Incorporating natural variation into IVF clinic league tables: The Expected Rank

Background. Rankings based on outcome are often used to present health care provider performance. These rankings do however not reflect that part of the variation in outcome between providers is caused by natural variation, and not by any differences in quality of care. The aim of this study is to compare standard methods for ranking with a novel method that takes into account natural variation. Methods. We used data on the number of treatment cycles and the number of pregnancies of 13 Dutch IVF clinics from 2004. We calculated the Expected Rank (ER), an estimate of the true rank of a provider, accounting for natural variation. We rescaled the ER to obtain the Percentile based on ER (PCER), that can be interpreted as the probability that a clinic is worse than a randomly selected other clinic. We also calculated a measure for rankability ρ, which is the part of variation between providers that is due to true differences (as opposed to natural variation). Results. The expected ranks ranged from 1.4 to 11.9 instead of the original ranks 1-13. The ER showed that some clinics performed very similar, which would be disregarded when using standard ranks. The PCER ranged from 7% to 88%. Rankability was substantial (ρ = 0.9). Conclusion. The Expected Rank provides a way to combine the attractiveness of a ranking, a single number and easy interpretation, with reliable analyses that does justice to the providers, and also allows individual comparisons

A comparison of the beta-geometric model with landmarking for dynamic prediction of time to pregnancy

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Проблема развития финансовой системы Украины в условиях глобализации

Целью исследования является изучение взаимодействия фондовых рынков Восточной Европе на примере нескольких стран.Метою дослідження є вивчення взаємодії фондових ринків Східної Європи на прикладі декількох країн

The impact of a self-administered coping intervention on emotional wellbeing in women awaiting the outcome of IVF treatment: a randomised controlled trial

STUDY QUESTION What is the effect of the positive reappraisal coping intervention (PRCI) on anxiety in women awaiting the outcome of an IVF/ICSI cycle? SUMMARY ANSWER Women reported significantly more anxiety during the waiting period than before treatment, but the use of the PRCI did not significantly reduce anxiety during the waiting period. WHAT IS KNOWN ALREADY Waiting for the outcome of IVF/ICSI treatment after embryo transfer is one of the most stressful periods of fertility treatments. At present, no evidence-based coping interventions are available to assist women though this waiting period. The PRCI has been designed to address this unmet need by promoting positive reappraisal coping. STUDY DESIGN, SIZE, DURATION A three-armed randomized controlled trail (RCT) was designed to evaluate the PRCI in women undergoing IVF/ICSI. Data were collected between October 2010 and June 2012. A total of 377 participants were randomized to receive either the PRCI and emotional monitoring, emotional monitoring only, or routine care. Only the PRCI-monitoring group received the coping intervention, comprising an explanatory leaflet and ten statements to be read at least once in the morning and once in the evening. PARTICIPANT, MATERIALS, SETTING, METHODS To capture the general impact of the PRCI, all three groups completed questionnaires at three time points: just before the waiting period (time 1: stimulation phase), on Day 10 of the 14-day waiting period (time 2: waiting period) and 6 weeks after the start of the waiting period (time 3: 6-week follow-up). In addition, to capture the specific impacts of the PRCI on the days of the waiting period, the PRCI-monitoring group and the monitoring-control group also rated their emotions and reactions daily, for the 14-day waiting period. MAIN RESULTS AND THE ROLE OF CHANCE Of the women who agreed to participate and who met eligibility criteria, 377 were randomized. All study participants reported significantly more anxiety and depression during the waiting period than before treatment (P < 0.001). The mean difference in anxiety between time 1 versus time 2 was 1.465 (95% CI 1.098–1.832). The mean difference in depression between time 1 versus time 2 was 0.514 (95% CI 0.215–0.813). Use of the PRCI did not significantly reduce anxiety or depression, or daily negative emotions during the waiting period. However, patients randomized to the PRCI reported significantly more positive emotions during the waiting period (P < 0.001) than the monitoring-control group, and reported the intervention to be easy to use, and as having a positive psychological effect. No significant differences were found between the groups in treatment outcome. LIMITATIONS, REASONS FOR CAUTION The lack of difference observed in the present study for anxiety levels between the PRCI and the monitoring-control group could have been due to the effects of monitoring itself or its ability to attenuate or obscure the effects of the PRCI intervention in unknown ways. A randomized group of women who used only the PRCI without daily monitoring would provide more insight. WIDER IMPLICATIONS OF THE FINDINGS The PRCI was shown to help women reinterpret the demands of the waiting period in a more positive way. These results are consistent with previous studies showing that positive reappraisal coping is a useful strategy for unpredictable and uncontrollable situations represented by a medical waiting period. This simple low cost self-help coping intervention increases positive affect during the waiting period in an IVF/ICSI treatment

Comparing methods to combine functional loss and mortality in clinical trials for amyotrophic lateral sclerosis

Objective: Amyotrophic lateral sclerosis (ALS) clinical trials based on single end points only partially capture the full treatment effect when both function and mortality are affected, and may falsely dismiss efficacious drugs as futile. We aimed to investigate the statistical properties of several strategies for the simultaneous analysis of function and mortality in ALS clinical trials. Methods: Based on the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, we simulated longitudinal patterns of functional decline, defined by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and conditional survival time. Different treatment scenarios with varying effect sizes were simulated with follow-up ranging from 12 to 18 months. We considered the following analytical strategies: 1) Cox model; 2) linear mixed effects (LME) model; 3) omnibus test based on Cox and LME models; 4) composite time-to-6-point decrease or death; 5) combined assessment of function and survival (CAFS); and 6) test based on joint modeling framework. For each analytical strategy, we calculated the empirical power and sample size. Results: Both Cox and LME models have increased false-negative rates when treatment exclusively affects either function or survival. The joint model has superior power compared to other strategies. The composite end point increases false-negative rates among all treatment scenarios. To detect a 15% reduction in ALSFRS-R decline and 34% decline in hazard with 80% power after 18 months, the Cox model requires 524 patients, the LME model 794 patients, the omnibus test 526 patients, the composite end poi

Південноукраїнські історики та російська академічна еліта: етапи та напрямки співпраці у другій половині ХІХ – на початку XX ст.

У статті на широкій джерельній базі досліджено інфраструктурні та особисті зв’язки між південноукраїнськими істориками та академіками Санкт-Петербурзької (Російської) Академії наук впродовж другої половини ХІХ ст. – 1920-х років.The article, based on a great number of sources, researches the infrastructural and personal contacts between the historians of South Ukraine and academicians of the St.-Petersburg Academy of Sciences throughout the second half of the ХІХ century – 1920-ies

Optimizing intensive care capacity using individual length-of-stay prediction models

Introduction Effective planning of elective surgical procedures requiring postoperative intensive care is important in preventing cancellations and empty intensive care unit (ICU) beds. To improve planning, we constructed, validated and tested three models designed to predict length of stay (LOS) in the ICU in individual patients. Methods Retrospective data were collected from 518 consecutive patients who underwent oesophagectomy with reconstruction for carcinoma between January 1997 and April 2005. Three multivariable linear regression models for LOS, namely preoperative, postoperative and intra-ICU, were constructed using these data. Internal validation was assessed using bootstrap sampling in order to obtain validated estimates of the explained variance (r2). To determine the potential gain of the best performing model in day-to-day clinical practice, prospective data from a second cohort of 65 consecutive patients undergoing oesophagectomy between May 2005 and April 2006 were used in the model, and the predictive performance of the model was compared with prediction based on mean LOS. Results The intra-ICU model had an r2 of 45% after internal validation. Important prognostic variables for LOS included greater patient age, comorbidity, type of surgical approach, intraoperative respiratory minute volume and complications occurring within 72 hours in the ICU. The potential gain of the best model in day-to-day clinical practice was determined relative to mean LOS. Use of the model reduced the deficit number (underestimation) of ICU days by 65 and increased the excess number (overestimation) of ICU days by 23 for the cohort of 65 patients. A conservative analysis conducted in the second, prospective cohort of patients revealed that 7% more oesophagectomies could have been accommodated, and 15% of cancelled procedures could have been prevented. Conclusion Patient characteristics can be used to create models that will help in predicting LOS in the ICU. This will result in more efficient use of ICU beds and fewe

Cytokine Release in HR-HPV(+) Women without and with Cervical Dysplasia (CIN II and III) or Carcinoma, Compared with HR-HPV(−) Controls

Aims. We investigated the effect of HR-HPV infection on the capacity of the cytokine network in whole blood cultures during carcinogenesis of cervical carcinoma. Methods. Thirty-nine women with moderate dysplasia, severe dysplasia, cervical carcinoma, or without dysplasia formed the study group. The control group consisted of 10 HR-HPV-negative women without CIN. Whole blood cultures were stimulated with phytohemagglutinin (PHA) and concentrations of tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin 2 (IL-2), interleukin 12 (IL-12), interleukin 4 (IL-4), and interleukin 10 (IL-10) were determined by ELISAs. Results. A significant increase in cytokine release was detected in HR-HPV-positive women without dysplasia. In women with cervical cancer, release of IFNγ and IL-12 was of the same magnitude as in HR-HPV-positive women without clinical manifestations. Most Th1-type/Th2-type ratios decreased form CIN II to CIN III, and increased from CIN III to invasive carcinoma. Conclusions. (1) Infection with HR-HPV without expression of cervical dysplasia induces activation of the cytokine network. (2) Increases in ratios of Th1-type to Th2-type cytokines at the stage of cervical carcinoma were found by comparison with stage CIN III. (3) Significant changes in the kinetics of cytokine release to a Th2-type immune response in blood of women with cervical dysplasia occurred progressively from CIN II to CIN III

Individualized ovarian stimulation in IVF/ICSI treatment : it is time to stop using high FSH doses in predicted low responders

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