgery causing significant pain for which adequate analgesia is required. Our aim was to investigate if the intraoperative administration of IV tramadol decreases the need for postoperative pain medication in children. Because tramadol has well-known pro-emetic effects, we also assessed the incidence of postoperative nausea and vomiting (PONV). METHODS: We performed a retrospective observational study in 314 children aged 1-13 years undergoing elective adenotonsillectomy. We identified 160 children who had received standard pain medication consisting of IV paracetamol and ketorolac and compared them with a group of 154 children who had received in addition a perioperative infusion of tramadol. RESULTS: 32.5% of the patients in the tramadol group versus 83.8% of the patients in the standard group required postoperative administration of piritramide (p < 0.0001). Groups did not differ with respect to the postoperative need for anti-emetics but in the tramadol group more patients had received prophylactic therapy with odansetron or dexamethasone (P < 0.0001). CONCLUSION: The results of this retrospective study indicate that intraoperative tramadol administration in combination with prophylactic antiemetic therapy decreases the need for piritramide in the immediate postoperative period without increasing the incidence of PONV after tonsillectomy in children.

The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients.

BACKGROUND: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[(18)F]fluoro-17ß-oestradiol (FES) or 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. METHODS: A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests. RESULTS: The FES-PET/CT strategy decreased the number of biopsies by 39 ± 9%, while upfront FDG-PET/CT increased the number of biopsies by 38 ± 15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1 ± 3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness. CONCLUSIONS: The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1 ± 3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.

[Somatic screening in child and adolescent psychiatry: a descriptive pilot study]. / Somatische screening in kinder- en jeugdpsychiatrie: een descriptieve pilotstudie.

BACKGROUND: Somatic disorders occur more often in psychiatric patients than in the general population. Somatic symptoms can cause or increase psychiatric symptoms. Psychiatric symptoms and their treatment can have an effect on the physical state of the patient. A pilot study involving an adult outpatient population has demonstrated that 62% of the patients studied had new clinically relevant symptoms. So far, no other data are available relating to somatic screening in child and adolescent psychiatry. AIM: To assess whether somatic screening of children and adolescents newly referred to a department of child and adolescent psychiatry in the Netherlands gives added value to the diagnosis and treatment policy. METHOD: In a pilot study 43 newly referred patients aged between 6 and 18 were screened by means of somatic history, a physical examination and blood parameters. On this basis we could calculate the percentage of somatic symptoms and , where necessary, follow-up treatment could be applied. RESULTS: One or more clinically relevant disorders were found in almost 56% of the children and adolescents investigated. The disorders included dysmorphic anomalies, weight and height deviations, raised thyroid hormone levels, dyslipidaemia, anaemia and vitamin D and B12 deficiency. Advice about a healthy lifestyle was given to 44% of the patients. An antipsychotic medication in 25% of the patients was changed, in the case of 16% of the patients a family doctor was contacted about subsequent treatment and 19% of the patients were referred to a medical specialist. CONCLUSION: Although the results of the pilot study indicate that somatic screening does provide added value, more research is needed in order to optimise the screening procedure.

Diagnostic accuracy and cost-effectiveness of dermoscopy in primary care: a cluster randomized clinical trial.

OBJECTIVES: To determine the DA and cost-effectiveness of the dermoscope in primary care for skin lesions suspected of malignancy. METHODS: In a cluster randomized clinical trial, 48 Dutch general practices were randomized to either intervention group using a dermoscope or control group using only naked-eye examination. A total of 194 lesions from 170 patients in the intervention group and 222 lesions from 211 patients in the control group were analysed for DA and cost-effectiveness. RESULTS: The percentage of correctly diagnosed lesions in intervention group and control group was 50.5% and 40.5% respectively. This was 61.5% and 22.2% for melanomas. In the intervention group, three malignancies were treated with the expectative treatment option compared to none in the control group. The odds ratio (OR) of a correct diagnosis in the intervention group, compared to control group, was 1.51 (95% CI: 0.96­2.37) P = 0.07. Consequently, the relative risk was 1.25. The incremental cost-effectiveness ratio was €89 (95% CI −€60 to €598), indicating that using a dermoscope costs an additional €89 for one additional correctly diagnosed patient. Additional analyses showed better effects of dermoscopy compared to the control group for 98% of the bootstrap resamples. CONCLUSIONS: The probability of a correct diagnosis was 1.25 times higher using a dermoscope than without a dermoscope. Although this difference is marginally not statistically significant, dermoscopy in general practice appears to be cost effective. We therefore think that GPs should be trained to use a dermoscope, although they should realize that even with the use of a dermoscope not all lesions will be diagnosed correctly.

Which screening strategy should be offered to women with BRCA1 or BRCA2 mutations? A simulation of comparative cost-effectiveness.

BACKGROUND: There is no consensus on the most effective strategy (mammography or magnetic resonance imaging (MRI)) for screening women with BRCA1 or BRCA2 mutations. The effectiveness and cost-effectiveness of the Dutch, UK and US screening strategies, which involve mammography and MRI at different ages and intervals were evaluated in high-risk women with BRCA1 or BRCA2 mutations. METHODS: Into a validated simulation screening model, outcomes and cost parameters were integrated from published and cancer registry data. Main outcomes were life-years gained and incremental cost-effectiveness ratios. The simulation was situated in the Netherlands as well as in the United Kingdom, comparing the Dutch, UK and US strategies with the population screening as a reference. A discount rate of 3% was applied to both costs and health benefits. RESULTS: In terms of life-years gained, the strategies from least to most cost-effective were the UK, Dutch and US screening strategy, respectively. However, the differences were small. Applying the US strategy in the Netherlands, the costs were €43 800 and 68 800 for an additional life-year gained for BRCA1 and BRCA2, respectively. At a threshold of €20 000 per life-year gained, implementing the US strategy in the Netherlands has a very low probability of being cost-effective. Stepping back to the less-effective UK strategy would save relatively little in costs and results in life-years lost. When implementing the screening strategies in the United Kingdom, the Dutch, as well as the US screening strategy have a high probability of being cost-effective. CONCLUSION: From a cost-effectiveness perspective, the Dutch screening strategy is preferred for screening high-risk women in the Netherlands as well as in the United Kingdom.

Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme.

BACKGROUND: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology. METHODS: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel. RESULTS: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified. CONCLUSION: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.

Safety and cost-effectiveness of shortening hospital follow-up after breast cancer treatment.

BACKGROUND: In the Netherlands, the first 5 years of follow-up after treatment for breast cancer are carried out in hospital with yearly mammography. After this, for patients aged over 60 years who have undergone mastectomy, there is a shift of care to the National Screening Programme (NSP) for mammography every 2 years. After breast-conserving therapy follow-up is perfomed by the general practitioner (GP), with mammography every second year and physical examination annually. The aim of this study was to evaluate the clinical effects and costs of four different strategies for follow-up after breast cancer treatment. METHODS: An extended and validated simulation model for breast cancer follow-up was used. The current guidelines for follow-up (baseline strategy) and three less intensive follow-up strategies were evaluated. The main outcome measure was the detection rate of small tumours (2 cm or smaller) and associated costs for each strategy. RESULTS: Shortening the follow-up time in hospital by shifting care to the NSP or GP after 2 years instead of 5 years of hospital follow-up, lowering the age of referral to the NSP or GP from 60 to 50 years, and termination of annual physical examination by the GP after hospital follow-up did not decrease the detection of small tumours. In addition, a substantial decrease in costs was observed with simplified follow-up. CONCLUSION: Decreasing hospital follow-up time, lowering the age of referral to the NSP or GP, and termination of annual physical examinations would lead to a substantial reduction in costs while maintaining the possibility of detecting small breast cancers.

Costs and cost-effectiveness analysis of treatment in children with eczema by nurse practitioner vs. dermatologist: results of a randomized, controlled trial and a review of international costs.

BACKGROUND: In a randomized, controlled trial (RCT) on childhood eczema we reported that substituting nurse practitioners (NPs) for dermatologists resulted in similar outcomes of eczema severity and in the quality of life, and higher patient satisfaction. OBJECTIVES: To determine costs and cost-effectiveness of care provided by NPs vs. dermatologists and to compare our results with those in studies from other countries. METHODS: We estimated the healthcare costs, family costs and the costs in other sectors alongside the RCT. All the costs were linked to quality of life [Infants' Dermatitis Quality of Life Index (IDQOL), Children's Dermatology Life Quality Index (CDLQI)] and to patient satisfaction (Client Satisfaction Questionnaire-8) to determine the incremental cost-effectiveness ratio (ICER). We also examined all the reported studies on the costs of childhood eczema. RESULTS: The mean annual healthcare costs, family costs and costs in other sectors were €658, €302 and €21, respectively, in the NP group and €801, €608 and €0·93, respectively, in the dermatologist group. The ICER in the NP group compared with the dermatologist group indicated €925 and €751 savings per one point less improvement in IDQOL and CDLQI, respectively, and €251 savings per one point more satisfaction in the NP group at 12 months. The mean annual healthcare costs and family costs varied considerably in the six identified studies. CONCLUSIONS: Substituting NPs for dermatologists is both cost-saving and cost-effective. The treatment of choice is that provided by the NPs as it is similarly effective to treatment provided by a dermatologist with a higher parent satisfaction. International comparisons are difficult because the types of costs determined, the units and unit prices, and eczema severity all differ between studies.

A randomized controlled trial in children with eczema: nurse practitioner vs. dermatologist.

Background We hypothesized that a nurse practitioner would improve the quality of life of a child with eczema more than a dermatologist because of a structured intervention and more consultation time. Objectives To compare the level of care by nurse practitioners with that by dermatologists in children with eczema. Methods New referrals aged < or = 16 years with a diagnosis of eczema were recruited. In a randomized, parallel-group study with a follow-up period of 1 year, 160 participants were randomized either to conventional care from a dermatologist or to care from a nurse practitioner. The primary outcome measure was change in quality of life at 12 months, as assessed by the Infants' Dermatitis Quality of Life Index (IDQOL) for children aged < or = 4 years, and by the illustrated version of the Children's Dermatology Life Quality Index (CDLQI) for children aged 4-16 years. Secondary outcomes were changes in IDQOL and CDLQI at 4 and 8 months, family impact of childhood atopic dermatitis (Dermatitis Family Impact Questionnaire, DFI), eczema severity (objective SCORAD) and patient satisfaction (Client Satisfaction Questionnaire-8, CSQ-8) at 4, 8 and 12 months. Results The mean IDQOL in the dermatologist group improved significantly from 11.6 [SD 8.1; 95% confidence interval (CI) 9.0-14.2] at the baseline to 5.6 (SD 3.9; 95% CI 4.3-7.0) at 12 months with a mean change from the baseline of -6.5 (SD 6.6; 95% CI -14.2 to -8.9; P < 0.001). The mean IDQOL in the nurse practitioner group improved significantly from 10.7 (SD 4.9; 95% CI 9.1-12.3) at baseline to 5.7 (SD 5.4; 95% CI 4.0-7.5) at 12 months with a mean change from the baseline of -4.9 (SD 5.5; 95% CI -6.8 to -3.0; P < 0.001). The between-groups difference was (-)1.7 (95% CI -4.6 to 1.2; P = 0.26). The mean CDLQI in the dermatologist group improved significantly from 12.1 (SD 6.3; 95% CI 9.9-14.2) at baseline to 5.6 (SD 4.2; 95% CI 4.2-7.1) at 12 months with a mean change from the baseline of -5.9 (SD 6.0; 95% CI -8.0 to -3.9; P < 0.001). The mean CDLQI in the nurse practitioner group improved significantly from 10.0 (SD 4.4; 95% CI 8.5-11.4) at the baseline to 4.9 (SD 3.5; 95% CI 3.7-6.1) at 12 months with a mean change from the baseline of -5.2 (SD 4.0; 95% CI -6.6 to -3.8; P < 0.001). The between-groups difference was (-)0.7 (95% CI -3.3 to 1.7; P = 0.55). The between-groups comparison was not significant for the IDQOL and the CDLQI at baseline or 4, 8 and 12 months. Both treatment groups showed significant improvement in DFI and objective SCORAD at 12 months. The between-groups comparison was not significant at baseline or 4, 8 and 12 months. Significantly higher satisfaction levels were observed at 4, 8 and 12 months in the nurse practitioner group. Conclusions The level of care provided by a nurse practitioner in terms of the improvement in the eczema severity and the quality of life outcomes was comparable with that provided by a dermatologist. In addition, the parents were more satisfied with the care that was provided by a nurse practitioner.

The role of apoptotic cell death in the radiosensitising effect of gemcitabine.

BACKGROUND: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis. METHODS: Tumour cells were treated with gemcitabine, radiation, or the combination. 0-72 h after treatment, cells were collected for cell-cycle analysis and apoptosis determination. Caspase 8 and 9, Bid and tBid expression were determined by western blot. The mitochondrial membrane potential was determined using flow cytometry. An RT(2) Profiler PCR Array for human apoptotic genes was performed after the combination or TRAIL treatment. RESULTS: Gemcitabine and radiation resulted in an early S-phase block immediately after treatment, after which the cells moved synchronously through the cell cycle. When cell-cycle distribution returned to pre-treatment levels, an increased induction of apoptosis was observed with activation of caspase 8 and 9 and a reduction of the mitochondrial membrane potential. Gene expression after treatment with radiosensitising conditions was comparable with expression after the TRAIL treatment. CONCLUSION: A role for the cell-cycle perturbations and the induction of apoptosis could be attributed to the radiosensitising effect of gemcitabine. Apoptosis induction was comparable with the apoptotic pathway observed after the TRAIL treatment, that is the involvement of the extrinsic apoptosis pathway.

Echocardiographic assessment of left ventricular untwist rate: comparison of tissue Doppler and speckle tracking methodologies.

AIMS: The study was designed to test the influence of the temporal resolution, at which tissue Doppler imaging (TDI) and speckle tracking imaging (STI) operate, on the accurate assessment of left ventricular (LV) untwist rate (UR). METHODS AND RESULTS: Echo imaging and invasive LV pressure measurements were performed during right atrial (RA) pacing and dobutamine challenge in eight pigs. LV torsion and torsional rate profiles were analysed from grey scale and tissue Doppler data (apical and basal short axis) at frame rates of 82 +/- 17 and 183 +/- 14 Hz, respectively. Temporal subsampling of TDI data sets was performed at 82 +/- 6 Hz in order to mimic the mean temporal resolution of STI and the LV torsional curves were again extracted. At rest, LV UR values were comparable for both imaging techniques. However, during dobutamine stimulation, TDI estimated peak UR was predominantly higher than UR measured by STI (-112.1 +/- 64.5 degrees /s vs. -75.5 +/- 31.4 degrees /s, P < 0.05). The similarity of LV UR measurements with respect to the STI/TDI data was examined by a Bland-Altman analysis. CONCLUSION: Although both methods regarding LV UR correlated well, these methods cannot be interchanged. STI showed a bias to underestimate UR at high values.

The Salmonella Enteritidis TolC outer membrane channel is essential for egg white survival.

Salmonella Enteritidis has developed the potential to contaminate eggs by surviving in the antimicrobial environment of the hen's egg white. This has led to a worldwide pandemic of foodborne salmonellosis infections in humans due to the consumption of contaminated eggs and egg-derived products. The molecular mechanisms of Salmonella Enteritidis egg white survival are not fully clear. Using in vivo expression technology and promoter-reporter fusions we showed that the promoter of the tolC gene, encoding the TolC outer membrane channel that is used by multidrug efflux pumps to export harmful molecules and to secrete bacterial products, is activated by egg white at the chicken body temperature. Using a Salmonella Enteritidis tolC deletion mutant we showed that TolC has an important role in egg white survival. Chromatographic separation techniques and subsequent testing of antimicrobial activities of separated egg white fractions led to the identification of ovotransferrin as the egg white antimicrobial factor which is capable of inhibiting growth of a tolC deletion strain but not the wild type strain. We provide evidence that TolC protects Salmonella Enteritidis against ovotransferrin-mediated growth inhibition in egg white.