UNASSIGNED: Respiratory syncytial virus (RSV) is one of the most common virus causing community-acquired pneumonia (CAP) in children. To guide the prevention, diagnosis and treatment of RSV, we aimed to analyze the epidemiology of RSV in hospitalized children with CAP.
UNASSIGNED: A total of 9,837 hospitalized children (≤14 years old) with CAP from January 2010 to December 2019 were reviewed. Using the real-time polymerase chain reaction (RT-PCR), the oropharyngeal swab specimens were collected and tested for RSV, influenza virus A (INFA), influenza virus B (INFB), parainfluenza virus (PIV), enterovirus (EV), coronavirus (CoV), human metapneumovirus (HMPV), human bocavirus (HBoV), human rhinovirus (HRV), and adenovirus (ADV) for each patient.
UNASSIGNED: The detection rate of RSV was 15.3% (1,507/9,837). From 2010 to 2019, the RSV detection rate showed a wavy change (χ2=166.982, P<0.001), with the highest detection rate in 2011 (158/636, 24.8%). RSV can be detected throughout the year, with the highest detection rate in February (123/482, 25.5%). Children younger than 0.5 years old had the highest detection rate (410/1,671, 24.5%). The detection rate of RSV in male children (1,024/6,226, 16.4%) was higher than that in female children (483/3,611, 13.4%) (P<0.001). A proportion of 17.7% (266/1,507) of RSV positive cases were also co-infected with other viruses, and INFA (41/266, 15.4%) was the most common coinfection virus. After adjusting for potential confounders, the RSV-positive children were associated with increased risk of severe pneumonia [odds ratio (OR) 1.26, 95% confidence interval (CI): 1.04 to 1.53, P=0.019]. Moreover, children with severe pneumonia had significantly lower cycle threshold (CT) values of RSV than those without severe pneumonia (28.88±3.89 vs. 30.42±3.33, P<0.01). Patients with coinfection (38/266, 14.3%) had a higher risk of severe pneumonia than those without coinfection (142/1,241, 11.4%), but the difference was not statistically significant (OR 1.39, 95% CI: 0.94 to 2.05, P=0.101).
UNASSIGNED: The detection rate of RSV in CAP hospitalized children changed by years, months, ages, and sexes. CAP hospitalized children with RSV are more likely to develop severe pneumonia than those without RSV. Policy makers and doctors should make timely adjustments to prevention measures, medical resources and treatment options based on these epidemiological characteristics.

Effective treatment of pneumonia requires timely administration of appropriate antimicrobials but standard diagnostic tests take around 48 h to generate results. Highly accurate, rapid molecular tests have been developed for identifying organisms in lower respiratory tract samples, however their impact on antibiotic use is unknown. The aim of this study was to assess the impact of syndromic molecular point-of-care testing compared to conventional diagnostic testing, on antibiotic use.
In this pragmatic, randomised controlled trial, we enrolled critically ill adults with pneumonia. Patients were assigned (1:1) to molecular testing of samples at the point-of-care or routine clinical care. The primary outcome was the proportion of patients who received results-directed antimicrobial therapy.
200 patients were randomly assigned to point-of-care testing (n = 100) or the control group (n = 100). 85 patients had community acquired pneumonia (42 in the mPOCT group and 43 in the control group), 69 hospital acquired pneumonia (30 in mPOCT and 39 in control) and 46 ventilator associated pneumonia (28 in mPOCT and 18 in control). The median [IQR] time to results was 1.7 [1.6-1.9] hours for point-of-care testing and 66.7 [56.7-88.5] hours for standard diagnostics (difference of -65.0 h, 95%CI -68.0 to -62.0; p < 0.0001). 71 (71%) patients in the point-of-care testing arm had pathogens detected compared to 51 (51%) in the control arm (difference of 20%, 95%CI 7 to 33; p = 0.004). 80 (80%) of patients in the point-of-care group received results-directed therapy, compared with 29 (29%) of 99 in the control group (difference of 51%, 95%CI 39-63; p < 0.0001). Time to results-directed therapy was 2.3 [1.8-7.2] hours in the mPOCT group and 46.1 [23.0-51.5] hours in the control group (difference of -43.8 h, 95% CI -48.9 to -38.6; p < 0.0001). 42 (42%) patients in mPOCT group had antibiotics de-escalated compared with 8 (8%) of 98 in the control group (difference of 34%, 95%CI 23-45; p < 0.0001). Time to de-escalation was 4.8 [2.4-13.0] hours in the mPOCT group compared with 46.5 [26.3-48.6] hours in the control group (difference of -41.4 h, 95%CI -53 to -29.7; p < 0.0001). There was no major difference in antibiotic duration or in clinical or safety outcomes between the two groups.
Use of molecular point-of-care testing in patients with pneumonia returned results more rapidly and identified more pathogens than conventional testing. This was associated with improvements in appropriate antimicrobial use and appeared safe.

Pneumonia is the top communicable cause of death worldwide. Accurate prognostication of patient severity with Community Acquired Pneumonia (CAP) allows better patient care and hospital management. The Pneumonia Severity Index (PSI) was developed in 1997 as a tool to guide clinical practice by stratifying the severity of patients with CAP. While the PSI has been evaluated against other clinical stratification tools, it has not been evaluated against multiple classic machine learning classifiers in various metrics over large sample size.
In this paper, we evaluated and compared the prediction performance of nine classic machine learning classifiers with PSI over 34,720 adult (age 18+) patient records collected from 749 hospitals from 2009 to 2018 in the United States on Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) and Average Precision (Precision-Recall AUC).
Machine learning classifiers, such as Random Forest, provided a statistically highly(p < 0.001) significant improvement (∼33% in PR AUC and ∼6% in ROC AUC) compared to PSI and required only 7 input values (compared to 20 parameters used in PSI).
Because of its ease of use, PSI remains a very strong clinical decision tool, but machine learning classifiers can provide better prediction accuracy performance. Comparing prediction performance across multiple metrics such as PR AUC, instead of ROC AUC alone can provide additional insight.

Pneumonia (PNA) may complicate the Severe Alcohol Withdrawal Syndrome (SAWS), with ICU admission, mechanical ventilation (MV), prolonged length of stay (LOS), and adverse events.
To examine the onset, features and courses of PNA in patients with SAWS to aid management.
A 33 month contiguous review of SAWS and PNA was conducted at an urban public hospital.
There were 279 episodes of Alcohol Withdrawal Syndrome (AWS) among 255 patients. Males predominated (91%) with a mean age of 45.8 years (range 23-73), of whom 31% (87/279) developed SAWS with ICU management. Direct ICU admission occurred for 62 patients; 25 were transferred for delirium, seizures, escalating sedation, PNA or other complications. PNA was identified for 34 ICU direct admissions and 13 ward patients. Ten transfers to the ICU also developed PNA for an ICU total of 44/87 (51%), of whom 82% (36/44) required MV. Another 10 ICU patients without PNA received MV for high dose sedation or respiratory failure. Most ICU patients (72/87 (83%)), including all with MV, required IV infusion of sedation. MV prolonged LOS, but LOS for PNA with MV was similar to all MV. ICU transfers had longer LOS with greater use of MV than direct admits (p<0.05). PNA was identified before ICU admission or transfer for 73% (32/44 (p<0.05)), and usually before intubation. Most PNA was Community Acquired Pneumonia (CAP) with P. Pneumoniae frequently cultured.
PNA with SAWS is predominately CAP and occurs early. Focused ICU admission with respiratory support are priorities of initial management.

Community acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and ventilator associated pneumonia (VAP) are all associated with significant mortality and cause huge expense to health care services around the world. Early, appropriate antimicrobial therapy is crucial for effective treatment. Syndromic diagnostic testing using novel, rapid multiplexed molecular platforms represents a new opportunity for rapidly targeted antimicrobial therapy to improve patient outcomes and facilitate antibiotic stewardship. In this article we review the currently available testing platforms and discuss the potential benefits and pitfalls of rapid testing in pneumonia.

BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients.
METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians.
RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death.
CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

OBJECTIVE: Neutrophil to lymphocyte ratio (NLR) as calculated from the white cell differential blood count is considered a promising marker for the prognosis of patients with various diseases, including sepsis. This study was designed to assess the possible use of neutrophil-to-lymphocyte ratio in the prediction of survival outcomes in patients with community acquired pneumonia (CAP). A secondary objective was to compare the prognostic accuracy of NLR with the commonly used severity scores of sepsis SOFA, APACHE II and SAPS II.
METHODS: This was a retrospective study based on data extracted from 26 patients suffering from acute CAP. The study period was from February 01, 2017 until April 30, 2017. All patients with CAP were presented in the Emergency Department (ED) of the University Hospital of Patras, Greece and were treated after admission in the Internal Medicine Department. The neutrophil-to-lymphocyte ratio (NLR) was calculated from the white blood cell count (WBC) values measured from a peripheral venous blood specimen drawn on admission. It was then compared with C-reactive protein (CRP) serum levels and the sepsis calculated prognostic scores APACHE II, SAPS II and SOFA. The impact of the above parameters was evaluated in relation to the final outcome.
RESULTS: The mean period of hospitalization for the enrolled patients was 9.3 days (SD 5.8 days). Twenty-four patients (92.3%) got finally discharged from the hospital and two (7.7%) died during the hospitalization. Mean NLR and serum CRP values on admission were 10.2 ± 8.8 (min 1.4; max 34.7) and 11.4 ± 11 mg/dL (min 0.4; max 42.6) respectively. Based on the correlation analysis, serum CRP was more strongly positively correlated with NLR (r = 0.543, P = 0.004), than total WBC (r = 0.454, P = 0.02). None of the biomarkers of inflammation measured or computed in the study (CRP, WBC, NLR) showed any correlation with either the days of hospitalization or the sepsis prognostic scores.
CONCLUSIONS: NLR shows a statistical significant correlation to the commonly used inflammatory markers CRP and total WBC in the small sample size of patients with CAP that we assessed. Although NLR is a simple, cheap and rapidly available measurement in the ED, future, larger prospective studies are warranted to confirm its possible value as a prognostic index in sepsis patients with CAP.

Community acquired pneumonia (CAP) is the leading infectious cause of mortality worldwide with approximately 10% of patients hospitalized requiring intensive care unit (ICU) admission. The ability to predict clinical stability (CS) and treatment failure (TF) enables the clinician to alter antibiotics appropriately, facilitate a timely ICU admission, or arrange a suitable discharge. The detection of CS and TF can be difficult and changes in clinical signs may be subtle or delayed. Thus clinical scores and biomarkers are routinely used to identify severity and monitor clinical progression. The evidence, however, is vast and the definitive role of these systems is at times difficult to elucidate. The aim of this review is to analyse the current literature and to provide a rational and clinically focused view of the predictive utility of various systems used to identify CS and TF in CAP.

Chest X-ray (CXR) is the primary diagnostic tool for community-acquired pneumonia (CAP). Some authors recently proposed that thoracic ultrasound (TUS) could valuably flank or even reliably substitute CXR in the diagnosis and follow-up of CAP. We investigated the clinical utility of TUS in a large sample of patients with CAP, to challenge the hypothesis that it may be a substitute for CXR.
Out of 645 consecutive patients with a CXR-confirmed CAP diagnosed in the emergency room of our hospital over a three-years period, 510 were subsequently admitted to our department of Internal Medicine. These patients were evaluated by TUS by a well-trained operator who was blinded of the initial diagnosis. TUS scans were performed both at admission and repeated at day 4-6th and 9-14th during stay.
TUS identified 375/510 (73.5%) of CXR-confirmed lesions, mostly located in posterior-basal or mid-thoracic areas of the lungs. Pleural effusion was detected in 26.9% of patients by CXR and in 30.4% by TUS. TUS documented the change in size of the consolidated areas as follows: 6.3 ± 3.4 cm at time 0, 2.5 ± 1.8 at 4-6 d, 0.9 ± 1.4 at 9-14 d. Out of the 12 patients with delayed CAP healing, 7 of them turned out to have lung cancer.
TUS allowed to detect lung consolidations in over 70% of patients with CXR-confirmed CAP, but it gave false negative results in 26.5% of cases. Our longitudinal results confirm the role of TUS in the follow-up of detectable lesions. Thus, TUS should be regarded as a complementary and monitoring tool in pneumonia, instead of a primary imaging modality.

Clinical research in rare diseases, including alpha-1 antitrypsin deficiency (AATD), faces challenges not shared by common disease research. These challenges may include the limited number of patient volunteers available for research, lack of natural history studies on which to base many clinical trial interventions, an urgency for the development of drug therapies given the often poor prognosis of rare diseases and uncertainties about appropriate biomarkers and clinical outcomes critical to clinical trial design. To address these challenges and initiate formal discussions among key stakeholders-patients, researchers, industry, federal regulators-the Alpha-1 Foundation hosted the Clinical Trial Design for Alpha-1 Antitrypsin Deficiency: A Model for Rare Diseases conference February 3-4, 2014 in Bethesda, Maryland. Discussions at the conference led to the conclusions that 1) adaptive designs should be considered for rare disease clinical trials yet more dialogue and study is needed to make these designs feasible for smaller trials and to address current limitations; 2) natural history studies, including the identification of appropriate biomarkers are critically needed and precompetitive collaborations may offer a means of creating these costly studies; and 3) patient registries and databases within the rare disease community need to be more publicly available and integrated, particularly for AATD. This report summarizes the discussions leading to these conclusions.