Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta-analysis, network meta-analysis and health economic evaluation.

INTRODUCTION: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. METHODS AND ANALYSIS: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. ETHICS AND DISSEMINATION: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021231276.

Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study.

OBJECTIVES: To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women. DESIGN: A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation. SETTING: Five inner city UK National Health Service hospitals PARTICIPANTS: Multiethnic pregnant women at 12+0 and 15+6 weeks' gestation with risk factors for gestational diabetes. INTERVENTIONS: 2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, adherence and follow-up. SECONDARY OUTCOME MEASURES: Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs. RESULTS: Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks' and 34% (SD 41) at 36 weeks' gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference -0.6, 95% CI -1.2 to 0.0 and -2.69, 95% CI -5.26 to -0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence. CONCLUSIONS: A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol. TRIAL REGISTRATION NUMBER: ISRCTN48872100.

Quality indicators for breast cancer care: A systematic review.

OBJECTIVES: We evaluated breast cancer (BC) care quality indicators (QIs) in clinical pathways and integrated health care processes. METHODS: Following protocol registration (Prospero no: CRD42021228867), relevant documents were identified, without language restrictions, through a systematic search of bibliographic databases (EMBASE, Scopus, Web of Science, MEDLINE), health care valuable representatives and the World Wide Web in April 2021. Data concerning QIs, measurement tools and compliance standards were extracted from European and North American sources in duplicate with 98% reviewer agreement. RESULTS: There were 89 QIs found from 22 selected documents (QI per document mean 13.5 with standard deviation 11.9). The Belgian (38 QIs) and the EUSOMA (European Society of Breast Cancer Specialists) (34 QIs) documents were the ones that best reported the QIs. No identical QI was identified in all the documents analysed. There were 67/89 QIs covering processes (75.3%) and 11/89 (12.4%) for each structure and outcomes QIs. There were 21/89 QIs for diagnosis (30.3%), 43/89 for treatment (48.3%), and 19/89 for staging, counselling, follow-up and rehabilitation (21.4%). Of 67 process QIs and 11 outcome QIs, 20/78 (26%) did not report a minimum standard of care. Shared decision making was only included as a QI in the Italian document. CONCLUSION: More than half of countries have not established a national clinical pathway or integrated breast cancer care process to achieve the excellence of BC care. There was heterogeneity in QIs for the evaluation of BC care quality. Over two-thirds of the clinical pathways and integrated health care processes did not provide a minimum auditable standard of care for compliance, leaving open the definition of best practice. There is a need for harmonisation of BC care QIs.