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Introduction: Health technology assessment (HTA) is a standardized methodology that allows the assessment technologies' value. By incorporating the perspective of stakeholders in a public consultation process, transparency and quality of decisions can be improved., Objective: To describe the active stakeholder consultation process for rapid HTAs in an Argentinean, independent, academic, non-profit HTA agency, assessing its initial five years., Methods: Since 2017, we have been conducting an active public consultation process for rapid HTA documents, inviting producers, healthcare professionals, and patient organizations to provide comments, and their input may lead to changes in the HTA documents. Changes were classified as major (changes to the coverage recommendation), intermediate (changes in efficacy, net benefit, or cost-effectiveness that did not change coverage recommendations), and minor modifications (other changes)., Results: From May 2017-August 2022, 308 rapid HTA (rHTA) reports were published, and 3,438 invitations were sent. 140 rHTA (45.5%) received a total of 228 comments. Comments came from producers in 53% (n = 112) and healthcare professional organizations in 31.2% (n = 66). Technologies evaluated were drugs in 37% (n = 114), procedures in 35.5% (n = 109), diagnostic methods in 15.3% (n = 47), and devices in 12.2% (n = 38). Out of 308 rHTA documents, 120 (39%) were modified-mostly minor adjustments (n = 100; 80%), followed by major (n = 12; 10%) and intermediate modifications (n = 8; 6.4%)., Conclusion: Implementing an active stakeholder involvement process in HTA is feasible in a low- to middle-income country context and strengthens and improves the HTA process., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pregnant persons are susceptible to significant complications following COVID-19, even death. However, worldwide COVID-19 vaccination coverage during pregnancy remains suboptimal., Objective: This study assessed the safety and effectiveness of COVID-19 vaccines administered to pregnant persons and shared this evidence via an interactive online website., Methods: We followed Cochrane methods to conduct this living systematic review. We included studies assessing the effects of COVID-19 vaccines in pregnant persons. We conducted searches every other week for studies until October 2023, without restrictions on language or publication status, in ten databases, guidelines, preprint servers, and COVID-19 websites. The reference lists of eligible studies were hand searched to identify additional relevant studies. Pairs of review authors independently selected eligible studies using the web-based software COVIDENCE. Data extraction and risk of bias assessment were performed independently by pairs of authors. Disagreements were resolved by consensus. We performed random-effects meta-analyses of adjusted relative effects for relevant confounders of comparative studies and proportional meta-analyses to summarize frequencies from one-sample studies using R statistical software. We present the GRADE certainty of evidence from comparative studies. Findings are available on an interactive living systematic review webpage, including an updated evidence map and real-time meta-analyses customizable by subgroups and filters., Results: We included 177 studies involving 638,791 participants from 41 countries. Among the 11 types of COVID-19 vaccines identified, the most frequently used platforms were mRNA (154 studies), viral vector (51), and inactivated virus vaccines (17). Low to very low-certainty evidence suggests that vaccination may result in minimal to no important differences compared to no vaccination in all assessed maternal and infant safety outcomes from 26 fewer to 17 more events per 1000 pregnant persons, and 13 fewer to 9 more events per 1000 neonates, respectively. We found statistically significant reductions in emergency cesarean deliveries (9%) with mRNA vaccines, and in stillbirth (75-83%) with mRNA/viral vector vaccines. Low to very low-certainty evidence suggests that vaccination during pregnancy with mRNA vaccines may reduce severe cases or hospitalizations in pregnant persons with COVID-19 (72%; 95% confidence interval [CI] 42-86), symptomatic COVID-19 (78%; 95% CI 21-94), and virologically confirmed SARS-CoV-2 infection (82%; 95% CI 39-95). Reductions were lower with other vaccine types and during Omicron variant dominance than Alpha and Delta dominance. Infants also presented with fewer severe cases or hospitalizations due to COVID-19 and laboratory-confirmed SARS-CoV-2 infection (64%; 95% CI 37-80 and 66%; 95% CI 37-81, respectively)., Conclusions: We found a large body of evidence supporting the safety and effectiveness of COVID-19 vaccines during pregnancy. While the certainty of evidence is not high, it stands as the most reliable option available, given the current absence of pregnant individuals in clinical trials. Results are shared in near real time in an accessible and interactive format for scientists, decision makers, clinicians, and the general public. This living systematic review highlights the relevance of continuous vaccine safety and effectiveness monitoring, particularly in at-risk populations for COVID-19 impact such as pregnant persons, during the introduction of new vaccines., Clinical Trial Registration: PROSPERO: CRD42021281290., (© 2024. The Author(s).)

This Systematic Review assesses the economic impact of Respiratory Syncytial Virus (RSV) in Latin America and the Caribbean (LAC) in relation to healthcare resource utilization and associated costs. We searched online databases from January 2012 to November 2022 to identify eligible publications. We identified 12 publications that reported direct costs, indirect costs, and resources associated with RSV and its complications. The primary direct medical resources reported were medical services, diagnostics tests and procedures, and length of stay (LOS). Direct total costs per patient ranged widely from $563 to $19,076. Direct costs are, on average, 98% higher than indirect costs. Brazil reported a higher total cost per patient than Colombia, El Salvador, México, Panamá, and Puerto Rico, while for indirect costs per patient, El Salvador and Panamá had higher costs than Brazil, Colombia, and Mexico. The mean LOS in the general ward due to RSV was 6.9 days (range 4 to 20 days) and the mean Intensive Care Unit LOS was 9.1 days (range 4 to 16 days). In many countries of the LAC region, RSV represents a considerable economic burden on health systems, but significant evidence gaps were identified in the region. More rigorous health economic studies are essential to better understand this burden and to promote effective healthcare through an informed decision-making process. Vaccination against RSV plays a critical role in mitigating this burden and should be a priority in public health strategies.

Objective: Patients with COVID-19 who require hospitalization in an intensive care unit, in addition to being at risk of presenting premature death, have higher rates of complications. This study aimed to describe mortality, rehospitalizations, quality of life, and symptoms related to postintensive care syndrome (PICS) and prolonged COVID-19 in patients with COVID-19 discharged from the intensive care unit in hospitals in Argentina., Methods: A cross-sectional study was conducted in 4 centers in the Autonomous City and province of Buenos Aires as of December 2022. The variables of interest were mortality after discharge, rehospitalization, health-related quality of life, post-COVID-19-related symptoms, cognitive status, and PICS. Data collection was by telephone interview between 6 and 18 months after discharge., Results: A total of 124 patients/families were contacted. Mortality was 7.3% (95% CI: 3.87-13.22) at 14.46 months of follow-up after discharge. Patients reported a reduction of the EQ-5D-3L visual analog scale of 13.8 points, reaching a mean of 78.05 (95% CI: 73.7-82.4) at the time of the interview. Notably, 54.4% of patients (95% CI: 41.5-66.6) reported cognitive impairment and 66.7% (95% CI: 53.7-77.5) developed PICS, whereas 37.5% (95% CI: 26-50.9) had no symptoms of prolonged COVID-19., Conclusion: The results showed a significant impact on the outcomes studied, consistent with international evidence., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures., Objectives: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC., Methods: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097)., Results: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country., Conclusions: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bardach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective.: Motivation for the study. Treatment options for HER2-positive breast cancer were evaluated, focusing on the efficacy and safety of trastuzumab-emtansine (T-DM1) compared to other anti-HER2 therapies. Main findings. Trastuzumab-deruxtecan (T-DXd) and PyroCap emerged as promising alternatives, showing substantial improvements in progression-free survival for locally advanced or metastatic breast cancer. T-DM1 showed superior efficacy to the other treatments. Implications. Our findings could inform healthcare decision-making processes to optimize strategies for HER2-positive breast cancer, and potentially improve health outcomes and quality of life. We aimed to study the efficacy and safety of trastuzumab-emtansine (T-DM1) versus other anti-HER2 therapies in HER2+ breast cancer (BC)., Materials and Methods.: We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs). Our study focused on patients undergoing treatment for unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (mBC), which included regimens involving trastuzumab and taxanes. Additionally, we considered cases within the first 6 months of treatment for HER2+ early breast cancer (EBC)., Results.: A total of 23 RCTs and 41 reports were included in our analysis. LABC and mBC showed no statistically significant difference in any of the comparisons of T-DM1 versus the other anti-HER2+ therapies. When assessing progression-free survival (PFS), trastuzumab-deruxtecan (T-DXd) and PyroCap demonstrated greater efficacy compared to other treatments (Hazard Ratio [HR]: 3.57; 95% confidence interval [CI]: 2.75-4.63 and HR: 1.82; 95% CI: 1.35-2.44; respectively), while T-DM1 alone exhibited superior effectiveness compared to LapCap (HR: 0.65; 95% CI: 0.55-0.77), TrasCap (HR: 0.65; 95% CI: 0.46-0.91), LapCapCitu (HR: 0.60; 95% CI: 0.33-1.10), Nera (HR: 0.55; 95% CI: 0.39-0.77), and Cap (HR: 0.37; 95% CI: 0.28-0.49)., Conclusions.: NMA allows a ranking based on the comparative efficacy and safety among the interventions available. Although superior to other schemes, T-DM1 showed a lower efficacy performance in PFS and overall response rate and a trend towards worse overall survival than T-DXd.

Background: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, causing bacteremic pneumonia, meningitis, sepsis, and other invasive pneumococcal diseases. Evidence supports nasopharyngeal pneumococcal carriage as a reservoir for transmission and precursor of pneumococcal disease., Objectives: To estimate the pneumococcal nasopharyngeal burden in all age groups in Latin America and the Caribbean (LAC) before, during, and after the introduction of pneumococcal vaccine conjugate (PVC)., Methods: Systematic literature review of international, regional, and country-published and unpublished data, together with reports including data from serotype distribution in nasopharyngeal carriage in children and adults from LAC countries following Cochrane methods. The protocol was registered in PROSPERO database (ID: CRD42023392097)., Results: We included 54 studies with data on nasopharyngeal pneumococcal carriage and serotypes from 31,803 patients. In children under five years old, carriage was found in 41% and in adults over 65, it was 26%. During the study period, children under five showed a colonization proportion of 34% with PCV10 serotypes and 45% with PCV13 serotypes. When we analyze the carriage prevalence of PCV serotypes in all age groups between 1995 and 2019, serotypes included in PCV10 and those included in PCV13, both showed a decreasing trend along analysis by lustrum., Conclusion: The data presented in this study highlights the need to establish national surveillance programs to monitor pneumococcal nasopharyngeal carriage to monitor serotype prevalence and replacement before and after including new pneumococcal vaccines in the region. In addition, to analyze differences in the prevalence of serotypes between countries, emphasize the importance of approaches to local realities to reduce IPD effectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Brizuela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Obesity is a major health problem worldwide as it can lead to high blood pressure, heart disease, stroke, diabetes, and insulin resistance. The prevalence of overweight and obesity is increasing worldwide across different age groups. There is evidence of an inverse relationship between calcium intake and body weight. The clinical relevance of a small reduction in body weight has been questioned. However, at a population level, a small effect could mitigate the observed global trends., Objectives: To assess the effects of calcium supplementation on weight loss in individuals living with overweight or obesity., Search Methods: We searched CENTRAL, MEDLINE, Embase, LILACS (Latin American and Caribbean Health Science Information database), and two clinical trials registries. The date of the last search of all databases (except Embase) was 10 May 2023. No language restrictions were applied., Selection Criteria: We included randomised controlled trials evaluating the effect of calcium in participants with overweight or obesity of any age or gender. We excluded studies in participants with absorption problems. We included studies of any dose with a minimum duration of two months. We included the following comparisons: calcium supplementation versus placebo, calcium-fortified food or beverage versus placebo, or calcium-fortified food or beverage versus non-calcium-fortified food or beverage. We excluded studies that evaluated the effect of calcium and vitamin D or mixed minerals compared to placebo., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. Our primary outcomes were body weight, health-related quality of life, and adverse events. Our secondary outcomes were anthropometric measures other than body weight, all-cause mortality, and morbidity., Main Results: We found 18 studies that evaluated the effect of calcium compared to placebo or control, with a total of 1873 randomised participants (950 participants in the calcium supplementation groups and 923 in the control groups). All included studies gave oral calcium supplementation as the intervention. We did not find any studies evaluating calcium-fortified foods. We excluded 38 studies, identified four ongoing studies, and listed one study as 'awaiting classification'. Sixteen studies compared calcium supplementation to placebo; two studies compared different doses of calcium supplementation. Doses ranged from very low (0.162 g of calcium/day) to high (1.5 g of calcium/day). Most studies were performed in the USA and Iran, lasted less than six months, and included only women. Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in little to no difference in body weight (mean difference (MD) -0.15 kg, 95% confidence interval (CI) -0.55 to 0.24; P = 0.45, I 2 = 46%; 17 studies, 1317 participants; low-certainty evidence). We downgraded the certainty of the evidence by two levels for risk of bias and heterogeneity. None of the included studies reported health-related quality of life, all-cause mortality, or morbidity/complications as outcomes. Only five studies assessed or reported adverse events. Low-certainty evidence suggests a low frequency of adverse events, with no clear difference between intervention and control groups. Moderate-certainty evidence shows that calcium supplementation compared to placebo or control probably results in a small reduction in body mass index (BMI) (MD -0.18 kg/m 2 ,95% CI -0.22 to -0.13; P < 0.001, I 2 = 0%; 9 studies, 731 participants) and waist circumference (MD -0.51 cm, 95% CI -0.72 to -0.29; P < 0.001, I 2 = 0%; 6 studies, 273 participants). Low-certainty evidence suggests that calcium supplementation compared to placebo or control may result in a small reduction in body fat mass (MD -0.34 kg, 95% CI -0.73 to 0.05; P < 0.001, I 2 = 97%; 12 studies, 812 participants)., Authors' Conclusions: Calcium supplementation for eight weeks to 24 months may result in little to no difference in body weight in people with overweight or obesity. The current evidence is of low certainty, due to concerns regarding risk of bias and statistical heterogeneity. We found that the degree of heterogeneity might be partly explained by calcium dosage, the presence or absence of a co-intervention, and whether an intention-to-treat analysis was pursued. While our analyses suggest that calcium supplementation may result in a small reduction in BMI, waist circumference, and fat mass, this evidence is of low to moderate certainty. Future studies could investigate the effect of calcium supplementation on lean body mass to explore if there is a change in body composition., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Currently, gonadotrophin releasing hormone (GnRH) analogues are used to prevent premature ovulation in ART cycles. However, their costs remain high, the route of administration is invasive and has some adverse effects. Oral progestogens could be cheaper and effective to prevent a premature LH surge., Objectives: To evaluate the effectiveness and safety of using progestogens to avoid spontaneous ovulation in women undergoing controlled ovarian hyperstimulation (COH)., Search Methods: We searched the Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase and PsycINFO in Dec 2021. We contacted study authors and experts to identify additional studies., Selection Criteria: We included randomised controlled trials (RCTs) that included progestogens for ovulation inhibition in women undergoing controlled ovarian hyperstimulation (COH)., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane, including the risk of bias (RoB) assessment. The primary review outcomes were live birth rate (LBR) and oocyte pick-up cancellation rate (OPCR). Secondary outcomes were clinical pregnancy rate (CPR), cumulative pregnancy, miscarriage rate (MR), multiple pregnancies, LH surge, total and MII oocytes, days of stimulation, dose of gonadotropins, and moderate/severe ovarian hyperstimulation syndrome (OHSS) rate. The primary analyses were restricted to studies at overall low and some concerns RoB, and sensitivity analysis included all studies. We used the GRADE approach to assess the certainty of evidence., Main Results: We included 14 RCTs (2643 subfertile women undergoing ART, 47 women used oocyte freezing for fertility preservation and 534 oocyte donors). Progestogens versus GnRH antagonists We are very uncertain of the effect of medroxyprogesterone acetate (MPA) 10 mg compared with cetrorelix on the LBR in poor responders (odds ratio (OR) 1.25, 95% confidence interval (CI) 0.73 to 2.13, one RCT, N = 340, very-low-certainty evidence), suggesting that if the chance of live birth following GnRH antagonists is assumed to be 18%, the chance following MPA would be 14% to 32%. There may be little or no difference in OPCR between progestogens and GnRH antagonists, but due to wide Cs (CIs), we are uncertain (OR 0.92, 95%CI 0.42 to 2.01, 3 RCTs, N = 648, I² = 0%, low-certainty evidence), changing the chance of OPCR from 4% with progestogens to 2% to 8%. Given the imprecision found, no conclusions can be retrieved on CPR and MR. Low-quality evidence suggested that using micronised progesterone in normo-responders may increase by 2 to 6 the MII oocytes in comparison to GnRH antagonists. There may be little or no differences in gonadotropin doses. Progestogens versus GnRH agonists Results were uncertain for all outcomes comparing progestogens with GnRH agonists. One progestogen versus another progestogen The analyses comparing one progestogen versus another progestogen for LBR did not meet our criteria for primary analyses. The OPCR was probably lower in the MPA 10 mg in comparison to MPA 4 mg (OR 2.27, 95%CI 0.90 to 5.74, one RCT, N = 300, moderate-certainty evidence), and MPA 4 mg may be lower than micronised progesterone 100 mg, but due to wide CI, we are uncertain of the effect (OR 0.81, 95%CI 0.43 to 1.53, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 5% with MPA 4 mg to 5% to22%, and from 17% with micronised progesterone 100 mg to 8% to 24%. When comparing dydrogesterone 20 mg to MPA, the OPCR is probably lower in the dydrogesterone group in comparison to MPA 10 mg (OR 1.49, 95%CI 0.80 to 2.80, one RCT, N = 520, moderate-certainty evidence), and it may be lower in dydrogesterone group in comparison to MPA 4 mg but due to wide confidence interval, we are uncertain of the effect (OR 1.19, 95%CI 0.61 to 2.34, one RCT, N = 300, low-certainty evidence), changing the chance of OPCR from 7% with dydrogesterone 20 to 6-17%, and in MPA 4 mg from 12% to 8% to 24%. When comparing dydrogesterone 20 mg to micronised progesterone 100 mg, the OPCR is probably lower in the dydrogesterone group (OR 1.54, 95%CI 0.94 to 2.52, two RCTs, N=550, I² = 0%, moderate-certainty evidence), changing OPCR from 11% with dydrogesterone to 10% to 24%. We are very uncertain of the effect in normo-responders of micronised progesterone 100 mg compared with micronised progesterone 200 mg on the OPCR (OR 0.35, 95%CI 0.09 to 1.37, one RCT, N = 150, very-low-certainty evidence). There is probably little or no difference in CPR and MR between MPA 10 mg and dydrogesterone 20 mg. There may be little or no differences in MII oocytes and gonadotropins doses. No cases of moderate/severe OHSS were reported in most of the groups in any of the comparisons., Authors' Conclusions: Little or no differences in LBR may exist when comparing MPA 4 mg with GnRH agonists in normo-responders. OPCR may be slightly increased in the MPA 4 mg group, but MPA 4 mg reduces the doses of gonadotropins in comparison to GnRH agonists. Little or no differences in OPCR may exist between progestogens and GnRH antagonists in normo-responders and donors. However, micronised progesterone could improve by 2 to 6 MII oocytes. When comparing one progestogen to another, dydrogesterone suggested slightly lower OPCR than MPA and micronised progesterone, and MPA suggested slightly lower OPCR than the micronised progesterone 100 mg. Finally, MPA 10 mg suggests a lower OPCR than MPA 4 mg. There is uncertainty regarding the rest of the outcomes due to imprecision and no solid conclusions can be drawn., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Antimicrobial resistance is a pressing global health concern, leading to 4.95 million deaths in 2019. We conducted a systematic review and meta-analysis to assess the lethality attributed to infections caused by multidrug-resistant organisms (MDROs) in Latin America and the Caribbean. A comprehensive search of major databases retrieved relevant studies from 2000-2022. We included 54 observational studies, primarily from Brazil, Argentina, and Colombia. The most commonly studied organism was methicillin-resistant Staphylococcus aureus. The overall unadjusted case fatality rate related to MDROs was 45.0%; higher adjusted lethality was observed in persons infected with MDROs than in those infected with other pathogens (adjusted odds ratio 1.93, 95% CI 1.58-2.37). A higher lethality rate was seen in patients who did not receive appropriate empirical treatment (odds ratio 2.27, 95% CI 1.44-3.56). These findings underscore the increased lethality associated with antimicrobial resistance in Latin America and the Caribbean.

The Laser Interferometer Space Antenna (LISA) will be the first space-based gravitational wave observatory. LISA uses continuous-wave, infrared laser beams propagating among three widely separated spacecrafts to measure their distances with picometer accuracy via time-delay interferometry. These measurements put very high demands on the laser wavefront and are thus very sensitive to any deposits on laser optics that could be induced by laser-induced molecular contamination (LIMC). In this work, we describe the results of an extensive experimental test campaign assessing LIMC related risks for LISA. We find that the LIMC concern for LISA, even considering the high demands on the laser wavefront, may be greatly reduced compared to that observed at shorter wavelengths or with pulsed laser radiation. This result is very promising for LISA as well as for other space missions using continuous-wave, infrared laser radiation, e.g., in free space laser communication or quantum key distribution.

Study Question: Does a personalized embryo transfer (pET) guided by tests for endometrial receptivity (TER) increase the effectiveness of ART procedures?, Summary Answer: The use of TER-guided pET is not supported by current published evidence in women without repeated implantation failure (RIF), while in women with RIF more research is needed to assess a potential benefit., What Is Known Already: Implantation rates are still far from ideal, especially in some patients that have RIF with good-quality embryos. As a potential solution, a wide range of diverse TER use different sets of genes to identify displacements of the window of implantation to adjust the individual length of progesterone exposure in a pET., Study Design, Size, Duration: A systematic review with meta-analysis was performed. Search terms included endometrial receptivity analysis, ERA, personalized embryo transfer. CENTRAL, PubMed, Embase, reference lists, clinical trials registers, and conference proceedings (search date October 2022) were searched, with no language restrictions., Participants/materials, Setting, Methods: Randomized controlled trials (RCTs) and cohort studies comparing a pET guided by TER vs standard embryo transfer (sET) in different subgroups that undergo ART were identified. We also investigated pET in non-receptive-TER vs sET in receptive-TER, and pET in a specific population vs sET in a general population. Risk of bias (RoB) was assessed with the Cochrane tool and ROBINS-I. Only those with low/moderate RoB underwent meta-analysis. The GRADE approach was used to evaluate the certainty of evidence (CoE)., Main Results and the Role of Chance: We screened 2136 studies and included 35 (85% used ERA and 15% used other TER). Two studies were RCTs comparing endometrial receptivity analysis (ERA)-guided pET vs sET in women with no history of RIF. In women without RIF, no important differences (moderate-CoE) were found in live birth rates and clinical pregnancy rates (CPR). We also performed a meta-analysis of four cohort studies that were adjusted for confounding. In agreement with the RCTs, no benefits were found in women without RIF. However, in women with RIF, low CoE suggests that pET might improve the CPR (OR 2.50, 95% CI 1.42-4.40)., Limitations, Reasons for Caution: We found few studies with low RoB. Only two RCTs in women without RIF were published, and none in women with RIF. Furthermore, the heterogeneity observed in populations, interventions, co-interventions, outcomes, comparisons, and procedures limited the pooling of many of the included studies., Wider Implications of the Findings: In the population of women without RIF, in agreement with previously published reviews, pET did not prove to be more effective than sET and, therefore, it precludes the routine use of this strategy in this population until more evidence is available. However, more research is advisable in women with RIF as low-certainty evidence from observational studies adjusted for confounders suggests that the CPR might be higher with pET guided by TER in this population. Although this review presents the best available evidence, it is still insufficient to change current policies., Study Funding/competing Interest(s): No specific funding was obtained for this study. There are no conflicts of interest to declare., Registration Number: PROSPERO CRD42022299827., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Assessment of COVID-19 vaccines safety during pregnancy is urgently needed., Methods: We conducted a systematic review and meta-analysis to evaluate the safety of COVID-19 vaccines, including their components and technological platforms used in other vaccines during pregnancy and animal studies to complement direct evidence. We searched literature databases from its inception to September 2021 without language restriction, COVID-19 vaccine websites, and reference lists of other systematic reviews and the included studies. Pairs of reviewers independently selected, data extracted, and assessed the risk of bias of the studies. Discrepancies were resolved by consensus. (PROSPERO CRD42021234185)., Results: We retrieved 8,837 records from the literature search; 71 studies were included, involving 17,719,495 pregnant persons and 389 pregnant animals. Most studies (94%) were conducted in high-income countries, were cohort studies (51%), and 15% were classified as high risk of bias. We identified nine COVID-19 vaccine studies, seven involving 309,164 pregnant persons, mostly exposed to mRNA vaccines. Among non-COVID-19 vaccines, the most frequent exposures were AS03 and aluminum-based adjuvants. A meta-analysis of studies that adjusted for potential confounders showed no association with adverse outcomes, regardless of the vaccine or the trimester of vaccination. Neither the reported rates of adverse pregnancy outcomes nor reactogenicity exceeded expected background rates, which was the case for ASO3- or aluminum-adjuvanted non-COVID-19 vaccines in the proportion meta-analyses of uncontrolled studies/arms. The only exception was postpartum hemorrhage after COVID-19 vaccination (10.40%; 95% CI: 6.49-15.10%), reported by two studies; however, the comparison with non-exposed pregnant persons, available for one study, found non-statistically significant differences (adjusted OR 1.09; 95% CI 0.56-2.12). Animal studies showed consistent results with studies in pregnant persons., Conclusion: We found no safety concerns for currently administered COVID-19 vaccines during pregnancy. Additional experimental and real-world evidence could enhance vaccination coverage. Robust safety data for non-mRNA-based COVID-19 vaccines are still needed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Pierre M. Buekens reports financial support was provided by Bill & Melinda Gates Foundation]., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Detailed information is needed on the dynamic pattern of antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Latin America and the Caribbean (LAC)., Objectives: To conduct a systematic review of AMR in N. gonorrhoeae in LAC., Methods: Electronic searches without language restrictions were conducted in PubMed, Embase, Cochrane Library, EconLIT, Cumulative Index of Nursing and Allied Health Literature, Centre for Reviews and Dissemination, and Latin American and Caribbean Literature in Health Sciences. Studies were eligible if published between 1 January 2011 and 13 February 2021, conducted in any LAC country (regardless of age, sex and population) and measured frequency and/or patterns of AMR to any antimicrobial in N. gonorrhoeae. The WHO Global Gonococcal Antimicrobial Surveillance Programme (WHO-GASP) for LAC countries and Latin American AMR SurveillanceNetwork databases were searched. AMR study quality was evaluated according to WHO recommendations., Results: AMR data for 38, 417 isolates collected in 1990-2018 were included from 31 publications, reporting data from Argentina, Brazil, Colombia, Peru, Uruguay, Venezuela and WHO-GASP. Resistance to extended-spectrum cephalosporins was infrequent (0.09%-8.5%). Resistance to azithromycin was up to 32% in the published studies and up to 61% in WHO-GASP. Resistance to penicillin, tetracycline and ciprofloxacin was high (17.6%-98%, 20.7%-90% and 5.9%-89%, respectively). Resistance to gentamicin was not reported, and resistance to spectinomycin was reported in one study., Conclusions: This review provides data on resistance to azithromycin, potentially important given its use as first-line empirical treatment, and indicates the need for improved surveillance of gonococcal AMR in LAC. Trial registration: Registered in PROSPERO, CRD42021253342., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Neisseria gonorrhoeae causes gonorrhoea, a globally neglected but increasing disease. This systematic review and meta-analysis reviewed the epidemiology and economic burden of gonorrhoea in Latin America and the Caribbean (LAC)., Methods: We searched PubMed, EMBase, Cochrane Library, EconLIT, CINAHL, CRD, LILACS, Global Health, Global Dissertations and Theses, SciELO, Web of Science databases, countries' ministries of health, and the IHME's Global Burden of Disease databases. Studies published in the last 10 years (20 years for economic studies) were included if conducted in any LAC country, without language restrictions. The main outcome measures were incidence/prevalence, proportion of co-infections, case fatality rates, specific mortality/hospitalisation rates, direct/indirect costs, and impact of gonorrhoea on quality of life. To assess evidence quality, we used a checklist developed by the US National Heart, Lung, and Blood Institute for observational studies and trial control arms, the Cochrane Effective Practice Organization of Care Group tool for randomised controlled trials, and the CICERO checklist for economic studies., Results: We identified 1290 articles; 115 included epidemiological studies and one included an economic study. Ministry of health data from Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay were identified. Gonorrhoea prevalence was 1.46% (95% confidence interval [CI] 1.00-2.00%) from 48 studies and 5.68% (95% CI 4.23-7.32%) from 58 studies for non-high-risk and high-risk populations, respectively. Cumulative incidence for the high-risk population was 2.05 cases per 100 persons/year. Few published studies were rated as "good" in the risk of bias assessments. Variations in the methodology of the sources and limited information found in the countries' surveillance systems hinder the comparison of data., Conclusion: The burden of gonorrhoea in LAC is not negligible. Our results provide public health and clinical decision support to assess potential interventions to prevent gonorrhoea., Trial Registration: The protocol is registered on PROSPERO (CRD42021253342). The study was funded by GlaxoSmithKline Biologicals SA (GSK study identifier VEO-000025)., (© 2023. The Author(s).)

Introduction: Numerous vaccines have been evaluated and approved for coronavirus disease 2019 (COVID-19). Since pregnant persons have been excluded from most clinical trials of COVID-19 vaccines, sufficient data regarding the safety of these vaccines for the pregnant person and their fetus have rarely been available at the time of product licensure. However, as COVID-19 vaccines have been deployed, data on the safety, reactogenicity, immunogenicity, and efficacy of COVID-19 vaccines for pregnant persons and neonates are becoming increasingly available. A living systematic review and meta-analysis of the safety and effectiveness of COVID-19 vaccines for pregnant persons and newborns could provide the information necessary to help guide vaccine policy decisions., Methods and Analysis: We aim to conduct a living systematic review and meta-analysis based on biweekly searches of medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries to systematically identify relevant studies of COVID-19 vaccines for pregnant persons. Pairs of reviewers will independently select, extract data, and conduct risk of bias assessments. We will include randomized clinical trials, quasi-experimental studies, cohort, case-control, cross-sectional studies, and case reports. Primary outcomes will be the safety, efficacy, and effectiveness of COVID-19 vaccines in pregnant persons, including neonatal outcomes. Secondary outcomes will be immunogenicity and reactogenicity. We will conduct paired meta-analyses, including prespecified subgroup and sensitivity analyses. We will use the grading of recommendations assessment, development, and evaluation approach to evaluate the certainty of evidence., Competing Interests: The authors have no conflicts of interest to disclose, (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy., Methods: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy., Results: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (ROR F/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The ROR F/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses., Conclusions: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future., Registration: The study protocol was registered in PROSPERO (CRD42019120905)., (© 2022 John Wiley & Sons Ltd.)

In order to prioritize public policies to reduce the consumption of sugar-sweetened beverages in Argentina, Brazil, El Salvador and Trinidad and Tobago and to identify information gaps related to the burden of disease attributable to their consumption, a policy dialogue was held with government members, civil society organizations, researchers and communicators from Latin American and Caribbean countries. Presentations and deliberative workshops were conducted using semi-structured data collection tools and group discussions. The prioritized interventions were tax increases, front labeling, restriction of advertising, promotion and sponsorship, and modifications regarding the school environment. The main perceived barrier was the interference from the food industry. This dialogue among decision-makers led to the identification of priority public policies to reduce the consumption of sugar-sweetened beverages in the region.

This systematic review describes herpes zoster (HZ) economic burden in terms of healthcare resource use and cost outcomes in the Latin America and Caribbean (LAC) region. We searched online databases from 1 January 2000 to 20 February 2020 to identify eligible publications. We identified 23 publications that reported direct costs, indirect costs, and resources associated with HZ and its complications. The primary direct medical resources reported in the different studies were visits to doctors, transportation, days in the hospital, nursing, medication schedules, and physical therapy. Direct total costs per patient ranged from $99.99 to $4177.91. The highest cost was found in Brazil. Direct costs are, in average, 81.39% higher than indirect costs. The cost per patient that includes postherpetic neuralgia treatment is 115% higher on average for the directs and 73% for the indirect costs. Brazil reported a higher total cost per patient than Argentina and Mexico, while for indirect costs per patient, Brazil and Argentina had higher costs than Mexico, respectively. A meta-analysis on the number of days due to HZ hospitalization, performed on non-immunosuppressed patients over 65 years of age from three studies, resulted in a cumulative measure of 4.5 days of hospitalization. In the LAC region, the economic burden of HZ and associated complications is high, particularly among high-risk populations and older age groups. Preventative strategies such as vaccination could help avoid or reduce the HZ-associated disease economic burden in the LAC region.

Background: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury., Objectives: To assess the effects of different timing (early and standard) of KRT initiation on death and recovery of kidney function in critically ill patients with AKI., Search Methods: We searched the Cochrane Kidney and Transplant's Specialised Register to 4 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register, ClinicalTrials and LILACS to 1 August 2022., Selection Criteria: We included all randomised controlled trials (RCTs). We included all patients with AKI in the ICU regardless of age, comparing early versus standard KRT initiation. For safety and cost outcomes, we planned to include cohort studies and non-RCTs., Data Collection and Analysis: Data were extracted independently by two authors. The random-effects model was used, and results were reported as risk ratios(RR) for dichotomous outcomes and mean difference(MD) for continuous outcomes, with 95% confidence intervals (CI)., Main Results: We included 12 studies enrolling 4880 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early KRT initiation may have little to no difference on the risk of death at day 30 (12 studies, 4826 participants: RR 0.97,95% CI 0.87 to 1.09; I²= 29%; low certainty evidence), and death after 30 days (7 studies, 4534 participants: RR 0.99, 95% CI 0.92 to 1.07; I² = 6%; moderate certainty evidence). Early KRT initiation may make little or no difference to the risk of death or non-recovery of kidney function at 90 days (6 studies, 4011 participants: RR 0.91, 95% CI 0.74 to 1.11; I² = 66%; low certainty evidence); CIs included both benefits and harms. Low certainty evidence showed early KRT initiation may make little or no difference to the number of patients who were free from KRT (10 studies, 4717 participants: RR 1.07, 95% CI 0.94 to1.22; I² = 55%) and recovery of kidney function among survivors who were free from KRT after day 30 (10 studies, 2510 participants: RR 1.02, 95% CI 0.97 to 1.07; I² = 69%) compared to standard treatment. High certainty evidence showed early KRT initiation increased the risk of hypophosphataemia (1 study, 2927 participants: RR 1.80, 95% CI 1.33 to 2.44), hypotension (5 studies, 3864 participants: RR 1.54, 95% CI 1.29 to 1.85; I² = 0%), cardiac-rhythm disorder (6 studies, 4483 participants: RR 1.35, 95% CI 1.04 to 1.75; I² = 16%), and infection (5 studies, 4252 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%); however, it is uncertain whether early KRT initiation increases or reduces the number of patients who experienced any adverse events (5 studies, 3983 participants: RR 1.23, 95% CI 0.90 to 1.68; I² = 91%; very low certainty evidence). Moderate certainty evidence showed early KRT initiation probably reduces the number of days in hospital (7 studies, 4589 participants: MD-2.45 days, 95% CI -4.75 to -0.14; I² = 10%) and length of stay in ICU (5 studies, 4240 participants: MD -1.01 days, 95% CI -1.60 to -0.42; I² = 0%)., Authors' Conclusions: Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Advances in embryo culture media have led to a shift in in vitro fertilisation (IVF) practice from cleavage-stage embryo transfer to blastocyst-stage embryo transfer. The rationale for blastocyst-stage transfer is to improve both uterine and embryonic synchronicity and enable self selection of viable embryos, thus resulting in better live birth rates., Objectives: To determine whether blastocyst-stage (day 5 to 6) embryo transfer improves the live birth rate (LBR) per fresh transfer, and other associated outcomes, compared with cleavage-stage (day 2 to 3) embryo transfer., Search Methods: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL, from inception to October 2021. We also searched registers of ongoing trials and the reference lists of studies retrieved., Selection Criteria: We included randomised controlled trials (RCTs) which compared the effectiveness of IVF with blastocyst-stage embryo transfer versus IVF with cleavage-stage embryo transfer., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. Our primary outcomes were LBR per fresh transfer and cumulative clinical pregnancy rates (cCPR). Secondary outcomes were clinical pregnancy rate (CPR), multiple pregnancy, high-order multiple pregnancy, miscarriage (all following first embryo transfer), failure to transfer embryos, and whether supernumerary embryos were frozen for transfer at a later date (frozen-thawed embryo transfer). We assessed the overall quality of the evidence for the main comparisons using GRADE methods., Main Results: We included 32 RCTs (5821 couples or women). The live birth rate following fresh transfer was higher in the blastocyst-stage transfer group (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06 to 1.51; I 2 = 53%; 15 studies, 2219 women; low-quality evidence). This suggests that if 31% of women achieve live birth after fresh cleavage-stage transfer, between 32% and 41% would do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR. A post hoc analysis showed that vitrification could increase the cCPR. This is an interesting finding that warrants further investigation when more studies using vitrification are published. The CPR was also higher in the blastocyst-stage transfer group, following fresh transfer (OR 1.25, 95% CI 1.12 to 1.39; I 2 = 51%; 32 studies, 5821 women; moderate-quality evidence). This suggests that if 39% of women achieve a clinical pregnancy after fresh cleavage-stage transfer, between 42% and 47% will probably do so after fresh blastocyst-stage transfer. We are uncertain whether blastocyst-stage transfer increases multiple pregnancy (OR 1.05, 95% CI 0.83 to 1.33; I 2 = 30%; 19 studies, 3019 women; low-quality evidence) or miscarriage rates (OR 1.12, 95% CI 0.90 to 1.38; I 2 = 24%; 22 studies, 4208 women; low-quality evidence). This suggests that if 9% of women have a multiple pregnancy after fresh cleavage-stage transfer, between 8% and 12% would do so after fresh blastocyst-stage transfer. However, a sensitivity analysis restricted only to studies with low or 'some concerns' for risk of bias, in the subgroup of equal number of embryos transferred, showed that blastocyst transfer probably increases the multiple pregnancy rate. Embryo freezing rates (when there are frozen supernumerary embryos for transfer at a later date) were lower in the blastocyst-stage transfer group (OR 0.48, 95% CI 0.40 to 0.57; I 2 = 84%; 14 studies, 2292 women; low-quality evidence). This suggests that if 60% of women have embryos frozen after cleavage-stage transfer, between 37% and 46% would do so after blastocyst-stage transfer. Failure to transfer any embryos was higher in the blastocyst transfer group (OR 2.50, 95% CI 1.76 to 3.55; I 2 = 36%; 17 studies, 2577 women; moderate-quality evidence). This suggests that if 1% of women have no embryos transferred in planned fresh cleavage-stage transfer, between 2% and 4% probably have no embryos transferred in planned fresh blastocyst-stage transfer. The evidence was of low quality for most outcomes. The main limitations were serious imprecision and serious risk of bias, associated with failure to describe acceptable methods of randomisation., Authors' Conclusions: There is low-quality evidence for live birth and moderate-quality evidence for clinical pregnancy that fresh blastocyst-stage transfer is associated with higher rates of both than fresh cleavage-stage transfer. We are uncertain whether blastocyst-stage transfer improves the cCPR derived from fresh and frozen-thawed cycles following a single oocyte retrieval. Although there is a benefit favouring blastocyst-stage transfer in fresh cycles, more evidence is needed to know whether the stage of transfer impacts on cumulative live birth and pregnancy rates. Future RCTs should report rates of live birth, cumulative live birth, and miscarriage. They should also evaluate women with a poor prognosis to enable those undergoing assisted reproductive technology (ART) and service providers to make well-informed decisions on the best treatment option available., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: COVID-19 is rapidly spreading causing extensive burdens across the world. Effective vaccines to prevent COVID-19 are urgently needed., Methods and Findings: Our objective was to assess the effectiveness and safety of COVID-19 vaccines through analyses of all currently available randomized clinical trials. We searched the databases CENTRAL, MEDLINE, Embase, and other sources from inception to June 17, 2021 for randomized clinical trials assessing vaccines for COVID-19. At least two independent reviewers screened studies, extracted data, and assessed risks of bias. We conducted meta-analyses, network meta-analyses, and Trial Sequential Analyses (TSA). Our primary outcomes included all-cause mortality, vaccine efficacy, and serious adverse events. We assessed the certainty of evidence with GRADE. We identified 46 trials; 35 trials randomizing 219 864 participants could be included in our analyses. Our meta-analyses showed that mRNA vaccines (efficacy, 95% [95% confidence interval (CI), 92% to 97%]; 71 514 participants; 3 trials; moderate certainty); inactivated vaccines (efficacy, 61% [95% CI, 52% to 68%]; 48 029 participants; 3 trials; moderate certainty); protein subunit vaccines (efficacy, 77% [95% CI, -5% to 95%]; 17 737 participants; 2 trials; low certainty); and viral vector vaccines (efficacy 68% [95% CI, 61% to 74%]; 71 401 participants; 5 trials; low certainty) prevented COVID-19. Viral vector vaccines decreased mortality (risk ratio, 0.25 [95% CI 0.09 to 0.67]; 67 563 participants; 3 trials, low certainty), but comparable data on inactivated, mRNA, and protein subunit vaccines were imprecise. None of the vaccines showed evidence of a difference on serious adverse events, but observational evidence suggested rare serious adverse events. All the vaccines increased the risk of non-serious adverse events., Conclusions: The evidence suggests that all the included vaccines are effective in preventing COVID-19. The mRNA vaccines seem most effective in preventing COVID-19, but viral vector vaccines seem most effective in reducing mortality. Further trials and longer follow-up are necessary to provide better insight into the safety profile of these vaccines., Competing Interests: The authors have declared that no competing interests exist.

Background: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure., Objectives: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension., Search Methods: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions., Selection Criteria: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures., Data Collection and Analysis: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence., Main Results: The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I 2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I 2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eight studies; I 2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; seven studies ; I 2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I 2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I 2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I 2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I 2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I 2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I 2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I 2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I 2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies; I 2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I 2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I 2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events., Authors' Conclusions: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Medication errors are preventable events that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional or patient. Medication errors in hospitalised adults may cause harm, additional costs, and even death., Objectives: To determine the effectiveness of interventions to reduce medication errors in adults in hospital settings., Search Methods: We searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers on 16 January 2020.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) and interrupted time series (ITS) studies investigating interventions aimed at reducing medication errors in hospitalised adults, compared with usual care or other interventions. Outcome measures included adverse drug events (ADEs), potential ADEs, preventable ADEs, medication errors, mortality, morbidity, length of stay, quality of life and identified/solved discrepancies. We included any hospital setting, such as inpatient care units, outpatient care settings, and accident and emergency departments., Data Collection and Analysis: We followed the standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care (EPOC) Group. Where necessary, we extracted and reanalysed ITS study data using piecewise linear regression, corrected for autocorrelation and seasonality, where possible.  MAIN RESULTS: We included 65 studies: 51 RCTs and 14 ITS studies, involving 110,875 participants. About half of trials gave rise to 'some concerns' for risk of bias during the randomisation process and one-third lacked blinding of outcome assessment. Most ITS studies presented low risk of bias. Most studies came from high-income countries or high-resource settings. Medication reconciliation -the process of comparing a patient's medication orders to the medications that the patient has been taking- was the most common type of intervention studied. Electronic prescribing systems, barcoding for correct administering of medications, organisational changes, feedback on medication errors, education of professionals and improved medication dispensing systems were other interventions studied. Medication reconciliation Low-certainty evidence suggests that medication reconciliation (MR) versus no-MR may reduce medication errors (odds ratio [OR] 0.55, 95% confidence interval (CI) 0.17 to 1.74; 3 studies; n=379). Compared to no-MR, MR probably reduces ADEs (OR 0.38, 95%CI 0.18 to 0.80; 3 studies, n=1336 ; moderate-certainty evidence), but has little to no effect on length of stay (mean difference (MD) -0.30 days, 95%CI -1.93 to 1.33 days; 3 studies, n=527) and quality of life (MD -1.51, 95%CI -10.04 to 7.02; 1 study, n=131).  Low-certainty evidence suggests that, compared to MR by other professionals, MR by pharmacists may reduce medication errors (OR 0.21, 95%CI 0.09 to 0.48; 8 studies, n=2648) and may increase ADEs (OR 1.34, 95%CI 0.73 to 2.44; 3 studies, n=2873). Compared to MR by other professionals, MR by pharmacists may have little to no effect on length of stay (MD -0.25, 95%CI -1.05 to 0.56; 6 studies, 3983). Moderate-certainty evidence shows that this intervention probably has little to no effect on mortality during hospitalisation (risk ratio (RR) 0.99, 95%CI 0.57 to 1.7; 2 studies, n=1000), and on readmissions at one month (RR 0.93, 95%CI 0.76 to 1.14; 2 studies, n=997); and low-certainty evidence suggests that the intervention may have little to no effect on quality of life (MD 0.00, 95%CI -14.09 to 14.09; 1 study, n=724).  Low-certainty evidence suggests that database-assisted MR conducted by pharmacists, versus unassisted MR conducted by pharmacists, may reduce potential ADEs (OR 0.26, 95%CI 0.10 to 0.64; 2 studies, n=3326), and may have no effect on length of stay (MD 1.00, 95%CI -0.17 to 2.17; 1 study, n=311).  Low-certainty evidence suggests that MR performed by trained pharmacist technicians, versus pharmacists, may have little to no difference on length of stay (MD -0.30, 95%CI -2.12 to 1.52; 1 study, n=183). However, the CI is compatible with important beneficial and detrimental effects. Low-certainty evidence suggests that MR before admission may increase the identification of discrepancies compared with MR after admission (MD 1.27, 95%CI 0.46 to 2.08; 1 study, n=307). However, the CI is compatible with important beneficial and detrimental effects. Moderate-certainty evidence shows that multimodal interventions probably increase discrepancy resolutions compared to usual care (RR 2.14, 95%CI 1.81 to 2.53; 1 study, n=487). Computerised physician order entry (CPOE)/clinical decision support systems (CDSS) Moderate-certainty evidence shows that CPOE/CDSS probably reduce medication errors compared to paper-based systems (OR 0.74, 95%CI 0.31 to 1.79; 2 studies, n=88).  Moderate-certainty evidence shows that, compared with standard CPOE/CDSS, improved CPOE/CDSS probably reduce medication errors (OR 0.85, 95%CI 0.74 to 0.97; 2 studies, n=630). Low-certainty evidence suggests that prioritised alerts provided by CPOE/CDSS may prevent ADEs compared to non-prioritised (inconsequential) alerts (MD 1.98, 95%CI 1.65 to 2.31; 1 study; participant numbers unavailable). Barcode identification of participants/medications Low-certainty evidence suggests that barcoding may reduce medication errors (OR 0.69, 95%CI 0.59 to 0.79; 2 studies, n=50,545). Reduced working hours Low-certainty evidence suggests that reduced working hours may reduce serious medication errors (RR 0.83, 95%CI 0.63 to 1.09; 1 study, n=634). However, the CI is compatible with important beneficial and detrimental effects. Feedback on prescribing errors Low-certainty evidence suggests that feedback on prescribing errors may reduce medication errors (OR 0.47, 95%CI 0.33 to 0.67; 4 studies, n=384). Dispensing system Low-certainty evidence suggests that dispensing systems in surgical wards may reduce medication errors (OR 0.61, 95%CI 0.47 to 0.79; 2 studies, n=1775)., Authors' Conclusions: Low- to moderate-certainty evidence suggests that, compared to usual care, medication reconciliation, CPOE/CDSS, barcoding, feedback and dispensing systems in surgical wards may reduce medication errors and ADEs. However, the results are imprecise for some outcomes related to medication reconciliation and CPOE/CDSS. The evidence for other interventions is very uncertain. Powered and methodologically sound studies are needed to address the identified evidence gaps. Innovative, synergistic strategies -including those that involve patients- should also be evaluated., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objectives.: To assess how and in what extent the electronic nicotine delivery systems (ENDS) use substituted the consumption of traditional combustible cigarettes (c-cigarettes, c-cig)., Materials and Methods.: We performed a systematic review of the literature up to August 2019 in scientific databases. Primary outcomes were proportion of complete or partial substitution of conventional to electronic cigarettes and related economic aspects. Secondary outcomes were odds ratio of substitution and country-wise time trends., Results.: We retrieved 3,628 references and included 49 studies, providing economic and epidemiological data. Economic studies of cross-price elasticity showed that combustible cigarettes are partially substitutable for electronic cigarettes. Most studies reported that electronic cigarettes consumption prevalence increased over time. Three studies reported a significant reduction of combustible cigarettes consumed per day among dual users (combustible- plus electronic- cigarettes users) versus combustible-cigarettes users. The pooled adjusted odds ratio of quitting combustible cigarettes among electronic cigarettes users versus never or past electronic cigarettes (e-cigarettes, e-cig) users was 1.19 (95% confidence interval 1.09 to 1.30; heterogeneity score 0%). Longitudinal studies showed globally a growing prevalence of electronic cigarettes use, mainly in adolescents. A negative relationship between consumption and price increase of electronic and combustible cigarettes was found., Conclusion.: The chance of quitting smoking combustible cigarettes among current electronic nicotine delivery systems users was increased with respect to never- or past- electronic nicotine delivery systems users. Economic studies reported that electronic cigarette is partially substitutable for combustible cigarettes.

Objectives: To evaluate uterine tamponade devices' effectiveness for atonic refractory postpartum haemorrhage (PPH) after vaginal birth and the effect of including them in institutional protocols., Search Strategy: PubMed, EMBASE, CINAHL, LILACS, POPLINE, from inception to January 2021., Study Selection: Randomised and non-randomised comparative studies., Outcomes: Composite outcome including surgical interventions (artery ligations, compressive sutures or hysterectomy) or maternal death, and hysterectomy., Results: All included studies were at high risk of bias. The certainty of the evidence was rated as very low to low. One randomised study measured the effect of the condom-catheter balloon compared with standard care and found unclear results for the composite outcome (relative risk [RR] 2.33, 95% CI 0.76-7.14) and hysterectomy (RR 4.14, 95% CI 0.48-35.93). Three comparative studies assessed the effect of including uterine balloon tamponade in institutional protocols. A stepped wedge cluster randomised controlled trial suggested an increase in the composite outcome (RR 4.08, 95% CI 1.07-15.58) and unclear results for hysterectomy (RR 4.38, 95% CI 0.47-41.09) with the use of the condom-catheter or surgical glove balloon. One non-randomised study showed unclear effects on the composite outcome (RR 0.33, 95% CI 0.11-1.03) and hysterectomy (RR 0.49, 95% CI 0.04-5.38) after the inclusion of the Bakri balloon. The second non-randomised study found unclear effects on the composite outcome (RR 0.95, 95% CI 0.32-2.81) and hysterectomy (RR 1.84, 95% CI 0.44-7.69) after the inclusion of Ebb or Bakri balloon., Conclusions: The effect of uterine tamponade devices for the management of atonic refractory PPH after vaginal delivery is unclear, as is the role of the type of device and the setting., Tweetable Abstract: Unclear effects of uterine tamponade devices and their inclusion in institutional protocols for atonic refractory PPH after vaginal delivery., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Background: Rapid assessment of COVID-19 vaccine safety during pregnancy is urgently needed., Methods: We conducted a rapid systematic review, to evaluate the safety of COVID-19 vaccines selected by the COVID-19 Vaccines Global Access-Maternal Immunization Working Group in August 2020, including their components and their technological platforms used in other vaccines for pregnant persons. We searched literature databases, COVID-19 vaccine pregnancy registries, and explored reference lists from the inception date to February 2021 without language restriction. Pairs of reviewers independently selected studies through COVIDENCE, and performed the data extraction and the risk of bias assessment. Discrepancies were resolved by consensus. Registered on PROSPERO (CRD42021234185)., Results: We retrieved 6757 records and 12 COVID-19 pregnancy registries from the search strategy; 38 clinical and non-clinical studies (involving 2,398,855 pregnant persons and 56 pregnant animals) were included. Most studies (89%) were conducted in high-income countries and were cohort studies (57%). Most studies (76%) compared vaccine exposures with no exposure during the three trimesters of pregnancy. The most frequent exposure was to AS03 adjuvant, in the context of A/H1N1 pandemic influenza vaccines, (n = 24) and aluminum-based adjuvants (n = 11). Only one study reported exposure to messenger RNA in lipid nanoparticles COVID-19 vaccines. Except for one preliminary report about A/H1N1 influenza vaccination (adjuvant AS03), corrected by the authors in a more thorough analysis, all studies concluded that there were no safety concerns., Conclusion: This rapid review found no evidence of pregnancy-associated safety concerns of COVID-19 vaccines or of their components or platforms when used in other vaccines. However, the need for further data on several vaccine platforms and components is warranted, given their novelty. Our findings support current WHO guidelines recommending that pregnant persons may consider receiving COVID-19 vaccines, particularly if they are at high risk of exposure or have comorbidities that enhance the risk of severe disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Buekens Pierre M. reports financial support was provided by Bill & Melinda Gates Foundation., (Copyright © 2021. Published by Elsevier Ltd.)

The epidemiology and burden of Herpes Zoster (HZ) are largely unknown, and there are no recent reviews summarizing the available evidence from the Latin America and Caribbean (LAC) region. We conducted a systematic review and meta-analysis to characterize the epidemiology and burden of HZ in LAC. Bibliographic databases and grey literature sources were consulted to find studies published (January 2000 -February 2020) with epidemiological endpoints: cumulative incidence and incidence density (HZ cases per 100,000 person-years), prevalence, case-fatality rates, HZ mortality, hospitalization rates, and rates of each HZ complication. Twenty-six studies were included with most studies coming from Brazil. No studies reported the incidence of HZ in the general population. In population at higher risk, the cumulative incidence ranged from 318-3,423 cases of HZ per 100,000 persons per year of follow-up. The incidence density was 6.4-36.5 cases per 1,000 person-years. Age was identified as a major risk factor towards HZ incidence which increase significantly in people >50 years of age. Hospitalization rates ranged from 3%-35.7%. The in-hospital HZ mortality rate ranged from 0%-36%. Overall, HZ mortality rates were found to be higher in females across all age groups and countries. The incidence of HZ complications (such as post-herpetic neuralgia, ophthalmic herpes zoster, and Ramsay Hunt syndrome) was higher in the immunosuppressed compared to the immunocompetent population. Acyclovir was the most frequently used therapy. Epidemiological data from Ministry of Health databases (Argentina, Brazil, Colombia, Chile y Mexico) and Institute for Health Metrics and Evaluation's Global Burden of Disease project reported stable rates of hospitalizations and deaths over the last 10 years. High-risk groups for HZ impose a considerable burden in LAC. They could benefit from directed healthcare initiatives, including adult immunization, to prevent HZ occurrence and its complications., Competing Interests: The authors have read the journal’s policy and have the following competing interests: AB, AC, TA, CP, MS, and DB received grant support from GlaxoSmithKline Biologicals SA, which funded the development and publication of this article. JG and JN are employees of GlaxoSmithKline Biologicals SA. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Hypertension is a major public health problem that increases the risk of cardiovascular and kidney diseases. Several studies have shown an inverse association between calcium intake and blood pressure, as small reductions in blood pressure have been shown to produce rapid reductions in vascular disease risk even in individuals with normal blood pressure ranges. This is the first update of the review to evaluate the effect of calcium supplementation in normotensive individuals as a preventive health measure., Objectives: To assess the efficacy and safety of calcium supplementation versus placebo or control for reducing blood pressure in normotensive people and for the prevention of primary hypertension., Search Methods: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to September 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 9), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Ongoing Trials Register, ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions., Selection Criteria: We selected trials that randomised normotensive people to dietary calcium interventions such as supplementation or food fortification versus placebo or control. We excluded quasi-random designs. The primary outcomes were hypertension (defined as blood pressure ≥ 140/90 mmHg) and blood pressure measures., Data Collection and Analysis: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risks of bias. We used the GRADE approach to assess the certainty of evidence., Main Results: The 2020 updated search identified four new trials. We included a total of 20 trials with 3512 participants, however we only included 18 for the meta-analysis with 3140 participants. None of the studies reported hypertension as a dichotomous outcome. The effect on systolic and diastolic blood pressure was: mean difference (MD) -1.37 mmHg, 95% confidence interval (CI) -2.08, -0.66; 3140 participants; 18 studies; I 2 = 0%, high-certainty evidence; and MD -1.45, 95% CI -2.23, -0.67; 3039 participants; 17 studies; I 2 = 45%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those younger than 35 years was: MD -1.86, 95% CI -3.45, -0.27; 452 participants; eight studies; I 2 = 19%, moderate-certainty evidence; MD -2.50, 95% CI -4.22, -0.79; 351 participants; seven studies ; I 2 = 54%, moderate-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for those 35 years or older was: MD -0.97, 95% CI -1.83, -0.10; 2688 participants; 10 studies; I 2 = 0%, high-certainty evidence; MD -0.59, 95% CI -1.13, -0.06; 2688 participants; 10 studies; I 2 = 0%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for women was: MD -1.25, 95% CI -2.53, 0.03; 1915 participants; eight studies; I 2 = 0%, high-certainty evidence; MD -1.04, 95% CI -1.86, -0.22; 1915 participants; eight studies; I 2 = 4%, high-certainty evidence, respectively. The effect on systolic and diastolic blood pressure for men was MD -2.14, 95% CI -3.71, -0.59; 507 participants; five studies; I 2 = 8%, moderate-certainty evidence; MD -1.99, 95% CI -3.25, -0.74; 507 participants; five studies; I 2 = 41%, moderate-certainty evidence, respectively. The effect was consistent in both genders regardless of baseline calcium intake. The effect on systolic blood pressure was: MD -0.02, 95% CI -2.23, 2.20; 302 participants; 3 studies; I 2 = 0%, moderate-certainty evidence with doses less than 1000 mg; MD -1.05, 95% CI -1.91, -0.19; 2488 participants; 9 studies; I 2 = 0%, high-certainty evidence with doses 1000 to 1500 mg; and MD -2.79, 95% CI -4.71, 0.86; 350 participants; 7 studies = 8; I 2 = 0%, moderate-certainty evidence with doses more than 1500 mg. The effect on diastolic blood pressure was: MD -0.41, 95% CI -2.07, 1.25; 201 participants; 2 studies; I 2 = 0, moderate-certainty evidence; MD -2.03, 95% CI -3.44, -0.62 ; 1017 participants; 8 studies; and MD -1.35, 95% CI -2.75, -0.05; 1821 participants; 8 studies; I 2 = 51%, high-certainty evidence, respectively. None of the studies reported adverse events., Authors' Conclusions: An increase in calcium intake slightly reduces both systolic and diastolic blood pressure in normotensive people, particularly in young people, suggesting a role in the prevention of hypertension. The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion. Even small reductions in blood pressure could have important health implications for reducing vascular disease. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease. There is a great need for adequately-powered clinical trials randomising young people. Subgroup analysis should involve basal calcium intake, age, sex, basal blood pressure, and body mass index. We also require assessment of side effects, optimal doses and the best strategy to improve calcium intake., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Dementia is a progressive global cognitive impairment syndrome. In 2010, more than 35 million people worldwide were estimated to be living with dementia. Some people with mild cognitive impairment (MCI) will progress to dementia but others remain stable or recover full function. There is great interest in finding good predictors of dementia in people with MCI. The Mini-Mental State Examination (MMSE) is the best-known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research and community settings., Objectives: To determine the accuracy of the Mini Mental State Examination for the early detection of dementia in people with mild cognitive impairment SEARCH METHODS: We searched ALOIS (Cochrane Dementia and Cognitive Improvement Specialized Register of diagnostic and intervention studies (inception to May 2014); MEDLINE (OvidSP) (1946 to May 2014); EMBASE (OvidSP) (1980 to May 2014); BIOSIS (Web of Science) (inception to May 2014); Web of Science Core Collection, including the Conference Proceedings Citation Index (ISI Web of Science) (inception to May 2014); PsycINFO (OvidSP) (inception to May 2014), and LILACS (BIREME) (1982 to May 2014). We also searched specialized sources of diagnostic test accuracy studies and reviews, most recently in May 2014: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). No language or date restrictions were applied to the electronic searches and methodological filters were not used as a method to restrict the search overall so as to maximize sensitivity. We also checked reference lists of relevant studies and reviews, tracked citations in Scopus and Science Citation Index, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on MMSE for dementia diagnosis to try to locate possibly relevant but unpublished data., Selection Criteria: We considered longitudinal studies in which results of the MMSE administered to MCI participants at baseline were obtained and the reference standard was obtained by follow-up over time. We included participants recruited and clinically classified as individuals with MCI under Petersen and revised Petersen criteria, Matthews criteria, or a Clinical Dementia Rating = 0.5. We used acceptable and commonly used reference standards for dementia in general, Alzheimer's dementia, Lewy body dementia, vascular dementia and frontotemporal dementia., Data Collection and Analysis: We screened all titles generated by the electronic database searches. Two review authors independently assessed the abstracts of all potentially relevant studies. We assessed the identified full papers for eligibility and extracted data to create two by two tables for dementia in general and other dementias. Two authors independently performed quality assessment using the QUADAS-2 tool. Due to high heterogeneity and scarcity of data, we derived estimates of sensitivity at fixed values of specificity from the model we fitted to produce the summary receiver operating characteristic curve., Main Results: In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer's disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis., Authors' Conclusions: Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Around 184,000 deaths per year could be attributable to sugar-sweetened beverages (SSBs) consumption worldwide. Epidemiological and decision models are important tools to estimate disease burden. The purpose of this study was to identify models to assess the burden of diseases attributable to SSBs consumption or the potential impact of health interventions., Methods: We carried out a systematic review and literature search up to August 2018. Pairs of reviewers independently selected, extracted, and assessed the quality of the included studies through an exhaustive description of each model's features. Discrepancies were solved by consensus. The inclusion criteria were epidemiological or decision models evaluating SSBs health interventions or policies, and descriptive SSBs studies of decision models. Studies published before 2003, cost of illness studies and economic evaluations based on individual patient data were excluded., Results: We identified a total of 2766 references. Out of the 40 included studies, 45% were models specifically developed to address SSBs, 82.5% were conducted in high-income countries and 57.5% considered a health system perspective. The most common model's outcomes were obesity/overweight (82.5%), diabetes (72.5%), cardiovascular disease (60%), mortality (52.5%), direct medical costs (57.35%), and healthy years -DALYs/QALYs- (40%) attributable to SSBs. 67.5% of the studies modelled the effect of SSBs on the outcomes either entirely through BMI or through BMI plus diabetes independently. Models were usually populated with inputs from national surveys -such us obesity prevalence, SSBs consumption-; and vital statistics (67.5%). Only 55% reported results by gender and 40% included children; 30% presented results by income level, and 25% by selected vulnerable groups. Most of the models evaluated at least one policy intervention to reduce SSBs consumption (92.5%), taxes being the most frequent strategy (75%)., Conclusions: There is a wide range of modelling approaches of different complexity and information requirements to evaluate the burden of disease attributable to SSBs. Most of them take into account the impact on obesity, diabetes and cardiovascular disease, mortality, and economic impact. Incorporating these tools to different countries could result in useful information for decision makers and the general population to promote a deeper implementation of policies to reduce SSBs consumption., Prospero Protocol Number: CRD42020121025 ., (© 2021. The Author(s).)

Background: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783)., Methods: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables., Results: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks., Conclusion: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission., Competing Interests: The authors have declared that no competing interests exist.

Aim: To perform a systematic review to determine the efficacy/safety of PGx-guided opioid therapy for chronic/postoperative pain. Materials & methods: We searched PubMed and other specialized databases. Articles were considered if they compared the efficacy/safety of PGx-guided opioid therapy versus usual care. The risk of bias assessment was performed using Cochrane tools. Results: A total of 3794 records were retrieved. Only five were included for data extraction. A lower requirement of analgesics during postoperative in the PGx-guided intervention arm was reported in two studies. Also, two studies reported significant pain improvement in favor of the PGx-guided therapy when analyzing the subgroup of patients with a high-risk CYP2D6 phenotype. Conclusion: Despite the findings described, information on the efficacy/safety of this intervention is scarce.

Introduction: In Latin America, tobacco smoking prevalence is between 6.4% and 35.2%. Governments have been making efforts to support the regulation of advertising and, in many cases, banning advertising and promotion of tobacco altogether. The objective of this study was to evaluate the potential impact on health and economic outcomes of optimizing a ban on tobacco advertising and sponsorship in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru., Methods: We built a probabilistic microsimulation model, considering natural history, direct health system costs, and quality of life impairment associated with main tobacco-related diseases. We followed individuals in hypothetical cohorts and calculated health outcomes on an annual basis to obtain aggregated 10-year population health outcomes (deaths, events, healthy years of life) and costs. To populate the model, we performed a rapid review of literature to calculate intervention effectiveness., Results: With current policies, over 10 years, in Argentina, Bolivia, Brazil, Chile, and Colombia a total of 50,000 deaths and 364,000 disease events will be averted, saving $7.2 billion. If the seven countries strengthened their policies and implemented a comprehensive ban with 100% compliance, 98,000 deaths and 648,000 events would be averted over 10 years, saving almost $15 billion in healthcare costs., Conclusions: Optimizing a ban on tobacco advertising and sponsorship would substantially reduce deaths, diseases, and health care costs attributed to smoking. Latin American countries should not delay the full implementation of this strategy.

Background and Objectives: Breast cancer (BC) is the most common cancer in women. It imposes a huge disease burden and a significant impact on health-related quality of life (HRQoL). Our study focused on HRQoL of patients with BC in Latin America and the Caribbean (LAC). We conducted a systematic review to identify relevant articles published between 2008 and August 2018. We conducted several meta-analyses and subgroup analyses by country, disease stage, and instrument used (Prospective Register Of Systematic Reviews registration number: CRD42018106835)., Results: From 2,265 initial references, we finally included 75 articles (8,806 participants) that assessed HRQoL. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 and B23 modules (34 studies; 8 countries; 4,866 participants) were the most used instruments, followed by the Short Form 36-item, the abbreviated version of the World Health Organization Quality of Life instrument, and the Functional Assessment of Cancer Therapy - Breast instrument. Only four studies reported specific HRQoL data of patients with metastatic disease. Half the studies were rated as having moderate quality (38/75), and 38% (29/75) as high quality. We identified substantial heterogeneity. As expected, the meta-analyses revealed that patients with metastatic disease reported lower HRQoL values and high symptom burden compared with patients at earlier stages. Similar results can be observed when we compared patients with early breast cancer in active treatment phases versus those in follow-up., Conclusion: This study provides a synthesis of breast cancer HRQoL reported in LAC and exposes existing evidence gaps. Patients with BC in active treatment or with metastatic disease had worse HRQoL compared with survivors during the follow-up period., Implications for Practice: This systematic review provides an exhaustive synthesis of breast cancer health-related quality of life in women in the Latin American and Caribbean region. Patients with breast cancer in active treatment or with metastatic disease had worse health-related quality of life compared with survivors during the different follow-up periods. This study also shows important evidence and methods gaps that can help inform future research., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Objective: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth., Data Sources: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted., Study Eligibility Criteria: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study., Methods: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability., Results: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis., Conclusion: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), mortality remains high. These patients require mechanical ventilation, which has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival. This is an updated version of the review first published in 2013., Objectives: To assess the benefits and harms of high versus low levels of PEEP in adults with ALI and ARDS., Search Methods: For our previous review, we searched databases from inception until 2013. For this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and the Web of Science from inception until May 2020. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov; www.controlled-trials.com), and we screened the reference lists of included studies., Selection Criteria: We included randomised controlled trials that compared high versus low levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours., Data Collection and Analysis: Two review authors assessed risk of bias and extracted data independently. We contacted investigators to identify additional published and unpublished studies. We used standard methodological procedures expected by Cochrane., Main Results: We included four new studies (1343 participants) in this review update. In total, we included 10 studies (3851 participants). We found evidence of risk of bias in six studies, and the remaining studies fulfilled all criteria for low risk of bias. In eight studies (3703 participants), a comparison was made between high and low levels of PEEP, with the same tidal volume in both groups. In the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. In the main analysis, we assessed mortality occurring before hospital discharge only in studies that compared high versus low PEEP, with the same tidal volume in both groups. Evidence suggests that high PEEP may result in little to no difference in mortality compared to low PEEP (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.04; I² = 15%; 7 studies, 3640 participants; moderate-certainty evidence). In addition, high PEEP may result in little to no difference in barotrauma (RR 1.00, 95% CI 0.64 to 1.57; I² = 63%; 9 studies, 3791 participants; low-certainty evidence). High PEEP may improve oxygenation in patients up to the first and third days of mechanical ventilation (first day: mean difference (MD) 51.03, 95% CI 35.86 to 66.20; I² = 85%; 6 studies, 2594 participants; low-certainty evidence; third day: MD 50.32, 95% CI 34.92 to 65.72; I² = 83%; 6 studies, 2309 participants; low-certainty evidence) and probably improves oxygenation up to the seventh day (MD 28.52, 95% CI 20.82 to 36.21; I² = 0%; 5 studies, 1611 participants; moderate-certainty evidence). Evidence suggests that high PEEP results in little to no difference in the number of ventilator-free days (MD 0.45, 95% CI -2.02 to 2.92; I² = 81%; 3 studies, 1654 participants; low-certainty evidence). Available data were insufficient to pool the evidence for length of stay in the intensive care unit., Authors' Conclusions: Moderate-certainty evidence shows that high levels compared to low levels of PEEP do not reduce mortality before hospital discharge. Low-certainty evidence suggests that high levels of PEEP result in little to no difference in the risk of barotrauma. Low-certainty evidence also suggests that high levels of PEEP improve oxygenation up to the first and third days of mechanical ventilation, and moderate-certainty evidence indicates that high levels of PEEP improve oxygenation up to the seventh day of mechanical ventilation. As in our previous review, we found clinical heterogeneity - mainly within participant characteristics and methods of titrating PEEP - that does not allow us to draw definitive conclusions regarding the use of high levels of PEEP in patients with ALI and ARDS. Further studies should aim to determine the appropriate method of using high levels of PEEP and the advantages and disadvantages associated with high levels of PEEP in different ARDS and ALI patient populations., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Most post-licensure vaccine pharmacovigilance in low- and middle-income countries (LMICs) are passive reporting systems. These have limited utility for maternal immunization pharmacovigilance in LMIC settings and need to be supplemented with active surveillance. Our study's main objective was to identify existing perinatal data collection systems in LMICs that collect individual information on maternal and neonatal health outcomes and could be developed to inform active safety surveillance of novel vaccines for use during pregnancy., Methods: A scoping review was performed following the Arksey and O'Malley six-stage approach. We included studies describing electronic or mixed paper-electronic data collection systems in LMICs, including research networks, electronic medical records, and custom software platforms for health information systems. Medline PubMed, EMBASE, Global Health, Cochrane Library, LILACS, Bibliography of Asian Studies (BAS), and CINAHL were searched through August 2019. We also searched grey literature including through Google and websites of existing relevant perinatal data collection systems, as well as contacted authors of key studies and experts in the field to validate the information and identify additional sources of relevant unpublished information., Results: A total of 11,817 records were identified. The full texts of 264 records describing 96 data collection systems were assessed for eligibility. Eight perinatal data collection systems met our inclusion criteria: Global Network's Maternal Newborn Health Registry, International Network for the Demographic Evaluation of Populations and their Health; Perinatal Informatic System; Pregnancy Exposure Registry & Birth Defects Surveillance; SmartCare; Open Medical Record System; Open Smart Register Platform and District Health Information Software 2. These selected systems were qualitatively characterized according to seven different domains: governance; system design; system management; data management; data sources, outcomes and data quality., Conclusion: This review provides a list of active maternal and neonatal data collection systems in LMICs and their characteristics as well as their outreach, strengths, and limitations. Findings could potentially help further understand where to obtain population-based high-quality information on outcomes to inform the conduct of maternal immunization active vaccine safety surveillance activities and research in LMICs.

The use of substandard and counterfeit medicines (SCM) leads to significant health and economic consequences, like treatment failure, rise of antimicrobial resistance, extra expenditures of individuals or households and serious adverse drug reactions including death. Our objective was to systematically search, identify and compare relevant available mobile applications (apps) for smartphones and tablets, which use could potentially affect clinical and public health outcomes. We carried out a systematic review of the literature in January 2020, including major medical databases, and app stores. We used the validated Mobile App Rating Scale (MARS) to assess the quality of apps, (1 worst score, 3 acceptable score, and 5 best score). We planned to evaluate the accuracy of the mobile apps to detect SCM. We retrieved 335 references through medical databases and 42 from Apple, Google stores and Google Scholar. We finally included two studies of the medical database, 25 apps (eight from the App Store, eight from Google Play, eight from both stores, and one from Google Scholar), and 16 websites. We only found one report on the accuracy of a mobile apps detecting SCMs. Most apps use the imprint, color or shape for pill identification, and only a few offer pill detection through photographs or bar code. The MARS mean score for the apps was 3.17 (acceptable), with a maximum of 4.9 and a minimum of 1.1. The 'functionality' dimension resulted in the highest mean score (3.4), while the 'engagement' and 'information' dimensions showed the lowest one (3.0). In conclusion, we found a remarkable evidence gap about the accuracy of mobile apps in detecting SCMs. However, mobile apps could potentially be useful to screen for SCM by assessing the physical characteristics of pills, although this should still be assessed in properly designed research studies., Competing Interests: The authors have declared that no competing interests exist.

Calcium supplementation and fortification are strategies widely used to prevent adverse outcome in population with low-calcium intake which is highly frequent in low-income settings. We aimed to determine the effectiveness and cost-effectiveness of calcium fortified foods on calcium intake and related health, or economic outcomes. We performed a systematic review and meta-analysis involving participants of any age or gender, drawn from the general population. We searched PubMed, Agricola, EMBASE, CINAHL, Global Health, EconLit, the FAO website and Google until June 2019, without language restrictions. Pair of reviewers independently selected, extracted data and assessed the risk of bias of included studies using Covidence software. Disagreements were resolved by consensus. We performed meta-analyses using RevMan 5.4 and subgroup analyses by study design, age group, and fortification levels. We included 20 studies of which 15 were randomized controlled trials (RCTs), three were non-randomised studies and two were economic evaluations. Most RCTs had high risk of bias on randomization or blinding. Most represented groups were women and children from 1 to 72 months, most common intervention vehicles were milk and bakery products with a fortification levels between 96 and 1200 mg per 100 g of food. Calcium intake increased in the intervention groups between 460 mg (children) and 1200 mg (postmenopausal women). Most marked effects were seen in children. Compared to controls, height increased 0.83 cm (95% CI 0.00; 1.65), plasma parathyroid hormone decreased -1.51 pmol/L, (-2.37; -0.65), urine:calcium creatinine ratio decreased -0.05, (-0.07; -0.03), femoral neck and hip bone mineral density increased 0.02 g/cm 2 (0.01; 0.04) and 0.03 g/cm 2 (0.00; 0.06), respectively. The largest cost savings (43%) reported from calcium fortification programs came from prevented hip fractures in older women from Germany. Our study highlights that calcium fortification leads to a higher calcium intake, small benefits in children's height and bone health and also important evidence gaps for other outcomes and populations that could be solved with high quality experimental or quasi-experimental studies in relevant groups, especially as some evidence of calcium supplementation show controversial results on the bone health benefit on older adults.

Introduction: Disease burden due to tobacco smoking in Latin America remains very high. The objective of this study was to evaluate the potential impact of implementing smoke-free air interventions on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a mathematical model., Aims and Methods: We built a probabilistic Monte Carlo microsimulation model, considering natural history, direct health system costs, and quality of life impairment associated with main tobacco-related diseases. We followed individuals in hypothetical cohorts and calculated health outcomes on an annual basis to obtain aggregated 10-year population health outcomes (deaths and events) and costs. To populate the model, we completed an overview and systematic review of the literature. Also, we calibrated the model comparing the predicted disease-specific mortality rates with those coming from local national statistics., Results: With current policies, for the next 10 years, a total of 137 121 deaths and 917 210 events could be averted, adding 3.84 million years of healthy life and saving USD 9.2 billion in these seven countries. If countries fully implemented smoke-free air strategies, it would be possible to avert nearly 180 000 premature deaths and 1.2 million events, adding 5 million healthy years of life and saving USD 13.1 billion in direct healthcare., Conclusions: Implementing the smoke-free air strategy would substantially reduce deaths, diseases, and health care costs attributed to smoking. Latin American countries should not delay the full implementation of this strategy., Implications: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds quality evidence on the potential health effects and savings of implementing smoke-free air policies in countries representing almost 80% of the Latin America and the Caribbean population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19., Methods: We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020., Results: We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues., Conclusions: There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence)., Systematic Review Registration: Protocol available on the OSF website: https://tinyurl.com/vvbgqya., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To compare the effectiveness of starting the ovarian stimulation on the early follicular phase ("Conventional") with the newer range of non-conventional approaches starting in the luteal phase ("Luteal"), random-start, and studies implementing them in DuoStim ("Conventional"+"Luteal")., Methods: Systematic review. We searched CENTRAL, PubMed, and Embase, on March 2020. We included randomized and non-randomized controlled trials that compared "Luteal," random-start ovarian stimulation or DuoStim with "Conventional"; we analyzed them by subgroups: oocyte freezing and patients undergoing ART treatments, both, in the general infertile population and among poor responders., Results: The following results come from a sensitivity analysis that included only the low/moderate risk of bias studies. When comparing "Luteal" to "Conventional," clinically relevant differences in MII oocytes were ruled out in all subgroups. We found that "Luteal" probably increases the COH length both, in the general infertile population (OR 2.00 days, 95% CI 0.81 to 3.19, moderate-quality evidence) and in oocyte freezing cycles (MD 0.85 days, 95% CI 0.53 to 1.18, moderate-quality evidence). When analyzing DuoStim among poor responders, we found that it appears to generate a higher number of MII oocytes in comparison with a single "Conventional" (MD 3.35, 95%CI 2.54-4.15, moderate-quality evidence)., Conclusion: Overall, this systematic review of the available data demonstrates that in poor responders, general infertile population and oocyte freezing for cancer stimulation in the late follicular and luteal phases can be utilized in non-conventional approaches such as random-start and DuoStim cycles, offering similar outcomes to the conventional cycles but potentially with increased flexibility, within a reduced time frame. However, more well-designed trials are required to establish certainty.

Introduction: The burden of disease attributable to tobacco use in Latin America is very high. Our objective was to evaluate the 10-year potential impact of current legislation related to cigarette packaging and warnings and expected effects of moving to a higher level of strategies implementing cigarette plain packaging on health and cost outcomes in Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, and Peru, using a microsimulation model., Aims and Methods: We used a probabilistic state-transition microsimulation model, considering natural history, costs, and quality of life losses associated with main tobacco-related diseases. We followed up individuals in hypothetical cohorts and calculated health outcomes annually to obtain aggregated long-term population health outcomes and costs. We performed a literature review to estimate effects and analyzed studies and information from ministries, relevant organizations, and national surveys. We calibrated the model comparing the predicted disease-specific mortality rates with local statistics., Results: Current graphic warnings already in place in each country could avert, during 10 years, 69 369 deaths and 638 295 disease events, adding 1.2 million years of healthy life and saving USD 5.3 billion in the seven countries. If these countries implemented plain packaging strategies, additional 155 857 premature deaths and 4 133 858 events could be averted, adding 4.1 million healthy years of life and saving USD 13.6 billion in direct health care expenses of diseases attributable to smoking., Conclusions: Latin American countries should not delay the implementation of this strategy that will alleviate part of the enormous health and financial burden that tobacco poses on their economies and health care systems., Implications: Tobacco smoking is the single most preventable and premature mortality cause in the world. The Framework Convention on Tobacco Control, supported by the World Health Organization, introduced a package of evidence-based measures for tobacco control. This study adds evidence on the potential health effects and savings of implementing cigarette plain packaging in countries representing almost 80% of the Latin American population; findings are valuable resources for policy makers in the region., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: A frozen embryo transfer (FET) cycle is when one or more embryos (frozen during a previous treatment cycle) are thawed and transferred to the uterus. Some women undergo fresh embryo transfer (ET) cycles with embryos derived from donated oocytes. In both situations, the endometrium is primed with oestrogen and progestogen in different doses and routes of administration., Objectives: To evaluate the most effective endometrial preparation for women undergoing transfer with frozen embryos or embryos from donor oocytes with regard to the subsequent live birth rate (LBR)., Search Methods: The Cochrane Gynaecology and Fertility Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, LILACS, trials registers and abstracts of reproductive societies' meetings were searched in June 2020 together with reference checking and contact with study authors and experts in the field to identify additional studies., Selection Criteria: Randomised controlled trials (RCTs) evaluating endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. We analysed all available interventions versus placebo, no treatment, or between each other. The primary review outcome was live birth rate. Secondary outcomes were clinical and multiple pregnancy, miscarriage, cycle cancellation, endometrial thickness and adverse effects., Main Results: Thirty-one RCTs (5426 women) were included. Evidence was moderate to very low-quality: the main limitations were serious risk of bias due to poor reporting of methods, and serious imprecision. Stimulated versus programmed cycle We are uncertain whether a letrozole-stimulated cycle compared to a programmed cycle, for endometrial preparation, improves LBR (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.49 to 3.26; 100 participants; one study; very low-quality evidence). Stimulating with follicle stimulating hormone (FSH), letrozole or clomiphene citrate may improve clinical pregnancy rate (CPR) (OR 1.63, 95% CI 1.12 to 2.38; 656 participants; five studies; I 2 = 11%; low-quality evidence). We are uncertain if they reduce miscarriage rate (MR) (OR 0.79, 95% CI 0.36 to 1.71; 355 participants; three studies; I 2 = 0%; very low-quality evidence). Endometrial thickness (ET) may be reduced with clomiphene citrate (mean difference(MD) -1.04, 95% CI -1.59 to -0.49; 92 participants; one study; low-quality evidence). Other outcomes were not reported. Natural versus programmed cycle We are uncertain of the effect from a natural versus programmed cycle for LBR (OR 0.97, 95% CI 0.74 to 1.28; 1285 participants; four studies; I 2 = 0%; very low-quality evidence) and CPR (OR 0.79, 95% CI 0.62 to 1.01; 1249 participants; five studies; I 2 = 60%; very low-quality evidence), while a natural cycle probably reduces the cycle cancellation rate (CCR) (OR 0.60, 95% CI 0.44 to 0.82; 734 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and ET. No study reported other outcomes. Transdermal versus oral oestrogens From low-quality evidence we are uncertain of the effect transdermal compared to oral oestrogens has on CPR (OR 0.86, 95% CI 0.59 to 1.25; 504 participants; three studies; I 2 = 58%) or MR (OR 0.55, 95% CI 0.27 to 1.09; 414 participants; two studies; I 2 = 0%). Other outcomes were not reported. Day of starting administration of progestogen When doing a fresh ET using donated oocytes in a synchronised cycle starting progestogen on the day of oocyte pick-up (OPU) or the day after OPU, in comparison with recipients that start progestogen the day prior to OPU, probably increases the CPR (OR 1.87, 95% CI 1.13 to 3.08; 282 participants; one study, moderate-quality evidence). We are uncertain of the effect on multiple pregnancy rate (MPR) or MR. It probably reduces the CCR (OR 0.28, 95% CI 0.11 to 0.74; 282 participants; one study; moderate-quality evidence). No study reported other outcomes. Gonadotropin-releasing hormone (GnRH) agonist versus control A cycle with GnRH agonist compared to without may improve LBR (OR 2.62, 95% CI 1.19 to 5.78; 234 participants; one study; low-quality evidence). From low-quality evidence we are uncertain of the effect on CPR (OR 1.08, 95% CI 0.82 to 1.43; 1289 participants; eight studies; I 2 = 20%), MR (OR 0.85, 95% CI 0.36 to 2.00; 828 participants; four studies; I 2 = 0%), CCR (OR 0.49, 95% CI 0.21 to 1.17; 530 participants; two studies; I 2 = 0%) and ET (MD -0.08, 95% CI -0.33 to 0.16; 697 participants; four studies; I 2 = 4%). No study reported other outcomes. Among different GnRH agonists From very low-quality evidence we are uncertain if cycles among different GnRH agonists improves CPR or MR. No study reported other outcomes. GnRH agonists versus GnRH antagonists GnRH antagonists compared to agonists probably improves CPR (OR 0.62, 95% CI 0.42 to 0.90; 473 participants; one study; moderate-quality evidence). We are uncertain of the effect on MR and MPR. No study reported other outcomes. Aspirin versus control From very low-quality evidence we are uncertain whether a cycle with aspirin versus without improves LBR, CPR, or ET. Steroids versus control From very low-quality evidence we are uncertain whether a cycle with steroids compared to without improves LBR, CPR or MR. No study reported other outcomes., Authors' Conclusions: There is insufficient evidence on the use of any particular intervention for endometrial preparation in women undergoing fresh donor cycles and frozen embryo transfers. In frozen embryo transfers, low-quality evidence showed that clinical pregnancy rates may be improved in a stimulated cycle compared to a programmed one, and we are uncertain of the effect when comparing a programmed cycle to a natural cycle. Cycle cancellation rates are probably reduced in a natural cycle. Although administering a GnRH agonist, compared to without, may improve live birth rates, clinical pregnancy rates will probably be improved in a GnRH antagonist cycle over an agonist cycle. In fresh synchronised oocyte donor cycles, the clinical pregnancy rate is probably improved and cycle cancellation rates are probably reduced when starting progestogen the day of or day after donor oocyte retrieval. Adequately powered studies are needed to evaluate each treatment more accurately., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)