Designing an exploratory phase 2b platform trial in NASH with correlated, co-primary binary endpoints.

Non-alcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD) and a disease with high unmet medical need. Platform trials provide great benefits for sponsors and trial participants in terms of accelerating drug development programs. In this article, we describe some of the activities of the EU-PEARL consortium (EU Patient-cEntric clinicAl tRial pLatforms) regarding the use of platform trials in NASH, in particular the proposed trial design, decision rules and simulation results. For a set of assumptions, we present the results of a simulation study recently discussed with two health authorities and the learnings from these meetings from a trial design perspective. Since the proposed design uses co-primary binary endpoints, we furthermore discuss the different options and practical considerations for simulating correlated binary endpoints.

Deaths of Despair: A Scoping Review on the Social Determinants of Drug Overdose, Alcohol-Related Liver Disease and Suicide.

BACKGROUND: There is a lack of consensus on the social determinants of Deaths of Despair (DoD), i.e., an increase in mortality attributed to drug overdose, alcohol-related liver disease, and suicide in the United States (USA) during recent years. The objective of this study was to review the scientific literature on DoD with the purpose of identifying relevant social determinants and inequalities related to these mortality trends. METHODS: Scoping review focusing on the period 2015-2022 based on PubMed search. Articles were selected according to the following inclusion criteria: published between 1 January 2000 and 31 October 2021; including empirical data; analyzed DoD including the three causes defined by Case and Deaton; analyzed at least one social determinant; written in English; and studied DoD in the USA context only. Studies were excluded if they only analyzed adolescent populations. We synthesized our findings in a narrative report specifically addressing DoD by economic conditions, occupational hazards, educational level, geographical setting, and race/ethnicity. RESULTS: Seventeen studies were included. Overall, findings identify a progressive increase in deaths attributable to suicide, drug overdose, and alcohol-related liver disease in the USA in the last two decades. The literature concerning DoD and social determinants is relatively scarce and some determinants have been barely studied. However different, however, large inequalities have been identified in the manner in which the causes of death embedded in the concept of DoD affect different subpopulations, particularly African American, and Hispanic populations, but blue collar-whites are also significantly impacted. Low socioeconomic position and education levels and working in jobs with high insecurity, unemployment, and living in rural areas were identified as the most relevant social determinants of DoD. CONCLUSIONS: There is a need for further research on the structural and intermediate social determinants of DoD and social mechanisms. Intersectional and systemic approaches are needed to better understand and tackle DoD and related inequalities.

Severe Infections Due to Respiratory Viruses.

Severe viral infections may result in severe illnesses capable of causing acute respiratory failure that could progress rapidly to acute respiratory distress syndrome (ARDS), related to worse outcomes, especially in individuals with a higher risk of infection, including the elderly and those with comorbidities such as asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. In addition, in cases of severe viral pneumonia, co-infection with bacteria such as Streptococcus pneumoniae and Staphylococcus aureus is related to worse outcomes. Respiratory viruses like influenza, rhinovirus, parainfluenza, adenovirus, metapneumovirus, respiratory syncytial virus, and coronavirus have increasingly been detected. This trend has become more prevalent, especially in critically ill patients, due to the availability and implementation of molecular assays in clinical practice. Respiratory viruses have been diagnosed as a frequent cause of severe pneumonia, including cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia. In this review, we will discuss the epidemiology, diagnosis, clinical characteristics, management, and prognosis of patients with severe infections due to respiratory viruses, with a focus on influenza viruses, non-influenza viruses, and coronaviruses.

The case for planetary health prevention.

The lack of preparedness and the adoption of a reactive approach underlie many mistakes in handling the COVID-19 pandemic. We need a vision with a proactive approach to planetary health prevention, that is suited for addressing the neglected systemic determinants of health which generate disease, inequality and environmental degradation, and capable of anticipating known and unknown risks, and foreseeing possible threatening scenarios. To achieve a healthy, equitable and sustainable future, it is time to make health prevention planetary.

Health Inequalities in the Time of COVID-19: The Globally Reinforcing Need to Strengthen Health Inequalities Research Capacities.

The full impact of coronavirus disease 2019 (COVID-19) is yet to be well established; however, as the pandemic spreads, and early results emerge, unmet needs are being revealed, and pressing questions are being asked about who is most affected, how, where, and in what ways government responses might be exacerbating inequalities. A number of scholars have called for more in-depth critical research on COVID-19 and health inequalities to produce a strong empirical evidence based on these issues. There are also justifiable concerns about the scarcity of health-equity actions oriented analyses of the situation and calls for more empirical evidence on COVID-19 and health inequalities. A preliminary condition to establish this type of information is strong capacity to conduct health inequalities research. Worldwide, however, this type of capacity is limited, which, alongside other challenges, will likely hinder capacities of many countries to develop comprehensive equity-oriented COVID-19 analyses, and adequate responses to present and future crises. The current pandemic reinforces the pending need to invest in and strengthen these research capacities. These capacities must be supported by widespread recognition and concern, cognitive social capital, and greater commitment to coordinated, transparent action, and responsibility. Otherwise, we will remain inadequately prepared to respond and meet our society's unmet needs.

A Prospective Cohort of SARS-CoV-2-Infected Health Care Workers: Clinical Characteristics, Outcomes, and Follow-up Strategy.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) outbreaks, health care workers (HCWs) are at a high risk of infection. Strategies to reduce in-hospital transmission between HCWs and to safely manage infected HCWs are lacking. Our aim was to describe an active strategy for the management of COVID-19 in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected HCWs and investigate its outcomes. METHODS: A prospective cohort study of SARS-CoV-2-infected health care workers in a tertiary teaching hospital in Barcelona, Spain, was performed. An active strategy of weekly polymerase chain reaction screening of HCWs for SARS-CoV-2 was established by the Occupational Health department. Every positive HCW was admitted to the Hospital at Home Unit with daily assessment online and in-person discretionary visits. Clinical and epidemiological data were recorded. RESULTS: Of the 590 HCWs included in the cohort, 134 (22%) were asymptomatic at diagnosis, and 15% (89 patients) remained asymptomatic during follow-up. A third of positive cases were detected during routine screening. The most frequent symptoms were cough (68%), hyposmia/anosmia (49%), and fever (41%). Ten percent of the patients required specific treatment at home, while only 4% of the patients developed pneumonia. Seventeen patients required a visit to the outpatient clinic for further evaluation, and 6 of these (1%) required hospital admission. None of the HCWs included in this cohort required intensive care unit admission or died. CONCLUSIONS: Active screening for SARS-CoV-2 among HCWs for early diagnosis and stopping in-hospital transmission chains proved efficacious in our institution, particularly due to the high percentage of asymptomatic HCWs. Follow-up of HCWs in Hospital at Home units is safe and effective, with low rates of severe infection and readmission.

Pneumococcal superinfection in COVID-19 patients: A series of 5 cases.

BACKGROUND: In the context of the COVID-19 pandemic the risk of misdiagnosis of other causes of respiratory infection is likely. In this work we aim to describe the clinical characteristics, treatment and outcome of pneumococcal infection in COVID-19 patients. PATIENTS AND METHODS: Every COVID-19 patient presenting with concomitant pneumococcal pneumonia during March 2020 in a tertiary teaching Hospital In Barcelona, Spain. RESULTS: Five patients with PCR confirmed COVID19 or clinical and radiological suspicion were diagnosed of pneumococcal infection. In all cases chest X-ray were abnormal, with unilateral or bilateral infiltrates. Procalcitonin showed to be not sensitive enough to detect pneumococcal infection. Antibiotherapy was promptly started in all five cases with subsequent satisfactory evolution. CONCLUSION: International guidelines do not include the universal screening for bacterial co-infection. Radiological pattern of COVID-19 can be indistinguishable from that of pneumococcus pneumonia and frequency of co-infection is not well stablished, therefore clinicians should be aware of the possible SARS-CoV-2-pneumococcus association to avoid misdiagnosis and delay antibiotic therapy.

INTRODUCCIÓN: En el contexto de la pandemia por COVID-19 el riesgo de errores en el diagnóstico de otras causas de infección respiratoria es elevado. En este trabajo describimos las características clínicas, el tratamiento y la evolución de los pacientes con coinfección por COVID-19 y neumococo. PACIENTES Y MÉTODOS: Todos los pacientes con COVID-19 que presentaron neumonía neumocócica durante marzo 2020 en un hospital universitario de Barcelona, España. RESULTADOS: Cinco pacientes con COVID-19 confirmada por PCR o sospecha radiológica fueron diagnosticados de infección por neumococo. En todos los casos la radiografía de tórax era patológica con infiltrado unilateral o bilateral. La procalcitonina demostró no ser suficientemente sensible para detectar la infección neumocócica. La antibioterapia fue iniciada de manera precoz en los 5 casos con evolución satisfactoria. CONCLUSIONES: Las guías internacionales no incluyen el cribado universal para coinfección bacteriana. El patrón radiológico del COVID-19 puede ser indistinguible de la neumonía neumocócica, y la frecuencia de la coinfección no ha sido establecida. Los clínicos deben de ser conscientes de la posible asociación de SARS-CoV-2 y neumococo para evitar errores diagnósticos y retrasos en el tratamiento antibiótico.

Risk of Secondary Infection Waves of COVID-19 in an Insular Region: The Case of the Balearic Islands, Spain.

The Spanish government declared the lockdown on March 14th, 2020 to tackle the fast-spreading of COVID-19. As a consequence, the Balearic Islands remained almost fully isolated due to the closing of airports and ports, these isolation measures and the home-based confinement have led to a low prevalence of COVID-19 in this region. We propose a compartmental model for the spread of COVID-19 including five compartments (Susceptible, Exposed, Presymptomatic Infective, Diseased, and Recovered), and the mobility between municipalities. The model parameters are calibrated with the temporal series of confirmed cases provided by the Spanish Ministry of Health. After calibration, the proposed model captures the trend of the official confirmed cases before and after the lockdown. We show that the estimated number of cases depends strongly on the initial dates of the local outbreak onset and the number of imported cases before the lockdown. Our estimations indicate that the population has not reached the level of herd immunization necessary to prevent future outbreaks. While the low prevalence, in comparison to mainland Spain, has prevented the saturation of the health system, this low prevalence translates into low immunization rates, therefore facilitating the propagation of new outbreaks that could lead to secondary waves of COVID-19 in the region. These findings warn about scenarios regarding after-lockdown-policies and the risk of second outbreaks, emphasize the need for widespread testing, and could potentially be extrapolated to other insular and continental regions.

Skin Manifestations in COVID-19: Prevalence and Relationship with Disease Severity.

BACKGROUND: Data on the clinical patterns and histopathology of SARS-CoV-2 related skin lesions, as well as on their relationship with the severity of COVID-19 are limited. METHODS AND MATERIALS: Retrospective analysis of a prospectively collected cohort of patients with SARS-CoV-2 infection in a teaching hospital in Barcelona, Spain, from 1 April to 1 May 2020. Clinical, microbiological and therapeutic characteristics, clinicopathological patterns of skin lesions, and direct immunofluorescence and immunohistochemical findings in skin biopsies were analyzed. RESULTS: Fifty-eight out of the 2761 patients (2.1%) either consulting to the emergency room or admitted to the hospital for COVID-19 suspicion during the study period presented COVID-19 related skin lesions. Cutaneous lesions could be categorized into six patterns represented by the acronym "GROUCH": Generalized maculo-papular (20.7%), Grover's disease and other papulo-vesicular eruptions (13.8%), livedo Reticularis (6.9%), Other eruptions (22.4%), Urticarial (6.9%), and CHilblain-like (29.3%). Skin biopsies were performed in 72.4%, including direct immunofluorescence in 71.4% and immunohistochemistry in 28.6%. Patients with chilblain-like lesions exhibited a characteristic histology and were significantly younger and presented lower rates of systemic symptoms, radiological lung infiltrates and analytical abnormalities, and hospital and ICU admission compared to the rest of patients. CONCLUSION: Cutaneous lesions in patients with COVID-19 appear to be relatively rare and varied. Patients with chilblain-like lesions have a characteristic clinicopathological pattern and a less severe presentation of COVID-19.

Coronavirus disease 2019 and slums in the Global South: lessons from Medellín (Colombia).

The coronavirus disease 2019 (COVID-19) pandemic is hitting the world's most vulnerable people hardest, primarily the communities living in slums in the Global South. Lockdown, handwashing and social distancing are impossible privileges for many urban dwellers - measures which make structural inequities more visible, exacerbating racial, gender and class differences. There are many social determinants of health to explain these inequalities that trigger a high prevalence of infectious and chronic diseases. In Medellín (Colombia), it is a challenge to cope with this crisis, especially when the resources and aid provided by the government and institutions are limited. Yet, an organized social response is happening in some communes and slums, with high community participation, as a potentially effective key to control the pandemic. Once the emergency is over, communities in slums will have to face the social and economic reactivation, and effectively react to the multiple social and psychological consequences, new waves of COVID-19 or other pandemics.

Hospital at home for the management of COVID-19: preliminary experience with 63 patients.

Alternatives to conventional hospitalization are needed to increase health systems resilience in the face of COVID-19 pandemic. Herein, we describe the characteristics and outcomes of 63 patients admitted to a single HaH during the peak of COVID-19 in Barcelona. Our results suggest that HaH seems to be a safe and efficacious alternative to conventional hospitalization for accurately selected patients with COVID-19.