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We developed a practical influenza forecast model based on real-time, geographically focused, and easy to access data, designed to provide individual medical centers with advanced warning of the expected number of influenza cases, thus allowing for sufficient time to implement interventions. Secondly, we evaluated the effects of incorporating a real-time influenza surveillance system, Google Flu Trends, and meteorological and temporal information on forecast accuracy. Forecast models designed to predict one week in advance were developed from weekly counts of confirmed influenza cases over seven seasons (2004-2011) divided into seven training and out-of-sample verification sets. Forecasting procedures using classical Box-Jenkins, generalized linear models (GLM), and generalized linear autoregressive moving average (GARMA) methods were employed to develop the final model and assess the relative contribution of external variables such as, Google Flu Trends, meteorological data, and temporal information. A GARMA(3,0) forecast model with Negative Binomial distribution integrating Google Flu Trends information provided the most accurate influenza case predictions. The model, on the average, predicts weekly influenza cases during 7 out-of-sample outbreaks within 7 cases for 83% of estimates. Google Flu Trend data was the only source of external information to provide statistically significant forecast improvements over the base model in four of the seven out-of-sample verification sets. Overall, the p-value of adding this external information to the model is 0.0005. The other exogenous variables did not yield a statistically significant improvement in any of the verification sets. Integer-valued autoregression of influenza cases provides a strong base forecast model, which is enhanced by the addition of Google Flu Trends confirming the predictive capabilities of search query based syndromic surveillance. This accessible and flexible forecast model can be used by individual medical centers to provide advanced warning of future influenza cases.

Molecular diagnostics are revolutionising the clinical practice of infectious disease. Their effects will be significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes. PCR is the most well-developed molecular technique up to now, and has a wide range of already fulfilled, and potential, clinical applications, including specific or broad-spectrum pathogen detection, evaluation of emerging novel infections, surveillance, early detection of biothreat agents, and antimicrobial resistance profiling. PCR-based methods may also be cost effective relative to traditional testing procedures. Further advancement of technology is needed to improve automation, optimise detection sensitivity and specificity, and expand the capacity to detect multiple targets simultaneously (multiplexing). This review provides an up-to-date look at the general principles, diagnostic value, and limitations of the most current PCR-based platforms as they evolve from bench to bedside.

In this randomized clinical trial in patients presenting to U.S. emergency departments with an acute uncomplicated cutaneous abscess, drainage plus trimethoprim–sulfamethoxazole therapy for a week was associated with modest clinical benefits as compared with drainage alone. Between 1993 and 2005, annual emergency department visits for skin and soft-tissue infections in the United States increased from 1.2 million to 3.4 million, primarily because of an increased incidence of abscesses. 1 , 2 During this period, community-associated methicillin-resistant Staphylococcus aureus (MRSA) emerged as the most common cause of purulent skin and soft-tissue infections in many parts of the world. 3 Trimethoprim–sulfamethoxazole, which has retained in vitro activity against community-associated MRSA, is among the most commonly prescribed antibiotics to treat these infections. 4 The primary treatment of a cutaneous abscess is drainage. 5 Whether adjunctive antibiotics lead to improved outcomes in patients with uncomplicated . . .

The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.

With the emergence of new SARS-CoV-2 variants has come significant variations in disease manifestation, severity, and duration in non-hospitalized infected patients. To characterize symptom patterns and risk factors associated with symptom severity and duration, COVID-19 and influenza-like illness (ILI) outpatients and their contacts were enrolled at two sites in the United States of America and one site in Thailand. COVID-19 infection was confirmed at enrollment with a positive antigen or PCR test. Baseline demographics and medical histories were collected from participants at enrollment and daily self-reported symptom questionnaires were obtained to assess symptom severity and duration. Risk factors associated with symptom severity and duration were determined by multivariate logistic regression and Cox proportional hazards model. Two hundred and forty one participants meeting the eligibility criteria were enrolled, including 174 confirmed COVID-19 cases (9% Delta and 90% Omicron), 33 ILI cases, and 34 healthy contacts. COVID-19 participants had a shorter median symptom duration of 9.0 (95% CI, 8.0-11.0) days than ILI participants. Infection with the Delta variant resulted in a longer symptom alleviation period compared to infection with the Omicron variant. The most commonly reported symptoms among COVID-19 participants were reported in the nasal and chest/respiratory domains of the FLU-PRO Plus. Participants infected with the Delta variant reported more symptoms overall, with significantly more symptoms affecting eyes and senses reported. 55% of SARS-CoV-2-positive participants reached a negative N1 Ct value by the day 14 study time point. No risk factors for moderate to severe symptoms were identified in this outpatient cohort. Male sex was associated with a shorter symptom duration. Symptom manifestation varied among Delta and Omicron variants. Few risk factors were identified for increased symptom severity or duration.

The abuse of psychoactive 'bath salts' containing cathinones such as 3,4-methylenedioxypyrovalerone (MDPV) is a growing public health concern, yet little is known about their pharmacology. Here, we evaluated the effects of MDPV and related drugs using molecular, cellular, and whole-animal methods. In vitro transporter assays were performed in rat brain synaptosomes and in cells expressing human transporters, while clearance of endogenous dopamine was measured by fast-scan cyclic voltammetry in mouse striatal slices. Assessments of in vivo neurochemistry, locomotor activity, and cardiovascular parameters were carried out in rats. We found that MDPV blocks uptake of [(3)H]dopamine (IC(50)=4.1 nM) and [(3)H]norepinephrine (IC(50)=26 nM) with high potency but has weak effects on uptake of [(3)H]serotonin (IC(50)=3349 nM). In contrast to other psychoactive cathinones (eg, mephedrone), MDPV is not a transporter substrate. The clearance of endogenous dopamine is inhibited by MDPV and cocaine in a similar manner, but MDPV displays greater potency and efficacy. Consistent with in vitro findings, MDPV (0.1-0.3 mg/kg, intravenous) increases extracellular concentrations of dopamine in the nucleus accumbens. Additionally, MDPV (0.1-3.0 mg/kg, subcutaneous) is at least 10 times more potent than cocaine at producing locomotor activation, tachycardia, and hypertension in rats. Our data show that MDPV is a monoamine transporter blocker with increased potency and selectivity for catecholamines when compared with cocaine. The robust stimulation of dopamine transmission by MDPV predicts serious potential for abuse and may provide a mechanism to explain the adverse effects observed in humans taking high doses of 'bath salts' preparations.

Bloodstream infection (BSI) and sepsis are rising in incidence throughout the developed world. The spread of multi-drug resistant organisms presents increasing challenges to treatment. Surviving BSI is dependent on rapid and accurate identification of causal organisms, and timely application of appropriate antibiotics. Current culture-based methods used to detect and identify agents of BSI are often too slow to impact early therapy and may fail to detect relevant organisms in many positive cases. Existing methods for direct molecular detection of microbial DNA in blood are limited in either sensitivity (likely the result of small sample volumes) or in breadth of coverage, often because the PCR primers and probes used target only a few specific pathogens. There is a clear unmet need for a sensitive molecular assay capable of identifying the diverse bacteria and yeast associated with BSI directly from uncultured whole blood samples. We have developed a method of extracting DNA from larger volumes of whole blood (5 ml per sample), amplifying multiple widely conserved bacterial and fungal genes using a mismatch- and background-tolerant PCR chemistry, and identifying hundreds of diverse organisms from the amplified fragments on the basis of species-specific genetic signatures using electrospray ionization mass spectrometry (PCR/ESI-MS). We describe the analytical characteristics of the IRIDICA BAC BSI Assay and compare its pre-clinical performance to current standard-of-care methods in a collection of prospectively collected blood specimens from patients with symptoms of sepsis. The assay generated matching results in 80% of culture-positive cases (86% when common contaminants were excluded from the analysis), and twice the total number of positive detections. The described method is capable of providing organism identifications directly from uncultured blood in less than 8 hours. The IRIDICA BAC BSI Assay is not available in the United States.

The COVID-19 pandemic accelerated the adoption of the hospital at home (HAH) model, driven by the 2020 CMS Acute Hospital Care at Home waiver that removed financial barriers to reimbursement. With more than 330 hospitals across 130 health systems implementing HAH, this care model offers promising outcomes and experiences while addressing rising health care costs and an aging population. However, further research is needed to define its scalability, appropriate patient populations, and long-term viability. To address these gaps, Cleveland Clinic and Mayo Clinic established the Cleveland Clinic-Mayo Clinic (CCMC) Home-Based Care Research Consortium. The consortium focuses on creating a national registry, standardizing data, and developing evidence-based care pathways to evaluate the impact of HAH on patient safety, outcomes, and costs. Additionally, it aims to identify which populations and conditions can benefit most, ensuring equitable and high-quality care delivery. The consortium also prioritizes caregiver well-being, exploring virtual and hybrid models to address workforce challenges and enhance provider satisfaction. Recognizing health equity as essential, it emphasizes enrolling diverse populations and collaborating with community organizations to address social determinants of health. The consortium will also focus on true cost savings, workforce efficiency, and integration with home-based care programs, taking into account recent advances in technology and artificial intelligence. By fostering collaboration and rigorous research, the CCMC Consortium seeks to refine HAH into a scalable, sustainable, and equitable care model that meets the evolving demands of modern health care.

Background Prophylaxis for pulmonary embolism (PE) after total joint arthroplasty (TJA) presents the clinical dilemma of balancing the risk of postoperative thrombotic risk and anticoagulation-related complications such as bleeding, hematoma formation, and infection. Risk stratification of patients undergoing TJA is needed to tailor prophylaxis based on thrombotic and bleeding risk. Questions/purposes The purpose of this study was to identify the preoperative comorbidities that were associated with an increased risk of symptomatic PE after joint arthroplasty in a large group of patients who had TJAs and who were treated with either aspirin or warfarin. Methods We conducted a retrospective study of 26,391 primary and revision TJAs performed at our institution between January 2000 and April 2011. A total of 24,567 patients received warfarin prophylaxis for 6 weeks (targeted international normalized ratio of 1.5–2.0) and 1824 patients received 325 mg aspirin twice daily. Symptomatic patients with decreased oxygen saturation were evaluated for PE using either a ventilation/perfusion scan or multidetector CT scan. Symptomatic PEs occurring in patients within 90 days postoperatively identified with CT or ventilation/perfusion scans were considered complications related to surgery, and fatal PEs were those that occurred in patients who died during the hospital admission owing to cardiopulmonary failure after PE. Using a logistic regression analysis, a nomogram was created to predict postoperative symptomatic PE risk. Results Risk of postoperative symptomatic PE after primary and revision TJAs was 1.1%. Risk of postoperative fatal PE was 0.02%. Elevated BMI (p < 0.035), procedures on the knee (p < 0.006), higher Charlson Comorbidity Index (p < 0.015), chronic obstructive pulmonary disorder (p = 0.006), atrial fibrillation (p < 0.001), anemia (p < 0.001), presence of deep vein thrombosis (p < 0.001), and depression (p = 0.012) were independent risk factors for symptomatic PE. Based on these risk factors and derived scoring criteria, patients can be classified into low- (0.35%), medium- (1.4%), and high- (9.3%) risk categories. Conclusions Patients who are obese, undergo knee procedures, have an elevated Charlson Comorbidity Index, chronic obstructive pulmonary disease, atrial fibrillation, anemia, depression, or postoperative deep vein thrombosis are at greater risk of having a postoperative PE develop. These risk factors should be considered when deciding on postoperative anticoagulation prophylaxis. Level of Evidence Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Only 45% of people currently living with HIV infection in sub-Saharan Africa are aware of their HIV status. Unmet testing needs may be addressed by utilizing the Emergency Department (ED) as an innovative testing venue in low and middle-income countries (LMICs). The purpose of this review is to examine the burden of HIV infection described in EDs in LMICs, with a focus on summarizing the implementation of various ED-based HIV testing strategies. We performed a systematic review of Pubmed, Embase, Scopus, Web of Science and the Cochrane Library on June 12, 2016. A three-concept search was employed with emergency medicine (e.g., Emergency department, emergency medical services), HIV/AIDS (e.g., human immunodeficiency virus, acquired immunodeficiency syndrome), and LMIC terms (e.g., developing country, under developed countries, specific country names). The search returned 2026 unique articles. Of these, thirteen met inclusion criteria and were included in the final review. There was a large variation in the reported prevalence of HIV infection in the ED population ranging from to 2.14% in India to 43.3% in Uganda. The proportion HIV positive patients with previously undiagnosed infection ranged from 90% to 65.22%. In the United States ED-based HIV testing strategies have been front and center at curbing the HIV epidemic. The limited number of ED-based studies we observed in this study may represent the paucity of HIV testing in this venue in LMICs. All of the studies in this review demonstrated a high prevalence of HIV infection in the ED and an extraordinarily high percentage of previously undiagnosed HIV infection. Although the numbers of published reports are few, these diverse studies imply that in HIV endemic low resource settings EDs carry a large burden of undiagnosed HIV infections and may offer a unique testing venue.