Understanding the Burden of Respiratory Syncytial Virus in Older Adults in Latin America: An Expert Perspective on Knowledge Gaps.

Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems.A graphical plain language summary is available with this article.

[Comparative analysis of clinical characteristics, evolution and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID Study)]. / Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (Registro ECCOVID).

INTRODUCTION: Clinical features and outcomes of SARSCoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. METHODS: Multicenter and prospective registry of patients =18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. RESULTS: A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized patients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hospitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hospitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. CONCLUSION: Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 during the second wave in Argentina were more seriously ill and had a higher mortality.

Introducción: Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos: Registro multicéntrico y prospectivo de pacientes = 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolución a 30 días. Resultados: Se incluyeron un total de 1691 pacientes (primera ola n = 809, segunda ola n = 882). Los pacientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospitalización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p < 0,001) y presentaron mayor mortalidad (11% vs. 26%, p < 0.001). Comparando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión: Comparados con los pacientes internados durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

[Human monkeypox: epidemiological and clinical characteristics of a series of cases]. / Viruela símica humana: características epidemiológicas y clínicas de una serie de casos.

INTRODUCTION: Monkeypox It is a zoonotic disease. The etiologic agent is the monkeypox virus. Since January 1, 2022, monkeypox cases have been reported to the World Health Organization (WHO) in 110 Member States across 6 WHO regions. METHODS: The present work is a descriptive-observational-retrospective cohort in the first instance, and prospective at the end, where the epidemiological characteristics, clinical presentation and complications collected by telephone call on day 28, are described 75 patients diagnosed with monkeypox, confirmed by RT-PCR (corresponding to 7% of the cases reported in Argentina). It was developed between July 12, 2022 and October 6, 2022. RESULTS: The affected population was entirely cisgender men, 70 (93.3%) identified as men who have sex with men (MSM). Fifty-one (68%) were co-infected with HIV, 50 (98%) were receiving ART. All patients presented mucocutaneous manifestations. The rash manifested with a variety of lesions: papular, vesicular, and pustular. In 26 (44.1%) the systemic symptoms presented prior to the appearance of the rash, being the increase in body temperature the most frequent. Thirty-four (45.3%) of the patients reported some complication, with proctitis being the most frequent followed by penile edema. Sequelae were observed in 40 (53.3%), the most frequent being skin scars. CONCLUSION: In this case series we were able to observe mostly mild symptoms, with anogenital lesions being the most frequent clinical presentation. The presence of sequelae, the social and emotional impact of this disease make a multidisciplinary approach necessary.

Introducción: Es una enfermedad zoonótica cuyo agente etiológico es el virus de la viruela símica. Desde el 1 de enero de 2022, se han notificado casos de viruela símica a la Organización Mundial de la Salud (OMS) en 110 Estados Miembros en las 6 regiones de la OMS. Métodos: El presente trabajo es un estudio observacional descriptivo de cohorte retrospectivo en primera instancia, y prospectivo al final, donde se describen las características epidemiológicas, la presentación clínica, y las complicaciones recabadas mediante llamado telefónico al día 28 en 75 pacientes con diagnóstico de viruela símica confirmado por RT-PCR (correspondientes al 7% de los casos notificados en Argentina). Fue desarrollado entre el 12 de julio de 2022 y el 6 de octubre de 2022. Resultados: La población afectada fue en su totalidad hombres cisgénero, 70 (93.3%) identificados como hombres que tienen sexo con hombres (HSH). Cincuenta y uno (68%) estaban coinfectados con HIV, 50 (98%) estaban recibiendo TARV. Todos los pacientes presentaron manifestaciones mucocutáneas. El exantema se manifestó con variedad de lesiones: papulares, vesiculares y pustulosas. En 26 (44.1%) los síntomas sistémicos se presentaron previos a la aparición del exantema, siendo el aumento de la temperatura corporal el más frecuente. Treinta y cuatro (45.3%) de los pacientes reportaron alguna complicación, siendo la proctitis la más frecuente seguida por edema de pene. Se observaron secuelas en 40 (53.3%), siendo la más frecuente las cicatrices cutáneas. Conclusión: En esta serie de casos pudimos observar mayormente cuadros leves, siendo las lesiones anogenitales la presentación clínica más frecuente. La presencia de secuelas, el impacto social y emocional de esta enfermedad hacen necesario un enfoque multidisciplinario.

Análisis comparativo de las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola de la pandemia (REGISTRO ECCOVID) / Comparative analysis of clinical characteristics, evolu tion and mortality of hospitalized patients with COVID-19 during the first and second wave of the pandemic (ECCOVID STUDY)

Resumen Introducción : Las características clínicas y evolutivas de los pacientes con diagnóstico de COVID-19 pueden diferir entre las distintas olas de la pandemia. El objetivo de este estudio fue comparar las características clínicas, evolución y mortalidad de pacientes hospitalizados por COVID-19 durante la primera y segunda ola en Argentina. Métodos : Registro multicéntrico y prospectivo de pacientes ≥ 18 años con diagnóstico confirmado de COVID-19 internados en 18 hospitales de Argentina durante la primera (marzo a octubre 2020) y la segunda ola (marzo a julio 2021) de la pandemia. Se compararon variables demográficas, características clínicas, y evolu ción a 30 días. Resultados : Se incluyeron un total de 1691 pacien tes (primera ola n = 809, segunda ola n = 882). Los pa cientes hospitalizados durante la segunda ola tenían mayor edad (mediana 53 años vs. 61 años, p < 0.001), comorbilidades (71% vs. 77%, p = 0.007) y requerimiento de oxígeno (21% vs. 62%, p < 0.001). Durante la hospi talización, los pacientes de la segunda ola requirieron más oxigenoterapia (49% vs. 85%, p < 0.001), asistencia mecánica respiratoria (12% vs. 22%, p <0,001) y presen taron mayor mortalidad (11% vs. 26%, p < 0.001). Compa rando únicamente a los que requirieron oxigenoterapia durante la hospitalización, la mortalidad a los 30 días fue de 20% y 30% p < 0.001 en la primera y segunda ola respectivamente. Conclusión : Comparados con los pacientes interna dos durante la primera ola, los internados durante la segunda ola de SARS-CoV-2 en Argentina presentaron mayor gravedad y mortalidad.

Abstract Introduction : Clinical features and outcomes of SARS-CoV-2 infections may change between different waves of the pandemic. The objective of this study was to compare clinical characteristics and outcomes between two cohorts of patients hospitalized for COVID-19 during the first and second waves in Argentina. Methods : Multicenter and prospective registry of patients ≥18 years old with a confirmed diagnosis of COVID-19 admitted to 18 hospitals in Argentina during the first wave (March to October 2020) and second wave (March to July 2021) of the pandemic. Demographics, clinical characteristics, and outcomes of these patients were compared. Results : A total of 1691 patients were included (first wave n = 809, second wave n = 882). Hospitalized pa tients during the second wave were older (median 53 years vs. 61 years, p < 0.001), had more comorbidities (71% vs. 77%, p=0.007) and required more supplemental oxygen at admission (21% vs 62%, p < 0.001). During hos pitalization, patients of the second wave required more supplemental oxygen (49% vs. 85%, p < 0.001), invasive ventilation (12% vs. 22%, p < 0.001) and had higher 30- day mortality (11% vs. 26%, p < 0.001). Comparing only patients who required supplemental oxygen during hos pitalization, 30-day mortality was 20% and 30% p < 0.001 for the first and second wave, respectively. Conclusion : Compared to patients admitted during the first wave, patients admitted with SARS-CoV2 dur ing the second wave in Argentina were more seriously ill and had a higher mortality.

Viruela símica humana: características epidemiológicas y clínicas de una serie de casos / Human monkeypox: epidemiological and clinical charac teristics of a series of cases

Resumen Introducción : Es una enfermedad zoonótica cuyo agente etiológico es el virus de la viruela símica. Desde el 1 de enero de 2022, se han notificado casos de viruela símica a la Organización Mundial de la Salud (OMS) en 110 Estados Miembros en las 6 regiones de la OMS. Métodos : El presente trabajo es un estudio observa cional descriptivo de cohorte retrospectivo en primera instancia, y prospectivo al final, donde se describen las características epidemiológicas, la presentación clínica, y las complicaciones recabadas mediante llamado telefó nico al día 28 en 75 pacientes con diagnóstico de viruela símica confirmado por RT-PCR (correspondientes al 7% de los casos notificados en Argentina). Fue desarrollado entre el 12 de julio de 2022 y el 6 de octubre de 2022. Resultados : La población afectada fue en su totalidad hombres cisgénero, 70 (93.3%) identificados como hom bres que tienen sexo con hombres (HSH). Cincuenta y uno (68%) estaban coinfectados con HIV, 50 (98%) esta ban recibiendo TARV. Todos los pacientes presentaron manifestaciones mucocutáneas. El exantema se mani festó con variedad de lesiones: papulares, vesiculares y pustulosas. En 26 (44.1%) los síntomas sistémicos se presentaron previos a la aparición del exantema, siendo el aumento de la temperatura corporal el más frecuente. Treinta y cuatro (45.3%) de los pacientes reportaron algu na complicación, siendo la proctitis la más frecuente se guida por edema de pene. Se observaron secuelas en 40 (53.3%), siendo la más frecuente las cicatrices cutáneas. Conclusión : En esta serie de casos pudimos observar mayormente cuadros leves, siendo las lesiones anogeni tales la presentación clínica más frecuente. La presencia de secuelas, el impacto social y emocional de esta enfer medad hacen necesario un enfoque multidisciplinario.

Abstract Introduction : Monkeypox It is a zoonotic disease. The etiologic agent is the monkeypox virus. Since January 1, 2022, monkeypox cases have been reported to the World Health Organization (WHO) in 110 Member States across 6 WHO regions. Methods : The present work is a descriptive-ob servational-retrospective cohort in the first instance, and prospective at the end, where the epidemiological characteristics, clinical presentation and complications collected by telephone call on day 28, are described 75 patients diagnosed with monkeypox, confirmed by RT-PCR (corresponding to 7% of the cases reported in Argentina). It was developed between July 12, 2022 and October 6, 2022. Results : The affected population was entirely cis gender men, 70 (93.3%) identified as men who have sex with men (MSM). Fifty-one (68%) were co-infected with HIV, 50 (98%) were receiving ART. All patients presented mucocutaneous manifestations. The rash manifested with a variety of lesions: papular, vesicular, and pustular. In 26 (44.1%) the systemic symptoms presented prior to the appearance of the rash, being the increase in body temperature the most frequent. Thirty-four (45.3%) of the patients reported some complication, with proctitis being the most frequent followed by penile edema. Se quelae were observed in 40 (53.3%), the most frequent being skin scars. Conclusion: In this case series we were able to ob serve mostly mild symptoms, with anogenital lesions being the most frequent clinical presentation. The pres ence of sequelae, the social and emotional impact of this disease make a multidisciplinary approach necessary.

Safety and effectiveness of RBD-specific polyclonal equine F(ab´)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: A retrospective cohort study.

BACKGROUND: Passive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population. METHODS: We conducted a retrospective cohort study at "Hospital de Campaña Escuela-Hogar" (HCEH) in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach. FINDINGS: Subsequent clinical records of 446 non-exposed (Controls) and 395 exposed (EPIC) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95% CI: 0.46-0.96) P = 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n = 379), OR 0.58 (95% CI 0.39 to 0.85) P = 0.005. Overall and serious adverse events were not significantly different between groups. CONCLUSIONS: In this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.

Monkeypox: Another Sexually Transmitted Infection?

Monkeypox virus is a zoonotic DNA virus (Poxviridae family), identified in 1958 in Asian monkeys (mostly Macaca fascicularis) in a polio vaccine research animal facility in Copenhagen, Denmark [...].

A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance.

OBJECTIVES: Uncomplicated urinary tract infections (uUTIs) are a common problem in female patients. Management is mainly based on empirical prescribing, but there are concerns about overtreatment and antimicrobial resistance (AMR), especially in patients with recurrent uUTIs. METHODS: A multidisciplinary panel of experts met to discuss diagnosis, treatment, prevention, guidelines, AMR, clinical trial design and the impact of COVID-19 on clinical practice. RESULTS: Symptoms remain the cornerstone of uUTI diagnosis, and urine culture is necessary only when empirical treatment fails or rapid recurrence of symptoms or AMR is suspected. Specific antimicrobials are first-line therapy (typically nitrofurantoin, fosfomycin, trimethoprim/sulfamethoxazole and pivmecillinam, dependent on availability and local resistance data). Fluoroquinolones are not first-line options for uUTIs primarily due to safety concerns but also rising resistance rates. High-quality data to support most non-antimicrobial approaches are lacking. Local AMR data specific to community-acquired uUTIs are needed, but representative information is difficult to obtain; instead, identification of risk factors for AMR can provide a basis to guide empirical antimicrobial prescribing. The COVID-19 pandemic has impacted the management of uUTIs in some countries and may have long-lasting implications for future models of care. CONCLUSION: Management of uUTIs in female patients can be improved without increasing complexity, including simplified diagnosis and empirical antimicrobial prescribing based on patient characteristics, including a review of recent antimicrobial use and past pathogen resistance profiles, drug availability and guidelines. Current data for non-antimicrobial approaches are limited. The influence of COVID-19 on telehealth could provide an opportunity to enhance patient care in the long term.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Impacto de la viremia de bajo grado en el riesgo de fallo virológico en pacientes con infección por VIH-1 / Impact of low-grade viremia on the risk of virological failure in patients with HIV-1 infection on antiretroviral therapy

Resumen Introducción: Cargas virales (CV) entre 20-200 copias/mL se consideran cargas virales de bajo grado (CVBG). Su implicancia clínica y manejo no han sido definidos. Objetivo: Evaluar el impacto de CVBG en el riesgo de desarrollo posterior de fallo virológico (FV). Pacientes y Métodos: Se incluyeron pacientes ≥ 18 años, desde enero de 2009 a diciembre de 2019, con infección por VIH-1 con CV< 20 copias/mL, por un mínimo de seis meses y/o en dos muestras consecutivas bajo tratamiento anti-retroviral . Se realizó seguimiento de las CV estrati ficándolas: CV < 20 copias/mL, CVBG (20-50 copias/mL y 51-200 copias/mL) y FV. Mediana de seguimiento 25 meses (IQR 15-31). Resultados: Fueron incluidos 1.416 pacientes con CV < 20 copias/ mL bajo TARV. De ellos, 797 permanecieron con CV< 20 copias/mL durante el seguimiento, 144 presentaron CV entre 20-50 copias/mL, 384 entre 51-200 copias/mL y 91 presentaron FV sin CVBG previa. De los 528 pacientes que tuvieron CVBG, 110 (20,1%) fallaron, riesgo 3,45 veces superior respecto a los que no tuvieron CVBG previa. El riesgo de FV fue 3,27 mayor para aquellos que tuvieron CVBG entre 51-200 copias/mL vs 20-50 copias/mL. Discusión: El estudio permite relacionar la CVBG con el FV posterior, siendo el mayor riesgo CVBG entre 51-200 copias/mL.

Abstract Background: Viral loads (VL) between 20-200 copies/mL are considered low-grade viral loads (LGVL). Its clinical implications and management have not been defined. Aim: To evaluate the impact of LGVL on the risk of subsequent development of virological failure (VF). Methods: Patients ≥ 18 years, with HIV-1 infection who had VL < 20 copies/mL for at least six months and/or in two consecutive samples under antiretroviral therapy (ART) were included, between January 1st, 2009 and December 31, 2019. Follow-up of the VLs was carried out stratifying them in VL < 20 copies/mL, LGVL (20-50 copies/mL and 51-200 copies/mL) and VF. Median follow-up 25 months (IQR 15-31). Results: 1,416 patients were included who reached VL < 20 copies/ml under ART, 797 patients remained with CV < 20 copies/mL during follow-up, 144 patients had VL between 21-50 copies/mL, 384 between 51-200 copies/mL and 91 had VF without previous LGVL. Out of 528 patients who had LGVL, 110 failed, risk 3.45 times higher than those who had no previous LGVL. Risk 3.27 times higher of VF for those who had LGVL between 51-200 copies/mL compared to 20-50 copies/mL. Discussion: The study allows to relate the LGVL with VF. This association was observed more frequently with LGVL between 51-200 copies/mL

Remdesivir: su papel en el tratamiento de la COVID-19 / Remdesivir in the treatment of COVID-19

RESUMEN En su artículo publicado en la Revista Argentina de Salud Pública (RASP), Cristian Dorati y col. concluyen que no existe evidencia de alta calidad que permita recomendar el uso de remdesivir (RDV) para el tratamiento de pacientes con enfermedad por el nuevo coronavirus (COVID-19). En la misma revista, Manuel Lago concluye que el metaanálisis y el reanálisis bayesiano apoyan la existencia de un efecto favorable del tratamiento con RDV sobre la mortalidad de pacientes con neumonía por COVID-19. Los resultados del estudio Solidaridad, conducido por la Organización Mundial de la Salud, no apoyan la sugerencia de que RDV pueda prevenir una fracción sustancial de todas las muertes. El intervalo de confianza es compatible con la prevención de una pequeña fracción de todas las muertes, pero también es compatible con la prevención de ninguna muerte. La aprobación de RDV por parte de las agencias regulatorias no se basó en los datos de mortalidad, sino en la evidencia surgida del estudio ACTT-1, que demostró menor tiempo de recuperación en los pacientes hospitalizados por COVID-19. Los sujetos aleatorizados de la rama RDV se recuperaron en 10 días versus 15 días para quienes recibieron placebo. En momentos en los cuales el sistema de salud muestra alta ocupación de camas de cuidados intensivos, acortar el tiempo de recuperación puede ser de gran importancia. A pesar de la ausencia de evidencia de la disminución de mortalidad asociada al uso de RDV, su uso en pacientes hospitalizados podría ofrecer beneficios en término de mayor disponibilidad de camas. El costo del fármaco es elevado, su disminución permitiría el tratamiento de una mayor cantidad de pacientes, con la consiguiente reducción del tiempo de hospitalización. Es necesario generar mayor evidencia en relación con los beneficios que pueda ofrecer el tratamiento con RDV para los pacientes con COVID-19.

ABSTRACT Cristian Dorati et al., in their article published in the Revista Argentina de Salud Pública (RASP) conclude that there is no high-quality evidence to recommend remdesivir (RDV) for the treatment of patients with coronavirus disease (COVID-19). In the same journal, Manuel Lago, concludes that the meta-analysis and the Bayesian reanalysis support the existence of a favorable effect of RDV treatment on the mortality of patients with COVID-19 pneumonia. The results of the SOLIDARITY trial, conducted by the World health Organization, do not support the suggestion that RDV can prevent a substantial fraction of all deaths. The confidence interval supports the prevention of a small fraction of all deaths, but it also supports the prevention of no deaths. The approval of RDV by the regulatory agencies was not based on mortality data but on the evidence from the ACTT-1 study that demonstrated shorter recovery times in patients hospitalized for COVID-19. Subjects randomized to the RDV arm recovered in 10 days versus 15 days for those who received placebo. At times when the health system shows a high occupancy of intensive care beds, shortening the recovery time can be of great importance. Despite the absence of evidence of a decrease in mortality associated with the use of RDV, its use in hospitalized patients could offer benefits in terms of greater availability of beds. The costs of the drug are high, a reduction in them would allow a greater number of patients to be treated, thus shortening the length of hospitalization. More evidence needs to be generated regarding the benefits that RDV treatment can offer.

Highlights of an Expert Advisory Board on Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AE-COPD) in Latin America.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and usually progressive lung disease that affects millions of people worldwide and is the sixth leading cause of death in the Americas. Viral and bacterial respiratory tract infections and air pollution may cause acute exacerbations of COPD (AE-COPD) ranging from mild, moderate to severe. The greatest proportion of the overall COPD burden on the health system is due to disease exacerbations. There is limited evidence regarding the etiology and burden of AE-COPD in Latin America (LATAM). Methods: To respond to this gap in evidence, an Advisory Board with regional pneumologists and infectious disease experts was convened in September 2018 in Panama City, Panama, to: 1) review the burden of AE-COPD in LATAM; 2) evaluate the etiology of AE-COPD in LATAM; and 3) assess and compare the local/regional guidelines to confirm the etiology, characterize, and manage AE-COPD. Results: The results of the meeting showed that there is a high prevalence of AE-COPD in LATAM countries, limited evidence on etiology data, and discrepancies in the case definitions and symptomology (ie, severity) classifications used in LATAM. Conclusion: The Advisory Board discussions further resulted in recommendations for future research on the impact on the epidemiology and burden of disease, on establishing standardized AE-COPD case definition guidelines, and on studying the etiology of both moderate and severe AE-COPD cases.

Remdesivir su papel en el tratamiento de la COVID-19 / Remdesivir in the treatment of COVID-19

En su artículo publicado en la Revista Argentina de Salud Pública (RASP), Cristian Dorati y col. concluyen que no existe evidencia de alta calidad que permita recomendar el uso de remdesivir (RDV) para el tratamiento de pacientes con enfermedad por el nuevo coronavirus (COVID-19). En la misma revista, Manuel Lago concluye que el metaanálisis y el reanálisis bayesiano apoyan la existencia de un efecto favorable del tratamiento con RDV sobre la mortalidad de pacientes con neumonía por COVID-19. Los resultados del estudio Solidaridad, conducido por la Organización Mundial de la Salud, no apoyan la sugerencia de que RDV pueda prevenir una fracción sustancial de todas las muertes. El intervalo de confianza es compatible con la prevención de una pequeña fracción de todas las muertes, pero también es compatible con la prevención de ninguna muerte. La aprobación de RDV por parte de las agencias regulatorias no se basó en los datos de mortalidad, sino en la evidencia surgida del estudio ACTT-1, que demostró menor tiempo de recuperación en los pacientes hospitalizados por COVID-19. Los sujetos aleatorizados de la rama RDV se recuperaron en 10 días versus 15 días para quienes recibieron placebo. En momentos en los cuales el sistema de salud muestra alta ocupación de camas de cuidados intensivos, acortar el tiempo de recuperación puede ser de gran importancia. A pesar de la ausencia de evidencia de la disminución de mortalidad asociada al uso de RDV, su uso en pacientes hospitalizados podría ofrecer beneficios en término de mayor disponibilidad de camas. El costo del fármaco es elevado, su disminución permitiría el tratamiento de una mayor cantidad de pacientes, con la consiguiente reducción del tiempo de hospitalización. Es necesario generar mayor evidencia en relación con los beneficios que pueda ofrecer el tratamiento con RDV para los pacientes con COVID-19

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults: A Consensus Statement Regarding Initial Strategies.

BACKGROUND: Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. RESEARCH QUESTION: There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. STUDY DESIGN AND METHODS: This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. RESULTS: The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. INTERPRETATION: This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia.

Consenso Argentino intersociedades de Infección Urinaria 2018-2019 - Parte I / Consenso Argentino Intersociedades de Infección Urinaria 2018-2019 - Parte I

La Sociedad Argentina de Infectología y otras sociedades científicas han actualizado estas recomendaciones utilizando, además de información internacional, la de un estudio multicéntrico prospectivo sobre infecciones del tracto urinario del adulto realizado en Argentina durante 2016-2017. La bacteriuria asintomática debe ser tratada solo en embarazadas, a quienes también se las debe investigar sistemáticamente; los antibióticos de elección son nitrofurantoína, amoxicilina, amoxicilina-clavulánico, cefalexina y trimetoprima-sulfametoxazol. Ante procedimientos que impliquen lesión con sangrado del tracto urinario se recomienda solicitar urocultivo para pesquisar bacteriuria asintomática, y, si resultara positivo, administrar antimicrobianos según sensibilidad desde inmediatamente antes hasta 24 horas luego de la intervención. En mujeres, la cistitis puede ser tratada con nitrofurantoina, cefalexina, o fosfomicina y no se recomienda usar trimetoprima-sulfametoxazol o fluoroquinolonas; en pielonefritis puede emplearse ciprofloxacina, cefixima o cefalexina si el tratamiento es ambulatorio o ceftriaxona, cefazolina o amikacina si es hospitalario. En los hombres, las infecciones del tracto urinario se consideran siempre complicadas. Se recomienda tratamiento con nitrofurantoina o cefalexina por 7 días, o bien monodosis con fosfomicina. Para la pielonefritis en hombres se sugiere ciprofloxacina, ceftriaxona o cefixima si el tratamiento es ambulatorio y ceftriaxona o amikacina si es hospitalario. Se sugiere tratar las prostatitis bacterianas agudas con ceftriaxona o gentamicina. En cuanto a las prostatitis bacterianas crónicas, si bien su tratamiento de elección hasta hace poco fueron las fluoroquinolonas, la creciente resistencia y ciertas dudas sobre la seguridad de estas drogas obligan a considerar el uso de alternativas como fosfomicina.

The Argentine Society of Infectious Diseases and other scientific societies have updated these recommendations based on data on urinary tract infections in adults obtained from a prospective multicenter study conducted in Argentina during 2016-2017. Asymptomatic bacteriuria should be treated only in pregnant women, who should also be systematically investigated; the antibiotics of choice are nitrofurantoin, amoxicillin, clavulanic/amoxicillin, cephalexin and trimethoprim-sulfamethoxazole. In procedures involving injury to the urinary tract with bleeding, it is recommended to request urine culture and, in the presence of bacteriuria, antimicrobial treatment according to sensitivity should be prescribed from immediately before up to 24 hours after the intervention. In women, cystitis can be treated with nitrofurantoin, cephalexin or fosfomycin, while trimethoprim-sulfamethoxazole and fluoroquinolones are not recommended; pyelonephritis can be treated with ciprofloxacin, cefixime or cephalexin in ambulatory women or ceftriaxone, cefazolin or amikacin in those who are hospitalized. In men, urinary tract infections are always considered complicated; nitrofurantoin or cephalexin are recommended for 7 days, alternatively fosfomycin should be given in a single dose. In men, ciprofloxacin, ceftriaxone or cefixime are suggested for pyelonephritis on ambulatory treatment whereas ceftriaxone or amikacin are recommended for hospitalized patients. Acute bacterial prostatitis can be treated with ceftriaxone or gentamicin. Fluoroquinolones were the choice treatment for chronic bacterial prostatitis until recently; they are no longer recommended due to the increasing resistance and recent concerns regarding the safety of these drugs; alternative antibiotics such as fosfomycin are to be considered.