Is it possible to estimate the minimal clinically important treatment effect needed to change practice in preterm birth prevention? Results of an obstetrician survey used to support the design of a trial

<p>Abstract</p> <p>Background</p> <p>Sample sizes for obstetrical trials are often based on the opinion of investigators about clinically important effect size. We surveyed Canadian obstetricians to investigate clinically important effect sizes required before introducing new treatments into practice to prevent preterm birth.</p> <p>Methods</p> <p>Questionnaires were mailed to practicing obstetricians, asking the magnitude of pregnancy prolongation required to introduce treatments into practice. The three prophylactic treatments were of increasing invasiveness: vaginal progesterone, intramuscular progesterone, and cervical cerclage. We also asked about the perceived most relevant outcome measures for obstetrical trials and current obstetrical practice in preterm birth prevention.</p> <p>Results</p> <p>544/1293(42.1%) completed questionnaires were received. The majority of respondents required one or two weeks' increase in length of gestation before introducing vaginal (372,77.1%), and intramuscular progesterone(354,67.9%). At least three weeks increase was required before introducing prophylactic cervical cerclage(326,62.8%). Clinicians who already used a treatment required a smaller difference before introducing it into practice. Decreasing neonatal morbidity was cited as the most important outcome for obstetrical trials (349,72.2%).</p> <p>Conclusion</p> <p>Obstetricians would require a larger increase in treatment effect before introducing more invasive treatments into practice. Although infant morbidity was perceived as a more important outcome, clinicians appeared willing to change practice on the basis of prolongation of pregnancy, a surrogate outcome. We found that there is not a single minimum clinically important treatment effect that will influence all practising clinicians: rather the effect size that will influence physicians is affected by the nature of the treatment, the reported outcome measure and the clinician's own current clinical practice.</p

Defining the short-term disease recurrence after loop electrosurgical excision procedure (LEEP)

Abstract Background The goal of cervical cancer screening is to identify dysplastic lesions for subsequent excision in order to prevent invasive disease. There is clinical equipoise, on how to best follow women for disease surveillance after treatment with some Canadian provinces exclusively performing colposcopy and some utilizing Human Papilloma Virus (HPV) testing in addition to cervical cytology. Loop Electrosurgical Excision Procedure (LEEP) is used to treat pre-invasive HPV-mediated disease and patients are typically followed for 12 months after disease excision. This study aims to quantify the prevalence of high-grade disease at the time of the second follow-up colposcopy visit, in a practice setting that utilizes laser ablation in addition to LEEP. Methods In a retrospective cohort study, consecutive patient charts were accessed through the electronic medical record system, ARIA, at the Tom Baker Cancer Centre, in Calgary, Alberta, from January 2010 to December 2015. Data was extracted and a REDCap database was used to compile pertinent information from charts meeting inclusion criteria. Descriptive and analytic statistics were performed. Results Of the 303 patients identified, 221 patients met inclusion criteria. 86% of these patients met discharge criteria from colposcopy after the second follow up visit. 31 (14%) were seen in a subsequent visit for abnormal findings. Of these, 7 (3.2%) underwent further treatment for high-grade disease/Cervical Intraepithelial Neoplasia (CIN 2/3). Of the 31, 23 (10.6%) had a third – negative – visit, resulting in discharge from colposcopy. One patient had a repeat LEEP for persistent Low-Grade Squamous Intraepithelial Lesion (LSIL). Conclusion In summary, our data demonstrates a prevalence of 3.2% of high-grade disease at the time of a second colposcopic follow up visit after treatment, in a setting which frequently utilizes laser ablation in combination with LEEP, for large lesions. This recurrence rate is consistent with most published literature on recurrence rates of CIN2/3

Progesterone in women with arrested premature labor, a report of a randomised clinical trial and updated meta-analysis

Background: Progesterone may be effective in prevention of premature birth in some high risk populations. Women with arrested premature labor are at risk of recurrent labor and maintenance therapy with standard tocolytics has not been successful. Methods: Randomized double blinded clinical trial of daily treatment with 200 mg vaginal progesterone in women with arrested premature labor and an updated meta-analysis. Results: The clinical trial was terminated early after 41 women were enrolled. Vaginal progesterone treatment did not change the median gestational age at delivery: 36+2 weeks versus 36+4 weeks, p = .865 nor increase the mean latency to delivery: 44.5 days versus 46.6 days, p = .841. In the updated meta-analysis, progesterone treatment did reduce delivery <37 weeks gestation and increase latency to delivery, but this treatment effect was not evident in the high quality trials: (OR 1.23, 95% CI 0.91, 1.67) and (−0.95 days, 95% CI −5.54, 3.64) respectively. Conclusion: Progesterone is not effective for preventing preterm birth following arrested preterm labor.Science, Faculty ofNon UBCStatistics, Department ofReviewedFacult

Need for supplemental oxygen at discharge in infants with bronchopulmonary dysplasia is not associated with worse neurodevelopmental outcomes at 3 years corrected age.

OBJECTIVES: To determine if chronic oxygen dependency (discharge home on supplemental oxygen) in children with bronchopulmonary dysplasia (BPD; defined as requirement for supplemental O2 at 36 weeks postmenstrual age) predicts neurodevelopmental disability rates and growth outcomes at 36 months corrected age (CA). STUDY DESIGN: Longitudinal cohort study. SETTING: Southern Alberta regional center located at high altitude. PARTICIPANTS: Preterm infants weighing ≤1250 grams with no BPD, BPD, and BPD with chronic oxygen dependency. MAIN OUTCOME MEASURES: Neurodevelopmental and growth outcomes. RESULTS: Of 1563 preterm infants admitted from 1995-2007, 1212 survived. Complete follow-up data were available for 1030 (85%) children. Children in BPD and BPD with chronic oxygen dependency groups had significantly lower birth weights, gestational ages, prolonged mechanical ventilation and oxygen supplementation and received more postnatal steroids, compared to those without BPD. Children with BPD and BPD with chronic oxygen dependency were more likely to be below the 5th centile in weight and height compared to those without BPD but there was little difference between the BPD and BPD with chronic oxygen dependency groups. After controlling for confounding variables, children who had BPD and BPD with chronic oxygen dependency had higher odds of neurodevelopmental disability compared to those without BPD [OR (odds ratio) 1.9 (95%CI 1.1 to 3.5) and OR 1.8 (1.1 to 2.9), respectively], with no significant difference between BPD and BPD with chronic oxygen dependency [OR 0.9 (95% CI 0.6 to 1.5)]. CONCLUSIONS: BPD and BPD with chronic oxygen dependency in children predicts abnormal neurodevelopmental outcomes at 36 months CA. However, the neurodevelopmental disability rates were not significantly higher in BPD with chronic oxygen dependency children compared to children with BPD only. Compared to those without BPD, growth is impaired in children with BPD and BPD with chronic oxygen dependency, but no difference between the latter two groups

Disability Status at 36 Months Corrected Age.

<p>Disability Status at 36 Months Corrected Age.</p

Discharge criteria of infant from NICU.

<p>Discharge criteria of infant from NICU.</p

Language outcomes at 36 months corrected age.

<p>*Pearson χ² test or Fisher’s Exact test.</p>§<p>Bonferroni correction applied to adjust for the three pairwise comparisons, thus confidence intervals are reported at the (1–0.05/3) % level.</p><p>BPD: bronchopulmonary dysplasia;</p

Proportional odds model of factors associated with neurodevelopmental disability.

<p>*Estimated odds ratios from proportional odds model; odds of mild or severe disability versus no disability, and odds of severe disability versus milder or no disability; Score test for the proportional odds assumption: p = 0.149; Likelihood ratio test for overall model significance: p<0.001.</p>§<p>The model was first run with No BPD as the reference category. In order to obtain estimates for BPD with chronic oxygen dependency versus BPD, the model was run a second time, using BPD as the reference category.</p><p>BPD: bronchopulmonary dysplasia; NEC: necrotizing enterocolitis; IVH: intraventricular hemorrhage; SGA: small for gestational age; PDA: patent ductus arteriosus; RDS: respiratory distress syndrome; ROP: retinopathy of prematurity.</p