A novel high-power test for continuous outcomes truncated by death

Patient reported outcomes including quality of life (QoL) assessments are increasingly being included as either primary or secondary outcomes in randomized controlled trials. While making the outcomes more relevant for patients it entails a challenge in cases where death or a similar event makes the outcome of interest undefined. A pragmatic - and much used - solution is to assign diseased patient with the lowest possible QoL score. This makes medical sense, but creates a statistical problem since traditional tests such as t-tests or Wilcox tests potentially looses large amounts of statistical power. In this paper we propose a novel test that can keep the medical relevant composite outcome, but preserve full statistical power. The test is also applicable in other situations where a specific value (say 0 days alive outside hospitals) encodes a special meaning. The test is implemented in an R package which is available for download

Having a Ball: evaluating scoring streaks and game excitement using in-match trend estimation

Many popular sports involve matches between two teams or players where each team have the possibility of scoring points throughout the match. While the overall match winner and result is interesting, it conveys little information about the underlying scoring trends throughout the match. Modeling approaches that accommodate a finer granularity of the score difference throughout the match is needed to evaluate in-game strategies, discuss scoring streaks, teams strengths, and other aspects of the game. We propose a latent Gaussian process to model the score difference between two teams and introduce the Trend Direction Index as an easily interpretable probabilistic measure of the current trend in the match as well as a measure of post-game trend evaluation. In addition we propose the Excitement Trend Index - the expected number of monotonicity changes in the running score difference - as a measure of overall game excitement. Our proposed methodology is applied to all 1143 matches from the 2019-2020 National Basketball Association (NBA) season. We show how the trends can be interpreted in individual games and how the excitement score can be used to cluster teams according to how exciting they are to watch

Low validity of the Sensewear Pro3 activity monitor compared to indirect calorimetry during simulated free living in patients with osteoarthritis of the hip

BACKGROUND: To validate physical activity estimates by the Sensewear Pro3 activity monitor compared with indirect calorimetry during simulated free living in patients diagnosed with osteoarthritis of the hip pre or post total hip arthroplasty. METHODS: Twenty patients diagnosed with hip osteoarthritis (10 pre- and 10 post total hip arthroplasty; 40% female; age: 63.3 ± 9.0; BMI: 23.7 ± 3.7). All patients completed a 2 hour protocol of simulated free living with 8 different typical physical activity types. Energy consumption (kcal/min) was estimated by the Sense Wear pro3 Armband activity monitor and validated against indirect calorimetry (criterion method) by means of a portable unit (Cosmed K4b(2)). Bias and variance was analyzed using functional ANOVA. RESULTS: Mean bias during all activities was 1.5 Kcal/min 95%CI [1.3; 1.8] corresponding to 72% (overestimation). Normal gait speed showed an overestimation of 2.8 Kcal/min, 95%CI [2.3; 3.3] (93%) while an underestimation of -1.1 Kcal/min, 95%CI [-1.8; -0.3] (-25%) was recorded during stair climb. Activities dominated by upper body movements showed large overestimation with 4.37 Kcal/min, 95%CI [3.8; 5.1] (170%) being recorded during gardening. Both bias and variance appeared to be dependent on activity type. CONCLUSION: The activity monitor generally overestimated the energy consumption during common activities of low to medium intensity in the patient group. The size and direction of the bias was highly dependent on the activity type which indicates the activity monitor is of limited value in patients with hip osteoarthritis and that the results do not express the real energy expenditure

Pharmacokinetics of prednisolone in children: an open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease

Introduction: One in three Danish children under 3 years of age experience asthma-like symptoms, and one-third will later be diagnosed with asthma. Oral prednisolone is used in various formulations to treat acute asthma. However, the potential differences in bioequivalence between these formulations have never been examined in children despite interchangeable use in clinical practice. Methods and analysis: An open-label, randomised, two-treatment cross-over trial investigating the bioequivalence of different prednisolone formulations in children with airway disease. The included patients (6 months-11 years of age) are admitted to the Department of Paediatric and Adolescent Medicine Nordsjællands University Hospital, Hillerød, with asthma or asthma-like symptoms. The primary objective is to assess the bioequivalence between different prednisolone formulations herein area under the concentration time curve, Cmax and Tmax using saliva samples. The secondary objectives are to evaluate tolerability (five-point face scale), adverse events and severity of the disease. If the patient has an intravenous access for other purposes, the saliva samples will be validated with plasma samples. A total of 66 evaluable patients are needed according to European Medicines Agency Guideline on bioequivalence. Ethics and dissemination: Traditional pharmacokinetic trials are burdensome due to the extent of blood samples necessary to capture the time-dependant drug profile. Saliva sampling is far more acceptable for paediatric patients. In addition, this trial adheres to standard dosing strategies. No additional venepunctures are performed, and no additional prednisolone doses are administered. Guidelines for paediatric bioequivalence trials are warranted

Scaling up context-tailored clinical guidelines and training to improve childbirth care in urban, low-resource maternity units in Tanzania: A protocol for a stepped-wedged cluster randomized trial with embedded qualitative and economic analyses (The PartoMa Scale-Up Study)

While facility births are increasing in many low-resource settings, quality of care often does not follow suit; maternal and perinatal mortality and morbidity remain unacceptably high. Therefore, realistic, context-tailored clinical support is crucially needed to assist birth attendants in resource-constrained realities to provide best possible evidence-based and respectful care. Our pilot study in Zanzibar suggested that co-created clinical practice guidelines (CPGs) and low-dose, high-frequency training (PartoMa intervention) were associated with improved childbirth care and survival. We now aim to modify, implement, and evaluate this multi-faceted intervention in five high-volume, urban maternity units in Dar es Salaam, Tanzania (approximately 60,000 births annually). This PartoMa Scale-up Study will include four main steps: I. Mixed-methods situational analysis exploring factors affecting care; II. Co-created contextual modifications to the pilot CPGs and training, based on step I; III. Implementation and evaluation of the modified intervention; IV. Development of a framework for co-creation of context-specific CPGs and training, of relevance in comparable fields. The implementation and evaluation design is a theory-based, stepped-wedged cluster-randomised trial with embedded qualitative and economic assessments. Women in active labour and their offspring will be followed until discharge to assess provided and experienced care, intra-hospital perinatal deaths, Apgar scores, and caesarean sections that could potentially be avoided. Birth attendants\u27 perceptions, intervention use and possible associated learning will be analysed. Moreover, as further detailed in the accompanying article, a qualitative in-depth investigation will explore behavioural, biomedical, and structural elements that might interact with non-linear and multiplying effects to shape health providers\u27 clinical practices. Finally, the incremental cost-effectiveness of co-creating and implementing the PartoMa intervention is calculated. Such real-world scale-up of context-tailored CPGs and training within an existing health system may enable a comprehensive understanding of how impact is achieved or not, and how it may be translated between contexts and sustained.Trial registration number: NCT04685668