Power and sample size for cost-effectiveness analysis: fFN neonatal screening

Randomised controlled trials (RCTs) which involve cost-effectiveness evaluations rarely use health economic input when undertaking sample size calculations for the trial design; however, in studies undertaken with cost-effectiveness as the primary outcome, sample size calculations should be directly related to the cost-effectiveness result rather than to the effectiveness outcome alone. This paper reports on a case in which a clinical trial design sample size and power calculations were determined with regard to cost-effectiveness using the net monetary benefit (NMB) approach to demonstrate the feasibility of sample size calculation for cost-effectiveness in a real life setting.The proposed RCT of fetal fibronectin screening (fFN) for women with threatened pre-term labour is discussed, followed by the design of a preliminary model to inform the trial design calculation. The predictions from this pre-trial indicate potential cost-savings, but with a marginal detrimental impact on the effectiveness endpoint, neonatal morbidity. The NMB approach for cost-effectiveness is discussed and used to calculate the required sample sizes for different powers. The sample size calculations are then recalculated using a non-inferiority margin, to ensure that the NMB sample size for the trial was also sufficient to demonstrate non-inferiority for the effectiveness endpoint. Finally, a probabilistic analysis explored uncertainty in the model parameters and the impact on sample size.Considerations of economic assessments alongside clinical trials can and should be used to guide conventional trial design. This paper demonstrates the feasibility of such calculations, whilst simultaneously highlighting limitations and demonstrating the role for economic considerations to guide non-inferiority margins.     

A trial of an activating intervention for chronic back pain in primary care and physical therapy settings

In primary care and physical therapy settings, we evaluated an intervention for chronic back pain patients which incorporated fear reducing and activating techniques. Primary care patients seen for back pain in primary care were screened to identify persons with significant activity limitations 8-10 weeks after their visit. Eligible and willing patients were randomized (N=240). A brief, individualized program to reduce fear and increase activity levels was delivered by a psychologist and physical therapists. Over a 2 year follow-up period, intervention patients reported greater reductions in pain-related fear (P<0.01), average pain (P<0.01) and activity limitations due to back pain (P<0.01) relative to control patients. The percent with greater than a one-third reduction in Roland Disability Questionnaire scores at 6 months was 42% among Intervention patients and 24% among control patients (P<0.01). Over the 2 year follow-up, fewer intervention patients reported 30 or more days unable to carry out usual activities in the prior 3 months (P<0.01). The adjusted mean difference in activity limitation days was 4.5 days at 6 months, 2.8 days at 12 months, and 6.9 days at 24 months. No differences were observed in the percent unemployed or the percent receiving worker's compensation or disability benefits, but these outcomes were relatively uncommon. We conclude that an intervention integrating fear reducing and activating interventions into care for chronic back pain patients produced sustained reductions in patient fears, common activity limitations related to back pain, and days missed from usual activities due to back pain.     

Augmentation of exercise ventilation by medroxyprogesterone acetate

Summary. The influence of medroxyprogesterone acetate (MPA) on exercise performance was studied in a double-blind cross-over trial using six normal males to compare the exercise performance changes to those observed in a previous study of exercise responses of female subjects during the follicular and luteal phase of the menstrual cycle. A maximal progressive work exercise test on a cycle ergometer was performed after 2 weeks of placebo or MPA administration. Although five of six subjects spontaneously complained of increased exertional dyspnoea on MPA, no significant decreases were documented in maximal exercise time or in maximal oxygen consumption. A mean increase in exercise ventilation of 19% at low levels of exertion and 26% at high levels of exertion was documented, but no subject demonstrated evidence of ventilatory limitation. The increases in exercise ventilation observed in these male subjects after MPA administration were larger than those observed in the previous study comparing exercise ventilatory responses during follicular and luteal phases of the menstrual cycle. It seems possible that some other exercise-related modulator of the ventilatory response to exercise under the influence of progesterone is present in either male subjects receiving MPA or women with normal hormonal cycles.     

Meta‐Analysis of Therapist Effects in Psychotherapy Outcome Studies

In a meta-analysis, we examined factors that could account for the differences in therapist efficacy evidenced in psychotherapy outcome studies. The factors investigated were: (1) the use of a treatment manual, (2) the average level of therapist experience, (3) the length of treatment, and (4) the type of treatment (cognitive/behavioral versus psychodynamic). Data were obtained from fifteen psychotherapy outcome studies that produced 27 separate treatment groups. For each treatment group, the amount of outcome variance due to differences between therapists was calculated and served as the dependent variable for the meta-analysis. Each separate treatment group was coded on the above four variables, and multiple regression analyses related the independent variables to the size of therapist effects. Results indicated that the use of a treatment manual and more experienced therapists were associated with small differences between therapists, whereas more inexperienced therapists and no treatment manual were associated with larger therapist effects. The findings are discussed in terms of the design and the analysis of psychotherapy outcome research.     

Relation of melody complexity in infants' cries to language outcome in the second year of life: A longitudinal study

This study is part of the German Language Development Study's prospective longitudinal research programme on infants from birth until the age of 3 years. Thirty‐four infants were retrospectively classified into two groups (normal/delayed) by their language skills at 2.5 years of age. Frequency spectrograms and melodies of about 11,000 cries from the first 16 weeks of life were analysed using a CSL 4400. A Melody Complexity Index was calculated at monthly intervals. Infants with less than 45% complex melodies in their cries during the second month were found to be almost five times more likely to develop a language delay as infants with a higher proportion. For infants above the cut‐off of .45, development of a language delay condition could be ruled out with a probability of 89%. Although the results need to be interpreted cautiously, the data indicate a possible relation between early melody development and later language outcome.     

Monitoring the preterm fetus during labor

The purpose of this article is to discuss special challenges in monitoring the preterm fetus during labor, review implications of preterm fetal heart rate (FHR) patterns, and highlight appropriate nursing interventions that contribute to the best outcomes for mothers and babies. With the current incidence of preterm birth, monitoring the preterm fetus during labor is a common perinatal nursing responsibility. Most of the published research on this topic was conducted in the 1980s; there has been little attention to FHR monitoring during preterm labor in recent studies. There has been much more accumulated evidence about antepartum testing techniques involving electronic fetal monitoring (EFM) for the preterm fetus in contrast to FHR patterns during labor. Thus, this is an area of opportunity for nursing research. The perinatal nurse has a key role in promoting positive outcomes when caring for women during preterm labor. The condition of the fetus during labor and birth has a significant impact on the likelihood of survival and the odds of developing serious complications of prematurity.     

Referral,Genetic Counselling,and BRCA Testing in the Manitoba High-Grade Serous Ovarian Cancer Population, 2004–2019

Simple SummaryThis study was performed to better understand rates and factors that influence patients in accepting a referral to genetics or testing for genes that predispose them to ovarian cancer (BRCA1/2). Using multiple provincial databases and registries, the study team looked at data from 944 patients with high-grade ovarian cancer between 2004–2019. We found that the rate of genetic referrals fluctuated over time; however, the rate of genetic testing increased over the entire timeframe. Factors found to increase rates of referral and testing included age, cancer histology, history of oral contraceptive use, and family history of ovarian cancer. Increasing the rate of genetic testing will help patients and their health care team plan clinical management and treatment.Abstract(1) Background: The primary objective of this study was to examine the rate of genetic referral, BRCA testing, and BRCA positivity amongst all patients with high-grade serous ovarian cancers (HGSOC) from 2004–2019. The secondary objective was to analyze secondary factors that may affect the rates of referral and testing. (2) Methods: This population-based cohort study included all women diagnosed with HGSOC using the Manitoba Cancer Registry, CervixCheck registry, Medical Claims database at Manitoba Health, the Hospital Discharge abstract, the Population Registry, and Winnipeg Regional Health Authority genetics data. Data were examined for three different time cohorts (2004–2013, 2014–2016; 2017–2019) correlating to practice pattern changes. (3) Results: A total of 944 patients were diagnosed with HGSOC. The rate of genetic referrals changed over the three timeframes (20.0% → 56.7% → 36.6%) and rate of genetic testing increased over the entire timeframe. Factors found to increase rates of referral and testing included age, histology, history of oral contraceptive use, and family history of ovarian cancer. Prior health care utilization indicators did not affect genetic referral or testing. (4) Conclusion: The rate of genetic referral (2004–2016) and BRCA1/2 testing (2004–2019) for patients with a diagnosis of HGSOC increased over time. A minority of patients received a consultation for genetics counselling, and even fewer received testing for a BRCA1/2. Without a genetic result, it is difficult for clinicians to inform treatment decisions. Additional efforts are needed to increase genetics consultation and testing for Manitoban patients with HGSOC. Effects of routine tumour testing on rates of genetic referral will have to be examined in future studies.