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Background Uncomplicated episodes of prolonged acute cough are usually viral and self-limited, but despite evidence and recommendations to the contrary, they are often treated with antibiotics. Methods Mixed cross-sectional and prospective observational study of adults 18 years or older presenting to two urgent care centers with a cough of 7 to 56 days as their chief complaint. Factors associated with cough duration and clinical decisions were analyzed by univariate and multivariate logistic regression. Results Of the 125 enrolled patients, 118 (94%) received an antibiotic, 97 (78%) a cough suppressant, 87 (70%) a systemic corticosteroid, and 39 (31%) a chest X-ray (CXR). Longer duration of cough was associated with the presence of self-reported wheezing or noises (adjusted odds ratio 6.29, 95% CI 1.36–29.16) while the presence of both wheezing and crackles on a clinician chest exam was associated with shorter duration (aOR 0.03, 95% CI 0.00–0.27). A clinician was more likely to order a CXR in patients with dyspnea (aOR 3.01, 95% CI 1.21–7.49), less likely to prescribe a systemic corticosteroid in patients with crackles (aOR 0.27, 95% CI 0.09–0.82), and more likely to prescribe a cough suppressant to older patients (1.04 per additional year of age, 95% CI 1.01–1.07). Conclusions Systemic corticosteroids and cough suppressants are being prescribed at high rates in patients with uncomplicated acute cough in the urgent care setting. Additional studies to determine if similar rates are seen in other urgent care centers, or in other contemporary ambulatory settings are warranted. more...

Background Rapid point-of-care polymerase chain reaction (PCR) diagnostic tests generally provide a qualitative result of positive or negative only. Additional information about the relative viral load could be calculated. Such quantitative information might be useful for making treatment decisions. Methods We enrolled students at a university health center who presented with cough and 1 additional flu-like symptom from December 2016 to February 2017. Data were collected before, during, and 5 days after the clinic visit. All those enrolled in the study received a point-of-care PCR test (cobas Liat). For those patients that tested positive for influenza A, we investigated correlations between the relative viral load and measures of disease severity and recovery. Results One hundred thirty-five students tested positive for influenza A. We found a positive correlation between viral load and body temperature. Time since symptom onset seemed to have a negative correlation but was not statistically significant. We did not find any correlations between viral load and overall symptom severity or outcomes related to recovery. Conclusions Although we found a correlation between relative viral load and body temperature, for our study population of young, overall healthy adults, we did not find that relative viral load provided additional information that could help in determining treatment and disease outcomes. It could be that viral load does provide useful additional information for other groups of patients, such as young children or older adults. Further studies on those populations are warranted., Rapid point-of-care (POC) PCR tests can generate estimates of viral load. Viral loads at diagnosis using a POC PCR test are associated with body temperature. Among our population, viral load at diagnosis was not predictive of disease severity or recovery. more...

Background: Rapid influenza diagnostic tests that detect the presence of viral antigens are currently used throughout the United States but have poor sensitivity. The objective of this study was to identify if the use of a new highly accurate rapid point of care test would significantly increase the likelihood of guideline consistent care. Methods: We prospectively recruited 300 students at a university health clinic who presented with cough and 1 influenza-like illness symptom between December 2016 and February 2017 to receive care guided by a rapid polymerase chain reaction (PCR) test. Of the 300 patients receiving the PCR test, 264 had complete medical records and were compared to 771 who received usual care. We used a logistic regression model to identify whether PCR guided care was associated with guideline consistent care, based on the appropriate use of oseltamivir and antibiotics. We also assessed whether PCR guided care decreased the likelihood of return visits within 2 weeks by patients. Results: Logistic regression revealed that the odds of receiving guideline supported care did not significantly increase for patients who received PCR guided care (adjusted odds ratio [aOR], 1.24; 95% CI, 0.83–1.88). It significantly decreased the likelihood of an antibiotic prescription (aOR, 0.61; 95% CI, 0.40–0.94), increased the likelihood of receiving oseltamivir (aOR, 1.57; 95% CI, 1.09–2.28), and decreased the likelihood of return visit within 2 weeks (aOR, 0.19; 95% CI, 0.04–0.81). Conclusions: The use of a rapid PCR test did not significantly improve the likelihood of guideline consistent care. However, independent of test outcome, patients who received the test were more likely to receive an antiviral and less likely to receive an antibiotic or have a return visit within 2 weeks. more...

Communicable diseases are often virulent, i.e. they cause morbidity symptoms in those infected. While some symptoms may be transmission-enhancing, other symptoms are likely to reduce transmission potential. For human diseases, the reduction in transmission opportunities is commonly caused by reduced activity. There is limited data regarding the potential impact of virulence on transmission potential. We performed an exploratory data analysis of 324 influenza patients at a university health centre during the 2016/2017 influenza season. We classified symptoms as infectiousness-related or morbidity-related and calculated two scores. The scores were used to explore the relationship between infectiousness, morbidity (virulence), and activity level. We found a decrease in the activity level with increasing morbidity scores. There was no consistent pattern between an activity level and an infectiousness score. We also found a positive correlation between morbidity and infectiousness scores. Overall, we find that increasing virulence leads to increased infectiousness and reduced activity, suggesting a trade-off that can impact overall transmission potential. Our findings indicate that a reduction of systemic symptoms may increase host activity without reducing infectiousness. Therefore, interventions should target both systemic- and infectiousness-related symptoms to reduce overall transmission potential. Our findings can also inform simulation models that investigate the impact of different interventions on transmission. more...

A symptom-based mass screening and testing intervention (MSTI) can identify a large fraction of infected individuals during an infectious disease outbreak. China is currently using this strategy for the COVID-19 outbreak. However, MSTI might lead to increased transmission if not properly implemented. We investigate under which conditions MSTI is beneficial. more...

Directly observed therapy (DOT) is almost universally used for the treatment of TB. Several meta-analyses using different methods have assessed the effectiveness of DOT compared to self-administered therapy (SAT). The results of these meta-analyses often conflict with some concluding DOT is superior and others that there is little or no difference. Meta-analyses can guide policymaking, but such analyses must be reliable. To assess the validity of a previous meta-analysis, we tried to reproduce it. We encountered problems with the previous analysis that did not allow for a meaningful reproduction. We describe the issues we encountered here. We then performed a new meta-analysis comparing the treatment outcomes of adults given treatment with SAT versus DOT. Outcomes in the new analysis are loss to follow-up, treatment failure, cure, treatment completed, and all-cause mortality. All data, documentation, and code used to generate our results is provided. Our new analysis included four randomized and three observational studies with 1603 and 1626 individuals respectively. The pooled relative risks (RR) are as follows: Lost to follow-up (RR = 1.2, 95% CI 0.9, 1.7), Treatment Failure (RR = 1.1, 95% CI 0.6, 2), Cure (RR = 0.9, 95% CI 0.8, 1.1), Treatment Completion (RR = 1, 95% CI 0.9, 1.1), Mortality (RR = 0.9, 95% CI 0.6, 1.3). Based on data from our new meta-analysis, the magnitude of the difference between DOT and SAT for all reported outcomes is small, and none of the differences are statistically significant. more...

PURPOSE To evaluate the accuracy of signs and symptoms for the diagnosis of acute rhinosinusitis (ARS). METHODS We searched Medline to identify studies of outpatients with clinically suspected ARS and sufficient data reported to calculate the sensitivity and specificity. Of 1,649 studies initially identified, 17 met our inclusion criteria. Acute rhinosinusitis was diagnosed by any valid reference standard, whereas acute bacterial rhinosinusitis (ABRS) was diagnosed by purulence on antral puncture or positive bacterial culture. We used bivariate meta-analysis to calculate summary estimates of test accuracy. RESULTS Among patients with clinically suspected ARS, the prevalence of imaging confirmed ARS is 51% and ABRS is 31%. Clinical findings that best rule in ARS are purulent secretions in the middle meatus (positive likelihood ratio [LR+] 3.2) and the overall clinical impression (LR+ 3.0). The findings that best rule out ARS are the overall clinical impression (negative likelihood ratio [LR−] 0.37), normal transillumination (LR− 0.55), the absence of preceding respiratory tract infection (LR− 0.48), any nasal discharge (LR− 0.49), and purulent nasal discharge (LR− 0.54). Based on limited data, the overall clinical impression (LR+ 3.8, LR− 0.34), cacosmia (fetid odor on the breath) (LR+ 4.3, LR− 0.86) and pain in the teeth (LR+ 2.0, LR− 0.77) are the best predictors of ABRS. While several clinical decision rules have been proposed, none have been prospectively validated. CONCLUSIONS Among patients with clinically suspected ARS, only about one-third have ABRS. The overall clinical impression, cacosmia, and pain in the teeth are the best predictors of ABRS. Clinical decision rules, including those incorporating C-reactive protein, and use of urine dipsticks are promising, but require prospective validation. more...

The presence of antibodies to Zika virus (ZIKV) and dengue virus (DENV) can be detected in blood donations. Donation-based surveillance provides an alternative strategy to estimate population prevalence by detecting antibodies that are circulating. To estimate population prevalence, we conducted a systematic review of literature on the seroprevalence of ZIKV and DENV antibodies in blood donations. We searched PubMed and Web of Science for studies that reported the seroprevalence of ZIKV and DENV in blood donations. The title and abstract of each study were screened by 2 reviewers simultaneously for possible inclusion, and the full text of selected studies was reviewed to ensure that they met inclusion criteria (used primary data collection, reported evidence of immunoglobulin M (IgM) or immunoglobulin G (IgG) antibodies in the blood supply, and included a representative sample of the total population). Immunoglobin test measuring levels of antibodies to IgM and IgG and number of positive cases were extracted from each study. No exclusions were made based on language or country. Our initial search identified 1890 studies after excluding duplicates, of which 76 were assessed for full text eligibility to ensure that they met our final inclusion criteria. There were 14 studies included in our review; 11 examined the seroprevalence of DENV, and 3 examined ZIKV. The highest seroprevalence by IgM was 2.82% for DENV and 0.53% for ZIKV. Our results indicate that the seroprevalence of ZIKV and DENV antibody presence in countries with active transmission is higher than reports by traditional surveillance in some countries. This finding is expected due to the large percentage of asymptomatic cases. The highest seroprevalence was observed for IgG, which can persist over long periods of time compared to IgM. Screening of blood donations may help supplement traditional surveillance measures, especially during outbreak settings. more...

Vaccination is an effective method to protect against infectious diseases. An important consideration in any vaccine formulation is the inoculum dose, i.e., amount of antigen or live attenuated pathogen that is used. Higher levels generally lead to better stimulation of the immune response but might cause more severe side effects and allow for less population coverage in the presence of vaccine shortages. Determining the optimal amount of inoculum dose is an important component of rational vaccine design. A combination of mathematical models with experimental data can help determine the impact of the inoculum dose. We illustrate the concept of using data and models to inform inoculum dose determination for vaccines, wby fitting a mathematical model to data from influenza A virus (IAV) infection of mice and human parainfluenza virus (HPIV) infection of cotton rats at different inoculum doses. We use the model to map inoculum dose to the level of immune protection and morbidity and to explore how such a framework might be used to determine an optimal inoculum dose. We show how a framework that combines mathematical models with experimental data can be used to study the impact of inoculum dose on important outcomes such as immune protection and morbidity. Our findings illustrate that the impact of inoculum dose on immune protection and morbidity can depend on the specific pathogen and that both protection and morbidity do not necessarily increase monotonically with increasing inoculum dose. Once vaccine design goals are specified with required levels of protection and acceptable levels of morbidity, our proposed framework can help in the rational design of vaccines and determination of the optimal amount of inoculum., Author summary An important component of vaccines is the amount of pathogen inoculum, dead or alive, that is included in the vaccine. This inoculum dose, sometimes also referred to as antigen dose, needs to be large enough to induce good protective immunity. However, one usually also wants to keep the dose low to reduce costs, maximize the number of vaccine doses available, and minimize potential vaccine side effects. The inoculum dose is currently chosen based on limited data from clinical trials. In this study, we set up a framework that combines data with mathematical models to illustrate how such a combination could lead to better and more efficient determination of an optimal inoculum dose for vaccines. more...

Two different Al–5Ti–1B (wt-%) grain refiner rods (Rod A – a 'poor' refiner and Rod B – a 'standard' refiner) were examined using induced coupled plasma – optical emission spectroscopy (ICP-OES), computed tomography (CT) and scanning electron microscopy (SEM) equipped with energy dispersive X-ray (EDX) spectroscopy. CT with its digital geometrical processing allowed 3D images of non-destructed sections of the rod to be analysed. Results for Rod A revealed the presence of several types of inclusions up to several mm in size. Qualitative micro-chemical analysis using an SEM with EDX indicated that the inclusions were Ti, K and/or F rich. This would thus imply that the particles observed were, undissolved Ti/Al-Ti compounds namely Al3Ti and/or Al3Ti(Si), and potassium and fluoride spent salts namely KF-AlF3 flux. These findings are indicative of an inefficient, non-optimal manufacturing process. An assessment of the grain refining efficacy of both the rods using the TP1 test showed the standard rod (... more...

Background Acute rhinosinusitis (ARS) is a common primary care infection, but there have been no recent, comprehensive diagnostic meta-analyses. Aim To determine the accuracy of laboratory and imaging studies for the diagnosis of ARS. Design and setting Systematic review of diagnostic tests in outpatient, primary care, and specialty settings. Method The authors included studies of patients presenting with or referred for suspected ARS, and used bivariate meta-analysis to calculate summary estimates of test accuracy and the area under the receiver operating characteristic (ROC) curve. The authors also plotted summary ROC curves to explore heterogeneity, cutoffs, and the impact of different reference standards. Results Using antral puncture as the reference standard, A mode ultrasound (positive likelihood ratio [LR+] 1.71, negative likelihood ratio [LR−] 0.41), B mode ultrasound (LR+ 1.64, LR− 0.69), and radiography (LR+ 2.01, LR− 0.28) had only modest accuracy. Accuracy was higher using imaging as the reference standard for both ultrasound (LR+12.4, LR− 0.35) and radiography (LR+ 9.4, LR− 0.27), although this likely overestimates accuracy. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) both had clear threshold effects, and modest overall accuracy. The LR+ for ESR >30 and >40 were 4.08 and 7.40, respectively. A dipstick of nasal secretions for leucocyte esterase was highly accurate (LR+18.4, LR− 0.17) but has not been validated. Conclusion In general, tests were of limited value in the diagnosis of ARS. Normal radiography helps rule out sinusitis when negative, whereas CRP and ESR help rule in sinusitis when positive, although, given their limited accuracy as individual tests, they cannot be routinely recommended. Prospective studies integrating signs and symptoms with point-of-care CRP, dipstick, and/ or handheld B-mode ultrasound are needed. more...