Has the COVID-19 pandemic changed existing patterns of non-COVID-19 health care utilization? A retrospective analysis of six regions in Europe.

BACKGROUND: Resilience of national health systems in Europe remains a major concern in times of multiple crises and as more evidence is emerging relating to the indirect effects of the COVID-19 pandemic on health care utilization (HCU), resulting from de-prioritization of regular, non-pandemic healthcare services. Most extant studies focus on regional, disease specific or early pandemic HCU creating difficulties in comparing across multiple countries. We provide a comparatively broad definition of HCU across multiple countries, with potential to expand across regions and timeframes. METHODS: Using a cross-country federated research infrastructure (FRI), we examined HCU for acute cardiovascular events, elective surgeries and serious trauma. Aggregated data were used in forecast modelling to identify changes from predicted European age-standardized counts via fitted regressions (2017-19), compared against post-pandemic data. RESULTS: We found that elective surgeries were most affected, universally falling below predicted levels in 2020. For cardiovascular HCU, we found lower-than-expected cases in every region for heart attacks and displayed large sex differences. Serious trauma was the least impacted by the COVID-19 pandemic. CONCLUSION: The strength of this study comes from the use of the European Population Health Information Research Infrastructure's (PHIRI) FRI, allowing for rapid analysis of regional differences to assess indirect impacts of events such as pandemics. There are marked differences in the capacity of services to return to normal in terms of elective surgery; additionally, we found considerable differences between men and women which requires further research on potential sex or gender patterns of HCU during crises.

Delayed treatment in breast cancer patients during the COVID-19 pandemic: a population health information research infrastructure (PHIRI) case study.

BACKGROUND: The indirect impact of the coronavirus disease 2019 pandemic on healthcare services was studied by assessing changes in the trend of the time to first treatment for women 18 or older who were diagnosed and treated for breast cancer between 2017 and 2021. METHODS: An observational retrospective longitudinal study based on aggregated data from four European Union (EU) countries/regions investigating the time it took to receive breast cancer treatment. We compiled outputs from a federated analysis to detect structural breakpoints, confirming the empirical breakpoints by differences between the trends observed and forecasted after March 2020. Finally, we built several segmented regressions to explore the association of contextual factors with the observed changes in treatment delays. RESULTS: We observed empirical structural breakpoints on the monthly median time to surgery trend in Aragon (ranging from 9.20 to 17.38 days), Marche (from 37.17 to 42.04 days) and Wales (from 28.67 to 35.08 days). On the contrary, no empirical structural breakpoints were observed in Belgium (ranging from 21.25 to 23.95 days) after the pandemic's beginning. Furthermore, we confirmed statistically significant differences between the observed trend and the forecasts for Aragon and Wales. Finally, we found the interaction between the region and the pandemic's start (before/after March 2020) significantly associated with the trend of delayed breast cancer treatment at the population level. CONCLUSIONS: Although they were not clinically relevant, only Aragon and Wales showed significant differences with expected delays after March 2020. However, experiences differed between countries/regions, pointing to structural factors other than the pandemic.

PHIRI: lessons for an extensive reuse of sensitive data in federated health research.

BACKGROUND: The extensive and continuous reuse of sensitive health data could enhance the role of population health research on public decisions. This paper describes the design principles and the different building blocks that have supported the implementation and deployment of Population Health Information Research Infrastructure (PHIRI), the strengths and challenges of the approach and some future developments. METHODS: The design and implementation of PHIRI have been developed upon: (i) the data visiting principle-data does not move but code moves; (ii) the orchestration of the research question throughout a workflow that ensured legal, organizational, semantic and technological interoperability and (iii) a 'master-worker' federated computational architecture that supported the development of four uses cases. RESULTS: Nine participants nodes and 28 Euro-Peristat members completed the deployment of the infrastructure according to the expected outputs. As a consequence, each use case produced and published their own common data model, the analytical pipeline and the corresponding research outputs. All the digital objects were developed and published according to Open Science and FAIR principles. CONCLUSION: PHIRI has successfully supported the development of four use cases in a federated manner, overcoming limitations for the reuse of sensitive health data and providing a methodology to achieve interoperability in multiple research nodes.

Statistical Considerations for the Design and Analysis of Pragmatic Trials in Aging Research.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

A comprehensive review of hip arthroscopy techniques and outcomes.

Transforming the orthopedic landscape, hip arthroscopy pioneers a minimally invasive surgical approach for diagnosing and addressing hip pathologies. With its origins dating back to Burman's 1931 cadaveric study, this groundbreaking technique gained clinical relevance in 1939 through Takagi's report. However, the 1980s marked the actual emergence of hip arthroscopy for treating a wide range of hip disorders. Now, a staple in modern orthopedics, hip arthroscopy empowers patients with previously undiagnosed and untreated hip conditions, enabling them to obtain relief and reclaim their lives. By employing a compact camera and specialized tools, surgeons expertly navigate the hip joint, performing procedures from excising loose bodies and mending labral tears to addressing femoroacetabular impingement and tackling other intricate issues. This innovative approach has dramatically elevated patients' quality of life, allowing them to embrace targeted treatments and resume daily activities without resorting to lifestyle alterations.

Role of Renal Venous Oxygen Pressure for Renal Function Monitoring After Related Living-Donor Kidney Transplantation: Cohort Study.

BACKGROUND: Monitoring of renal function after kidney transplantation (KT) is performed by measuring serum creatinine (SCr), urine volumes (UV), and glomerular filtration rate (GFR). Other methods based on oxygen metabolism, such as the renal venous oxygen pressure (PrvO2), may be useful. The aim of this study was to explore the correlation between PrvO2 and SCr, UV, and GFR 5 days after KT (SCr5, UV5, and GFR5, respectively). METHODS: We conducted a prospective cohort study in adults scheduled for living donor KT. A venous blood sample was taken from the renal vein after declamping the renal artery, and blood gas determinations were made. Correlation analyses between PrvO2 and SCr5, UV5, and GFR5 were done by calculating Spearman's correlation coefficient with generalized linear models (GLM). A Spearman's correlation analysis was performed between the percentage decrease in SCr (%ΔSCr) and PrvO2. A GLM was also performed to determine the association of PrvO2 with slow graft function (SGF). RESULTS: The study included 42 patients, of whom 67% were men. The median age was 31 years (IQR, 27-43.5). PrvO2 was negatively correlated with SCr5 (ρ = -0.53, P = .003), and positively correlated with GFR5 (ρ = 0.49, P = .001) and %ΔSCr (ρ = 0.47, P = .002). A higher PrvO2 was associated with an increase in GFR in univariable (ß = 1.24, 95% CI, 0.56-1.93, P = .001) and multivariable (ß = 1.24, 95% CI, 0.53-1.94, P = .001) analyses. No association was found between PrvO2 and SGF. CONCLUSION: PrvO2 could be used to monitor renal function in the first 5 days after related living-donor KT, given its good correlation with SCr and GFR.

Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.

PURPOSE OF REVIEW: The first successful pig to human cardiac xenotransplantation in January 2022 represented a major step forward in the fields of heart failure, immunology, and applied genetic engineering, using a 10-gene edited (GE) pig. This review summarizes the evolution of preclinical modelling data which informed the use of each of the 10 genes modified in the 10-GE pig: GGTA1, Β4GalNT2, CMAH, CD46, CD55, TBM, EPCR, CD47, HO-1, and growth hormone receptor. RECENT FINDINGS: The translation of the 10-GE pig from preclinical modelling to clinical compassionate xenotransplant use was the culmination of decades of research combating rejection, coagulopathy, inflammation, and excessive xenograft growth. Understanding these 10 genes with a view to their combinatorial effects will be useful in anticipated xenotransplant clinical trials.

Federated causal inference based on real-world observational data sources: application to a SARS-CoV-2 vaccine effectiveness assessment.

INTRODUCTION: Causal inference helps researchers and policy-makers to evaluate public health interventions. When comparing interventions or public health programs by leveraging observational sensitive individual-level data from populations crossing jurisdictional borders, a federated approach (as opposed to a pooling data approach) can be used. Approaching causal inference by re-using routinely collected observational data across different regions in a federated manner, is challenging and guidance is currently lacking. With the aim of filling this gap and allowing a rapid response in the case of a next pandemic, a methodological framework to develop studies attempting causal inference using federated cross-national sensitive observational data, is described and showcased within the European BeYond-COVID project. METHODS: A framework for approaching federated causal inference by re-using routinely collected observational data across different regions, based on principles of legal, organizational, semantic and technical interoperability, is proposed. The framework includes step-by-step guidance, from defining a research question, to establishing a causal model, identifying and specifying data requirements in a common data model, generating synthetic data, and developing an interoperable and reproducible analytical pipeline for distributed deployment. The conceptual and instrumental phase of the framework was demonstrated and an analytical pipeline implementing federated causal inference was prototyped using open-source software in preparation for the assessment of real-world effectiveness of SARS-CoV-2 primary vaccination in preventing infection in populations spanning different countries, integrating a data quality assessment, imputation of missing values, matching of exposed to unexposed individuals based on confounders identified in the causal model and a survival analysis within the matched population. RESULTS: The conceptual and instrumental phase of the proposed methodological framework was successfully demonstrated within the BY-COVID project. Different Findable, Accessible, Interoperable and Reusable (FAIR) research objects were produced, such as a study protocol, a data management plan, a common data model, a synthetic dataset and an interoperable analytical pipeline. CONCLUSIONS: The framework provides a systematic approach to address federated cross-national policy-relevant causal research questions based on sensitive population, health and care data in a privacy-preserving and interoperable way. The methodology and derived research objects can be re-used and contribute to pandemic preparedness.

Weight Gain After 12 Months of Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV Patients.

Recent studies suggest that the introduction of antiretroviral agents such as integrase strand transfer inhibitors (INSTI) may lead to weight gain in people living with HIV (PLHIV). In this retrospective observational study, we report the weight changes observed in virologically suppressed HIV patients after 12 months of switching to bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) due to a national change in public policy in Mexico. Patients on prior regimens based on TDF/FTC or ABC/3TC plus non-nucleoside retrotranscriptase inhibitor, INSTI, or protease inhibitor were included. In the 399 patients analyzed, a significant weight increase was found, as well as an increase in body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol (LDL-C), glucose, creatinine, and CD4+ cells after 12 months of switching treatment (all p ≤ .001). Mean weight gain was 1.63 kg [confidence interval (95% CI): 1.14-2.11], whereas the average percentage of weight gained was 2.5% (95% CI: 1.83-3.17). After considering the confounding effect of baseline weight status, the change in weight and BMI did not present significant differences between any of the prior treatment schemes. In conclusion, PLHIV switching to BIC/F/TAF therapy experienced weight gain after the first year of switching treatment. Although this weight gain could be due to the switch in treatment regimen, it cannot be excluded that it was caused by other factors since no comparable control group could be used for comparison.

Effectiveness of a nationwide COVID-19 vaccination program in Mexico against symptomatic COVID-19, hospitalizations, and death: a retrospective analysis of national surveillance data.

OBJECTIVES: Vaccination has been effective in ameliorating the impact of COVID-19. Here, we report vaccine effectiveness (VE) of the nationally available COVID-19 vaccines in Mexico. METHODS: Retrospective analysis of a COVID-19 surveillance system to assess the VE of the BNT162b2, messenger RNA (mRNA)-12732, Gam-COVID-Vac, Ad5-nCoV, Ad26.COV2.S, ChAdOx1, and CoronaVac vaccines against SARS-CoV-2 infection, COVID-19 hospitalization, and death in Mexico. The VE was estimated using time-varying Cox proportional hazard models in vaccinated and unvaccinated adults, adjusted for age, sex, and comorbidities. VE was also estimated for adults with diabetes, aged ≥60 years, and comparing the predominance of SARS-CoV-2 variants B.1.1.519 and B.1.617.2. RESULTS: We assessed 793,487 vaccinated and 4,792,338 unvaccinated adults between December 24, 2020 and September 27, 2021. The VE against SARS-CoV-2 infection was the highest for fully vaccinated individuals with mRNA-12732 (91.5%, 95% confidence interval [CI] 90.3-92.4) and Ad26.COV2.S (82.2%, 95% CI 81.4-82.9); for COVID-19 hospitalization, BNT162b2 (84.3%, 95% CI 83.6-84.9) and Gam-COVID-Vac (81.4% 95% CI 79.5-83.1), and for mortality, BNT162b2 (89.8%, 95% CI 89.2-90.2) and mRNA-12732 (93.5%, 95% CI 86.0-97.0). The VE decreased for all vaccines in adults aged ≥60 years, people with diabetes, and periods of Delta variant predominance. CONCLUSION: All the vaccines implemented in Mexico were effective against SARS-CoV-2 infection, COVID-19 hospitalization, and death. Mass vaccination with multiple vaccines is useful to maximize vaccination coverage.

Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial.

Background: To prevent COVID-19 progression, low-cost alternatives that are available to all patients are needed. Diverse forms of thermotherapy have been proposed to prevent progression to severe/critical COVID-19. Objective: The aim of this study is to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Methods: A multicenter, open-label, parallel-group, randomized, adaptive trial is used to evaluate the efficacy and safety of local thermotherapy to prevent disease progression in hospitalized adult patients with mild-to-moderate COVID-19. Eligible hospitalized adult patients with symptoms of COVID-19 with ≤5 days from symptom onset, meeting criteria for mild or moderate COVID-19, were randomly assigned to the intervention consisting of local thermotherapy via an electric heat pad in the thorax (target temperature range 39.5­42°C) continuously for 90 min, twice daily, for 5 days, or standard care. The main outcome was the proportion of patients who progressed to severe-to-critical COVID-19 or death. Patients were randomized in a 1:1 ratio through a centralized computer-generated sequence of minimization with a random component of 20%. Participants and medical staff were not blinded to the intervention. Results: One-hundred and five participants (thermotherapy n = 54, control n = 51) with a median age of 53 (IQR: 41­64) years were included for analysis after the early cessation of recruitment due to the closure of all temporal COVID-19 units (target sample size = 274). The primary outcome of disease progression occurred in 31.4% (16/51) of patients in the control group vs. 25.9% (14/54) of those receiving thermotherapy (risk difference = 5.5%; 95%CI: −11.8­22.7, p = 0.54). Thermotherapy was well tolerated with a median total duration of thermotherapy of 900 (IQR: 877.5­900) min. Seven (13.7%) patients in the control group and seven (12.9%) in the thermotherapy group had at least one AE (p = 0.9), none of which were causally attributed to the intervention. No statistically significant differences in serum cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-17, and IFN-γ) were observed between day 5 and baseline among groups. Conclusion: Local thermotherapy was safe and well-tolerated. A non-statistically significant lower proportion of patients who experienced disease progression was found in the thermotherapy group compared to standard care. Local thermotherapy could be further studied as a strategy to prevent disease progression in ambulatory settings.Clinical Trial registration: www.clinicaltrials.gov, identifier: NCT04363541.

Simplified acute physiology score II and Mannheim peritonitis index are associated with in-hospital mortality in patients with abdominal sepsis admitted to ICU.

OBJECTIVE: The objective of this study was to assess the association and interaction of laboratory parameters, Simplified Acute Physiology Score II (SAPSII), Modified Shock Index (MSI), and Mannheim Peritonitis Index (MPI) with in-hospital mortality. MATERIAL AND METHODS: We conducted a single-center case-control study. Adult patients with abdominal sepsis were included from May 2015 to May 2020. Baseline characteristics, laboratory parameters, SAPSII, MSI, and MPI scores at admission were collected. A principal component (PC) analysis was applied to evaluate variable interactions. In-hospital mortality risk was determined through logistic regression models. RESULTS: One hundred and twenty-seven patients were identified, 60 of which were included for analyses. Non-survivors (48.4%) had a higher frequency of hypertension, lactate and MPI, and lower BE and alactic BE levels. Eight PCs were obtained, PC1 being a linear combination of pH, AG, cAG, alactic BE, bicarbonate, and BE. MPI (OR = 9.87, 95% CI: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, 95% CI: 1.01-1.14, p = 0.01), and PC1 (OR = 2.13, 95% CI: 1.12-4.76, p = 0.04) were significantly associated with mortality in univariate analysis, while MPI (OR = 10.1, 95% CI: 3.03-40.06, p = 0.0003) and SAPSII (OR = 1.07, CI95%: 1.01-1.14, p = 0.02) remained significant after adjusting for age and sex. CONCLUSION: MPI and SAPSII were associated with mortality, although the interaction of laboratory parameters was not.

OBJETIVO: Evaluar la asociación e interacción de los parámetros de laboratorio, SAPSII, MSI y MPI con la mortalidad intrahospitalaria. MATERIALES Y MÉTODOS: Nosotros realizamos un estudio de casos y controles de pacientes adultos con sepsis abdominal desde mayo 2015 a mayo 2020. Recolectamos las características basales, parámetros de laboratorio, SAPSII, MSI y MPI al ingreso. Se aplicó un Análisis de Componentes Principales. El riesgo de mortalidad intrahospitalaria se determinó mediante modelos de regresión logística. RESULTADOS: Identificamos 127 pacientes, 60 de los cuales se incluyeron. Los no supervivientes (48,4%) tuvieron mayor frecuencia de HAS, lactato y MPI, y menores niveles de EB y EB aláctico. Se obtuvieron ocho Componentes Principales (PC), siendo PC1 una combinación lineal de pH, AG, cAG, EB aláctico, bicarbonato y EB. MPI (OR = 9.87, IC95%: 3.07-36.61, p = 0.0002), SAPSII (OR = 1.07, IC95%: 1.01-1.14, p = 0.01) y PC1 (OR = 2.13, IC95%: 1.12-4.76, p = 0.04) se asociaron significativamente con la mortalidad en el análisis univariado, mientras que MPI (OR = 10.1, IC95%: 3.03-40.06, p = 0.0003) y SAPSII (OR = 1.07, IC 95%: 1.01-1.14, p = 0.02) permanecieron significativos después del ajuste por edad y sexo. CONCLUSIONES: MPI y SAPSII se asociaron con mortalidad, aunque la interacción de los parámetros de laboratorio no lo hizo.

Anatomical and Clinical Factors Associated With Valvulopathy and Aortopathy in Mexican Patients With Bicuspid Aortic Valves.

The bicuspid aortic valve (BAV) is associated with significant aortic valve dysfunction. We aimed to study Mexican patients with BAV to assess phenotypic expressions of BAV, and associations of valvulopathy and aortopathy and their predictors. A cross-sectional, retrospective study was designed. The patients were divided according to (1) normally or minimally dysfunctional BAV, (2) predominant aortic regurgitation (AR), and (3) predominant aortic stenosis (AS). A total of 189 patients were included with a high prevalence of males (68%). The overall median age was 42 (23 to 52) years. The distribution of fused BAV phenotypes was right-left fusion (77%), right noncoronary fusion (17%) and left noncoronary fusion (6%). AS-predominant group was the oldest with a high prevalence of hypertension, type 2 diabetes mellitus (T2DM), and raphe. In multivariable analysis T2DM (odds ratio [OR] 10.5 [95% confidence interval (CI) 2.1 to 52], p <0.01) and presence of raphe (OR 2.58 [95% CI 1.02 to 6.52], p = 0.04) were independently associated with AS. The AR-predominant group was composed mostly of males with significantly fewer cardiovascular risk factors. Male gender (OR 2.84 [95%CI 121 to 6.68], p = 0.01) and aortic dilatation (OR 3.58 [95% CI 1.73 to 7.39], p <0.01) were associated with AR-predominance in multivariable analysis. Aortic dilatation was associated with age (OR 1.03 [95% CI 1.008 to 1.05], p <0.01) and AR (OR 4.31 [95% CI 2.05 to 9.06], p <0.01). Independent factors associated with the root phenotype were male gender (OR 12.4 [95% CI 1.6 to 95], p <0.01) and AR (OR 5.25 [95% CI 2.18 to 12.6], p <0.01).In conclusion, in a mestizo population, the distribution of BAV-fused phenotypes was similar to European and North American populations, the presence of raphe and T2DM were independently associated with AS-predominance, and male gender and aortic dilatation were independently associated with AR-predominance.

[Stress, anxiety, and depression in health workers during the COVID-19 pandemic]. / Estrés, ansiedad y depresión en trabajadores de salud durante la pandemia por COVID-19.

Background: Mental health is an integral part of health. Having some psychiatric condition without treatment predisposes to a poor quality of life. These alterations have been found with an incidence of up to 50% in the general population. There are very few studies in Mexico on these conditions in health workers during the COVID-19 pandemic. Objective: To determine the prevalence of stress, anxiety, and depression during the COVID-19 pandemic in health workers. Material and methods: A descriptive, cross-sectional observational study was conducted on health workers in a tertiary hospital, through the application of randomized and self-completed surveys, in search of levels of stress, anxiety, and depression during the COVID-19 pandemic. Results: 44.7% of those surveyed showed depression, 83.1% anxiety, and 66.3% stress. The main groups affected were female staff, singles, and medical residents. Those with type 2 diabetes mellitus had higher anxiety and depression. Conclusion: The prevalence of stress, anxiety, and depression in health workers is similar to that of the general population in our study. Depression was the alteration most found. The scrutiny of alterations in mental health in health workers is of the utmost importance, with greater emphasis in the context of the aforementioned pandemic.

Introducción: la salud mental es parte integral de la salud. Tener algún padecimiento psiquiátrico sin tratamiento predispone a una mala calidad de vida. Estas alteraciones se han encontrado con una prevalencia de hasta 50% en la población general. En México hay muy pocos estudios acerca de la incidencia de dichos padecimientos en los trabajadores de la salud durante la pandemia por COVID-19. Objetivo: determinar la presencia de estrés, ansiedad y depresión durante la pandemia de COVID-19 en los trabajadores de la salud de un hospital de tercer nivel. Material y métodos: se realizó un estudio observacional transversal, descriptivo en los trabajadores de la salud de un hospital de tercer nivel, mediante la aplicación de encuestas aleatorizadas y autocomplementadas, en búsqueda de grado de estrés, ansiedad y depresión, durante la pandemia por COVID-19. Resultados: el 44.7% de los encuestados presentó depresión, 83.1% ansiedad y 66.3% estrés. Los principales grupos afectados fueron el personal femenino, solteros y médicos residentes. Aquellos con diabetes mellitus tipo 2 tuvieron mayor incidencia de ansiedad y depresión. Conclusión: la presencia de estrés, ansiedad y depresión en los trabajadores de la salud es similar a la de la población general en nuestro estudio. La depresión fue la alteración más encontrada. Es de suma importancia el escrutinio de alteraciones en la salud mental en los trabajadores de la salud, con mayor énfasis en el contexto de la pandemia mencionada.