SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Prognostic stratification and healthcare approach in patients with multiple pathologies

[ES] Los pacientes pluripatológicos constituyen una población prevalente y homogénea, caracterizada por su complejidad clínica, vulnerabilidad, consumo de recursos y mortalidad que requiere una asistencia integral y coordinada. Establecer un pronóstico certero en esta población resulta de utilidad para la toma de decisiones clínicas por parte de los profesionales, la planificación de las preferencias de pacientes y familiares, y el diseño de estrategias en el ámbito de la gestión sanitaria. También es importante para la investigación clínica, al facilitar la posible incorporación de estos pacientes a ensayos clínicos y otros estudios de intervención. Los índices PROFUND y PROFUNCTION son 2 instrumentos pronósticos que predicen de manera fidedigna el riesgo de fallecer o de sufrir un deterioro funcional, respectivamente. Para el abordaje asistencial de los pacientes pluripatológicos se propugna la construcción y ejecución de un plan de acción personalizado, consensuado y adaptado a la realidad del paciente. Este tendrá en cuenta el pronóstico, la evidencia y viabilidad de las intervenciones, así como la sinergia de las metas y estrategias del equipo sanitario con los valores y las preferencias de las personas para conseguir un modelo de salud centrado en apoyar la capacidad de las mismas para gestionar sus enfermedades. En este plan los principales ámbitos de intervención son: la promoción y prevención de la salud, la activación y autogestión del paciente y el cuidador, la red de apoyo social, la optimización farmacoterapéutica, la rehabilitación y medidas de preservación funcional y cognitiva, y la planificación anticipada de decisiones.[EN] Polypathological patients constitute a prevalent, fairly homogeneous population, which is characterised by high clinical complexity, substantial vulnerability and significant resource consumption, in addition to high mortality and the need for comprehensive, coordinated care. It is particularly important to establish a reliable prognosis in these patients. It is also extremely useful for professionals involved in the decision-making process for patients and their families in vital planning and their preferences, for strategic health planning in management fields, and for clinical research, by facilitating their incorporation into clinical trials and other intervention studies. Two prognostic instruments stand out in terms of suitability for polypathological patients: PROFUND and PROFUNCTION. The former faithfully stratifies the risk of dying at 12 months and four years and the latter, the risk of suffering a significant functional deterioration at 12 months. In terms of the healthcare approach in patients with multiple pathologies, creating and executing a consensual, personalised action plan that is adapted to the patient's reality is encouraged. The plan will consider the prognosis, and the evidence and viability of interventions; its ultimate aim will be to ensure the synergy and alignment of the health team's goals and strategies with peoples’ values and preferences, in order to achieve a more proactive health model focused on supporting patients in their ability to manage their illnesses. In the personalised action plan, the main areas of intervention are: health promotion and prevention; patient and caregiver activation and self-management; activation of a social support network and social support; optimisation of pharmacotherapy; rehabilitation, functional and cognitive preservation measures; and anticipated decision planning

Adaptation of the Palliative Prognostic Index in patients with advanced medical conditions

Los autores en representación de los investigadores del proyecto PALIAR.[Objetivo] Analizar el rendimiento del Palliative Prognostic Index (PPI) en los pacientes con enfermedades médicas en estadio avanzado, y recalibrarlo para adaptarlo al perfil de estos pacientes. [Métodos] Estudio prospectivo observacional multicéntrico. Se incluyeron pacientes con una o más enfermedades médicas avanzadas. Se analizó la calibración (bondad de ajuste de Hosmer-Lemeshow) y el poder discriminativo (curva ROC y área bajo la curva [AUC]) del PPI en la predicción de la mortalidad a los 180 días. La recalibración se llevó a cabo analizando las puntuaciones en el PPI de cada cuartil ascendente de probabilidad de fallecer. Se comparó la precisión del PPI con la obtenida con el índice de Charlson. [Resultados] La mortalidad global de los 1.788 pacientes fue del 37,5%. La calibración en la predicción de mortalidad fue buena (bondad de ajuste con p = 0,21), oscilando la probabilidad pronosticada entre 0-0,25 en el primer cuartil de riesgo, y 0,48-0,8 en el último cuartil. El poder discriminativo fue aceptable (AUC = 0,69; p < 0,0001). En los grupos recalibrados, la mortalidad de los pacientes con 0/1-2/2,5-9,5 ≥ 10 puntos fue del 13, 23, 39 y 68%, respectivamente. La sensibilidad y el valor predictivo negativo del punto de corte de la escala por encima de 0 fueron 96 y 87%, respectivamente; la especificidad y el valor predictivo positivo del punto de corte de la escala por encima de 9,5 fueron del 95 y 68%. La calibración del índice de Charslon fue buena (p = 0,2), y el poder discriminativo subóptimo (AUC = 0,52; p = 0,06). [Conclusiones] El PPI en los pacientes con enfermedades médicas en estadio avanzado puede ser de utilidad para el pronóstico de supervivencia a 6 meses.[Objective] To analyze the accuracy of the Palliative Prognostic Index (PPI) in patients with advanced medical diseases and to recalibrate it in order to adapt it to the profile of these patients. [Methods] Multicenter, prospective, observational study that included patients with one or more advanced medical diseases. Calibration (Hosmer-Lemeshow goodness of fit) and discriminative power (ROC and area under the curve [AUC]) of PPI were analyzed in the prediction of mortality at 180 days. Recalibration was carried out by analyzing the scores on the PPI of each quartile upward of dying probability. Accuracy of PPI was compared with that obtained for the Charlson index. [Results] Overall mortality of the 1.788 patients was 37.5%. Calibration in the prediction of mortality was good (goodness of fit with P=.21), the prognostic probabilities ranging from 0-0,25 in the first quartile of risk and from 0,48-0,8 in the last quartile. Discriminative power was acceptable (AUC=69; P=.0001). In recalibrated groups, mortality of patients with 0/1-2/2.5-9.5/≥10 points was 13, 23, 39 and 68%, respectively. Sensitivity (S) and negative predicative value (NPF) of the cutoff point above 0 points were 96 and 87%, respectively; while specificity (sp) and positive predictive value (PPV) of the cutoff point above 9.5 points were 95 and 68%. Calibration of the Charlson index was good (P=.2), and its discriminative power (AUC=.52; P=.06) was suboptimal. [Conclusions] PPI can be a useful tool in predicting 6-month survival of patients with advanced medical conditions.Peer Reviewe