Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER-2 positive breast cancer: systematic review and network meta-analysis. / Trastuzumab-emtansina versus otros regímenes anti-HER-2 en el cáncer de mama HER-2 positivo precoz o irresecable o metastásico: revisión sistemática y metaanálisis en red.

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.

OBJETIVO.: Motivación para realizar el estudio. Se evaluaron las opciones de tratamiento para el cáncer de mama HER-2-positivo, centrándose en la eficacia y seguridad de trastuzumab-emtansina (T-DM1) en comparación con otras terapias anti-HER-2. Principales hallazgos. Trastuzumab-deruxtecan (T-DXd)y PyroCap surgieron como alternativas prometedoras, mostrando mejoras sustanciales en la sobrevida libre de progresión para el cáncer de mama localmente avanzado o metastásico. T-DM1 mostró una eficacia superior a la de los demás tratamientos. Implicancias. Nuestros hallazgos podrían informar los procesos de toma de decisiones sanitarias para optimizar las estrategias para el cáncer de mama HER-2-positivo, y potencialmente mejorar los resultados de salud y la calidad de vida. Nuestro objetivo fue estudiar la eficacia y la seguridad de trastuzumab-emtansina (T-DM1) en comparación con otras terapias anti-HER-2 en el cáncer de mama (CM) HER-2 positivo. MATERIALES Y MÉTODOS.: Realizamos un metaanálisis de red (NMA, por sus siglas en inglés) de ensayos clínicos aleatorizados (ECA). Nuestro estudio se centró en pacientes sometidos al tratamiento para el cáncer de mama localmente avanzado no resecable (CMLA) o cáncer de mama metastásico (CMm), que incluía esquemas con trastuzumab y taxanos. Además, consideramos casos dentro de los primeros 6 meses de tratamiento para el cáncer de mama temprano (CMT) HER-2 positivo. RESULTADOS.: Se incluyeron en nuestro análisis un total de 23 ECA y 41 reportes. En CMLA y CMm, no se observaron diferencias estadísticamente significativas en ninguna de las comparaciones entre T-DM1 y otras terapias anti-HER-2 positivo. Al evaluar la sobrevida libre de progresión (SLP), trastuzumab-deruxtecan (T-DXd) y PyroCap demostraron una mayor eficacia en comparación con otros tratamientos (Hazard Ratio [HR]: 3,57; intervalo de confianza al 95% [IC 95%]: 2,75-4,63 y HR: 1.82; IC 95%: 1,35-2,44; respectivamente), mientras que T-DM1 por sí solo mostró una efectividad superior en comparación con LapCap (HR: 0,65; IC 95%: 0,55-0,77), TrasCap (HR: 0,65; IC 95%: 0,46-0,91), LapCapCitu (HR: 0,60; IC 95%: 0,33-1,1), Nera (HR: 0,55; IC 95%: 0,39-0,77) y Cap (HR: 0,37; IC 95%: 0,28-0,49). CONCLUSIONES.: Este NMA estableció un ranking basado en la eficacia y seguridad comparativas entre las intervenciones disponibles. Aunque superior a otros esquemas, T-DM1 mostró una menor eficacia en la SLP y la tasa de respuesta objetiva, y una tendencia hacia una sobrevida global peor que T-DXd.

Progestogens for prevention of luteinising hormone (LH) surge in women undergoing controlled ovarian hyperstimulation as part of an assisted reproductive technology (ART) cycle.

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.

¿Qué necesita nuestra región para fortalecer políticas públicas sobre bebidas azucaradas? diálogo de decisores / What does our region need in order to strengthen public policies on sugar-sweetened beverages? decision-makers' dialogue

Con el objetivo de priorizar políticas públicas para disminuir el consumo de bebidas azucaradas en Argentina, Brasil, El Salvador y Trinidad y Tobago e identificar las necesidades de información relacionadas con la carga de enfermedad atribuible a su consumo se realizó un diálogo de políticas en el que participaron miembros de gobierno, organizaciones de la sociedad civil, investigadores y comunicadores de países de Latinoamérica y el Caribe. Se llevaron a cabo exposiciones y talleres deliberativos utilizándose herramientas de recolección de datos semiestructuradas y discusiones grupales facilitadas. Las intervenciones priorizadas fueron el incremento de impuestos, el etiquetado frontal, la restricción de la publicidad, promoción y patrocinio y las modificaciones del entorno escolar. La principal barrera percibida fue la interferencia de la industria alimentaria. La realización de este diálogo de decisores permitió la identificación de las políticas públicas prioritarias para disminuir el consumo de bebidas azucaradas en la región.

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.

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: Update of a living systematic review and meta-analysis.

BACKGROUND: Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? METHODS AND FINDINGS: The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. CONCLUSIONS: Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. REVIEW PROTOCOL: Open Science Framework (https://osf.io/9ewys/).

Evidencia sobre las vacunas para COVID-19 en niñas, niños y adolescentes / Evidence on vaccines for COVID-19 in children and adolescents

En Argentina, tres de las vacunas contra el COVID-19 autorizadas por la entidad regulatoria local se aplican en menores de edad: la vacuna desarrollada por Sinopharm (BBIBP-CorV) para niños de 3 años o más, y las desarrolladas por Moderna (ARNm 1273) y Pfizer (BNT162b2) a partir de los 12 años. Dado que estas recomendaciones no coinciden exactamente con las emitidas por diferentes organismos internacionales y debido al corto plazo de seguimiento de los ensayos publicados, surgieron dudas fundamentalmente en relación a su seguridad. En este artículo, los autores sintetizan la evidencia disponible hasta el momento sobre las vacunas aplicadas en niños, niñas y adolescentes en nuestro país, basada en informes preliminares de ensayos clínicos y reportes de vigilancia epidemiológica. (AU)

In Argentina, three of the COVID-19 vaccines authorized by the local regulatory entity are applied to minors: the vaccine developed by Sinopharm (BBIBP-CorV) for children 3 years of age or older, and those developed by Moderna (RNAm1273) and Pfizer (BNT162b2) from the age of 12 and onwards. Given that these recommendations do not coincide exactly with those issued by different international organizations and due to the short follow-up period of the published trials, doubts arose fundamentally in relation to their safety. In this article, the authors summarize the evidence available to date on vaccines applied to children and adolescents in our country, based on preliminary studies of clinical trials and epidemiological surveillance reports. (AU)

Intercambio desde los cigarrillos convencionales a los sistemas electrónicos de administración de nicotina: revisión sistemática rápida con metaanálisis y aspectos económicos / Switching from cigarettes to electronic nicotine delivery system: rapid systematic review and meta-analysis and economic aspects

RESUMEN Objetivos. Evaluar cómo y en qué medida se produce un intercambio desde los cigarrillos convencionales (CC) a los sistemas electrónicos de administración de nicotina (SEAN). Materiales y métodos. Se realizó una revisión sistemática hasta agosto de 2019. El desenlace primario fue la proporción de un intercambio completo o parcial de CC a los SEAN y sus aspectos económicos. Los desenlaces secundarios como medidas de resultado fueron la probabilidad de intercambio y la tendencia en el intercambio por países. Resultados. Se encontraron 3628 referencias y se incluyeron 49 estudios con datos epidemiológicos y económicos. Los estudios económicos sobre la elasticidad cruzada de precios mostraron que los CC son parcialmente intercambiables por SEAN. La mayoría de los estudios reportaron que la prevalencia del consumo de cigarrillos electrónicos se incrementó con el tiempo. Tres estudios reportaron una reducción significativa de los CC consumidos por día entre fumadores duales (convencionales más SEAN) en comparación con los consumidores de CC. El odds ratio ajustado y combinado de dejar los CC entre consumidores de SEAN en comparación con quienes nunca consumieron o lo hicieron en el pasado fue de 1,19 (IC95%: 1,09-1,30; heterogeneidad 0%). Los estudios longitudinales mostraron una creciente prevalencia del uso de cigarrillos electrónicos, principalmente en adolescentes. Se encontró una relación negativa entre el consumo y aumento de precio de CC y electrónicos. Conclusión. La probabilidad de dejar de fumar CC entre consumidores habituales de SEAN se incrementó respecto a los consumidores que nunca o que solían consumir SEAN. Estudios económicos reportaron que los cigarrillos electrónicos son parcialmente intercambiables por los CC.

ABSTRACT 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.

Optimizing Tobacco Advertising Bans in Seven Latin American Countries: Microsimulation Modeling of Health and Financial Impact to Inform Evidence-Based Policy.

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.

Safety of COVID-19 vaccines, their components or their platforms for pregnant women: A rapid review.

BACKGROUND: Pregnant women with COVID-19 are at an increased risk of severe COVID-19 illness as well as adverse pregnancy and birth outcomes. Many countries are vaccinating or considering vaccinating pregnant women with limited available data about the safety of this strategy. Early identification of safety concerns of COVID-19 vaccines, including their components, or their technological platforms is therefore urgently needed. METHODS: We conducted a rapid systematic review, as the first phase of an ongoing full systematic review, to evaluate the safety of COVID-19 vaccines in pregnant women, including their components, and their technological platforms (whole virus, protein, viral vector or nucleic acid) used in other vaccines, following the Cochrane methods and the PRISMA statement for reporting (PROSPERO-CRD42021234185).We searched literature databases, COVID-19 and pregnancy registries from inception February 2021 without time or language restriction and explored the reference lists of relevant systematic reviews retrieved. We selected studies of any methodological design that included at least 50 pregnant women or pregnant animals exposed to the vaccines that were selected for review by the COVAX MIWG in August 2020 or their components or platforms included in the COVID-19 vaccines, and evaluated adverse events during pregnancy and the neonatal period.Pairs of reviewers independently selected studies through the COVIDENCE web software and performed the data extraction through a previously piloted online extraction form. Discrepancies were resolved by consensus. RESULTS: We identified 6768 records, 256 potentially eligible studies were assessed by full-text, and 37 clinical and non-clinical studies (38 reports, involving 2,397,715 pregnant women and 56 pregnant animals) and 12 pregnancy registries were included.Most studies (89%) were conducted in high-income countries. The most frequent study design was cohort studies (n=21), followed by surveillance studies, randomized controlled trials, and registry analyses. Most studies (76%) allowed comparisons between vaccinated and unvaccinated pregnant women (n=25) or animals (n=3) and reported exposures 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), followed by aluminum-based adjuvants (n=11). Aluminum phosphate was used in Respiratory Syncytial Virus Fusion candidate vaccines (n=3) and Tdap vaccines (n=3). Different aluminum-based adjuvants were used in hepatitis vaccines. The replication-deficient simian adenovirus ChAdOx1 was used for a Rift Valley fever vaccine. Only one study reported exposure to messenger RNA (mRNA) COVID-19 vaccines that also used lipid nanoparticles. 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 that were selected for review by the COVAX MIWG 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 women 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.

Direct Medical Costs, Productivity Loss Costs and Out-Of-Pocket Expenditures in Women with Breast Cancer in Latin America and the Caribbean: A Systematic Review.

OBJECTIVE: Our objective was to conduct a systematic review of the literature to identify, categorise, assess, and synthesise the healthcare costs of patients with breast cancer (BC) and their relatives in Latin America and the Caribbean (LAC). METHODS: In December 2020, we searched for published data in PubMed, LILACS, EMBASE, and other sources, including the grey literature. Studies were eligible if they were conducted in LAC and reported the direct medical costs, productivity loss costs, out-of-pocket expenditure, and other costs to patients with BC and their relatives. No restrictions were imposed on the type of BC population (metastatic BC or human epidermal growth factor receptor 2-positive/negative BC, among others). We summarised the characteristics and methodological approach of each study and the healthcare costs by cancer stage. We also developed and applied an original ad hoc instrument to assess the quality of the cost estimation studies. RESULTS: We identified 2725 references and 63 included studies. In total, 79.3% of the studies solely reported direct medical costs and five solely reported costs to patients and their relatives. Only 14.3% of the studies were classified as of high quality. The pooled weighted average direct medical cost per patient-year (year 2020 international dollars [I$]) by BC stage was I$13,179 for stage I, I$15,556 for stage II, I$23,444 for stage III, and I$28,910 for stage IV. CONCLUSION: This review provides the first synthesis of BC costs in LAC. Our findings show few high-quality costing studies in BC and a gap in the literature measuring costs to patients and their relatives. The high costs associated with the advanced stages of BC call into question the affordability of treatments and their accessibility for patients. Registered in PROSPERO (CRD42018106835).

Health-Related Quality of Life in Patients with Breast Cancer in Latin America and the Caribbean: A Systematic Review and Meta-Analysis.

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.

Switching from cigarettes to electronic nicotine delivery system: rapid systematic review and meta-analysis and economic aspects. / Intercambio desde los cigarrillos convencionales a los sistemas electrónicos de administración de nicotina: revisión sistemática rápida con metaanálisis y aspectos económicos.

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.

OBJETIVOS.: Evaluar cómo y en qué medida se produce un intercambio desde los cigarrillos convencionales (CC) a los sistemas electrónicos de administración de nicotina (SEAN). MATERIALES Y MÉTODOS.: Se realizó una revisión sistemática hasta agosto de 2019. El desenlace primario fue la proporción de un intercambio completo o parcial de CC a los SEAN y sus aspectos económicos. Los desenlaces secundarios como medidas de resultado fueron la probabilidad de intercambio y la tendencia en el intercambio por países. RESULTADOS.: Se encontraron 3628 referencias y se incluyeron 49 estudios con datos epidemiológicos y económicos. Los estudios económicos sobre la elasticidad cruzada de precios mostraron que los CC son parcialmente intercambiables por SEAN. La mayoría de los estudios reportaron que la prevalencia del consumo de cigarrillos electrónicos se incrementó con el tiempo. Tres estudios reportaron una reducción significativa de los CC consumidos por día entre fumadores duales (convencionales más SEAN) en comparación con los consumidores de CC. El odds ratio ajustado y combinado de dejar los CC entre consumidores de SEAN en comparación con quienes nunca consumieron o lo hicieron en el pasado fue de 1,19 (IC95%: 1,09-1,30; heterogeneidad 0%). Los estudios longitudinales mostraron una creciente prevalencia del uso de cigarrillos electrónicos, principalmente en adolescentes. Se encontró una relación negativa entre el consumo y aumento de precio de CC y electrónicos. CONCLUSIÓN.: La probabilidad de dejar de fumar CC entre consumidores habituales de SEAN se incrementó respecto a los consumidores que nunca o que solían consumir SEAN. Estudios económicos reportaron que los cigarrillos electrónicos son parcialmente intercambiables por los CC.

La suspensión de la presencialidad escolar: un resumen de la evidencia disponible a nivel internacional respecto de su efectividad para contener la actual pandemia deCOVID-19 / The suspension of school attendance: a summary of the evidence available at the international level regarding its effectiveness in containing the current COVID-19 pandemic

Tomando como excusa el análisis crítico del reciente informe suscripto por profesionales del Instituto de Cálculo de la Facultad de Ciencias Exactas y Naturales (UBA­CONICET) respecto del impacto de la suspensión de la presencialidad escolar como medida de control de la pandemia de COVID-19, que generó gran debate en Argentina, el autor de este artículo resume la evidencia a nivel internacional proveniente de revisiones sistemáticas sobre la eficacia y seguridad de este tipo de intervenciones, deteniéndose en cuándo, cómo y durante cuánto tiempo es razonable aplicarla. Por último, reflexiona y esboza propuestas que ayuden a fortalecer la racionalidad en la toma de decisiones. (AU)

Taking as an excuse the critical analysis of the recent report by professionals from the Instituto de Cálculo de la Facultad de Ciencias Exactas y Naturales (UBA­CONICET) regarding the impact of the suspension of school attendance as a measure to control the COVID-19 pandemic, which generated much debate in Argentina, the author of this article summarises the international evidence from systematic reviews on the efficacy and safety of this type of intervention, focusing on when,how and for how long it is reasonable to apply it. Finally, he reflects on and outlines proposals to help strengthen rationality in decision-making. (AU)