Choice of primary and secondary outcomes in randomised controlled trials evaluating treatment for uterine fibroids: a systematic review.

BACKGROUND: Core outcome sets aim to reduce research heterogeneity and standardise reporting, allowing meaningful comparisons between studies. OBJECTIVES: To report on outcomes used in randomised controlled trials (RCTs) investigating uterine fibroid treatments, towards the development of a core outcome set for fibroid research. SELECTION STRATEGY: Database search of MEDLINE, PubMed, EMBASE and CINAHL (inception to July 2021) for all English-language RCTs involving surgical or radiological fibroid treatments. DATA COLLECTION AND ANALYSIS: A total of 1885 texts were screened for eligibility by two reviewers independently according to PRISMA methodology. JADAD and Management of Otitis Media with Effusion in Cleft Palate (MOMENT) scores were used to assess methodological and outcome reporting quality of studies, respectively. Outcomes were mapped to nine domains. Non-parametric tests for correlation and to compare group medians were undertaken. MAIN RESULTS: There were 23 primary outcomes (23 outcome measures) and 173 secondary outcomes (95 outcome measures) reported in 60 RCTs (5699 participants). The domains with highest frequency of primary outcomes reported were bleeding and quality of life (QoL). The most frequent primary outcomes were postoperative pain, QoL and menstrual bleeding. No primary outcomes were mapped to fertility domains. Median MOMENT outcome score was 5 (interquartile range 3). There was correlation between MOMENT outcome score and JADAD scores (r = 0.491, P = 0.0001), publishing journal impact factor (r = 0.419, P = 0.008) and publication year (r = 0.332, P = 0.01). CONCLUSION: There is substantial variation in the outcomes reported in fibroid RCTs. There is a need for a core outcome set for fibroid research, to allow improved understanding regarding the effects of different treatments. TWEETABLE ABSTRACT: There is substantial variation in outcomes reported in uterine fibroid randomised controlled trials.

Appraisal of national and international uterine fibroid management guidelines: a systematic review.

BACKGROUND: Guidelines standardise high-quality evidence-based management strategies for clinicians. Uterine fibroids are a highly prevalent condition and may exert significant morbidity. OBJECTIVES: To appraise national and international uterine fibroid guidelines using the validated AGREE-II instrument. SELECTION STRATEGY: Database search of PubMed and EMBASE from inception to October 2020 for all published English-language uterine fibroid clinical practice guidelines. DATA COLLECTION AND ANALYSIS: In all, 939 abstracts were screened for eligibility by two reviewers independently. Three reviewers used the AGREE-II instrument to assess guideline quality in six domains. Recommendations were mapped to allow a narrative synthesis regarding areas of consensus and disagreement. MAIN RESULTS: Eight national guidelines (AAGL, SOGC 2014, ACOG, ACR, SOGC 2019, CNGOF, ASRM and SOGC 2015) and one international guideline (RANZOG) were appraised. The highest scoring guideline was RANZOG 2001(score 56.5%). None of the guidelines met the a priori criteria for being high-quality overall (score ≥66%). There were 166 recommendations across guidelines. There were several areas of disagreement and uncertainty. There were only three areas of consensus. Supporting evidence was not evident for many recommendations; 27.7% of recommendations were based on expert opinion only. CONCLUSIONS: There is a need for high-quality guidelines on fibroids given their heterogeneity across individuals and the large range of treatment modalities available. There are also areas of controversy in the management of fibroids (e.g. Ulipristal acetate, power morcellation), which should also be addressed in any guidelines. Future guidelines should be methodologically robust to allow high-quality decision-making regarding fibroid treatments. TWEETABLE ABSTRACT: Current national fibroid guidelines have deficiencies in quality when appraised using the validated AGREE instrument.

Safety and five-year re-intervention following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids.

OBJECTIVE: To examine the safety and re-intervention rates following magnetic resonance-guided focused ultrasound (MRgFUS) for uterine fibroids at 5 years. To assess how the non-perfused volume (NPV), fibroid signal intensity and use of gonadotrophin-releasing hormone analogues (GnRHa) affect the re-intervention rates. STUDY DESIGN: Cohort study of women undergoing MRgFUS for treatment of their uterine fibroids between 2003 and 2010. RESULTS: Of 280 women undergoing MRgFUS the rate of minor complications was 3.9% and there were 3 serious complications (1.1%) including one skin burn, a fibroid expulsion and one case of persistent neuropathy. The NPVs achieved following MRgFUS have increased as the experience with this treatment has grown. In a 5-year follow-up study of 162 women, the overall re-intervention rate was 58.64%, but in those treatments with greater than 50% NPV the re-intervention rate was 50%. CONCLUSION: MRgFUS treatment of uterine fibroids is a safe treatment for uterine fibroids. The re-intervention rate at 5 years is high, but the improvements in NPVs achieved may further improve the long term results.

The effects of hormones on urinary incontinence in postmenopausal women.

It has been established that the lower urinary tract is sensitive to the effects of estrogen, sharing a common embryological origin with the female genital tract, the urogenital sinus. Urge urinary incontinence is more prevalent after the menopause, and the peak prevalence of stress incontinence occurs around the time of the menopause. Many studies, however, indicate that the prevalence of stress incontinence falls after the menopause. Until recently, estrogen, usually as part of a hormone replacement therapy (HRT) regimen, was used for treatment of urinary incontinence in postmenopausal women. Although its use in the treatment of vaginal atrophy is well established, the effect of HRT on urinary continence is controversial. A number of randomized, placebo-controlled trials have examined the effects of estrogen, or estrogen and progestogen together, in postmenopausal continence and concluded that estrogens should not be used for the treatment of urge or stress incontinence. In this paper, we will review these recent studies and examine the evidence for the effects of estrogen on the postmenopausal urogenital tract.

The youngest victims of child maltreatment: what happens to infants in a court sample?

Current data show that infants represent an increasing proportion of cases of child maltreatment. To learn more about how infants fare in the current system and to provide baseline data against which to compare outcomes following recent legislative reforms, this study examined a subsample of infants in a sample of 200 care and protection cases brought before the Boston Juvenile Court in 1994. Child, parent, and case characteristics of infants 0 to 3 months of age (n = 46) were compared with characteristics of older children in the sample. All cases were followed prospectively for 4 years, and data were abstracted from court records. Results revealed that the infants were primarily children of substance abusers who had extensive prior histories of child protective service system involvement. Although the majority of the infants were eventually permanently removed from parental custody and adopted, many experienced time delays and multiple placements before achieving permanent homes.

Protecting seriously mistreated children: time delays in a court sample.

The study examined the progress through the child protective system of a sample of 206 severely abused and/or neglected children brought before the Boston Juvenile Court (BJC) on Care and Protection (C & P) petitions. Overall, children were in the system an average of 5 years from the filing of the first official report of mistreatment to the resolution of their cases. The families had been known to the state child protective service agency for an average of more than 2.5 years before the current court involvement. Once arraigned in juvenile court on the C & P, the average case took almost 1.5 years to reach a disposition. After disposition, children permanently removed from parental custody required, on average, an additional year and a half in Probate Court to reach a permanent placement. Of the more than twenty variables examined, including severity of mistreatment, protective service history, and parental mental illness, no meaningful pattern emerged which could predict delays. Our findings characterize the delays experienced by many abused and neglected children, and highlight the necessity of closer monitoring of the progress of cases through the protective and court systems.

Enhanced neuronal regeneration by retinoic acid of murine dorsal root ganglia and of fetal murine and human spinal cord in vitro.

This study demonstrates that retinoic acid (RA), an active metabolite of vitamin A, can act to enhance regeneration of neurites, at physiologic concentrations, in vitro. Explanted fragments of mouse dorsal root ganglia (DRG) and mouse and human spinal cord (SC) were maintained, in vitro, for periods up to 11 d. Murine DRG neurons were exposed to RA concentrations ranging from 100 microM to 1 nM, whereas neurons within murine and human SC explants were exposed to 10 microM to 10 nM RA. Results show that RA significantly (P less than 0.001) increases mean neurite length but not neurite number. Specifically, murine DRG neurons showed increases in mean neurite length of 30.7% with individual explants showing increases of up to 133.5%. Murine and human SC showed mean enhancements of 43.4 and 58.1%, respectively, but did so at lower concentrations of RA. The results indicate that RA may play a potentially critical role in neuronal regeneration.