Development and internal validation of risk scores to diagnose infectious mononucleosis among college students.

BACKGROUND: Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis. OBJECTIVE: To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM. DESIGN AND SETTING: Data were extracted from electronic health records of a university health centre and were divided into derivation (9/1/2015-10/31/2017) and a prospective temporal internal validation (11/1/2017-1/31/2019) cohort. METHOD: Independent predictors for the diagnosis of IM were identified in univariate analysis using the derivation cohort. Logistic regression models were used to develop 2 risk scores: 1 with only symptoms and signs (IM-NoLab) and 1 adding haematologic parameters (IM-Lab). Point scores were created based on the regression coefficients, and patients were grouped into risk groups. Primary outcomes were area under the receiver operating characteristic curve (AUROCC) and classification accuracy. RESULTS: The IM-NoLab model had 4 predictors and identified a low-risk group (7.9% with IM) and a high-risk group (22.2%) in the validation cohort. The AUROCC was 0.75 in the derivation cohort and 0.69 in the validation cohort. The IM-Lab model had 3 predictors and identified a low-risk group (3.6%), a moderate-risk group (12.5%), and a high-risk group (87.6%). The AUROCC was 0.97 in the derivation cohort and 0.93 in the validation cohort. CONCLUSION: We derived and internally validated the IM-NoLab and IM-Lab risk scores. The IM-Lab score in particular had very good discrimination and have the potential to reduce the need for diagnostic testing for IM.

Enhanced Photocatalytic Degradation of Malachite Green Dye Using Silver-Manganese Oxide Nanoparticles.

Efficient and excellent nanoparticles are required for the degradation of organic dyes in photocatalysis. In this study, silver-manganese oxide nanoparticles (Ag-Mn-NPs) were synthesized through a wet chemical precipitation method and characterized as an advanced catalyst that has enhanced photocatalytic activity under sunlight irradiation. The nanoparticles were characterized using scanning electron microscopy (SEM), XRD, UV-vis light spectra, and energy-dispersive X-ray (EDX) spectroscopy, revealing their spherical and agglomerated form. The EDX spectra confirmed the composition of the nanoparticles, indicating their presence in oxide form. These bimetallic oxide nanoparticles were employed as photocatalysts for the degradation of malachite green (MG) dye under sunlight irradiation in an aqueous medium. The study investigated the effects of various parameters, such as irradiation time, catalyst dosage, recovered catalyst dosage, dye concentration, and pH, on the dye's photodegradation. The results showed that Ag-Mn oxide nanoparticles exhibited high photocatalytic activity, degrading 92% of the dye in 100 min. A longer irradiation time led to increased dye degradation. Moreover, a higher catalyst dosage resulted in a higher dye degradation percentage, with 91% degradation achieved using 0.0017 g of the photocatalyst in 60 min. Increasing the pH of the medium also enhanced the dye degradation, with 99% degradation achieved at pH 10 in 60 min. However, the photodegradation rate decreased with increasing dye concentration. The Ag-Mn oxide nanoparticles demonstrate excellent potential as a reliable visible-light-responsive photocatalyst for the efficient degradation of organic pollutants in wastewater treatment.

Risk factors for the accuracy of the initial diagnosis of malaria cases in China: a decision-tree modelling approach.

BACKGROUND: Early accurate diagnosis and risk assessment for malaria are crucial for improving patients' terminal prognosis and preventing them from progressing to a severe or critical stage. This study aims to describe the accuracy of the initial diagnosis of malaria cases with different characteristics and the factors that affect the accuracy in the context of the agenda for a world free of malaria. METHODS: A retrospective study was conducted on 494 patients admitted to hospitals with a diagnosis of malaria from January 2014 through December 2016. Descriptive statistics were calculated, and decision tree analysis was performed to predict the probability of patients who may be misdiagnosed. RESULTS: Of the 494 patients included in this study, the proportions of patients seeking care in county-level, prefecture-level and provincial-level hospitals were 27.5% (n = 136), 26.3% (n = 130) and 8.3% (n = 41), respectively; the proportions of patients seeking care in clinic, township health centre and Centres for Disease Control and Prevention were 25.9% (n = 128), 4.1% (n = 20), and 7.9% (n = 39), respectively. Nearly 60% of malaria patients were misdiagnosed on their first visit, and 18.8% had complications. The median time from onset to the first visit was 2 days (IQR: 0-3 days), and the median time from the first visit to diagnosis was 3 days (IQR: 0-4 days). The decision tree classification of malaria patients being misdiagnosed consisted of six categorical variables: healthcare facilities for the initial diagnosis, time interval between onset and initial diagnosis, region, residence type, insurance status, and age. CONCLUSIONS: Insufficient diagnostic capacity of healthcare facilities with lower administrative levels for the first visit was the most important risk factor in misdiagnosing patients. To reduce diagnostic errors, clinicians, government decision-makers and communities should consider strengthening the primary care facilities, the time interval between onset and initial diagnosis, residence type, and health insurance status.

External Validation of the COVID-NoLab and COVID-SimpleLab Prognostic Tools.

Our objective was to externally validate 2 simple risk scores for mortality among a mostly inpatient population with COVID-19 in Canada (588 patients for COVID-NoLab and 479 patients for COVID-SimpleLab). The mortality rates in the low-, moderate-, and high-risk groups for COVID-NoLab were 1.1%, 9.6%, and 21.2%, respectively. The mortality rates for COVID-SimpleLab were 0.0%, 9.8%, and 20.0%, respectively. These values were similar to those in the original derivation cohort. The 2 simple risk scores, now successfully externally validated, offer clinicians a reliable way to quickly identify low-risk inpatients who could potentially be managed as outpatients in the event of a bed shortage. Both are available online (https://ebell-projects.shinyapps.io/covid_nolab/ and https://ebell-projects.shinyapps.io/COVID-SimpleLab/).

Lethal, Sublethal, and Offspring Effects of Fluralaner and Dinotefuran on Three Species of Bactrocera Fruit Flies.

Fruit flies cause substantial economic damage, and their management relies primarily on chemical insecticides. However, pesticide resistance has been reported in several fruit fly species, the mitigation of which is crucial to enhancing fruit fly control. Here, we assess the toxicity of a novel insecticide (fluralaner) and a common insecticide (dinotefuran) against three fruit fly species, Bactrocera dorsalis (Hendel), Bactrocera cucurbitae (Coquillett), and Bactrocera tau (Walker). Both pesticides exhibit robust lethal and sublethal effects against all three fruit fly species, with fluralaner being more potent. Fluralaner and dinotefuran suppress the reproductive capacities and survival rates of fruit flies. However, at the 50% lethal concentration, fluralaner stimulates the reproductive capacity of B. dorsalis and the survival rate of B. tau. Fluralaner also causes significant transgenerational effects, impacting the offspring hatching rate of B. cucurbitae and B. tau and reducing the proportion of female offspring. Thus, both pesticides exhibit high potential for controlling fruit flies. However, their application should be tailored according to species variations and the diverse effects they may induce. Collectively, the findings of this study outline the sublethal effects of two insecticides against fruit flies, helping to optimize their application to ensure the effective management of insecticide resistance.

Comparative Population Biology and Related Gene Expression in the Beta-Cypermethrin-Resistant Strains of Bactrocera dorsalis (Hendel).

Diptera and Lepidoptera species have the highest levels of insecticide resistance, and the mechanism of drug resistance has been studied in detoxification metabolism genes such as P450, GST, EST, and ABC. Since Bactrocera dorsalis are resistant to a variety of chemicals, the pattern and mechanism of resistance in Bactrocera dorsalis have been investigated from a variety of aspects such as detoxification metabolism genes, detoxification enzymes, intestinal symbiotic bacteria, and synergists in the world. In this study, 51 species and 149 detoxification metabolism genes were annotated in the Suppression Subtractive Hybridization (SSH) library, and 12 candidate genes related to beta-cypermethrin resistance were screened and quantitatively expressed in this library. Two genes were found to be upregulated in the egg stage, three genes in the larval stage, one gene in the pupal stage, and five genes in the adult stage, and four genes were found to be upregulated in the midgut and the malacca ducts in the midgut. The expression of cyp6g1, cyp6a22, GST-Epsilon9, and Trypsin-4 genes was upregulated in resistant strains, with the most obvious upregulation occurring in the midgut and the Malpighian tubules. These results provide new insights into the study of pesticide resistance in quarantine insects.

Reproductive behavior of fruit flies: courtship, mating, and oviposition.

Many species of the Tephritidae family are invasive and cause huge damage to agriculture and horticulture, owing to their reproductive characteristics. In this review, we have summarized the existing studies on the reproductive behavior of Tephritidae, particularly those regarding the genes and external factors that are associated with courtship, mating, and oviposition. Furthermore, we outline the issues that still need to be addressed in fruit fly reproduction research. The review highlights the implications for understanding the reproductive behavior of fruit flies and discusses methods for their integrated management and biological control. © 2023 Society of Chemical Industry.

Dynamics of Bactrocera dorsalis Resistance to Seven Insecticides in South China.

Bactrocera dorsalis is a highly invasive and destructive pest distributed worldwide. Chemical insecticides remain the primary measure for their control; however, this species has already developed resistance to several insecticides. In recent years, there have been several reports of monitoring B. dorsalis resistance in China, but continuous monitoring results are lacking and do not even span a decade. In this study, we monitored the dynamics of resistance to seven insecticides among 11 geographically distinct Chinese populations of B. dorsalis (2010-2013; follow-up in 2023). The 11 populations were found to adapt rapidly to antibiotic insecticides (spinosad, emamectin benzoate, and avermectin), reaching high levels of insecticide resistance in several areas. Overall, a decreasing trend in resistance to organophosphorus insecticides (chlorpyrifos and trichlorfon) was observed, whereas pyrethroid (beta-cypermethrin and cyhalothrin) resistance trends were observed to both increase and decrease. The monitoring of field resistance among different B. dorsalis populations over the duration of this study is important for improving the efficiency and sustainability of agricultural pest management, and the results provide a scientific basis for the development of more effective resistance management strategies.

Toxicity of Beauveria bassiana to Bactrocera dorsalis and effects on its natural predators.

Entomopathogenic fungi (EPF) are economical and environmentally friendly, forming an essential part of integrated pest management strategies. We screened six strains of Beauveria bassiana (B1-B6) (Hypocreales: Cordycipitaceae), of which B4 was the most virulent to Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). We further assessed the biological characteristics of strain B4 and the environmental factors influencing its ability to infect B. dorsalis. We also evaluated the effects of B4 on two of the natural predators of B. dorsalis. We found that strain B4 was the most virulent to 3rd instar larvae, pupae, and adult B. dorsalis, causing mortality rates of 52.67, 61.33, and 90.67%, respectively. B4 was not toxic to B. dorsalis eggs. The optimum B4 effects on B. dorsalis were achieved at a relative humidity of 91-100% and a temperature of 25°C. Among the six insecticides commonly used for B. dorsalis control, 1.8% abamectin emulsifiable concentrate had the strongest inhibitory effect on B4 strain germination. B4 spraying affected both natural enemies (Amblyseius cucumeris and Anastatus japonicus), reducing the number of A. cucumeris and killing A. japonicus adults. We found a valuable strain of EPF (B4) that is virulent against many life stages of B. dorsalis and has great potential for the biological control of B. dorsalis. We also provide an important theoretical and practical base for developing a potential fungicide to control B. dorsalis.

Lethal and sublethal effects of broflanilide on four tephritid pests (Diptera: Tephritidae).

BACKGROUND: Fruit flies are internationally important quarantine or invasive pests of many fruits and vegetables and can cause serious economic losses. Long-term reliance on insecticides for controlling these pests has led to increasing resistance to multiple insecticides; hence, a new agent is needed. In this study, the acute toxicity and sublethal effects of the novel insecticide broflanilide on four adult fruit fly species, Bactrocera dorsalis, Bactrocera cucurbitae, Bactrocera tau, and Bactrocera correcta, were evaluated. RESULTS: Broflanilide was effective against B. dorsalis and B. correcta, with lethal concentration values (amount required to kill 50% of animals; LC50 ) of 0.390 and 1.716 mg/L. However, for B. cucurbitae (19.673 mg/L) and B. tau (24.373 mg/L), the LC50 was 50-60 times higher than that of B. dorsalis. The survival rates of B. correcta and B. cucurbitae were significantly lower under LC50 treatment than those of the control (corrected for mortality rate). Sublethal concentrations of broflanilide stimulated fecundity in all species except B. tau. The hatching rate at LC50 was significantly lower for B. correcta and B. tau compared with the control and even more so for B. correcta, which was zero. CONCLUSION: Broflanilide is potentially an effective insecticide for controlling B. dorsalis and B. correcta. However, the variation in toxicity of broflanilide to the four fruit flies suggests that species variation needs to be carefully considered. Our results highlight the importance of clarifying the sublethal effects of insecticides on target insects to ensure the comprehensive evaluation and rational use of insecticides. © 2023 Society of Chemical Industry.

Derivation and validation of clinical prediction rules for diagnosis of infectious mononucleosis: a prospective cohort study.

OBJECTIVES: Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV). DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: 328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17-39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA. MAIN OUTCOME MEASURES: Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort. RESULTS: In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62-0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67-0.72) and good calibration. CONCLUSIONS: The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.

A Quantitative Study of the Decision Threshold for the Diagnosis of Infectious Mononucleosis.

BACKGROUND: Ordering a serologic test for infectious mononucleosis (IM) in all young patients with sore throat is costly and impractical. The test threshold to determine when to order a diagnostic test for IM based on the patient's symptoms has not been previously studied. OBJECTIVE: To determine the test threshold for IM in the management of patients with sore throat. DESIGN AND SETTING: Online surveys were sent to a convenience sample of US primary care clinicians regarding their decision making about whether or not to order a test for IM in a patient with sore throat. METHOD: 7 clinical vignettes were created, each with a different combinations of symptoms and signs. The probability of IM for each vignette was estimated by the investigator based on the number of symptoms present to generate a plausible range of disease probabilities. Clinicians were then asked to decide whether to test or not test for IM, and mixed-effect logistic regression was used to determine the test threshold for IM where half of physicians chose to test and half chose not to test. RESULTS: A total of 117 clinicians provided responses for a total of 819 clinical vignettes. The overall test threshold for IM as estimated using the logistic regression was 9.5% (95% CI: 8.2% to 10.9%). The test threshold for clinicians practicing greater than 10 years was significantly higher than for those practicing less or equal to 10 years (10.5% vs 7.3%, P = .02). No significant differences between specialties and practice sites were found with respect to the test threshold. CONCLUSION: This study identified a test threshold for IM of approximately 10% based on realistic clinical vignettes. This threshold was stable regarding the clinician's specialty and practice sites and could be used in the development of a clinical prediction rule to determine the cutoff for low- versus high-risk groups.

The impact of a rapid home test on telehealth decision-making for influenza: a clinical vignette study.

BACKGROUND: Home testing for influenza has the potential to aid triage and management decisions for patients with influenza-like illness. As yet, little is known about the effect of the home influenza testing on clinical decision-making via telehealth. The goal of this study was to determine the clinicians' decision thresholds for influenza and whether the availability of a home influenza test affects clinical decisions. METHODS: We identified primary care physicians at 4 different sites in the US, largely via in-person continuing education meetings. Clinicians were asked for each vignette whether to treat empirically ("rule in"), ask the patient come to the clinic for further evaluation ("test"), or neither test nor treat ("rule out"). They were then given the results of a home influenza test, and were again asked to select from these three options. We measured the agreement of physician estimates of the likelihood of influenza with the probability based on a clinical prediction model. The test and treatment thresholds of influenza were determined based on mixed-effect logistic regressions. RESULTS: In total, 202 clinicians made 570 sets of clinical decisions. Agreement between estimated and actual probability of influenza was fair. The test and treatment thresholds were 24% (95% CI: 22% to 25%) and 63% (95% CI: 58% to 65%) before revealing the actual likelihood of influenza. After providing the results of a home flu test the thresholds were similar, 26% (95% CI: 24% to 29%) and 59% (95% CI: 56% to 62%). However, approximately half of clinicians changed their cliical management decision after being given the home influenza test result, largely by categorizing more patients in the "rule out" and "rule in" groups, and reducing the need for in-person evaluation from 41% of patients to only 20%. CONCLUSION: In the context of a telehealth visit for a patient with influenza-like illness, we identified a test threshold of approximately 25% and a treatment threshold of approximately 60%. Adding the home influenza test results reduced uncertainty and significantly decreased the need for in-person visits.

Development and Validation of a Two-Step Predictive Risk Stratification Model for Coronavirus Disease 2019 In-hospital Mortality: A Multicenter Retrospective Cohort Study.

Objectives: An accurate prognostic score to predict mortality for adults with COVID-19 infection is needed to understand who would benefit most from hospitalizations and more intensive support and care. We aimed to develop and validate a two-step score system for patient triage, and to identify patients at a relatively low level of mortality risk using easy-to-collect individual information. Design: Multicenter retrospective observational cohort study. Setting: Four health centers from Virginia Commonwealth University, Georgetown University, the University of Florida, and the University of California, Los Angeles. Patients: Coronavirus Disease 2019-confirmed and hospitalized adult patients. Measurements and Main Results: We included 1,673 participants from Virginia Commonwealth University (VCU) as the derivation cohort. Risk factors for in-hospital death were identified using a multivariable logistic model with variable selection procedures after repeated missing data imputation. A two-step risk score was developed to identify patients at lower, moderate, and higher mortality risk. The first step selected increasing age, more than one pre-existing comorbidities, heart rate >100 beats/min, respiratory rate ≥30 breaths/min, and SpO2 <93% into the predictive model. Besides age and SpO2, the second step used blood urea nitrogen, absolute neutrophil count, C-reactive protein, platelet count, and neutrophil-to-lymphocyte ratio as predictors. C-statistics reflected very good discrimination with internal validation at VCU (0.83, 95% CI 0.79-0.88) and external validation at the other three health systems (range, 0.79-0.85). A one-step model was also derived for comparison. Overall, the two-step risk score had better performance than the one-step score. Conclusions: The two-step scoring system used widely available, point-of-care data for triage of COVID-19 patients and is a potentially time- and cost-saving tool in practice.

Accuracy of Signs, Symptoms, and Hematologic Parameters for the Diagnosis of Infectious Mononucleosis: A Systematic Review and Meta-Analysis.

BACKGROUND: The accuracy of individual symptoms, signs, and several easily obtainable hematologic parameters for diagnosing infectious mononucleosis (IM) still needs to be confirmed. Improving the diagnosis of IM based on the clinical findings could prompt physicians to identify better which patients need a diagnostic test for IM. This study performed a systematic review to determine the accuracy of symptoms, signs, and hematologic parameters in patients with suspected IM that used heterophile antibody test or viral capsid antigen tests as the reference standard. METHODS: The PubMed database was searched for all relevant articles. Two reviewers reviewed all studies in parallel and assessed the quality of the selected studies using the quality assessment of diagnostic accuracy studies 2 (QUADAS-2) criteria. The pooled measures of diagnostic performance were calculated by bivariate meta-analysis for each clinical finding, which included sensitivity, specificity, likelihood ratios, the diagnostic odds ratios, and the area under the receiver operating characteristic curve. RESULTS: Seventeen studies were included in our final analysis. The prevalence of IM ranged from 2.1% to 80% among prospective cohort studies. The presence of splenomegaly (positive likelihood ratio [LR+], 2.39; 95% confidence interval [CI], 1.11-5.51), palatal petechiae (LR+, 1.32-11.40), posterior cervical lymphadenopathy (LR+, 3.16; 95% CI, 1.45-5.20), and axillary or inguinal cervical lymphadenopathy (LR+, 3.05; 95 CI, 1.85-4.70) were moderately useful for ruling in IM. The most helpful hematologic parameters for ruling in IM include lymphocytes greater than 4 × 109/L and greater than 40% to 50%, or atypical lymphocytes greater than 40%. A combination of lymphocytes greater than 50% and atypical lymphocytes greater than 10% (LR+, 50.40; 95% CI, 8.43-162) was also found to be helpful to rule in disease. Most of the clinical findings have limited diagnostic value in ruling out the disease when absent. CONCLUSIONS: Although most symptoms and signs were unhelpful, the likelihood of IM is appreciably increased by several examination findings. Hematologic parameters were more accurate than symptoms and signs. Since most clinical findings have limited diagnostic value in ruling out the disease, physicians should not rely on the absence of any individual symptom or clinical sign for ruling out IM.

A Systematic Review of Clinical Prediction Rules for the Diagnosis of Influenza.

BACKGROUND: Clinical prediction rules (CPRs) can assist clinicians by focusing their clinical evaluation on the most important signs and symptoms, and if used properly can reduce the need for diagnostic testing. This study aims to perform an updated systematic review of clinical prediction rules and classification and regression tree (CART) models for the diagnosis of influenza. METHODS: We searched PubMed, CINAHL, and EMBASE databases. We identified prospective studies of patients presenting with suspected influenza or respiratory infection and that reported a CPR in the form of a risk score or CART-based algorithm. Studies had to report at a minimum the percentage of patients in each risk group with influenza. Studies were evaluated for inclusion and data were extracted by reviewers working in parallel. Accuracy was summarized descriptively; where not reported by the authors the area under the receiver operating characteristic curve (AUROCC), predictive values, and likelihood ratios were calculated. RESULTS: We identified 10 studies that presented 14 CPRs. The most commonly included predictor variables were cough, fever, chills and/or sweats, myalgias, and acute onset, all which can be ascertained by phone or telehealth visit. Most CPRs had an AUROCC between 0.7 and 0.8, indicating good discrimination. However, only 1 rule has undergone prospective external validation, with limited success. Data reporting by the original studies was in some cases inadequate to determine measures of accuracy. CONCLUSIONS: Well-designed validation studies, studies of interrater reliability between telehealth an in-person assessment, and studies using novel data mining and artificial intelligence strategies are needed to improve diagnosis of this common and important infection.

Development and Validation of the COVID-NoLab and COVID-SimpleLab Risk Scores for Prognosis in 6 US Health Systems.

PURPOSE: Develop and validate simple risk scores based on initial clinical data and no or minimal laboratory testing to predict mortality in hospitalized adults with COVID-19. METHODS: We gathered clinical and initial laboratory variables on consecutive inpatients with COVID-19 who had either died or been discharged alive at 6 US health centers. Logistic regression was used to develop a predictive model using no laboratory values (COVID-NoLab) and one adding tests available in many outpatient settings (COVID-SimpleLab). The models were converted to point scores and their accuracy evaluated in an internal validation group. RESULTS: We identified 1340 adult inpatients with complete data for nonlaboratory parameters and 741 with complete data for white blood cell (WBC) count, differential, c-reactive protein (CRP), and serum creatinine. The COVID-NoLab risk score includes age, respiratory rate, and oxygen saturation and identified risk groups with 0.8%, 11.4%, and 40.4% mortality in the validation group (AUROCC = 0.803). The COVID-SimpleLab score includes age, respiratory rate, oxygen saturation, WBC, CRP, serum creatinine, and comorbid asthma and identified risk groups with 1.0%, 9.1%, and 29.3% mortality in the validation group (AUROCC = 0.833). CONCLUSIONS: Because they use simple, readily available predictors, developed risk scores have potential applicability in the outpatient setting but require prospective validation before use.

Accuracy of Signs and Symptoms for the Diagnosis of Community-acquired Pneumonia: A Meta-analysis.

BACKGROUND: Community-acquired pneumonia (CAP) is an important source of morbidity and mortality. However, overtreatment of acute cough illness with antibiotics is an important problem, so improved diagnosis of CAP could help reduce inappropriate antibiotic use. METHODS: This was a meta-analysis of prospective cohort studies of patients with clinically suspected pneumonia or acute cough that used imaging as the reference standard. All studies were reviewed in parallel by two researchers and quality was assessed using the QUADAS-2 criteria. Summary measures of accuracy included sensitivity, specificity, likelihood ratios, the diagnostic odds ratio, and the area under the receiver operating characteristic curve (AUROCC) and were calculated using bivariate meta-analysis. RESULTS: We identified 17 studies, of which 12 were judged to be at low risk of bias and the remainder at moderate risk of bias. The prevalence of CAP was 10% in nine primary care studies and was 20% in seven emergency department studies. The probability of CAP is increased most by an abnormal overall clinical impression suggesting CAP (positive likelihood ratio [LR+] = 6.32, 95% CI = 3.58 to 10.5), egophony (LR+ = 6.17, 95% CI = 1.34 to 18.0), dullness to percussion (LR+ = 2.62, 95% CI = 1.14 to 5.30), and measured temperature (LR+ = 2.52, 95% CI = 2.02 to 3.20), while it is decreased most by the absence of abnormal vital signs (LR- = 0.25, 95% CI = 0.11 to 0.48). The overall clinical impression also had the highest AUROCC at 0.741. CONCLUSIONS: While most individual signs and symptoms were unhelpful, selected signs and symptoms are of value for diagnosing CAP. Teaching and performing these high value elements of the physical examination should be prioritized, with the goal of better targeting chest radiographs and ultimately antibiotics.

Accuracy of Biomarkers for the Diagnosis of Adult Community-acquired Pneumonia: A Meta-analysis.

BACKGROUND: Biomarkers such as C-reactive protein (CRP) and procalcitonin may help distinguish community-acquired pneumonia (CAP) from other causes of lower respiratory tract infection. METHODS: We performed a systematic review of the literature to identify prospective studies evaluating the accuracy of a biomarker in patients with acute cough or suspected CAP. We performed parallel abstraction of data regarding study inclusion, characteristics, quality, and test accuracy. Study quality was evaluated using QUADAS-2. Bivariate meta-analysis was performed using the mada package in R, and summary receiver operating characteristic (ROC) curves were created. RESULTS: Fourteen studies met our inclusion and exclusion criteria; three were at low risk of bias and four at moderate risk of bias, largely due to failure to prespecify diagnostic thresholds. Considering all studies regardless of the cutoff used, CRP was most accurate (area under the ROC curve = 0.802), followed by leukocytosis (0.777) and procalcitonin (0.771). Lipopolysaccharide-binding protein and fibrinogen are promising, but were only studied in a single report. For CRP and procalcitonin, the positive and negative likelihood ratios (LR+ and LR-, respectively) varied inversely based on the cutoff. For CRP, LR+ and LR- were 2.08 and 0.32 for a cutoff of 20 mg/L, 3.64 and 0.36 for a cutoff of 50 mg/L, and 5.89 and 0.47 for a cutoff of 100 mg/L. For procalcitonin, LR+ and LR- were 2.50 and 0.39 for a cutoff of 0.10 µg/L, 5.43 and 0.62 for a cutoff of 0.25 µg/L, and 8.25 and 0.76 for a cutoff of 0.50 µg/L. The combination of CRP >49.5 mg/L and procalcitonin >0.1 µg/L had LR+ of 2.24 and LR- of 0.44. CONCLUSIONS: The best evidence supports CRP as the preferred biomarker for diagnosis of outpatient CAP given its accuracy, low cost, and point-of-care availability.

Role of aldolase A in osteosarcoma progression and metastasis: in vitro and in vivo evidence.

Aldolase A (ALDOA) has been reported to be negative survival marker of osteosarcoma (OS) and may be implicated in OS development and progression. In the present study, we assessed for the first time the functional role of ALDOA in OS cell invasion and survival in vitro and in vivo, using human OS cell lines and an orthotopic xenograft nude mouse model. Overexpression and knockdown of ALDOA were respectively performed in MG-63 and U-2 OS cells, which showed relatively low and high constitutive ALDOA expression levels, respectively. Overexpression of ALDOA in MG-63 cells significantly increased in vitro cell invasion, matrix metalloproteinase (MMP)-2 expression, and cell survival against cisplatin-induced apoptosis. On the other hand, knockdown of ALDOA in U-2 cells markedly decreased in vitro cell invasion, MMP-2 expression, and cell survival against cisplatin-induced apoptosis. In an orthotopic xenograft nude mouse model, intra-tibial injection of MG-63 cells overexpressing ALDOA led to significantly increased primary tumor volume and pulmonary metastasis as well as decreased cell apoptosis in the primary tumors, compared with the controls. In contrast, intra-tibial injection of U-2 cells with knockdown of ALDOA led to markedly decreased primary tumor volume and pulmonary metastasis as well as increased cell apoptosis in the primary tumors, compared with the controls. In conclusion, our in vitro data indicate that ALDOA promotes OS cell invasion and survival, and our in vivo data demonstrate an important role of ALDOA in promoting OS tumor growth and metastasis. The present study provides the first in vitro and in vivo evidence supporting a critical functional role of ALDOA in OS progression and metastasis, suggesting that ALDOA could serve as a novel therapeutic target in OS. Additionally, our results suggest that ALDOA is involved in the development of OS chemoresistance.