Toward the Implementation of a Value Framework for Diagnostic Technologies: Operationalization, Piloting, and Validation in Latin America.

OBJECTIVES: In 2020, a group of 30 stakeholders from Latin America established 15 criteria for a diagnostic technologies value framework (D-VF) to help assess and inform decisions on diagnostic technologies. This article aims to present the operationalization, piloting, and initial validation of the framework for its implementation. METHODS: This work was carried out collaboratively with a variety of stakeholders. Three sequential phases were undertaken: (1) operationalization of the D-VF through a literature search for conceptual definitions and assessment tools, (2) piloting of the D-VF through a rapid health technology assessment document applying the methodology of the framework, and (3) a face validation process conducted through a virtual workshop, where usefulness and implementation aspects of the framework were assessed. RESULTS: The operationalization of the framework was conducted, and a methodological user guide was published. The D-VF criteria were applied in a health technology assessment document on human papilloma virus testing in cervical cancer screening. Also, an open-access training program was developed. Stakeholders agreed on the usefulness of the D-VF for assessment and decision-making stages of diagnostic technologies. However, they highlighted the need to improve technical capacities and the potential for added complexity when applying a D-VF with many criteria. The absence of an established value framework for diagnostic technologies in Latin America and the potential for strengthening technical capacities made the project valuable to those involved. CONCLUSIONS: The diagnostic technologies value framework was shown to be fit for implementation in real-life decision-making settings after the operationalization, piloting, and initial validation phases. Further experiences are important to support its implementation.

A Systematic Review of Value Criteria for Next-Generation Sequencing/Comprehensive Genomic Profiling to Inform Value Framework Development.

OBJECTIVES: To comprehensively identify and map an exhaustive list of value criteria for the assessment of next-generation sequencing/comprehensive genomic profiling (NGS/CGP), to be used as an aid in decision making. METHODS: We conducted a systematic review to identify existing value frameworks (VFs) applicable to any type of healthcare technology. VFs and criteria were mapped to a previously published Latin American (LA) VF to harmonize definitions and identify additional criteria and or subcriteria. Based on this analysis, we extracted a comprehensive, evidence-based list of criteria and subcriteria to be considered in the design of a NGS/CGP VF. RESULTS: A total of 42 additional VFs were compared with the LA VF, 88% were developed in high-income countries, 30% targeted genomic testing, and 16% specifically targeted oncology. A total of 242 criteria and subcriteria were extracted; 227 (94%) were fully/partially included in the LA VF; and 15 (6%) were new. Clinical benefit and economic aspects were the most common criteria. VFs oriented to genomic testing showed significant overlap with other VFs. Considering all criteria and subcriteria, a total of 18 criteria and 36 individual subcriteria were identified. CONCLUSIONS: Our study provides an evidence-based set of criteria and subcriteria for healthcare decision making useful for NGS/CGP as well as other health technologies. The resulting list can be beneficial to inform decision making and will serve as a foundation to co-create a multistakeholder NGS/CGP VF that is aligned with the needs and values of health systems and could help to improve patient access to high-value technologies.

Cost-effectiveness of COVID-19 vaccination in Latin America and the Caribbean: an analysis in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru.

OBJECTIVE: Our study analyzes the cost-effectiveness of the COVID-19 vaccination campaigns in Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, and Peru. METHODS: Using a previously published SVEIR model, we analyzed the impact of a vaccination campaign (2021) from a national healthcare perspective. The primary outcomes were quality adjusted life years (QALYs) lost and total costs. Other outcomes included COVID-19 cases, hospitalizations, deaths, and life years. We applied a discount rate of 3% for health outcomes. We modeled a realistic vaccination campaign in each country (the realistic country-specific campaign). Additionally, we assessed a standard campaign (similar, "typical" for all countries), and an optimized campaign (similar in all countries with higher but plausible population coverage). One-way deterministic sensitivity analyses were performed. FINDINGS: Vaccination was health improving as well as cost-saving in almost all countries and scenarios. Our analysis shows that vaccination in this group of countries prevented 573,141 deaths (508,826 standard; 685,442 optimized) and gained 5.07 million QALYs (4.53 standard; 6.03 optimized). Despite the incremental costs of vaccination campaigns, they had a total net cost saving to the health system of US$16.29 billion (US$16.47 standard; US$18.58 optimized). The realistic (base case) vaccination campaign in Chile was the only scenario, which was not cost saving, but it was still highly cost-effective with an ICER of US$22 per QALY gained. Main findings were robust in the sensitivity analyses. INTERPRETATION: The COVID-19 vaccination campaign in seven Latin American and Caribbean countries -that comprise nearly 80% of the region- was beneficial for population health and was also cost-saving or highly cost-effective.

The Development of a New International Generic Measure (EQ-HWB): Face Validity and Psychometric Stages in Argentina.

OBJECTIVES: This study aimed to present the face validity and psychometric stages performed in Spanish in Argentina, the only Spanish-speaking country of an international collaboration that undertook the construction of a new measure that can be used in economic evaluation across health, social care, and public health, the EQ EQ-HWB (EQ Health and Wellbeing). We also explored the relationship among 3-level version EQ-5D (EQ-5D-3L), 5-level version EQ-5D (EQ-5D-5L), and EQ-HWB. METHODS: Face validity was based on semistructured face to face interviews of a purposive sample to explore translatability of language and concepts of 97 candidate items, translated into Argentina Spanish. The psychometric evaluation using an online panel assessed the psychometric properties of 64 items that were carried forward (floor and ceiling effects, item correlations, known-group differences in relevant prespecified subgroups by the international and local teams, exploratory and confirmatory factor analysis, and item response theory). EQ-5D-3L, EQ-5D-5L, and EQ-HWB correlations were explored. RESULTS: In the face validity stage, 24 interviews with carers, general public, patients, and users of social services were included. Most items showed adequate face validity. In the psychometric assessment, 497 participants were recruited (64% reporting a long-term health condition). Most of the items showed adequate psychometrics in an Argentinian context. EQ-5D-3L and EQ-5D-5L had strong correlations, and EQ-HWB was moderately correlated to EQ visual analog scale. The Argentina team recommended 23 of the final 25 items. CONCLUSIONS: The assessment of Spanish items contributed to the overall development of EQ-HWB and helped inform the design of an internationally relevant 25-item and a short 9-item measure intended to be used in economic evaluations.

Impact of Lung Cancer on Health-Related Quality of Life, Financial Toxicity, and Household Economics in Patients From the Public and the Private Healthcare Sector in Argentina.

OBJECTIVES: Non-small cell lung cancer (NSCLC) is Argentina's first cause of cancer death. Most patients have an advanced stage at diagnosis, with poor expected survival. This study aimed to characterize the health-related quality of life (HRQOL) and economic impact of patients treated in the private healthcare sector and compare it with that of the public sector. METHODS: We undertook an observational cross-sectional study that extended a previous study to a referral private center in Argentina. Outcomes included the EuroQol EQ-5D-3L (to assess HRQOL), Comprehensive Score for Financial Toxicity (financial toxicity instrument), Work Productivity and Activity Impairment - General Health (to assess productivity loss), and out-of-pocket expenses in adults diagnosed of NSCLC. RESULTS: We included 30 consecutive patients from a private healthcare center (July 2021 to March 2022), totaling 131 patients (n = 101 from previous public study). The whole sample had low quality of life and relevant economic impact. Patients in the private healthcare sector showed lower disease severity and higher educational level and household income. In addition, private healthcare system patients showed higher utility (0.77 vs 0.73; P < .05) and lower impairment of daily activities (41% vs 59%; P = .01). Private health system patients also showed lower financial toxicity as measured by the Comprehensive Score for Financial Toxicity score (23.9 vs 20.14; P < .05) but showed no differences when financial toxicity was assessed as a dichotomic variable. CONCLUSIONS: Although patients with NSCLC treated in a private healthcare center in Argentina showed a relevant HRQOL and economic impact, this impact was smaller than the one observed in publicly funded hospitals.

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.

Mortalidad, Secuelas Clínicas y Calidad de Vida Luego del Alta de Unidades de Cuidados Intensivos en Pacientes con COVID-19: Estudio Multicéntrico Descriptivo en Argentina.

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.

Budget Impact Analysis of Olaparib in Combination with Bevacizumab for Maintenance Therapy for Ovarian Cancer in Argentina.

OBJECTIVES: To perform a budget impact analysis (BIA) of introducing olaparib as maintenance therapy in women who have BRCA mutations (BRCAm) with platinum-sensitive recurrent ovarian cancer (PSROC) in combination with bevacizumab in Argentina. METHODS: A BIA model was used to analyse over a 5-year time horizon the change in the health system's budget following the adoption of olaparib as maintenance therapy in BRCAm patients with PSROC. The BIA for each year was estimated by comparing the cost difference between the current scenario (treatment with bevacizumab) and the new scenario (the addition of olaparib) for a third-party payer. The BIA is estimated at the national health system level, and by healthcare sectors in Argentina (public sector, social security and private sector). International and national epidemiological data were used to determine the target patient population. Clinical efficacy, safety outcomes and duration of treatments were obtained from the pivotal clinical study report. Relevant direct medical costs were obtained from public data in Argentina and expert consultation. All the costs are reported in US dollars as of October 2022 ($1 = 152.59 Argentine pesos). A scenario analysis assessed the full coverage of the homologous recombination deficiency (HRD) test in Argentina. In addition, one-way sensitivity analysis was conducted to evaluate the model robustness. RESULTS: For a third-party payer with a cohort of 1,000,000 women covered, the estimated target population was 2 individuals in year 1 and 6 individuals in year 5. The incorporation of olaparib, with a wholesale price per pack of $3176.32, was associated with a weighted average of the budget impact per member per month (PMPM) of $0.062 for the national health system, being above the estimated health system budget impact threshold ($0.0153). By healthcare sector, the results of budget impact PMPM for year 5 ranged between $0.08 (public sector) and $0.114 (private sector). For all perspectives, the variables that most influenced the budget impact was the incidence of ovarian cancer, the drug acquisition cost and the treatment duration. CONCLUSIONS: The introduction of olaparib for the treatment of BRCAm women with PSROC has a high budget impact for all three health systems in Argentina.

Safety and Effectiveness of COVID-19 Vaccines During Pregnancy: A Living Systematic Review and Meta-analysis.

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.

Rotavirus Vaccine Impact since Its Introduction in the National Immunization Program of Argentina.

INTRODUCTION: Rotavirus (RV) is the most common cause of childhood diarrhea. Argentina introduced RV vaccination in the National Immunization Program in January 2015. This study evaluates the impact of RV vaccine implementation on the burden of acute diarrheal disease (ADD) and RV positive cases, and hospitalizations among children in Argentina. METHODS: A counterfactual time-series analysis was performed. Data on ADD (2013-2018) and RV diarrhea (2012-2018) cases in children aged < 5 years were collected from the National Healthcare Surveillance System (clinical and laboratory data). Data on hospital discharges following ADD and RV diarrhea (2011-2017) were retrieved from the Health Statistics and Information Office. All data were classified by the age groups < 1 year, < 2 years, 2-5 years. Vaccine impact was defined as the difference between the predicted time trend (simulated using 2012-2014 data) and the actual post-vaccination data (2015-2018). RESULTS: A significant reduction of 22.1% of notified ADD cases and 15.4% of hospital discharges following ADD among children < 2 years was observed in the 3 years after RV vaccine implementation. Data also showed a significant decline of 54.0% and 59.4% of notified RV cases in children < 2 and < 1 years, respectively, and a reduction of 39.3% and 40.8% in RV hospital discharges for the same age groups. CONCLUSION: This study shows a significant reduction in notified ADD cases and RV cases and hospital discharges following ADD and RV cases in children < 2 years after RV vaccine introduction in Argentina in 2015.

Safety, immunogenicity, and effectiveness of COVID-19 vaccines for pregnant persons: A protocol for systematic review and meta analysis.

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.

Safety of COVID-19 vaccines during pregnancy: A systematic review and meta-analysis.

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.

COVID-19 and pregnancy: An umbrella review of clinical presentation, vertical transmission, and maternal and perinatal outcomes.

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.

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.

Safety of components and platforms of COVID-19 vaccines considered for use in pregnancy: A rapid review.

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.

Demographic and clinical characteristics of individuals with traumatic spinal cord injury in Argentina from 2015 to 2019: a multicenter study.

STUDY DESIGN: Descriptive and ambispective study. OBJECTIVES: To describe the demographics, clinical characteristics, and etiologies of traumatic spinal cord injury (TSCI) in a metropolitan region of Argentina. SETTING: Five inpatient rehabilitation centers in Buenos Aires, Argentina. METHODS: We included all patients with acute TSCI who required hospital treatment at five rehabilitation facilities between 2015 and 2019. We collected data using portions of the International Spinal Cord Injury (SCI) Core Data Set. RESULTS: We registered 186 individuals as having TSCI. The males were 77% of the total sample. The mean age was 36 (SD ± 15.7) years. The distribution between paraplegia and tetraplegia was 50.3% and 49.7%, respectively. TSCI was complete in 57.3%. Including patients with motor complete SCI, the percentage reached 71.9% of the sample. Vehicular collisions were the leading cause of TSCI (47.3%), followed by falls (21.5%) and assaults (16.1%). CONCLUSIONS: We collected data about demographics, clinical characteristics, and aetiologies of TSCI for the first time in Argentina. The predominant demographic profile of the individuals with TSCI was of young males with complete SCI. We found the most important cause of TSCI was vehicular collisions. Implementation of road safety strategies in this target population might decrease the incidence of TSCI.

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 / Trastuzumab-emtansine versus other anti-HER2 regimens in early or unresectable or metastatic HER-2 positive breast cancer: systematic review and network meta-analysis

RESUMEN Objetivo. 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.

ABSTRACT Objective. 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.

[Risk factors for the development and recurrence of pressure ulcers in patients with spinal cord injury: A systematic review.] / Factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular: revisión sistemática.

Introduction: A spinal cord injury refers to the damage suffered in the spinal cord as a result of trauma, disease or degeneration. Every person with spinal cord injury is at risk of developing pressure ulcers, and almost everyone will develop at least one ulcer due to severe pressure during his or her life. Objective: To identify the studies that detected risk factors for the development and recurrence of pressure ulcers in patients with spinal cord injury; and, if possible, synthesize the evidence to determine whether an association exists between them. Methods: A systematic search was conducted in Medline, LILACS, SciELO and Cochrane until December 4, 2018. The following studies were included: observational studies, case-control studies, and prospective or retrospective cohort studies, which provided an adjusted analysis of the risk factors associated with the development and recurrence of pressure ulcers in patients with spinal cord injury. Results: 25 articles met the eligibility criteria and were included for analysis. A total of 30 risk factors were identified: 4 were demographic factors, 8 were related to the injury, 5 belonged to medical comorbidities, 3 to nutritional factors, 9 were psychological, cognitive, contextual and social factors and 1 was related to support surface. As regards the factors, 56.67 percent of them were classified as non-modifiable. Conclusion: 30 risk factors were identified for the development and recurrence of pressure ulcers in patients with spinal cord injury. However, we were not able to synthesize the evidence due to the heterogeneity of the articles included in this review.

Introducción: Una lesión medular hace referencia a los daños sufridos en la médula espinal a consecuencia de un traumatismo, enfermedad o degeneración. Todas las personas con lesión medular corren riesgo de desarrollar úlceras por presión y casi todas desarrollarán al menos una úlcera por presión grave durante su vida. Objetivo: Identificar los estudios que detectaron factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular. Y de ser posible, sintetizar la evidencia para detectar asociación entre los mismos. Método: Se realizó una búsqueda sistemática en Medline, LILACS, SciELO y Cochrane hasta el 4 de diciembre del año 2018. Se incluyeron estudios observacionales, casos-controles y de cohorte, retrospectivos o prospectivos, que realizaron un análisis ajustado de los factores de riesgo para el desarrollo y/o recurrencia de úlceras por presión en sujetos con lesión medular. Resultados: 25 artículos cumplieron los criterios de elegibilidad y fueron incluidos para el análisis. Se identificaron un total de 30 factores de riesgo, de los cuales 4 fueron factores demográficos, 8 relacionados con la lesión, 5 pertenecieron a comorbilidades médicas, 3 a factores nutricionales, 9 fueron factores psicológicos, cognitivos, contextuales y sociales y 1 estuvo relacionado con la superficie de apoyo. El 56,67% se clasificaron como no modificables. Conclusión: Se identificaron 30 factores de riesgo para la aparición y/o recurrencia de úlceras por presión en sujetos con lesión medular. No fue posible sintetizar la evidencia debido a la heterogeneidad presentada por los artículos incluidos en la presente revisión.

Parámetros esenciales para utilizar en modelos epidemiológicos de COVID-19 en Argentina Una revisión rápida / Essential parameters for use in epidemiological models of COVID-19 in Argentina: a rapid review

INTRODUCCIÓN: Los modelos de simulación para COVID-19 requieren una serie de parámetros epidemiológicos que varían en base a cuestiones propias de cada región y al momento de la pandemia que se esté atravesando. OBJETIVO: Esta revisión rápida presenta los parámetros epidemiológicos esenciales potencialmente utilizables en Argentina. MÉTODOS: Se realizó una búsqueda en las principales bases de datos y en buscadores de artículos en estado de preimpresión (preprints) de parámetros relacionados con la propagación del virus y evolución de la enfermedad, y el uso del sistema de salud. Para revisar los artículos seleccionados se utilizó una herramienta de evaluación de calidad apropiada al diseño del estudio. RESULTADOS: De las variables relacionadas con la propagación y evolución; el período de incubación es de 5,8 días (intervalos de confianza [IC95%]: 4,83-6,85), el período de infecciosidad es de 6,25 días (IC95%: 5,09-7,51), el número básico de reproducción es de 3,32 (IC95%: 3,24-3,39), y la tasa de fatalidad en pacientes infectados fue de 0,64% (IC95%: 0,5-0,78). De las variables relacionadas con el uso del sistema de salud, el tiempo de internación hospitalaria es de 5 días (rango intercuartílico [RIC]: 3-9), el tiempo de internación en una unidad de cuidados intensivos (UCI) es de 7 días (RIC: 4-11), el porcentaje de pacientes internados que requieren de UCI es de 26% (IC95%: 20-33) y, de estos, el porcentaje que requieren de ventilación mecánica es de 69% (IC95%: 61-75). DISCUSIÒN: Estudios recientes y datos de acceso públicos a nivel nacional muestran valores distintos a los relevados de la bibliografía internacional. La información recolectada en este trabajo puede contribuir a informar futuros modelamientos y tableros de control para predecir la dinámica de la epidemia en Argentina.