Oncologic outcomes after breast-conserving surgery with radiotherapy versus mastectomy in patients with Paget's disease of the breast: systematic review and meta-analysis.

BACKGROUND: The conventional approach to treatment for Paget's disease of the breast has been mastectomy, but there is an increasing trend to consider breast-conserving surgery (BCS) followed by radiotherapy (RT) in these patients. This study aimed to provide an updated systematic review and meta-analysis comparing outcomes after BCS with RT versus mastectomy in the treatment of Paget's disease of the breast. METHODS: Studies before May 2021 were included. Primary outcomes were overall survival and local recurrence. Separate analyses of Paget's disease associated with ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) were undertaken. Meta-regression was used to adjust for imbalance in the proportion of IDC among patients selected to undergo BCS versus mastectomy. RESULTS: Overall survival in patients with Paget's disease who underwent BCS with RT was higher than for those who underwent mastectomy with pooled mortality hazard ratio (HR) of 0.68, (95% per cent c.i. 0.45 to 1.01). Patients with Paget's disease with DCIS had higher overall survival after BCS with or without RT versus mastectomy, with adjusted HR of 0.14 (0.10 to 0.20) and 0.28 (0.22 to 0.36), respectively. For patients with Paget's disease and IDC, overall survival was lower for BCS with or without RT versus mastectomy, with adjusted HR of 0.84 (0.57 to 1.25) and 1.64 (1.04 to 2.58), respectively. In Paget's disease and IDC, local recurrence risk was much higher for BCS with RT, RR 26.8 (1.60 to 456) versus without RT, RR 51.8 (6.80 to 391). In patients with Paget's disease and DCIS, risk of local recurrence versus mastectomy was lower for BCS with RT 0.72 (0.11 to 4.50) but slightly higher for BCS alone 1.38 (0.09 to 21.20). CONCLUSION: BCS with RT may be a comparable treatment alternative to mastectomy for patients with Paget's disease with DCIS, and for selected patients with Paget's disease and IDC.

Smoke exposure and childhood atopic eczema and food allergy: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the effect of timing and type of smoke exposure on early allergy development. This study aimed to determine the relationship between early eczema or food allergy/hypersensitivity development in children by firstly investigating the effect of smoke exposure across critical development periods and secondly by analyzing effects of parental atcive or passive smoking. METHODS: Four databases (PubMed, Web of Science, Scopus and Embase) were searched in May 2022 and assessed by two independent reviewers. Case-control, cross-sectional or cohort studies reporting on smoke exposure from preconception to postnatal periods and atopic eczema, food allergy and/or hypersensitivity outcomes by age 3 years were included. The Newcastle-Ottawa Scale was used to assess study quality. Random effects model was used to estimate the pooled risk ratios. RESULTS: From 1689 identified records, 32 studies with nearly 190,000 subjects were included. Parental smoking during preconception, pregnancy and postnatal periods was generally not associated with the risk of eczema, food allergy and food sensitisation development by age 3 years. Maternal active smoking during pregnancy was negatively associated with self-reported doctor diagnosis of eczema (RR = 0.87, 95% CI 0.77-0.98; I2 = 50.56) and maternal passive smoking during pregnancy was positively associated with clinician assessment of eczema in one study (RR = 1.38; 95% CI 1.06-1.79). CONCLUSION: Our findings highlighted the importance of in utero programming in early-life allergy development. Despite the weak evidence, our results suggest pregnant women should minimise their contact with second-hand smoke to prevent offspring eczema development. There is a need for greater utilisation of objective allergy assessments in future studies.

Emollients in infancy to prevent atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Several studies have evaluated prophylactic emollients as a preventive strategy against atopic dermatitis (AD) and food allergy (FA). We aimed to synthesize the evidence on efficacy and safety of prophylactic emollients started during the first 6 weeks of infancy for prevention of AD and FA. METHODS: MEDLINE, Embase, CINAHL, BIOSIS, and the Cochrane Library databases were searched systematically for randomized controlled trials published between January 2000 and July 2020, which assessed the effects of prophylactic emollients initiated within the first 6 weeks of life on the development of AD within 24 months of age, compared to no treatment. Risk of bias and certainty of evidence were assessed using the Cochrane Collaboration's tool and GRADE process, respectively. RESULTS: Of the 1486 articles identified, 10 studies fulfilled inclusion criteria. In infants given emollients, there was no significant reduction on the development of AD (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.64, 1.10) compared to the control group. However, there was significant benefit of prophylactic emollients (RR 0.75, 95% CI 0.62-1.11) in the high-risk population (n = 8 studies). There was also significant benefit (RR 0.59, 95% CI 0.43, 0.81) in studies (n = 6) where emollients were used continuously to the point of AD assessment; but not when treatment was ceased for an interval before AD assessment. There were no protective effects on FA found. CONCLUSION: The prophylactic application of emollients initiated in early infancy may prevent AD, especially in high-risk populations and when used continuously. We hypothesize that emollients may delay rather than prevent AD.

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28 weeks, cinacalcet normalizes serum calcium (≤ 10.3 mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 - 68.52, I2 = 0%, pheterogeneity < 0·00001)]. Serum PTH levels decreased significantly after 2 weeks and up to 28 weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I2 = 92%, pheterogeneity < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI -0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option.

Multimodal prehabilitation in older adults before major abdominal surgery: a systematic review and meta-analysis.

PURPOSE: Multimodal prehabilitation aims to prepare frail older patients for major surgery. The objective of this review is to determine the benefits of pre-operative multimodal prehabilitation compared to standard care in older patients. METHODS: Data sources included MEDLINE, EMBASE, CENTRAL, CINAHL and PsychINFO. They were searched from inception to September 2021. Only randomized controlled trials (RCT) with an average study population age ≥ 65 that had undergone major abdominal operation with at least two components (physical, nutritional, psychological) of prehabilitation programs were included. RESULTS: Nine RCTs were included with a total of 823 patients, of whom 705 completed the study with 358 undergoing prehabilitation and 347 were controls. Significantly lower complications were observed in the prehabilitation group compared to control (OR 0.67; 95% CI 0.46 to 0.99; p = 0.04; I2 = 32%). A significant increase in 6-min walking distance (6MWD) from baseline to immediately prior to surgery (mean difference 35.1 m; 95%CI 11.6-58.4; p = 0.003; I2 = 67%) and 8 weeks post-surgery (mean difference 44.9 m; 95%CI 6.0-83.8; p = 0.02; I2 = 75%) was noted in the prehabilitation group. No difference was observed in length of stay (OR 0.59; 95% CI - 0.23 to 1.40; p = 0.16; I2 = 91%) or 30-day emergency department visit (OR 0.72; 95% CI 0.41 to 1.26; p = 0.25; I2 = 0%). Patient reported outcome measures were not significantly different. CONCLUSIONS: Amongst older patients, multimodal prehabilitation increases peri-operative functional capacity and may potentially decrease post-operative complications. Future studies should continue to focus on older patients who are frail as this is the group that prehabilitation would likely have a clinically significant impact on.

Zone 1 Aortic Arch Hybrid Endovascular Repair with Extra-anatomical Bypass: A Meta-analysis.

BACKGROUND: The aim of this meta-analysis is to determine the morbidity and mortality outcomes of adult patients with aortic arch disease managed with extra-anatomical bypass avoiding median sternotomy and cardiopulmonary bypass, with simultaneous or staged hybrid zone 1 endovascular aortic repair. METHODS: Systematic literature searches of the MEDLINE, EMBASE, and Cochrane databases were carried out to identify relevant studies on zone 1 hybrid arch repair. Extracted data were analyzed by random effects models. Primary outcomes included 30-day or in-hospital mortality. Longitudinal survival was analyzed up to 7 years from date of operation. Secondary outcomes included in-hospital morbidity, as well as late endoleak and reintervention. RESULTS: Twenty studies incorporating 348 patients were included. In-hospital or 30-day mortality was 10.1% (95% confidence interval, 6.7-14.9%). Overall operative technical success was 89.8% (83.7-93.8%). Early type 1 endoleak rate was 14.0% (7.4-24.7%). Stroke prevalence was 9.5% (6.1-14.3%). Spinal cord paraplegia prevalence was 3.8% (1.9-7.6%). Retrograde aortic dissection prevalence was 4.1% (1.5-10.6%). Survival at 1 year postoperatively was 77.2% (66.1-85.4%). Survival at 3 years postoperatively was 73.7% (59.2-84.4%). Survival beyond 4 years postoperatively (range 58-80 months) was 65.9% (53.6-76.4%). Late type 1 endoleak prevalence was 11.8% (5.5-23.7%). Overall rate of reintervention was 11.6% (6.4-20.1%). CONCLUSIONS: Zone 1 hybrid repair has evidence for satisfactory short- and long-term morbidity/mortality outcomes and may be considered as an alternative approach to aortic arch disease.

The Influence of Web-Based Tools on Maternal and Neonatal Outcomes in Pregnant Adolescents or Adolescent Mothers: Mixed Methods Systematic Review.

BACKGROUND: Pregnant adolescent women increasingly seek support during pregnancy and the puerperium through digital platforms instead of the traditional support system of family, friends, and the community. However, it is uncertain whether digital, web-based tools are reliable and effective in providing information to the user on a variety of topics such as fetal development, pregnancy outcomes, delivery, and breastfeeding to improve maternal and infant outcomes. OBJECTIVE: We aimed to identify web-based tools designed to promote knowledge, attitudes, and skills of pregnant adolescents or adolescent mothers and determine the efficacy of such web-based tools compared with conventional resources in promoting good pregnancy and infant outcomes. METHODS: A systematic search was conducted using Medline, Scopus, CINAHL, and PsycINFO for articles published from January 2004 to November 2020 to identify randomized trials and observational studies that evaluated digital, web-based platforms to deliver resources to pregnant adolescents. All articles written in the author's languages were included. Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. Risk of bias in each study was assessed using appropriate tools recommended by PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and the Joanna Briggs Institute. We adopted a qualitative synthesis and presented the results in a narrative format due to the heterogenous nature of the studies. RESULTS: Seven articles met the inclusion criteria and were analyzed. The majority of the studies were graded to be of low to moderate risk for bias. The research methodologies represented were varied, ranging from randomized (n=1) and nonrandomized controlled trials (n=1) and prospective cohort studies (n=1) to mixed methods studies (n=1) and longitudinal surveys (n=3). Four studies included active web-based interventions, and 3 described exposure to web-based tools, including the use of social media and/or other internet content. Web-based tools positively influenced treatment-seeking intentions (intervention 17.1%, control 11.5%, P=.003) and actual treatment-seeking behavior for depression among postpartum adolescents (intervention 14.1%, control 6.5%, P<.001). In contrast, readily available information on the internet may leave adolescents with increased anxiety. The critical difference lies in information curated by health care professionals specifically to address targeted concerns versus self-acquired data sourced from various websites. CONCLUSIONS: Despite almost universal web use, few studies have used this platform for health promotion and disease prevention. Social media interventions or web-based tools have the potential to positively influence both maternal and infant outcomes in adolescent pregnancy, but there is a need for more well-conducted studies to demonstrate the effectiveness of these support programs. The vastness of the information available on the web limits the ability of health care professionals to monitor or control sources of information sought by patients. Thus, it is important to create professionally curated platforms to prevent or limit exposure to potentially misleading or harmful information on the internet while imparting useful knowledge to the user. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020195854; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=195854.

Transradial Approach for Aortoiliac and Femoropopliteal Interventions: A Systematic Review and Meta-analysis.

PURPOSE: To present a systematic review and meta-analysis comparing the transradial approach for aortoiliac and femoropopliteal interventions to the traditional transfemoral access. METHODS: A search of the public domain databases MEDLINE, SCOPUS, Web of Science, and Cochrane Library Databases was performed to identify studies related to the use of the transradial approach for infra-aortic procedures. Meta-analysis was used to compare the transradial to the transfemoral route in terms of procedure success, complications, procedure parameters, and hospital length of stay. Results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Nineteen studies containing 638 patients with transradial access for lower limb interventions were selected. Lesions were treated from the aortic bifurcation down to the popliteal artery. The mean technical success rate was 90.9%, conversion to a transfemoral approach was necessary in 9.9%, and complications were reported in 1.9%. The meta-analysis included 4 comparative studies involving 114 transradial and 208 transfemoral procedures. There was no significant advantage of either approach in terms of procedure success (OR 5.0, 95% CI 0.49 to 50.83, p=0.17), but the risk of developing a complication was significantly lower (OR 0.25, 95% CI 0.07 to 0.86, p=0.03) with the transradial approach. CONCLUSION: Transradial access for lower limb endovascular interventions can be performed with comparable technical success and a lower overall complication profile compared to transfemoral access.

Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review.

INTRODUCTION: Febrile neutropenia (FN) is a serious side-effect of myelosuppressive chemotherapy. Several clinical trials and observational studies have evaluated the effects of prophylactic granulocyte colony-stimulating factors (G-CSFs) on risk of FN and related complications; however, no systematic reviews have focused on effectiveness in routine clinical practice. Here, we perform a systematic review assessing the comparative effectiveness of prophylaxis with a long-acting G-CSF (pegfilgrastim) versus short-acting G-CSFs (filgrastim, lenograstim, and filgrastim biosimilars) in cancer patients in real-world clinical settings. METHODS: A systematic review was performed based on a pre-specified protocol and was consistent with the Cochrane Collaboration Handbook (2009) and the Centre for Reviews and Dissemination's Guidance for Undertaking Reviews in Health Care (2011). MEDLINE, Embase, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases were searched for articles published from January 2002 to June 2014. Congress databases (MASCC/ASCO/ESMO) and Google Scholar were searched for abstracts published from January 2012 to August 2014. Filgrastim (NEUPOGEN®), lenograstim and nivestim (a filgrastim biosimilar) were the only short-acting G-CSFs and pegfilgrastim (Neulasta®) was the only long-acting G-CSF described in eligible studies. Outcomes of interest were FN, FN-related hospitalisation and other FN-related complications (death, chemotherapy dose delays and reductions, antimicrobial treatment, severe neutropenia and costs and resource use). RESULTS: Of 1259 unique records identified, 18 real-world observational studies met predefined inclusion criteria; 15 were retrospective studies, and 3 were prospective studies. Multiple tumour types, chemotherapy regimens and geographical regions were included. Seven studies provided statistical comparisons of the risk of FN; risk of FN among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in three studies, numerically lower in three studies, and numerically higher in one study. Six studies provided statistical comparisons of the risk of FN-related hospitalisation; risk of FN-related hospitalisation among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in all six studies, though some variation was seen in subanalyses. Data for other outcomes were sparse with available results being generally consistent with the results seen for risk of FN and FN-related hospitalisation. CONCLUSIONS: Based on the findings from this review of real-world comparative effectiveness studies, risks of FN and FN-related complications were generally lower for prophylaxis with pegfilgrastim versus prophylaxis with short-acting G-CSFs.

Progestational agents for treating threatened or established preterm labour.

BACKGROUND: Prematurity is not only the leading cause of perinatal morbidity and mortality but is associated with long-term impairment. Studies of various tocolytic agents have shown mixed results with little effect in improving pregnancy duration and insufficient data to confirm a definite beneficial effect on neonatal morbidity or mortality. Progesterone is known to have an inhibitory effect on uterine contractility and is thought to play a key role in the maintenance of pregnancy until term. OBJECTIVES: To determine if the use of progestational agents is effective as a form of treatment or co-treatment for women with threatened or established preterm labour with intact membranes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013), CENTRAL (The Cochrane Library 2013, Issue 10), MEDLINE (1966 to August 31 2013) and Embase (1974 to 31 August 2013). We checked the reference lists of all included studies to identify any additional studies and communicated with authors and the pharmaceutical industry. SELECTION CRITERIA: Randomised controlled trials that compared progestational agents, given either alone or in combination with other tocolytics, with a control group receiving another tocolytic, placebo or no treatment, for the treatment of preterm labour. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. MAIN RESULTS: Eight studies were included in this review, involving 563 women, but only seven studies, involving 538 women, contributed data for analyses. There are some data suggesting that the use of progestational agents results in a reduction of preterm deliveries at less than 37 weeks of gestation and an increase in birthweight. The use of a progestational agent may also reduce the frequency of uterine contractions, prolong pregnancy and attenuate the shortening of cervical length. However, the analysis was limited by the relatively small number of available studies. The power of the meta-analysis was also limited by the varying types, dosages and routes of administration of progesterone. AUTHORS' CONCLUSIONS: There is insufficient evidence to advocate progestational agents as a tocolytic for women presenting with preterm labour.

Major bleeding in patients with atrial fibrillation receiving vitamin K antagonists: a systematic review of randomized and observational studies.

AIMS: Clinical trials have shown that anticoagulation with vitamin K antagonists (VKAs), e.g. warfarin, decreases the risk of stroke in patients with atrial fibrillation (AF); however, increased bleeding risk is one of the safety concerns. The primary objective was to conduct a systematic review of the published literature, assessing the risk of major bleeding and mortality in patients with AF treated with VKAs. METHODS AND RESULTS: Online searches of MEDLINE, EMBASE, BIOSIS, and the Cochrane Library were performed to a pre-specified protocol from 1960 to March 2012 for randomized controlled trials (RCTs) and from January 1990 to March 2012 for observational studies. A total of 47 studies (16 RCTs and 31 observational studies) were included. Cumulative follow-up was 61,563 patient-years for RCTs and 484 241 patient-years for observational studies. The overall median incidence of major bleeding was 2.1 per 100 patient-years (range, 0.9-3.4 per 100 patient-years) for RCTs and 2.0 per 100 patient-years (range, 0.2-7.6 per 100 patient-years) for observational studies. With study year as a proxy for changing management patterns, some evidence of bleeding rates and/or their reporting increasing over time was noted. Mortality rates from observational studies were inadequately reported to allow comparison with those from RCT data. CONCLUSION: The median rate of major bleeding in observational studies and RCTs is similar. The larger heterogeneity in bleeding rates observed in a real-life setting could reflect a high variability in standard of care of patients on VKAs and/or methodological differences between observational studies and/or variability in data sources.

Efficacy and safety of echinocandin monotherapy and combination therapy for immunocompromised patients with systemic candidiasis: A systematic review and meta-analysis.

BACKGROUND: Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so. METHODS: A protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events. RESULTS: 547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of "treatment success" compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86). CONCLUSION: Our findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.

Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis.

Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.

A systematic review of quality and consistency of clinical practice guidelines on the primary prevention of food allergy and atopic dermatitis.

Background and aims: With an increasing number of Clinical Practice Guidelines (CPGs) addressing primary prevention of food allergy and atopic dermatitis, it is timely to undertake a comprehensive assessment of the quality and consistency of recommendations and evaluation of their implementability in different geographical settings. Methods: We systematically reviewed CPGs from 8 international databases and extensive website searches. Seven reviewers screened records in any language and then used the AGREE II and AGREE REX instruments to critically appraise CPGs published between January 2011 and April 2022. Results: Our search identified 2138 relevant articles, of which 30 CPGs were eventually included. Eight (27%) CPGs were shortlisted based on our predefined quality criteria of achieving scores >70% in the "Scope and Purpose" and "Rigour of Development" domains of the AGREE II instrument. Among the shortlisted CPGs, scores on the "Applicability" domain were generally low, and only 3 CPGs rated highly in the "Implementability" domain of AGREE-REX, suggesting that the majority of CPGs fared poorly on global applicability. Recommendations on maternal diet and complementary feeding in infants were mostly consistent, but recommendations on use of hydrolysed formula and supplements varied considerably. Conclusion: The overall quality of a CPG for Food Allergy and Atopic Dermatitis prevention did not correlate well with its global applicability. It is imperative that CPG developers consider stakeholders' preferences, local applicability, and adapt existing recommendations to each individual population and healthcare system to ensure successful implementation. There is a need for development of high-quality CPGs for allergy prevention outside of North America and Europe. PROSPERO registration number: CRD42021265689.

Carbetocin for preventing postpartum haemorrhage.

BACKGROUND: Postpartum haemorrhage (PPH) is one of the major contributors to maternal mortality and morbidity worldwide. Active management of the third stage of labour has been proven to be effective in the prevention of PPH. Syntometrine is more effective than oxytocin but is associated with more side effects. Carbetocin, a long-acting oxytocin agonist, appears to be a promising agent for the prevention of PPH. OBJECTIVES: To determine if the use of oxytocin agonist is as effective as conventional uterotonic agents for the prevention of PPH, and assess the best routes of administration and optimal doses of oxytocin agonist. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1 of 4), MEDLINE (1966 to 1 March 2011) and EMBASE (1974 to 1 March 2011). We checked references of articles and communicated with authors and pharmaceutical industry contacts. SELECTION CRITERIA: Randomised controlled trials which compared oxytocin agonist (carbetocin) with other uterotonic agents or with placebo or no treatment for the prevention of PPH. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS: We included 11 studies (2635 women) in the review. Six trials compared carbetocin with oxytocin; four of these were conducted for women undergoing caesarean deliveries, one was for women following vaginal deliveries and one did not state the mode of delivery clearly. The carbetocin was administered as 100 µg intravenous dosage across the trials, while oxytocin was administered intravenously but at varied dosages. Four trials compared intramuscular carbetocin and intramuscular syntometrine for women undergoing vaginal deliveries. Three of the trials were on women with no risk factor for PPH, while one trial was on women with risk factors for PPH. One trial compared the use of intravenous carbetocin with placebo. Use of carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics (risk ratio (RR) 0.62; 95% confidence interval (CI) 0.44 to 0.88; four trials, 1173 women) compared to oxytocin for those who underwent caesarean section, but not for vaginal delivery. Compared to oxytocin, carbetocin was associated with a reduced need for uterine massage following both caesarean delivery (RR 0.54; 95% CI 0.37 to 0.79; two trials, 739 women) and vaginal delivery (RR 0.70; 95% CI 0.51 to 0.94; one trial, 160 women). Pooled data also showed that carbetocin resulted in a lower risk of PPH compared to oxytocin in women who underwent caesarean delivery (RR 0.55; 95% CI 0.31 to 0.95; three trials, 820 women). This is, however, limited by the number of studies and risk of bias in the studies. Comparison between carbetocin and syntometrine showed a lower mean blood loss in women who received carbetocin compared to syntometrine (mean difference (MD) -48.84 ml; 95% CI -94.82 to -2.85; four trials, 1030 women). There was no statistically significant difference in terms of the need for therapeutic uterotonic agents, but the risk of adverse effects such as nausea and vomiting were significantly lower in the carbetocin group: nausea (RR 0.24; 95% CI 0.15 to 0.40; four trials, 1030 women); vomiting (RR 0.21; 95% CI 0.11 to 0.39; four trials, 1030 women). The incidence of postpartum hypertension was also significantly lower in women who received carbetocin compared to those who received syntometrine. Cost-effectiveness of carbetocin was investigated by one study published as an abstract, with limited data. AUTHORS' CONCLUSIONS: There is evidence to suggest that 100 µg of intravenous carbetocin is more effective than oxytocin for preventing PPH in women undergoing caesarean deliveries, but more studies are needed to validate this finding. Carbetocin is associated with less blood loss compared to syntometrine in the prevention of PPH for women who have vaginal deliveries and is associated with significantly fewer adverse effects. Further research is needed to analyse the cost-effectiveness of carbetocin as a uterotonic agent.

Carbetocin for preventing postpartum haemorrhage.

BACKGROUND: Postpartum haemorrhage (PPH) is one of the major contributors to maternal mortality and morbidity worldwide. Active management of the third stage of labour has been proven to be effective in the prevention of PPH. Syntometrine is more effective than oxytocin but is associated with more side effects. Carbetocin, a long-acting oxytocin agonist, appears to be a promising agent for the prevention of PPH. OBJECTIVES: To determine if the use of oxytocin agonist is as effective as conventional uterotonic agents for the prevention of PPH, and assess the best routes of administration and optimal doses of oxytocin agonist. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 March 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1 of 4), MEDLINE (1966 to 1 March 2011) and EMBASE (1974 to 1 March 2011). We checked references of articles and communicated with authors and pharmaceutical industry contacts. SELECTION CRITERIA: Randomised controlled trials which compared oxytocin agonist (carbetocin) with other uterotonic agents or with placebo or no treatment for the prevention of PPH. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, assessed risk of bias and extracted data. MAIN RESULTS: We included 11 studies (2635 women) in the review. Six trials compared carbetocin with oxytocin; four of these were conducted for women undergoing caesarean deliveries, one was for women following vaginal deliveries and one did not state the mode of delivery clearly. The carbetocin was administered as 100 µg intravenous dosage across the trials, while oxytocin was administered intravenously but at varied dosages. Four trials compared intramuscular carbetocin and intramuscular syntometrine for women undergoing vaginal deliveries. Three of the trials were on women with no risk factor for PPH, while one trial was on women with risk factors for PPH. One trial compared the use of intravenous carbetocin with placebo. Use of carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics (risk ratio (RR) 0.62; 95% confidence interval (CI) 0.44 to 0.88; four trials, 1173 women) compared to oxytocin for those who underwent caesarean section, but not for vaginal delivery. Compared to oxytocin, carbetocin was associated with a reduced need for uterine massage following both caesarean delivery (RR 0.54; 95% CI 0.37 to 0.79; two trials, 739 women) and vaginal delivery (RR 0.70; 95% CI 0.51 to 0.94; one trial, 160 women). There were no statistically significant differences between carbetocin and oxytocin in terms of risk of any PPH (blood loss greater than 500 ml) or in risk of severe PPH (blood loss greater than 1000 ml). Comparison between carbetocin and syntometrine showed a lower mean blood loss in women who received carbetocin compared to syntometrine (mean difference (MD) -48.84 ml; 95% CI -94.82 to -2.85; four trials, 1030 women). There was no statistically significant difference in terms of the need for therapeutic uterotonic agents, but the risk of adverse effects such as nausea and vomiting were significantly lower in the carbetocin group: nausea (RR 0.24; 95% CI 0.15 to 0.40; four trials, 1030 women); vomiting (RR 0.21; 95% CI 0.11 to 0.39; four trials, 1030 women). The incidence of postpartum hypertension was also significantly lower in women who received carbetocin compared to those who received syntometrine. Cost-effectiveness of carbetocin was investigated by one study published as an abstract, with limited data. AUTHORS' CONCLUSIONS: For women who undergo caesarean section, carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics compared to oxytocin, but there is no difference in the incidence of postpartum haemorrhage. Carbetocin is associated with less blood loss compared to syntometrine in the prevention of PPH for women who have vaginal deliveries and is associated with significantly fewer adverse effects. Further research is needed to analyse the cost-effectiveness of carbetocin as a uterotonic agent.

Trainee participation does not adversely affect the safety of thyroid surgery: Systematic review and meta-analysis.

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did not change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.

Quality and consistency of clinical practice guidelines on the prevention of food allergy and atopic dermatitis: Systematic review protocol.

Background and aims: Allergy prevention strategies have gained significant traction as a means to attenuate the growing burden of allergic diseases over the past decade. As the evidence base for primary prevention of food allergy (FA) and atopic dermatitis (AD) is constantly advancing, clinical practice guideline (CPG) recommendations on interventions for FA and AD prevention vary in quality and consistency among professional organizations. We present a protocol for a systematic review of CPGs on primary prevention of FA and AD. Methods: We will systematically review and appraise all CPGs addressing primary prevention of FA and AD and report our findings according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases and manual website searches from January 2011 to March 2021 without language or geographical restrictions, and supplemented by author contact, will generate the list of potentially relevant CPGs to screen. Evaluation of the methodological quality, consistency, and global applicability of shortlisted CPGs will be performed by members of the Allergy Prevention Work Group of the World Allergy Organization (WAO) using the Appraisal of Guidelines for Research and Evaluation (AGREE) II and AGREE-REX (Recommendations EXcellence). instruments. Guideline contents, consistency, and quality of the recommendations will be summarised in tabular and narrative formats. We aim to present consolidated recommendations from international guidelines of the highest methodological quality and applicability, as determined by AGREE II and AGREE-REX. Dissemination: This systematic review will provide a succinct overview of the quality and consistency of recommendations across all existing CPGs for FA and AD prevention, as well as crucial perspectives on applicability of individual recommendations in different geographical contexts. Results from this systematic review will be reported in a peer-reviewed journal. It will also inform a position statement by WAO to provide a practical framework to guide the development of future guidelines for allergy prevention worldwide. Prospero registration number: CRD42021265689.

Timing of breast surgery in premenopausal breast cancer patients.

BACKGROUND: The majority of women diagnosed with breast cancer undergo a multidisciplinary treatment with surgical intervention and radiotherapy or chemotherapy, or both. The importance of timing of tumour removal in relation to the menstrual cycle and its influence on disease-free survival and overall survival has been studied by researchers since 1989 but still remains speculative. OBJECTIVES: To determine if surgery performed either during the follicular or luteal phase of the menstrual cycle affects the overall and disease-free survival of premenopausal breast cancer patients. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Trials Register (January 2009), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 1), MEDLINE (1966 to January 2009), EMBASE (1974 to September 2006) and the WHO International Clinical Trials Registry Platform (ICTRP) search portal (July 2010). We checked references of articles and communicated with authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing breast surgery during the follicular phase of the menstrual cycle with the luteal phase in premenopausal women. Prospective non-RCTs or observational studies were considered if randomised studies were lacking. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed trial quality. MAIN RESULTS: Completed randomised trials were not found. There is one trial that is currently ongoing in Italy; the results have yet to be published.Two prospective observational studies had data on recurrence-free survival. One study reported an odds ratio for recurrence rate at one year (where > 1 favours the luteal phase) of 0.86 (95% confidence interval (CI) 0.69 to 1.08); 0.87 at two years (95% CI 0.69 to 1.09); 0.95 at three years (95% CI 0.75 to 1.21); 1.12 at four years (95% CI 0.87 to 1.43); and 1.12 at five years (95% CI 0.87 to 1.43). Another study reported a hazard ratio for overall survival of 1.02 (95% CI 0.995 to 1.04, P = 0.14) and for disease-free survival of 1.00 (95% CI 0.98 to 1.02, P = 0.92) at three years based on the last and first menstrual period. The results were not significant. There was no difference in the recurrence rate whether the surgery was done during the follicular or luteal phase of the menstrual cycle. AUTHORS' CONCLUSIONS: In the absence of RCTs, this review provides evidence from large prospective observational studies that timing of surgery does not show a significant effect on survival.