Performance of a SARS-CoV-2 antigen rapid immunoassay in patients admitted to the emergency department.

OBJECTIVES: Given the ongoing pandemic emergency, there is a need to identify SARS CoV-2 infection in various community settings. Rapid antigen testing is spreading worldwide, but diagnostic accuracy is extremely variable. Our study compared a microfluidic rapid antigen test with a reference molecular assay in patients admitted to the emergency department (ED) of a general hospital from October 2020 to January 2021. METHODS: Nasopharyngeal swabs collected in patients with suspected COVID-19 and in patients with no symptoms suggesting COVID-19, but requiring hospitalization, were obtained. RESULTS: 792 patients of median age 71 years were included. With a prevalence of 21%, the results showed: 68.7% (95% confidence interval [CI]: 60.9-75.5) sensitivity; 95.2% (95% CI: 93.1-96.7) specificity; 79.2% (95% CI: 71.4-85.3) positive predictive value (PPV); 91.9% (95% CI: 89.5-93.9) negative predictive value; 3.8 (95% CI: 2.7-5.3) positive likelihood ratio (LR+); and 0.09 (95% CI: 0.07-0.1) negative likelihood ratio (LR-). In the symptomatic subgroup, sensitivity increased to 81% (95% CI: 70.3-88.6) and PPV to 96.9% (95% CI: 88.5-99.5), along with an LR+ of 32 (95% CI: 8.2-125.4). CONCLUSIONS: The new rapid antigen test showed an overall excellent diagnostic performance in a challenging situation, such as that of an ED during the COVID-19 emergency.

Prevalence of respiratory viruses by Multiplex PCR: a four-and-a-half year retrospective study in an Italian general hospital.

Viruses are frequent causal agents of acute respiratory infections and the most common are influenza virus, respiratory syncytial virus (RSV), human parainfluenza virus (HPIV), human metapneumovirus (HMPV), rhinovirus (RV), adenovirus (AdV) and the four endemic human coronaviruses (HCoV) -229E, -NL63, -OC43, -HKU1. Multiplex real-time PCR platforms are becoming increasingly common in laboratories mostly in relation to the increased diagnostic sensitivity and reduced turnaround time. The aim of our study was to determine the prevalence of respiratory viruses in a population of patients within the S.S. Antonio e Biagio e Cesare Arrigo General Hospital catchment area of Alessandria, Italy, from January 2016 to June 2020. Therefore, we retrospectively analyzed the results of multiplex real-time PCR performed on nasopharyngeal swabs collected from consecutive patients with symptoms of respiratory infection. A total of 572 patients were included in the study subdivided as follows: pediatric 197/572 (34.4%), adults 200/572 (35%) and elderly 175/572 (30.6%). Among all samples, 235/572 (41.1%) were positive for a respiratory virus, of whom 189/235 (80.4%) were monomicrobial. The prevalence was: 15.5% (89/572) of rhinovirus/enterovirus (RV/EV); 9.4% (54/572) of RSV; 8.9% (51/572) of influenza virus; 5.4% (31/572) of AdV; 3.1% (18/572) of HCoV; 2.8% (16/572) of HPIV; and 2.3% (13/572) of HMPV. RV/EV were the pathogens most frequently involved in coinfections (34.7%, 16/46), followed by AdV (19.6%, 9/46) and influenza virus (19.6%, 9/46). Samples collected from the pediatric group were more frequently positive. The prevalence of positive pediatric samples compared to adults and elderly, respectively was: 28.4% (56/197) for RV/EV vs 10.5% (21/200) vs 6.9% (12/175), p<0.0001; 18.8% (37/197) for RSV vs 2% (4/200) vs 7.4% (13/175), p<0.0001; 13.7% (27/197) for AdV vs 1% (2/200) vs 1.1% (2/175), p<0.0001; and 6.6% (13/197) for HPIV vs 0.5% (1/200) vs 1.1% (2/175), (p<0.0001). With regard to seasonality, a significantly higher prevalence of influenza virus (p<0.0001) and RSV (p=0.029) was found during winter, with peaks in January-February. AdV peaked during winter 2018-2019 (p=0.004), while HCoV were detected with a significantly higher prevalence during winter 2019-2020 (p=0.037). With regard to HPIV, a significant peak from summer to fall 2018 was observed (p=0.016). Most viral respiratory infections have seasonal patterns and the prevalence of respiratory viruses varies according to the method, geographic area and population considered. Knowledge of local epidemiology is therefore crucial for implementation of prevention and treatment strategies.

Clinical Utility of Platelet Count for Screening of Malaria.

Light microscopy, immunochromatographic rapid diagnostic tests and molecular methods are widely used to diagnose malaria. The aim of this study was to find variables among commonly available urgent blood tests to identify patients with low probability of having malaria in small-scale healthcare facilities in which none of the described methods is feasible within a short time. Diagnosis of malaria was made by examining both stained thick and thin blood films by light microscopy. Two hundred and eleven samples were included. Reduced platelet count and increased values of C-reactive protein (CRP) and total bilirubin were the variables most strongly associated with malaria (P<0.0001). The best screening cut-off values obtained by receiver operating characteristic curve analysis for a negative result for malaria were: platelets ≥185,000 cells/µl; CRP ≤2 mg/dl; total bilirubin ≤0.28 mg/dl. The logistic regression model of log-transformed variables showed how platelet count was the only independent variable related to the odds of having a negative blood film result for malaria (odds ratio: 2.621; 95% confidence interval: 1.441-4.768; P=0.002). A platelet count of ≥185,000 cells/µl can be considered a screening value to identify patients with high-probability of a negative blood film result for malaria.

Evaluation of a multiplex gastrointestinal PCR panel for the aetiological diagnosis of infectious diarrhoea.

Background: Infectious diarrhoea is a significant cause of morbidity worldwide. Culture and microscopy are time-consuming and have a low yield. New rapid molecular methods such as multiplex PCR, have been recently introduced for aetiological diagnosis. Aim of this study was to compare the diagnostic yield of the FilmArray gastrointestinal panel with that of standard culture for aetiological diagnosis of infectious diarrhoea.Methods: We performed a retrospective analysis of results of stool samples already processed as part of routine clinical care in the interval from March 2016 to March 2019.Results: One hundred and eighty-three stool samples from as many patients were both cultured and tested by FilmArray and the comparison of diagnostic accuracy between culture and FilmArray with respect to Campylobacter spp., Salmonella spp., Shigella spp., Yersinia enterocolitica and Shiga-like toxin producing E. coli O157 gave the following results: 100% (95% confidence interval (CI): 85-100%) sensitivity; 93.4% (95% CI: 87.9-96.6%) specificity; 74.3% (95% CI: 57.5-86.4%) positive predictive value; 100% (95% CI: 96.7-100%) negative predictive value; 2.9 (95% CI: 1.6-5.1) positive likelihood ratio; zero negative likelihood ratio. By means of FilmArray gastrointestinal (GI) panel, we could identify 34.5% more pathogens (p = .001). Bacteria were mostly detected in patients with 6 or more years of age (χ2=17.1; p = .009) during summer.Conclusions: FilmArray GI panel showed a very good diagnostic performance compared to culture for diagnosis of infectious diarrhoea and gave a more detailed picture of the spectrum of the pathogens involved.

Diagnostic accuracy of a commercial multiplex PCR for the diagnosis of meningitis and encephalitis in an Italian general hospital.

Infectious meningitis and encephalitis are potentially life-threatening conditions caused mostly by bacterial and viral agents. Rapid diagnosis and prompt treatment are associated with a more favorable outcome. In recent years nucleic acid amplification tests have been developed to speed detection and identification of pathogens directly from cerebrospinal fluid (CSF). The aim of this study was to compare the diagnostic accuracy of a commercially available multiplex PCR assay for etiological diagnosis of infectious meningitis directly from CSF samples with culture. A secondary endpoint was to look for a possible screening threshold based on main CSF indices and urgent blood test results, to define CSF samples with low pre-test probability of PCR and/or culture-positive result. We performed a secondary analysis of results of CSF samples already processed as part of routine clinical care from February 2016 to December 2018. In all, 109 CSF samples were included in the study and a total of 14 bacteria were identified by either PCR, culture or both methods, along with nine samples positive for viruses. The comparison of PCR results with culture showed no significant difference: 7/109 (6.4%) vs 13/109 (11.9%) respectively, p=0.07. After exclusion of the isolates not detectable by the multiplex PCR panel, the diagnostic accuracy was: 100% (95% confidence interval (CI): 54.1% to 100%) sensitivity; 98.9% (95% CI: 93.5% to 99.9%) specificity; 85.7% (95% CI: 42% to 99.2%) positive predictive value; 100% (95% CI: 95.1% to 100%) negative predictive value; 96 (95% CI: 13.6 to 674.6) LR+; Zero LR-; Cohen's kappa: 0.918, p<0.0001. CSF protein value ≤ 28 mg/dl and CSF glucose/blood glucose ratio ≥0.78 were associated with both PCR-negative result for bacteria or viruses and culture-negative result. The multiplex PCR evaluated in this study showed a very good diagnostic performance compared to culture, and the thresholds found can be a useful tool to best choose which samples to test.

The effect of gender on methotrexate prescription attitudes in Italian rheumatoid arthritis patients: the MARI study.

OBJECTIVES: The MARI study investigated the prescription patterns of methotrexate (MTX) in patients presenting with rheumatoid arthritis (RA) in Italy. The primary aims of this cross-sectional analysis from the MARI study were to investigate the effect of gender on the prescription patterns and safety of MTX therapy. METHODS: The study enrolled 1336 patients with RA. Retrospective data included patients' clinical history, previous treatment with MTX and other DMARDs, and MTX modifications in the previous 12-month period. Cross-sectional data included information about current treatment with MTX (dose and route of administration, and adverse events), concomitant medications, disease activity, and modifications of MTX treatment at study entry. The prescription patterns of MTX, rates and causes of MTX modifications were analysed according to gender. RESULTS: There were no significant differences related to gender in the prescription patterns of MTX, either at 6 months after starting MTX or at the time of study entry. In the 12 months prior to study entry, women (4%) were more likely to undergo MTX modifications (dose or route of administration) compared to men (2%, p=0.032), due to subjective intolerance, but this difference was no longer significant after controlling for confounders. At study entry, a higher proportion of women (27%) reported tolerability issues (nausea and weakness) related to MTX compared to men (14%, p=0.001). Although a similar percentage of males and females changed dose or route of administration of MTX at the time of study entry, the reasons for such modifications were dissimilar between genders. Particularly, a higher proportion of women underwent MTX modification due to intolerance (women 6% vs. men 1%, p=0.002). CONCLUSIONS: In Italy, prescription patterns of MTX do not differ between genders. However, women seem to be at higher risk of adverse events leading to MTX modifications.

Influence of earthquakes on the occurrence of aortic aneurysm ruptures.

BACKGROUND: Catastrophic events have been correlated to increased incidence of cardio-vascular events, but no correlation between RAA and seismic activities have ever been investigated. METHODS: Hospital admissions related to RAA between January 2014 and December 2016 were retrospectively assessed in nine vascular centers of central Italy and correlated with date-matched seismic events. Correlation between RAA presentation and seismic event was first evaluated by Linear Regression analysis. Incidence of RAA events, mortality rate, and type of intervention were analyzed during seismic days (SD) and compared to outcomes during non-seismic days (nSD). RESULTS: A total of 376 patients were admitted with a diagnosis of RAA, and a total of 783 seismic events were reviewed. Twenty patients died before intervention (untreated). Open surgery was performed in 72.8%, endovascular treatment in 27.2%. General mortality at 30 days was 26.6% (30.5% for open surgery; 21.6% for endovascular treatment; P=0.24). Linear regression analysis between RAA and seismic periods revealed a significant correlation (slope=0.11±0.04, equation: y = 0.1143 x + 3.034, P=0.02). Incidence of RAA was 0.34 event per day during the entire period, 0.32 during nSD and 0.44 during SD (P=0.006). During seismic days, patients with RAA were older (80.5 years during SD vs. 77 years during nSD, P=0.12), were in poorer general condition at admission and remained untreated more frequently (8% SD vs. 4.7% nSD, P=0.3), and had a higher mortality rate at 30 days (46.2% SD vs. 27.2% nSD, P=0.012). CONCLUSIONS: During seismic days, the incidence of RAA is higher in comparison to non-seismic days. Patients with rupture during seismic days have a higher risk of death.

The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology.

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

Prospective study of the clinical performance of three BACTEC media in a modern emergency department: Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F.

The performance of 3 blood culture bottles (BACTEC Plus Aerobic/F, Plus Anaerobic/F, and Anaerobic Lytic/F) were analyzed with clinical specimens collected from 688 Emergency Department patients. A total of 270 strains belonging to 33 species were identified, with E. coli and S. aureus as the most frequently detected. Overall recovery rate (RR) of bacteria and yeast was equivalent in the Plus Aerobic/F vials (208 of 270 isolates; 77.0%) and Anaerobic Lytic/F vials (206 isolates; 76.3%) and significantly better than in the Plus Anaerobic/F vials (189 isolates; 70.0%). Median time to detection (TTD) was earliest with the Anaerobic Lytic/F vials (12.0h) compared with the Plus Aerobic/F (14.6h) and Plus Anaerobic/F vials (15.4h). Positivity rate (PR) was similar for Anaerobic Lytic/F vials (76.9%) and Plus Aerobic/F vials (76.5%), but better if compared with Plus Anaerobic/F vials (69.4%). The PR and TTD for the combination of Plus Aerobic/F with Anaerobic Lytic/F (94.5% and 12.3h, respectively) was significantly better than with Plus Aerobic/F with Plus Anaerobic/F (87.8% and 14.1h).

Osteonecrosis in human immunodeficiency virus (HIV)-infected patients: a multicentric case-control study.

Osteonecrosis (ON) is a rare disabling complication occurring in patients with human immunodeficiency virus (HIV) infection at a higher frequency than in the general population despite effective combination antiretroviral therapy being made available, as recently documented by several retrospective studies. We designed a multicentric case-control study among HIV-infected patients cared for at institutions in the Italian CISAI group (Italian Study Group for Adverse Events in HIV Infection) to search for additional predictors of ON in this special population. All centers which observed at least one case of ON were requested to report data for central re-evaluation. Parallel HIV-positive, ON-free controls were randomly selected and matched with confirmed cases of ON for sex, age and CD4 T-cell counts at the time of HIV diagnosis. Fifteen cases and controls were included in the final sample. Univariate statistical analyses revealed a significant association between ON and exposure to steroids (P = 0.001), exposure to one or more drugs in addition to HAART (Highly Active Anti-Retroviral Therapy) (P = 0.03), high titers of total serum IgE (P = 0.02), loss of working ability (P = 0.03), triglycerides levels over 200 mg/dL before antiretrovirals (P = 0.03) and cholesterol levels over 200 mg/dL before and after antiretrovirals (P = 0.03 and 0.05, respectively). High serum IgE levels and loss of working ability in advance of ON appeared for the first time as possible predictors of ON in HIV patients, while long-term exposure to steroids, combined hyperlipemia and chronic treatment with other drugs in addition to antiretrovirals were confirmed. Predicting and preventing ON in the individual HIV-infected patient is therefore a clinically challenging opportunity.

Determinants of thromboxane biosynthesis in rheumatoid arthritis: Role of RAGE and oxidant stress.

Thromboxane (TX) biosynthesis by platelets and other cells in response to inflammatory triggers may provide a link between chronic inflammatory disease and atherothrombosis in rheumatoid arthritis (RA). In this study, we investigated the determinants of TX biosynthesis in RA, with particular reference to enhanced oxidative stress, receptor for advanced glycation end-products (RAGE) hyperactivity, and anti-tumor necrosis factor (TNF) treatment. Fifty-four patients with RA and 20 healthy subjects were recruited and a cross-sectional comparison of urinary 11-dehydro-TXB(2), 8-iso-PGF(2alpha), and plasma endogenous secretory RAGE (esRAGE) levels was performed between patients and controls. Urinary 11-dehydro-TXB(2) was significantly higher in RA patients than in healthy controls [425 (309-592) vs 233 (158-327) pg/mg creatinine, P<0.0001]. Furthermore, urinary 8-iso-PGF(2alpha) [323 (221-515) vs 172 (91-292) pg/mg creatinine, P<0.0001] and plasma esRAGE [155 (100-240) vs 377 (195-486) pg/ml, P=0.001] were higher and lower, respectively, in patients than in controls. A direct correlation was found between urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) only in patients not on anti-TNF therapy (r=0.420, P=0.021). Conversely, patients on anti-TNF therapy showed significantly lower urinary 8-iso-PGF(2alpha) [284 (201-373) vs 404 (241-539) pg/mg creatinine, P=0.043] but not 11-dehydro-TXB(2) than anti-TNF-treated subjects, with esRAGE as the only independent predictor of 11-dehydro-TXB(2) in this group of patients (adjusted R(2)=0.496, beta=-0.725, SEM=0.025, P=0.001). In conclusion, we provide biochemical evidence of enhanced TX biosynthesis in patients with RA, driven, at least in part, by lipid peroxidation. Treatment with anti-TNF agents may blunt isoprostane generation in the absence of significant effects on TX biosynthesis. We suggest that RAGE hyperactivity may escape TNF blockade, thus contributing to persistent TX biosynthesis in this setting.

The burden of prevalent fractures on health-related quality of life in postmenopausal women with osteoporosis: the IMOF study.

OBJECTIVE: Vertebral fractures are a common complication of osteoporosis and may have a negative effect on health-related quality of life (HRQOL). We investigated the effect of prevalent vertebral fractures on HRQOL in patients with osteoporosis. METHODS: A cross-sectional multicenter study was carried out among postmenopausal women with primary osteoporosis attending primary care centers and hospital outpatient clinics: 234 women with vertebral fractures and 244 asymptomatic women. Women with secondary osteoporosis or taking medications that affect bone metabolism were excluded. All patients were questioned using the mini-Osteoporosis Quality of Life Questionnaire (mini-OQLQ), Medical Outcomes Study Short Form-36 (SF-36), and the EuroQuol-5D, after assessment of all clinical variables and anthropometric data. To assess comorbidity we used the Self-Administered Comorbidity Questionnaire (SCQ). Diagnosis of osteoporosis was confirmed in all patients by bone mineral density using dual energy x-ray absorptiometry. Radiographic evaluation was performed by a musculoskeletal radiologist. A total of 483 postmenopausal women, randomly matched for age out of 1579 healthy controls, were chosen to compare the SF-36 scores with respect to patients with and without vertebral fractures due to osteoporosis. A multivariable regression analysis was conducted to identify the strongest determinant for low HRQOL, adjusted for potential confounding variables such as comorbid conditions, education level, and psychosocial status. RESULTS: The vertebral fracture group had significantly lower scores than patients without fractures and controls in all domains of the generic and specific questionnaires. Women with only 1 prevalent fracture had statistically significantly lower HRQOL scores than those without fractures on SF-36 measures of bodily pain, physical functioning, and role function physical (all p < 0.01). HRQOL scores were lower in women with lumbar fractures compared with women with thoracic fractures only when the physical functioning and bodily pain dimensions approached statistical significance. Based on the multivariate analysis, the strongest determinant for low HRQOL was physical functioning (explained by number of vertebral fractures) followed by comorbidity score and age. Adjusted R2 in the final model was 35.9%. Using the SF-36 summary scales, comorbid conditions predominantly affected either mental or physical health (p < 0.0001). A significant correlation (p <0.0001) was found between total score on the mini-OQLQ and the mean SCQ comorbidity score. CONCLUSION: Our results confirm previous findings that HRQOL, assessed by generic and osteoporosis-specific instruments, is decreased in patients with vertebral fractures due to osteoporosis as a function of the number of vertebral fractures, presence of comorbid conditions, and age.

Effect of low dose methotrexate on bone density in women with rheumatoid arthritis: results from a multicenter cross-sectional study.

OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using data from a large multicenter, cross-sectional study on bone mineral density (BMD) in women with rheumatoid arthritis (RA). METHODS: We selected 731 female patients with RA divided into 2 groups on the basis of MTX use: never MTX users (n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease, and treatment related variables were collected for each patient. BMD was measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry. Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS) for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively. Mean T-score values at lumbar spine and femoral neck were comparable in the 2 groups, even after adjusting for age, menopausal status, body mass index (BMI), Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized linear model showed that age, menopause, BMI, HAQ score, and steroid use were significant independent predictors of BMD at lumbar or at femoral level, whereas MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI were significantly associated with the risk of osteoporosis. CONCLUSION: We found no negative effect of low dose MTX on BMD in women with RA.