Prevalence of obstetric violence in high-income countries: A systematic review of mixed studies and meta-analysis of quantitative studies.

INTRODUCTION: Obstetric violence, or mistreatment of women in obstetric care, can have severe consequences such as fear of future childbirth, post-traumatic stress disorder, and depression. MATERIAL AND METHODS: The primary objective was to estimate the prevalence of obstetric violence in high-income countries. The secondary objective was to extract the main domains of obstetric violence perceived by women from qualitative studies. Following prospective registration (PROSPERO CRD42023468570), PubMed, Web of Science, Scopus, CINAHL, Embase, and Cochrane Library were searched with no restrictions. Included studies were cross-sectional, cohort, mixed methods, and qualitative studies based on populations from high-income countries. The review was conducted by two independent reviewers. Risk of bias was assessed. Rates of obstetric violence were pooled using random effects model, computing 95% confidence intervals (CI) and assessing heterogeneity using I2 statistic. Funnel plots and Egger's test were used to detect potential reporting biases and small-study effects. RESULTS: Of the 1821 records screened, 25 studies were included: 14 quantitative and 2 mixed methods studies, comprising 60 987 women, and 9 qualitative studies were included, comprising an additional 4356 women. 81.25% of quantitative studies, including the quantitative component of the mixed methods studies, were considered satisfactory or better regarding risk of bias. The prevalence of obstetric violence was overall 45.3% (95% CI 27.5-63.0; I2 = 100.0%). The prevalence of specific forms of mistreatment was also estimated. Lack of access to analgesia was 17.3% (95% CI 6.9-27.7; I2 = 99.7%). Ignored requests for help was 19.2% (95% CI 11.7-26.6; I2 = 99.0%). Shouting and scolding 19.7% (95% CI 13.0-26.4; I2 = 98.7%). The use of fundal pressure during the second stage of labor (Kristeller maneuver) was 30.3% (95% CI 22.1-38.5; I2 = 97.6%). There was no funnel asymmetry. Lack of information and/or consent were the most frequent domains extracted from the qualitative articles and the qualitative component of the mixed methods studies. CONCLUSIONS: The results demonstrate that obstetric violence is a prevalent problem that women in high-income countries experience. Lack of information and/or consent were the domains most frequently described in the qualitative studies and the qualitative component of the mixed methods studies.

Prevalence of depression and anxiety in women with pelvic floor dysfunctions: A systematic review and meta-analysis.

BACKGROUND: Female pelvic floor dysfunction (PFD) is a common condition affecting the emotional well-being of women. OBJECTIVE: To estimate the prevalence of depressive and anxiety symptoms in women with PFD. SEARCH STRATEGY, SELECTION CRITERIA, DATA COLLECTION AND ANALYSIS: Following prospective registration (PROSPERO CRD42022362095) we conducted a search of three electronic databases (PubMed, Web of Science and Scopus) from inception to April 2023 without language restriction to capture studies reporting the prevalence of depression/anxiety among women with PFD (chronic pelvic pain [CPP], urinary incontinence [UI], pelvic organ prolapse [POP], and/or fecal incontinence [FI]). Only studies with validated tools were included. Data extraction and study quality assessment were performed by two independent reviewers. Stratifying by type of PFD, rates of depression and anxiety were pooled using random effects model computing 95% confidence interval (CI) and assessing heterogeneity using the I2 statistic. Funnel plots were used to detect potential reporting biases and small-study effects. MAIN RESULTS: The search yielded 767 articles, from which 54 studies containing 632 605 women were included. All the studies were high quality. The prevalence of depression was: CPP 26.8% (95% CI: 19.2-34.4, I2 = 98.7%; 12 studies, 4798 participants with 491 cases; Egger's P value = 0.009); UI 26.3% (95% CI: 19.4-33.2, I2 = 99.9%; 26 studies, a total of 346 114 participants with 25 050 cases; Egger's P value = 0.944); POP 34.9% (95% CI: 24.3-45.6, I2 = 68%; three studies, 297 participants with 104 cases; Egger's P value = 0.973); and FI 25.3% (95% CI: 0.68-49.9, I2 = 99.7%; six studies, 14 663 participants with 1773 cases; Egger's P value = 0.780). The prevalence of anxiety was: CPP 29.5% (95% CI: 16.3-42.7, I2 = 97.7%; nine studies, 2483 participants with 349 cases; Egger's P value = 0.001); UI 46.91% (95% CI: 39.1-54.6, I2 = 99.6%; 11 studies, 198 491 participants with 40 058 cases; Egger's P value = 0.337); and POP 28% (95% CI: 13.6-42.4, I2 = 89%; three studies with 355 participants with 90 cases; Egger's P value = 0.306). CONCLUSION: The prevalence of mental health illness was variable in the different types of PFDs. This meta-analysis helps quantify the burden of depression and anxiety in PFD and will help inform the policies regarding screening of emotional well-being by healthcare professionals engaged in care of women with PFD.

Persistent organic pollutant exposure as a risk factor of gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Findings related to the association between persistent organic pollutants (POPs) and gestational diabetes mellitus (GDM) are inconclusive. OBJECTIVES: To estimate the strength of the association between POP exposure and GDM in a systematic review with meta-analysis. SEARCH STRATEGY: MEDLINE, Scopus and Web of Science were searched until July 2023. SELECTION CRITERIA: Cohort and case-control studies analysing the association between POPs and GDM. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias using the Quality in Prognosis Studies scale (QUIPS). Standardised mean differences were pooled using random-effect models. MAIN RESULTS: Sixteen articles including 12 216 participants were selected. The risk of bias was high in four articles (25%), moderate in 11 (68.75%) and low in one (6.25%). Small mean difference between GDM cases and controls was observed for PFHpA (0.26, 95% confidence interval [CI] 0.1-0.35, I2 = 0.0%), PCB180 (0.37, 95% CI 0.19-0.56; I2 = 25.3%), BDE47 (0.23, 95% CI 0.0-0.45, I2 = 0%), BDE99 (0.36, 95% CI 0.14-0.59; I2 = 0%), BDE100 (0.42, 95% CI 0.19-0.64; I2 = 0%) and HCB (0.22, 95% CI 0.01-0.42, I2 = 39.6%). No considerable difference was observed for the rest of POPs. CONCLUSION: Small mean differences between GDM cases and controls were observed for some POPs. However, evidence shows mostly moderate quality and results were heterogeneous. Improved research methodology is needed to assess POPs and GDM risk.

The definition of unexplained infertility: A systematic review.

BACKGROUND: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta-analysis and best practice advice. OBJECTIVES: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis. SEARCH STRATEGY: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language. DATA COLLECTION AND ANALYSIS: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range. MAIN RESULTS: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid-luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies. CONCLUSIONS: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.

BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

A systematic review of robotic breast surgery versus open surgery.

Robotic-assisted breast surgery (RABS) is controversial. We systematically reviewed the evidence about RABS, comparing it to open conventional breast surgery (CBS). Following prospective registration (osf.io/97ewt), a search was performed in January 2023, without time or language restrictions, through bibliographic databases (PubMed, Web of Science, EMBASE, Scopus, Trip database and CDSR) and grey literature. Quality was assessed in duplicate using Qualsyst criteria (score range 0.0-1.0); reviewer agreement was 98%. The 16 selected studies (total patients: 334,804) had overall high quality (mean score 0.82; range 0.68-0.91). Nine of 16 (56.3%) were cohort studies, 2/16 (12.5%) RCTs, and 5/16 (31.3%) case-control studies. Taking p < 0.05 as the significance threshold, RABS versus CBS was better in aesthetic results and patient satisfaction (10/11 studies; 90%), was surgically costly (4/4 studies; 100%), time-consuming (9/13 studies; 69%), and less painful in the first 6-24 h (2/2 studies; 100%) and without statistically significant differences in complication rates (10/12 studies; 83%) or short-term oncological outcomes (10/10 studies; 100%). Surgical time could be dramatically reduced by training surgical teams, reaching no significant differences between approaches (p = 0.120). RABS was shown to be feasible and safe. The advantages of RABS and long-term outcomes need further research.

Colorectal cancer treatment guidelines and shared decision making quality and reporting assessment: Systematic review.

INTRODUCTION: Physicians must share decisions and choose personalised treatments regarding patients´ beliefs and values. OBJECTIVE: To analyse the quality of the recommendations about shared decision making (SDM) in colorectal (CRC) and anal cancer treatment clinical practice guidelines (CPGs) and consensus statements (CSs). METHODS: Guidelines were systematically reviewed following prospective registration (Prospero: CRD42021286146) without language restrictions searching 15 databases and 59 professional society websites from January 2010 to November 2021. A validated 31-item SDM quality assessment tool was employed to extract data in duplicate. RESULTS: We identified 134 guidelines. Only 46/134 (34.3 %) mentioned SDM. Fifteen (11.1 %) made clear, precise and actionable recommendations, while 9/134 (6.7 %) indicated the strength of the SDM-related recommendations. CPGs underpinned by systematic reviews reported SDM more often than those based on consensus or reviews (35.9 % vs 32.0 %; p = 0.031). Guidelines that reported following quality tools (i.e., AGREE II) more commonly commented about SDM than when it was not reported (75.0 % vs 32.0 %; p = 0.003). CONCLUSION AND PRACTICE IMPLICATIONS: Most of the CRC and anal treatment guidelines did not mention SDM and it was superficial. Guidelines based on systematic reviews and those using quality tools demonstrated better reporting of SDM. Recommendations about SDM in these guidelines merit urgent improvement.

Qualitative study exploring which research outcomes best reflect women's experiences of heavy menstrual bleeding: stakeholder involvement in development of a core outcome set.

OBJECTIVE: This work contributed to the development of a core outcome set (COS) for heavy menstrual bleeding (HMB). The objective was to determine which research outcomes best reflect how HMB affects women's lives and to identify additional research outcomes, not previously reported. It was important to explore and record participants' reasoning for prioritising outcomes and use this information to reinforce the patients' voice during later phases of the COS development. DESIGN: Patient workshop discussions and telephone interviews. SETTING: East London teaching hospital. PARTICIPANTS: Inclusion criteria were that participants must be over 18 years old, that either they or their partner had a history of HMB and that they had a good understanding of written and spoken English. RESULTS: 41 participants were recruited for the study. 8 women and 1 man completed the study. The eight female participants were representative of the different underlying causes and treatments for HMB. Participants ranged in age from their early 20s to their 60s and represented a range of ethnic groups. The five main themes that were identified as being important to patients were: 'restriction', 'relationships and isolation', 'emotions and self-perception', 'pain' and 'perceptions of treatment'. We identified eight coding nodes that did not correspond with our list of previously reported outcomes in studies of HMB. These nodes were consolidated and became five new outcomes for potential inclusion in the COS. CONCLUSIONS: HMB stops women living their lives as they would wish. It affects their relationships, education, careers, reproductive wishes, social life and mental health. This is a condition of girls and women in the prime of their lives, but for many, the constant threat of a heavy period starting means that they sacrifice that freedom. The societal and economic costs of women being incapacitated every month has an effect on everyone. TRIAL REGISTRATION: The COS study is registered with the COMET (Core Outcome Measures in Effectiveness Trials) Initiative-project reference number 789.

Assessing the Integrity of Clinical Trials Included in Evidence Syntheses.

Evidence syntheses of randomized clinical trials (RCTs) offer the highest level of scientific evidence for informing clinical practice and policy. The value of evidence synthesis itself depends on the trustworthiness of the included RCTs. The rising number of retractions and expressions of concern about the authenticity of RCTs has raised awareness about the existence of problematic studies, sometimes called "zombie" trials. Research integrity, i.e., adherence to ethical and professional standards, is a multi-dimensional concept that is incompletely evaluated for the RCTs included in current evidence syntheses. Systematic reviewers tend to rely on the editorial and peer-review system established by journals as custodians of integrity of the RCTs they synthesize. It is now well established that falsified and fabricated RCTs are slipping through. Thus, RCT integrity assessment becomes a necessary step in systematic reviews going forward, in particular because RCTs with data-related integrity concerns remain available for use in evidence syntheses. There is a need for validated tools for systematic reviewers to proactively deploy in the assessment of integrity deviations without having to wait for RCTs to be retracted by journals or expressions of concern issued. This article analyzes the issues and challenges in conducting evidence syntheses where the literature contains RCTs with possible integrity deficits. The way forward in the form of formal RCT integrity assessments in systematic reviews is proposed, and implications of this new initiative are discussed. Future directions include emphasizing ethical and professional standards, providing tailored integrity-specific training, and creating systems to promote research integrity, as improvements in RCT integrity will benefit evidence syntheses.

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.

International multi-stakeholder consensus statement on clinical trial integrity.

OBJECTIVE: To prepare a set of statements for randomised clinical trials (RCT) integrity through an international multi-stakeholder consensus. METHODS: The consensus was developed via: multi-country multidisciplinary stakeholder group composition and engagement; evidence synthesis of 55 systematic reviews concerning RCT integrity; anonymised two-round modified Delphi survey with consensus threshold based on the average percentage of majority opinions; and, a final consensus development meeting. Prospective registrations: (https://osf.io/bhncy, https://osf.io/3ursn). RESULTS: There were 30 stakeholders representing 15 countries from five continents including triallists, ethicists, methodologists, statisticians, consumer representatives, industry representatives, systematic reviewers, funding body panel members, regulatory experts, authors, journal editors, peer-reviewers and advisors for resolving integrity concerns. Delphi survey response rate was 86.7% (26/30 stakeholders). There were 111 statements (73 stakeholder-provided, 46 systematic review-generated, 8 supported by both) in the initial long list, with eight additional statements provided during the consensus rounds. Through consensus the final set consolidated 81 statements (49 stakeholder-provided, 41 systematic review-generated, 9 supported by both). The entire RCT life cycle was covered by the set of statements including general aspects (n = 6), design and approval (n = 11), conduct and monitoring (n = 19), reporting of protocols and findings (n = 20), post-publication concerns (n = 12), and future research and development (n = 13). CONCLUSION: Implementation of this multi-stakeholder consensus statement is expected to enhance RCT integrity.

Video Consultations and Safety App Targeting Pregnant Women Exposed to Intimate Partner Violence in Denmark and Spain: Nested Cohort Intervention Study (STOP Study).

BACKGROUND: Intimate partner violence (IPV) during pregnancy is a public health issue with wide-ranging consequences for both the mother and fetus, and interventions are needed. Therefore, the Stop Intimate Partner Violence in Pregnancy (STOP) cohort was established with the overall aim to identify pregnant women exposed to IPV through digital screening and offer women screening positive for IPV a digital supportive intervention. OBJECTIVE: The aim of this study was to (1) introduce the design and profile of the STOP cohort study, (2) assess the feasibility of implementing digital IPV screening among pregnant women, and (3) assess the feasibility of implementing a digital supportive intervention targeting pregnant women exposed to IPV. METHODS: Pregnant women attending antenatal care in the Region of Southern Denmark and in Andalucía, Spain were offered digital screening for IPV using validated scales (Abuse Assessment Screen and Women Abuse Screening Tool). Women who screened positive were eligible to receive a digital supportive intervention. The intervention consisted of 3-6 video consultations with an IPV counselor and a safety planning app. In Denmark, IPV counselors were antenatal care midwives trained by a psychologist specialized in IPV, whereas in Spain, the counselor was a psychologist. RESULTS: Data collection started in February 2021 and was completed in October 2022. Across Denmark and Spain, a total of 19,442 pregnant women were invited for IPV screening and 16,068 women (82.65%) completed the screening. More women in Spain screened positive for exposure to IPV (350/2055, 17.03%) than in Denmark (1195/14,013, 8.53%). Among the women who screened positive, only 31.39% (485/1545) were eligible to receive the intervention with only 104 (21.4%) of these women ultimately receiving it. CONCLUSIONS: Digital screening for IPV among pregnant women is feasible in an antenatal care context in Denmark and Spain; however, a digital supportive intervention during pregnancy appears to have limited feasibility as only a minor subgroup of women who screened positive for eligibility received the intervention. More research is needed on how to best support pregnant women exposed to IPV if universal IPV screening is to be implemented in antenatal care.

Ferritin screening and Iron treatment for maternal anemia and fetal growth restriction prevention - A multicenter randomized controlled trial (FAIR Study).

Background: Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. Methods and Analysis: FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks' gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. Discussion: The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Roles and responsibilities: Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. Steering committee: has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. Independent Data monitoring committee: comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee.

Decision Aids for Decision Making about Locally Advance Breast Cancer: A Systematic Review.

Locally advanced breast cancer (LABC) is a subset of breast cancer with locoregional progression without distant metastasis. The multimodality treatment (surgery, chemotherapy, radiotherapy, hormonal and targeted therapy if required) could significantly improve results in this specific group of patients. The complex and multiple options of treatment with similar mortality rates but different outcomes depending on the patient's desires, preferences and social environment require aid to facilitate the individual patient's decisions (e.g. Decision Aids (DAs) targeting patients considering primary or adjuvant treatment in LABC). In this context, DAs have been proven fundamental to help patients and clinicians share and agree on the best value option. The current systematic review aimed to evaluate the existing DAs related to these patients with LABC and identify current status and possible improvement areas (possible scarcity and heterogeneity of instruments, the status of their development, explanation of their purpose,…). No previous systematic reviews have been published on this topic. Following Prospero registration no: CRD42021286173, studies about LABC DAs were identified, without data or language restrictions, through a systematic search of bibliographic databases in December 2021. Quality was assessed using Qualsyst criteria (range 0.0-1.0). The quality of the 17 selected studies ranged from 0.46 to 0.95. Of them, 14/17 (82%) were DAs about treatment, only one (6%) about diagnosis, and 2/17 (12%) about the employment of DAs. No screening or follow-up DAs were retrieved. Twelve (70.6%) DAs were online tools. They varied broadly regarding their characteristics and purposes. Most of the studies focused on developing and testing different DAs (5/17; 29.4%) and their impact (7/17; 41.2%). Only 4/17 (23.5%) analysed their implementation and cost. These instruments have proven to improve patient's knowledge and decision-making, decrease patient anxiety, and patients tend to undergo treatment. However, nowadays, there is still a need for further research and consensus on methodology to develop practical DAs.

A comprehensive systematic review of colorectal cancer screening clinical practices guidelines and consensus statements.

High-quality clinical practice guidelines (CPGs) and consensus statements (CSs) are essential for evidence-based medicine. The purpose of this systematic review was to appraise the quality and reporting of colorectal cancer (CRC) screening CPGs and CSs. After prospective registration (Prospero no: CRD42021286156), a systematic review searched CRC guidances in duplicate without language restrictions in ten databases, 20 society websites, and grey literature from 2018 to 2021. We appraised quality with AGREE II (% of maximum score) and reporting with RIGHT (% of total 35 items) tools. Twenty-four CPGs and 5 CSs were analysed. The median overall quality and reporting were 54.0% (IQR 45.7-75.0) and 42.0% (IQR 31.4-68.6). The applicability had low quality (AGREE II score <50%) in 83% of guidances (24/29). Recommendations and conflict of interest were low-reported (RIGHT score <50%) in 62% guidances (18/29) and 69% (20/29). CPGs that deployed systematic reviews had better quality and reporting than CSs (AGREE: 68.5% vs. 35.5%; p = 0.001; RIGHT: 74.6% vs. 41.4%; p = 0.001). In summary, CRC screening CPGs and CSs achieved low quality and reporting. It is necessary a revision and an improvement of the current guidances. Their development should apply a robust methodology using proper guideline development tools to obtain high-quality evidence-based documents.

Benefits of Participation in Clinical Trials: An Umbrella Review.

Participation in randomised clinical trials (RCTs) entails taking part in the discovery of effects of health care interventions. The question of whether participants' outcomes are different to those of non-participants remains controversial. This umbrella review was aimed at assessing whether there are health benefits of participation in RCTs, compared to non-participation. After prospective registration (PROSPERO CRD42021287812), we searched the Medline, Scopus, Web of Science and Cochrane Library databases from inception to June 2022 to identify relevant systematic reviews with or without meta-analyses. Data extraction and study quality assessment (AMSTAR-2) were performed by two independent reviewers. Of 914 records, six systematic reviews summarising 380 comparisons of RCT participants with non-participants met the inclusion criteria. In two reviews, the majority of comparisons were in favour of participation in RCTs. Of the total of comparisons, 69 (18.7%) were in favour of participation, reporting statistically significant better outcomes for patients treated within RCTs, 264 (71.7%) comparisons were not statistically significant, and 35 (9.5%) comparisons were in favour of non-participation. None of the reviews found a harmful effect of participation in RCTs. Our findings suggest that taking part in RCTs may be beneficial compared to non-participation.

Systematic review of shared decision-making in guidelines about colorectal cancer screening.

INTRODUCTION: We aimed to systematically evaluate quality of shared decision-making (SDM) in colorectal cancer (CRC) screening clinical practice guidelines (CPGs) and consensus statements (CSs). METHODS: Search for CRC screening guidances was from 2010 to November 2021 in EMBASE, Web of Science, MEDLINE, Scopus and CDSR, and the World Wide Web. Three independent reviewers and an arbitrator rated the quality of each guidance using a SDM quality assessment tool (maximum score: 31). Reviewer agreement was 0.88. RESULTS: SDM appeared in 41/83 (49.4%) CPGs and 9/19 (47.4%) CSs. None met all the quality criteria, and 51.0% (52/102) failed to meet any quality items. Overall compliance was low (mean 1.63, IQR 0-2). Quality was better in guidances published after 2015 (mean 1, IQR 0-3 vs. mean 0.5, IQR 0-1.5; p = 0.048) and when the term SDM was specifically reported (mean 4.5, IQR 2.5-4.5 vs. mean 0.5, IQR 0-1.5; p < 0.001). CPGs underpinned by systematic reviews showed better SDM quality than consensus (mean 1, IQR 0-3 vs. mean 0, IQR 0-2, p = 0.040). CONCLUSION: SDM quality was suboptimal and mentioned in less than half of the guidances, and recommendations were scarce. Guideline developers should incorporate evidence-based SDM recommendations in guidances to underpin the translation of evidence into practice.

The effect of dynamic quadripolar radiofrequency on genitourinary atrophy and sexual satisfaction: A systematic review and meta-analysis.

BACKGROUND: Physiologic processes such as childbirth and menopause can alter vulvovaginal aesthetic appearance, reduce sexual satisfaction, and cause symptoms of vulvovaginal atrophy which affects a woman's quality of life. There is debate about whether dynamic quadripolar radiofrequency (DQRF) can be used to improve such conditions. We conducted a meta-analysis of studies among patients undergoing treatment with DQRF. METHODS: We conducted a literature search without language or article type restriction in PubMed, Cochrane library and Web of Science from inception to June 1, 2022. We included studies that reported outcomes of DQRF treatment. Article selection and data extraction in a predesigned data extraction form were conducted in duplicate. Individual studies reported outcomes in terms of the pre- and post-intervention repeated measures. Meta-analysis combined results across studies to produce effect sizes using random effects model with 95% confidence intervals (CI) taking into account sampling variance to adjust the estimated precision. PROSPERO: CRD42021227752. RESULTS: The search yielded 781 articles, from which 4 case series (127 participants) were included. Two studies reported a significant improvement in patient and medical evaluation assessments of vulvovaginal aesthetic appearance. Significant improvements were reported by three studies for patient assessed sexual satisfaction/discomfort, vaginal laxity and symptoms of genitourinary syndrome of menopause. Meta-analysis showed a trend towards improvement in aesthetic appearance (4 studies; 0.89; 95% CI -0.15 to 1.93; I2 75.0%) and sexual satisfaction (2 studies; 0.62; 95% CI -0.03 to 1.27; I2 0.0%). CONCLUSION: Dynamic quaripolar radiofrequency is a potentially promising intervention to improve vaginal laxity, appearance and sexual satisfaction, as observed in four monocentric case series. Further studies with a control group, well-defined methods of patient selection and longer follow-up periods are necessary to reach a definitive conclusion.

Protocol of Pakistan randomized and observational trial to evaluate coronavirus treatment among newly diagnosed patients with COVID-19: Azithromycin, Oseltamivir, and Hydroxychloquine.

Background & Objective: This study aimed to assess the clinical effectiveness of Hydroxychloroquine Sulfate (200 mg orally 8 hourlies thrice a day for 5 days), oseltamivir (75 mg orally twice a day for 5 days), and Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in seven groups). Methods & Analysis: An adaptive design is deployed, set within a comprehensive cohort study, to permit flexibility in fast-changing clinical and public health scenario. Primary outcomes include turning the test negative for coronavirus nucliec acid and in bringing about clinical improvement on day 7 of follow-up on a seven-point ordinal scale. The randomized study will recruit participants of either gender above 18 years of age who will test positive for SARS-CoV-2 on Quantitative Reverse Transcription Polymerase Chain Reaction (PCR). Pregnant or lactating females, and those with severe respiratory distress, or with serious comorbidities will be excluded. Randomization will be done maintaining concealment of allocation sequence using a computer-generated random number list. The sample size will be subjected to periodic reviews by National Data Safety and Monitoring Board. Ethics and Dissemination: The trial is approved by the National Bioethics Committee (No.4-87/NBC-471-COVID-19-05/20/) and institutional Ethical Review Committee. This clinical trial conducted under Good Clinical Practice is expected to inform patients clinical guidelines for the use of these drugs in newly diagnosed with SARS-CoV-2. Trial Registration: The trial was prospectively registered on April 08, 2020 at clinicaltrials.gov with ID: NCT04338698.