Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

The association between the degree of fever as measured in the emergency department and clinical outcomes of hospitalized adult patients.

BACKGROUND: Fever is a physiologic response to a wide range of pathologies and one of the most common complaints and clinical signs in the emergency medicine department (ED). The association between fever magnitude and clinical outcomes has been evaluated in specific populations with inconsistent results. OBJECTIVES: In this study we aimed to investigate the association between the degree of fever in the ED and clinical outcomes of hospitalized febrile adult patients. METHODS: This was a retrospective single-center cohort study of all the patients with maximal body temperature (BT) ≥ 38.0 °C, as recorded during the ED evaluation, who were hospitalized between January 2015 and December 2020. Patients with heatstroke were excluded. The primary outcome was 30-day all-cause mortality and secondary outcomes were intensive care unit (ICU) admission and development of acute kidney injury (AKI). RESULTS: Fever was recorded among 8.1% of patients evaluated in the ED. Elevated BT was associated with increased risk of hospital admission (70.3% vs. 49.4%, p < 0.001), 30-day mortality (12.3% vs. 2.6%, p < 0.001), ICU admission (5.7% vs. 2.8%, p < 0.001), and AKI 11.7% vs. 3.8%, p < 0.001). After exclusion of nine patients with heatstroke, 21,252 hospitalized febrile patients were included in the final analysis. BT > 39.7 °C was progressively associated with increased mortality (OR 1.64-2.22, 95% CI 1.16-2.81, p < 0.005) as compared to BT 38.0-38.1 °C. More AKI events were observed in patients with BT > 39.5 °C (OR 1.48-2.91, 95% CI 1.11-3.66, p < 0.007). Temperature between 39.2 and 39.5 °C was associated with lower mortality (OR 0.62-0.71, 95% CI 0.51-0.87, p < 0.001). In a multiple logistic regression analysis BT > 39.9 °C was independently associated with increased mortality and AKI. BT > 39.7 °C was progressively associated with an increased risk of ICU admission. CONCLUSION: Among febrile patients admitted to the hospital, BT > 39.5 °C was associated with adverse clinical course, as compared to patients with lower-grade fever (38.0-38.1 °C). These patients should be flagged on arrival to the ED and likely warrant more aggressive evaluation and treatment.

SARS-CoV-2 RNAaemia in children: An Iranian referral hospital-based study.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is generally detected in nasopharyngeal swabs, viral RNA can be found in other samples including blood. Recently, associations between SARS-CoV-2 RNAaemia and disease severity and mortality have been reported in adults, while no reports are available in pediatric patients with coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the mortality, severity, clinical, and laboratory findings of SARS-CoV-2 RNA detection in blood in 96 pediatric patients with confirmed COVID-19. Among all patients, 6 (6%) had SARS-CoV-2 RNAaemia. Out of the six patients with SARS-CoV-2 RNAaemia, four (67%) had a severe form of the disease, and two out of the 6 patients with SARS-CoV-2 RNAaemia passed away (33%). Our results show that the symptoms more commonly found in the cases of COVID-19 in the study (fever, cough, tachypnea, and vomiting), were found at a higher percentage in the patients with SARS-CoV-2 RNAaemia. Creatine phosphokinase and magnesium tests showed significant differences between the positive and negative SARS-CoV-2 RNAaemia groups. Among all laboratory tests, magnesium and creatine phosphokinase could better predict SARS-CoV-2 RNAemia with area under the curve  levels of 0.808 and 0.748, respectively. In conclusion, 67% of individuals with SARS-CoV-2 RNAaemia showed a severe COVID-19 and one-third of the patients with SARS-CoV-2 RNAaemia passed away. Our findings suggest that magnesium and creatine phosphokinase might be considered as markers to estimate the SARS-CoV-2 RNAaemia.

Neurological features and outcome in COVID-19: dementia can predict severe disease.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients.

PURPOSE: While fever may be a presenting symptom of COVID-19, fever at hospital admission has not been identified as a predictor of mortality. However, hyperthermia during critical illness among ventilated COVID-19 patients in the ICU has not yet been studied. We sought to determine mortality predictors among ventilated COVID-19 ICU patients and we hypothesized that fever in the ICU is predictive of mortality. MATERIALS AND METHODS: We conducted a retrospective cohort study of 103 ventilated COVID-19 patients admitted to the ICU between March 14 and May 27, 2020. Final follow-up was June 5, 2020. Patients discharged from the ICU or who died were included. Patients still admitted to the ICU at final follow-up were excluded. RESULTS: 103 patients were included, 40 survived and 63(61.1%) died. Deceased patients were older {66 years[IQR18] vs 62.5[IQR10], (p = 0.0237)}, more often male {48(68%) vs 22(55%), (p = 0.0247)}, had lower initial oxygen saturation {86.0%[IQR18] vs 91.5%[IQR11.5], (p = 0.0060)}, and had lower pH nadir than survivors {7.10[IQR0.2] vs 7.30[IQR0.2] (p < 0.0001)}. Patients had higher peak temperatures during ICU stay as compared to hospital presentation {103.3°F[IQR1.7] vs 100.0°F[IQR3.5], (p < 0.0001)}. Deceased patients had higher peak ICU temperatures than survivors {103.6°F[IQR2.0] vs 102.9°F[IQR1.4], (p = 0.0008)}. Increasing peak temperatures were linearly associated with mortality. Febrile patients who underwent targeted temperature management to achieve normothermia did not have different outcomes than those not actively cooled. Multivariable analysis revealed 60% and 75% higher risk of mortality with peak temperature greater than 103°F and 104°F respectively; it also confirmed hyperthermia, age, male sex, and acidosis to be predictors of mortality. CONCLUSIONS: This is one of the first studies to identify ICU hyperthermia as predictive of mortality in ventilated COVID-19 patients. Additional predictors included male sex, age, and acidosis. With COVID-19 cases increasing, identification of ICU mortality predictors is crucial to improve risk stratification, resource management, and patient outcomes.

Hyperpyrexia in patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health emergency, in which its effective treatment and prevention remain obscured. Hyperpyrexia is an elevation of body temperature above 106.7°F (41.5°C) due to an abnormally increased hypothalamic-thermoregulatory set. The pathophysiology, impact, and outcomes of hyperpyrexia in patients with COVID-19 have not yet been studied. Herein, we present clinical features and outcomes of six patients with COVID-19 who had developed hyperpyrexia during hospitalization. All patients expired shortly after the onset of hyperpyrexia. Hyperpyrexia seems to adversely impact the outcomes and mortality in patients with COVID-19. The underlying mechanisms of developing hyperpyrexia in COVID-19 are mysterious. We propose it may be caused by SARS-CoV-2-related brain injury, exuberant immune response, and thrombus formation. More research is needed to verify our results. Understanding the association between hyperpyrexia and SARS-CoV-2 will help to elucidate the COVID-19 pathogenesis, which is mandatory for developing effective treatment strategies.

Antibiotic modification versus withhold in febrile patients without evidence of bacterial infection, unresponsive to initial empiric regimen: a multicentre retrospective study conducted in Israel.

Prescribing antibiotics for febrile patients without proof of bacterial infection contributes to antimicrobial resistance. Lack of clinical response in these patients often leads to antibiotic escalation, although data supporting this strategy are scarce. This study compared outcomes of modifying, withholding, or continuing the same antibiotic regimen for such patients. Febrile or hypothermic stable patients with suspected infection, unresponsive to empiric antibiotic treatment, admitted to one of 15 internal medicine departments in three hospitals during a 5-year study period, were included. Patients with a definitive clinical or microbiological bacterial infection, malignancy, immunodeficiency, altered mental status, or need for mechanical ventilation were excluded. Participants were divided into groups based on treatment strategy determined 72 h after antibiotic initiation: antibiotic modified, withheld or continued. Outcomes measured included in-hospital and 30-day post-discharge-mortality rates, length of hospital stay (LOS) and days of antimicrobial therapy (DOT). A total of 486 patients met the inclusion criteria: 124 in the Antibiotic modified group, 67 in the Antibiotic withheld group and 295 in the Initial antibiotic continued group. Patient characteristics were similar among groups with no differences in mortality rates in-hospital (23% vs. 25% vs. 20%, p = 0.58) and within 30 days after discharge (5% vs. 3% vs. 4%, p = 0.83). Changing antibiotics led to longer LOS (9.0 ± 6.8 vs. 6.2 ± 5.6 days, p = 0.003) and more DOT (8.6 ± 6.0 vs. 3.2 ± 1.0 days, p < 0.001) compared to withholding treatment. Withholding as compared to modifying antibiotics, in febrile patients with no clear evidence of bacterial infection, is a safe strategy associated with decreased LOS and DOT.

Prognostic value of serum amyloid A in patients with COVID-19.

OBJECTIVE: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). METHODS: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. RESULTS: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = - 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were - 5.569, - 6.967, and - 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. CONCLUSION: SAA can be used as a predictor of the prognosis in patients with COVID-19.

Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian, China.

PURPOSE: We aimed to report the clinical characteristics of 194 cases coronavirus disease-19 (COVID-19) in Huanggang, Hubei and Taian, Shandong. METHODS: We retrospectively investigated the clinical, laboratory characteristics and CT imaging of confirmed cases of COVID-19 from January 22 to February 28, 2020 in Huanggang Central Hospital and The Second Affiliated Hospital of Shandong First Medical University. Real time PCR was used to detect the new coronavirus in respiratory samples. Immunohistochemical staining was used to detect the expressions of ACE2 in tissues. RESULTS: Among the 194 patients infected with COVID-19, 108 patients were male, with a median age of 48.3 years. The average preclinical period was 7.44 day. Except for 37 severe or critically ill patients, the rest of the 157 patients exhibited mild or moderate symptoms. 190 (97.94%) patients were confirmed during the three times nucleic acid test. The main clinical symptom of the patients were fever, sore throat and cough, which accounted for 146 cases (75.26%), 98 (50.52%) and 86 cases (44.33%), respectively. 30 patients (15.46%) showed liver dysfunction. Imaging examination showed that 141 patients (72.68%) showed abnormal density shadow, while 53 cases (27.32%) had no obvious abnormality in the parenchyma of both lungs. Up to now, 109 cases have been discharged from the hospital, and 9 patients died. The ACE2 expression levels were up-regulated in patients of severe type and critically ill type. CONCLUSION: Clinical symptoms, laboratory tests and CT imaging should be combined for comprehensive analysis to diagnose COVID-19. ACE2 may be the receptor of COVID-19.

Significance of body temperature in elderly patients with sepsis.

BACKGROUND: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. METHODS: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Infection at diagnosis-a unique challenge in acute myeloid leukemia treatment in developing world.

PURPOSE: A large number of AML patients present with infection at the time of initial presentation in Indian settings. There is lack of published data on the proportion of patients with infection at initial presentation and its impact on induction mortality. METHODS: A retrospective audit of patients with newly diagnosed AML more than 14 years of age, who underwent standard induction chemotherapy between the periods of January 2011 to December 2018, was done. Infection at presentation if any was documented. Induction mortality was defined as death happening within 28 days of starting induction chemotherapy. RESULTS: Among a total of 315 cases of AML, 96 (30%) patients underwent induction chemotherapy with 7 + 3 regimen. Documented infection at baseline was present in 30 (31%) of patients. Another 10 patients had fever at the time of presentation but without any documented infection focus. Fifteen patients died within 4 weeks of induction amounting to induction mortality of 15.6%. Induction mortality was 28% among patients with infection at baseline compared with 7% without baseline infections (P = 0.01). CONCLUSION: Around 40% of patients had fever at the time of presentation, and 31% had documented infections. Baseline infections led to increase in induction mortality. We would like to propose that infection at baseline is to be considered as one of the potential variables in the predictive scoring system for induction mortality in developing countries.

Association Between Postoperative Body Temperature and All-Cause Mortality After Off-Pump Coronary Artery Bypass Graft Surgery: A Retrospective Observational Study.

BACKGROUND: Inadvertent perioperative hypothermia is common in patients undergoing off-pump coronary artery bypass grafting (OPCAB). We investigated the association between early postoperative body temperature and all-cause mortality in patients undergoing OPCAB. METHODS: We reviewed the electronic medical records of 1714 patients who underwent OPCAB (median duration of follow-up, 47 months). Patients were divided into 4 groups based on body temperature at the time of intensive care unit admission after surgery (moderate-to-severe hypothermia, <35.5°C; mild hypothermia, 35.5°C-36.5°C; normothermia, 36.5°C-37.5°C; and hyperthermia, ≥37.5°C). Cox proportional hazards models were used to assess the association between body temperature and all-cause mortality. The association between early postoperative changes in body temperature and all-cause mortality was also assessed by dividing the patients into 4 categories according to the body temperature measured at postoperative intensive care unit admission and the average body temperature during the first 3 postoperative days. RESULTS: Compared to the normothermia group, the adjusted hazard ratios of all-cause mortality were 2.030 (95% confidence interval, 1.407-2.930) in the moderate-to-severe hypothermia group and 1.445 (95% confidence interval, 1.113-1.874) in the mild hypothermia group. Patients who were hypothermic at postoperative intensive care unit admission but attained normothermia thereafter were at a lower risk of all-cause mortality compared to patients who did not regain normothermia (adjusted hazard ratio, 0.631; 95% confidence interval, 0.453-0.878), while they were still at a higher risk of all-cause mortality than those who were consistently normothermic (adjusted hazard ratio, 1.435; 95% confidence interval, 1.090-1.890). CONCLUSIONS: Even mild early postoperative hypothermia was associated with all-cause mortality after OPCAB. Patients who regained normothermia postoperatively were at lower risk of all-cause mortality compared to those who did not.

Postimplantation Syndrome Is Not Associated with Myocardial Injury after Noncardiac Surgery after Endovascular Aneurysm Repair.

BACKGROUND: Postimplantation syndrome (PIS) is the clinical and biochemical expression of an inflammatory response following endovascular aneurysm repair (EVAR), with a reported incidence ranging from 2% to 100%. Although generally benign, some studies report an association between PIS and postoperative major adverse cardiovascular events (MACEs). Nonetheless, the role of PIS in postoperative myocardial injury after noncardiac surgery (MINS) is unknown. This work aims to evaluate the relationship between PIS and MINS in a subset of EVAR patients, as well as assess the impact of PIS in all-cause mortality. METHODS: All patients undergoing elective standard EVAR between January 2008 and June 2017, and with at least one measurement of contemporary (cTnI) or high sensitivity troponin I (hSTnI) in the first 48h after surgery, were retrospectively analyzed. PIS was defined as the presence of fever and leukocytosis in the postoperative period in the absence of infectious complications. MINS was defined as the value exceeding the 99th percentile of a normal reference population with a coefficient of variation <10%, which was >0.032 ng/mL for cTnI and 0.0114 (female) and 0.027 ng/mL (male) for hSTnI. Patients' demographics, comorbidities, medication, access, and anesthesia were also evaluated. RESULTS: One hundred thirty-three consecutive patients were included (95.5% male; mean age 75.66 ± 7.13 years). Mean follow-up was 46.35 months. Survival rate was 86.5%, 80.5%, and 57.6% at 1, 3, and 5 years of follow-up, with 2 fatalities at 30 days of follow-up. The prevalence of PIS was 11.4%. MACE occurred in 2.3% of the patients, while MINS was reported in 16.5% of the patients. No association was found between PIS and patients' gender, comorbidities, type of anesthesia, or transfusional support. The type of graft used significantly affected the prevalence of PIS, with all cases reported when polyester grafts were used (P = 0.031). MACE occurred in 2.3% of the patients, while MINS was reported in 16.5% of the patients. PIS was found to be significantly associated with postoperative MACE (P = 0.001), but not MINS. Survival analysis revealed no differences between patients with or without PIS regarding 30-day mortality as well as long-term all-cause mortality. American Society of Anesthesiologists score (hazard ratio [HR] 2.157, 95% confidence interval [CI] 1.07-4.33, P = 0.031) and heart failure (HR 2.284, 95% CI 1.25-4.18, P = 0.008) were found to be independently associated with increased long-term all-cause mortality in this cohort of patients. CONCLUSIONS: PIS is a common complication after EVAR, occurring in 11.4% of the patients from this cohort. Graft type seems to significantly affect the risk of PIS, since all reported cases occurred when polyester grafts were used. PIS did not influence 30-day or long-term survival and was found to be significantly associated with postoperative MACE but not MINS, suggesting the involvement of different pathophysiological mechanisms.

Admission Body Temperature in Critically Ill Patients as an Independent Risk Predictor for Overall Outcome.

INTRODUCTION: Body temperature (BT) abnormalities are frequently observed in critically ill patients. We aimed to assess admission BT in a heterogeneous critically ill patient population admitted to an intensive care unit (ICU) as a prognostic parameter for intra-ICU and long-term mortality. METHODS: A total of 6,514 medical patients (64 ± 15 years) admitted to a German ICU between 2004 and 2009 were included. A follow-up of patients was performed retrospectively. The association of admission BT with both intra-ICU and long-term mortality was investigated by logistic regression. RESULTS: Patients with hypothermia (<36°C BT) were clinically worse and had more pronounced signs of multi-organ failure. Admission BT was associated with adverse overall outcome, with a 2-fold increase for hyperthermia (mortality 12%; odds ratio [OR] 1.80, 95% confidence interval [CI] 1.43-2.26; p < 0.001), and a 4-fold increase for the risk of hypothermia (mortality 24%; OR 4.05, 95% CI 3.38-4.85; p < 0.001) with respect to intra-ICU and long-term mortality. Moreover, hypothermia was even more harmful than hyperthermia, and both were strongly associated with intra-ICU mortality, especially in patients admitted with acute coronary syndrome (hypothermia: hazard ratio 6.12, 95% CI 4.12-9.11; p < 0.001; hyperthermia: OR 2.70, 95% CI 1.52-4.79; p< 0.001). CONCLUSION: Admission BT is an independent risk predictor for both overall intra-ICU and long-term mortality in critically ill patients admitted to an ICU. Therefore, BT at admission might not only serve as a parameter for individual risk stratification but can also influence individual therapeutic decision-making.

Shock and Early Death in Hematologic Patients with Febrile Neutropenia.

Empirical antibiotic therapy with a beta-lactam is the standard of care in febrile neutropenia (FN) and is given to prevent early death. The addition of vancomycin is recommended in certain circumstances, but the quality of evidence is low, reflecting the lack of clinical data. In order to characterize the epidemiology of early death and shock in FN, we reviewed all episodes of FN from 2003 to 2017 at University Hospital, Federal University of Rio de Janeiro, and looked at factors associated with shock at first fever and early death (within 3 days from first fever) by univariate and multivariate analyses. Among 1,305 episodes of FN, shock occurred in 42 episodes (3.2%) and early death in 15 (1.1%). Predictors of shock were bacteremia due to Escherichia coli (odds ratio [OR], 8.47; 95% confidence interval [95% CI], 4.08 to 17.55; P < 0.001), Enterobacter sp. (OR, 7.53; 95% CI, 1.60 to 35.33; P = 0.01), and Acinetobacter sp. (OR, 6.95; 95% CI, 1.49 to 32.36; P = 0.01). Factors associated with early death were non-Hodgkin's lymphoma (OR, 3.57; 95% CI, 1.18 to 10.73; P = 0.02), pneumonia (OR, 21.36; 95% CI, 5.72 to 79.72; P < 0.001), shock (OR, 11.64: 95% CI, 2.77 to 48.86; P = 0.01), and bacteremia due to Klebsiella pneumoniae (OR, 5.91; 95% CI, 1.11 to 31.47; P = 0.03). Adequate empirical antibiotic therapy was protective (OR, 0.23; 95% CI, 0.07 to 0.81; P = 0.02). Shock or early death was not associated with Gram-positive bacteremia; catheter-related, skin, or soft tissue infection; or inadequate Gram-positive coverage. These data challenge guideline recommendations for the empirical use of vancomycin at first fever in neutropenic patients.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections.

OBJECTIVE: To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis). STUDY DESIGN: Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt. RESULTS: Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths. CONCLUSIONS: Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI.

The outcomes of childhood convulsive status epilepticus.

BACKGROUND: Few studies focus specifically on childhood convulsive status epilepticus (CSE). Geographical differences and study design may influence research findings. A comprehensive understanding of the outcomes of childhood CSE needs to bear these factors in mind when examining the published literature. A systematic review of the outcome of childhood CSE was carried out more than a decade ago. Since then, there have been major prospective studies (in the United Kingdom, the United States of America, and in sub-Saharan Africa (SSA)) focused on childhood CSE. METHODS: Six major prospective studies are described, and their results combined through a narrative synthesis with findings of the earlier systematic review. The following CSE outcomes are described: (1) recurrence; (2) short-term mortality; (3) subsequent epilepsy; (4) neurological, cognitive, and behavioral impairments outside of epilepsy; (5) long-term mortality; (6) association with hippocampal injury and mesial temporal sclerosis (MTS); and (7) white matter changes. RESULTS: One-year recurrence after the first-ever CSE, whether its prolonged febrile seizures (PFS) or non-PFS, is 16% (95% confidence interval [CI]: 10-24). Twenty percent will have a recurrence within 4 years. Case fatality during hospitalization in high income countries is 2.7-5.2%, and 15% in SSA. The cumulative incidence of subsequent epilepsy nine years post-CSE is 25% (95% CI: 16-36). Neurological, cognitive, and behavioral impairments outside of epilepsy are detectable within 6 weeks of CSE. This persists at one year, and by 9 years follow-up, at least at third of subjects will be affected. Long-term mortality ranges from 5 to 17%, with the true estimate at 9 years follow-up to be 8% with standardized mortality ratio of 46. Mesial temporal sclerosis is uncommon, and decreased hippocampal volume is seen in both PFS and non-PFS. Duration is not but etiology/CSE type is, associated with outcome. CONCLUSION: Childhood CSE is associated with substantial morbidity and mortality. Etiology but not duration is the main determinant. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

Mortality due to scrub typhus - report of five cases.

Scrub typhus is largely ignored in India particularly during outbreaks of viral fever. The disease course is often complicated leading to fatalities in the absence of treatment. However, if diagnosed early and a specific treatment is initiated, the cure rate is high. We report here five cases of scrub typhus to highlight the fact that high clinical suspicion for such a deadly disease is an absolute necessity.

Spatiotemporal Patterns and Diffusion of the 1918 Influenza Pandemic in British India.

The factors that drive spatial heterogeneity and diffusion of pandemic influenza remain debated. We characterized the spatiotemporal mortality patterns of the 1918 influenza pandemic in British India and studied the role of demographic factors, environmental variables, and mobility processes on the observed patterns of spread. Fever-related and all-cause excess mortality data across 206 districts in India from January 1916 to December 1920 were analyzed while controlling for variation in seasonality particular to India. Aspects of the 1918 autumn wave in India matched signature features of influenza pandemics, with high disease burden among young adults, (moderate) spatial heterogeneity in burden, and highly synchronized outbreaks across the country deviating from annual seasonality. Importantly, we found population density and rainfall explained the spatial variation in excess mortality, and long-distance travel via railroad was predictive of the observed spatial diffusion of disease. A spatiotemporal analysis of mortality patterns during the 1918 influenza pandemic in India was integrated in this study with data on underlying factors and processes to reveal transmission mechanisms in a large, intensely connected setting with significant climatic variability. The characterization of such heterogeneity during historical pandemics is crucial to prepare for future pandemics.

Lactate clearance as a prognostic marker of mortality in severely ill febrile children in East Africa.

BACKGROUND: Hyperlactataemia (HL) is a biomarker of disease severity that predicts mortality in patients with sepsis and malaria. Lactate clearance (LC) during resuscitation has been shown to be a prognostic factor of survival in critically ill adults, but little data exist for African children living in malaria-endemic areas. METHODS: In a secondary data analysis of severely ill febrile children included in the Fluid Expansion as Supportive Therapy (FEAST) resuscitation trial, we assessed the association between lactate levels at admission and LC at 8 h with all-cause mortality at 72 h (d72). LC was defined as a relative lactate decline ≥ 40% and/or lactate normalisation (lactate < 2.5 mmol/L). RESULTS: Of 3170 children in the FEAST trial, including 1719 children (57%) with Plasmodium falciparum malaria, 3008 (95%) had a baseline lactate measurement, 2127 (71%) had HL (lactate ≥ 2.5 mmol/L), and 1179 (39%) had severe HL (≥ 5 mmol/L). Within 72 h, 309 children (10.3%) died, of whom 284 (92%) had baseline HL. After adjustment for potential confounders, severe HL was strongly associated with mortality (Odds Ratio (OR) 6.96; 95% CI 3.52, 13.76, p < 0.001). This association was not modified by malaria status, despite children with malaria having a higher baseline lactate (median 4.6 mmol/L vs 3 mmol/L; p < 0.001) and a lower mortality rate (OR = 0.42; p < 0.001) compared to non-malarial cases. Sensitivity and specificity analysis identified a higher lactate on admission cut-off value predictive of d72 for children with malaria (5.2 mmol/L) than for those with other febrile illnesses (3.4 mmol/L). At 8 h, 2748/3008 survivors (91%) had a lactate measured, 1906 (63%) of whom had HL on admission, of whom 1014 (53%) fulfilled pre-defined LC criteria. After adjustment for confounders, LC independently predicted survival after 8 h (OR 0.24; 95% CI 0.14, 0.42; p < 0.001). Absence of LC (< 10%) at 8 h was strongly associated with death at 72 h (OR 4.62; 95% CI 2.7, 8.0; p < 0.001). CONCLUSIONS: Independently of the underlying diagnosis, HL is a strong risk factor for death at 72 h in children admitted with severe febrile illnesses in Africa. Children able to clear lactate within 8 h had an improved chance of survival. These findings prompt the more widespread use of lactate and LC to identify children with severe disease and monitor response to treatment. TRIAL REGISTRATION: ISRCTN69856593 Registered 21 January 2009.