Determining a urinary-specific antibiogram and risk factors of trimethoprim/sulfamethoxazole, ciprofloxacin and multidrug resistance among Enterobacterales in primary care.

BACKGROUND: Risk factors for ciprofloxacin or MDR in primary care urine specimens are not well defined. OBJECTIVES: We created a primary care-specific antibiogram for Escherichia coli isolates from cases with complicated and uncomplicated urinary tract infection (UTI) and evaluated risk factors for ciprofloxacin, trimethoprim/sulfamethoxazole and MDR among Enterobacterales. METHODS: We conducted a cross-sectional study to determine resistance and risk factors by collecting urine cultures from all patients (≥18 years) presenting with provider-suspected UTI at two primary care, safety-net clinics in Houston, TX, USA between November 2018 and March 2020. RESULTS: Among 1262 cultures, 308 cultures grew 339 uropathogens. Patients with Enterobacterales (n = 199) were mostly female (93.5%) with a mean age of 48.5 years. E. coli was the predominant uropathogen isolated (n = 187/339; 55%) and had elevated trimethoprim/sulfamethoxazole (43.6%) and ciprofloxacin (29.5%) resistance, low nitrofurantoin (1.8%) resistance, and no fosfomycin resistance. Among E. coli, 10.6% were ESBL positive and 24.9% had MDR. Birth outside the U.S.A., prior (2 year) trimethoprim/sulfamethoxazole resistance, and diabetes mellitus were associated with trimethoprim/sulfamethoxazole resistance. Prior (60 day) fluoroquinolone use, prior ciprofloxacin resistance and both diabetes mellitus and hypertension were strongly associated with ciprofloxacin resistance. Prior fluoroquinolone use and a history of resistance to any studied antibiotic were associated with MDR, while pregnancy was protective. CONCLUSIONS: We found elevated resistance to UTI-relevant antimicrobials and novel factors associated with resistance; these data can be incorporated into clinical decision tools to improve organism and drug concordance.

Demographics and clinical features associated with rates of electronic message utilization in the primary care setting.

INTRODUCTION: Electronic messages are growing as an important form of patient-provider communication, particularly in the primary care setting. However, adoption of healthcare technology has been under-utilized by underserved patient populations. The purpose of this study was to describe how adoption and utilization of electronic messaging occurred within a large primary care urban-based patient population. METHODS: In this retrospective study, the frequency of electronic messages initiated by adult outpatient primary care patients was observed. Patients were classified as either non-portal adopters, non-message utilizers, low message utilizers, and high message utilizers. Logistic regression modeling was used to compare factors associated with message utilization rates to determine disparities in access. RESULTS: Among a sample of 27,453 ethnically diverse adult patients from the Houston, Texas Metropolitan area, 33,497 unique messages were sent (1.22 messages/patient). Message burden was predominantly derived by a small number of high utilizers (individuals who sent 3 or more messages), who comprised 15.7 % of the study population (n = 4302) but accounted for 77 % of the message volume (n = 25,776). These high utilizers were typically older, White, English speaking, from middle to upper income zip codes, had higher number of comorbidities, and a higher number of clinical visits. CONCLUSIONS: Most inbox messages were generated by a small number of patients. While it was reassuring to see older and sicker individuals utilizing electronic messaging, patients from minority and/or lower income background utilized electronic messaging much less. This may propagate systematic bias and decrease the level of care for traditionally underserved patients.

Submersion Injuries and the Cost of Injury Associated with Drowning Events in the United States, 2006-2015.

INTRODUCTION: The World Health Organization has reported submersion injuries as the third most common cause of death due to unintentional injury in the world. Greater detail in the rates, risk factors, and healthcare associated costs of submersion injuries could be instrumental in demonstrating the need for further funding and intervention. METHODS: The study was a cross-sectional analysis of a nationally representative dataset of inpatient and emergency department (ED) encounters between 2006 and 2015 in the United States (US). Healthcare utilization costs were provided within the datasets and adjusted to reflect actual charges and provider fees. Lastly, the final cost values were adjusted to the 2020 US dollar (USD) and summarized using a log adjusted mean. RESULTS: On average, there were 11,873 submersion injuries per year that presented to the ED in the US. Resulting in a rate where approximately 9 out of every 100,000 ED visits were associated with a submersion injury. Slightly more than 6% died in the ED, 24.2% were admitted, and 69.3% were discharged from the ED. In total, annual cost of submersion injuries in the US for ED care is approximately $12.5 million, inpatient care is approximately $27.5 million, and total annual healthcare cost exceeds $40 million. DISCUSSION: While these results only represent a fraction of the total cost associated with submersion injuries, it remains substantial and unchanged over the 10-year study period. Certain demographic groups showed higher rates of injury and disease burden, thus bearing a greater amount of the cost.

Impact of COVID-19 lockdown on patient-provider electronic communications.

BACKGROUND: SARS CoV-2 virus (COVID-19) impacted the practice of healthcare in the United States, with technology being used to facilitate access to care and reduce iatrogenic spread. Since then, patient message volume to primary care providers has increased. However, the volume and trend of electronic communications after lockdown remain poorly described in the literature. METHODS: All incoming inbox items (telephone calls, refill requests, and electronic messages) sent to providers from patients amongst four primary care clinics were collected. Inbox item rates were calculated as a ratio of items per patient encountered each week. Trends in inbox rates were assessed during 12 months before and after lockdown (March 1st, 2020). Logistic regression was utilized to examine the effects of the lockdown on inbox item rate post-COVID-19 lockdown as compared to the pre-lockdown period. RESULTS: Before COVID-19 lockdown, 2.07 new inbox items per encounter were received, which increased to 2.83 items after lockdown. However, only patient-initiated electronic messages increased after lockdown and stabilized at a rate higher than the pre-COVID-19 period (aRR 1.27, p-value < 0.001). In contrast, prescription refill requests and telephone calls quickly spiked, then returned to pre-lockdown levels. CONCLUSION: Based on our observations, providers experienced a quick increase in all inbox items. However, only electronic messages had a sustained increase, exacerbating the workload of administrators, staff, and clinical providers. This study directly correlates healthcare technology adoption to a significant disruptive event but also shows additional challenges to the healthcare system that must be considered with these changes.

Asking About "Prostitution", "Sex Work" and "Transactional Sex": Question Wording and Attitudes Toward Trading Sexual Services.

This study explored the impact of question wording on attitudes toward trading sexual services. There are no previous research agendas investigating how views on the trade in sex are susceptible to question word choice. We utilized an original survey to assess how three different concepts used to represent the exchange of sexual services impact on the reported level of acceptability among respondents. The concepts we selected were "prostitution," "sex work", and "transactional sex." We also explored the contrasting effects of predictor variables based on question wording, such as general sexual attitudes and positive and negative associations with trading sex. We found that attitudes toward the trading of sex is partially a function of question wording. Respondents were more likely to translate negative associations with the exchange of sexual services into unacceptability when assigned a question using the term prostitution. The results indicated that prostitution is a stigmatized word, resonating more negatively with respondents as compared to sex work or transactional sex. When asked about transactional sex, respondents were less likely to translate an attitude into an assessment on acceptability, indicating that the term is vague. Sex work elicited more neutral responses on acceptability. The results suggest that sex work would be the most useful term to use in dialogue and debate regarding the trade in sexual services. Sex work does not appear to be imbued with the same sense of negativity as prostitution and the meaning of sex work seems clearer than transactional sex.

Prevalence and predictors of urine culture contamination in primary care: A cross-sectional study.

BACKGROUND: Antimicrobial resistance is a global health threat. To slow resistance and preserve antibiotics, stewardship interventions are increasingly promoted and mandated. Urine cultures are the most common microbiological test in the outpatient setting. Contamination most likely occurs during urine collection from surrounding vaginal, perineal, and epidermal flora. Sample contamination can lead to incorrect diagnosis, unnecessary or inappropriate treatment, poor patient outcomes, and higher costs. Therefore, ensuring proper collection of urinary samples serves as a prime diagnostic stewardship target, one that international nursing societies increasingly endorse as an opportunity for nurse involvement. OBJECTIVES: Determine the prevalence, predictors, and antibiotic prescribing associated with contaminated urine cultures in primary care clinics. DESIGN: Cross-sectional study. SETTING: Two adult safety-net clinics in Houston, Texas. PARTICIPANTS: 1265 clinical encounters among 1114 primary care patients. METHODS: We reviewed charts from office visits among patients who had a urine culture ordered between November 2018 and March 2020. Patient demographics, culture results and prescription orders were captured for each visit. Culture results were defined as no growth, contaminated (i.e., mixed flora, non-uropathogens, or ≥3 bacterial species isolated), or low-count (102-105 colony forming units (CFU)/mL) or high-count (>105 CFU/mL) uropathogen-positive. We performed multinomial logistic regression to identify predictors independently associated with contaminated cultures. RESULTS: Our study evaluated 1265 cultures from 1114 patients that were primarily female (84 %), of Hispanic/Latino (74.4 %) or Black/African American (18.9 %) race/ethnicity with a mean age of 43 years. Out of 1265 urine cultures, 264 (20.9 %) had no growth, 694 (54.9 %) were contaminated, 159 (12.6 %) were low-count positive, and 148 (11.7 %) were high-count positive. Female sex, pregnancy, and obesity were associated with contaminated cultures (multinomial adjusted odds ratios: 15.89, 14.34, 1.93, respectively; 95 % confidence intervals: 10.25-24.61, 8.03-25.61, 1.32-2.81, respectively). Antibiotic prescribing was significantly higher among symptomatic patients with contaminated cultures compared to those with no growth. CONCLUSION: Urine culture contamination occurred frequently in our clinics, and obesity, female sex and pregnancy were independent risk factors for contamination. The association of pregnancy and contamination is particularly concerning as pregnant females are routinely screened and treated for asymptomatic bacteriuria in the United States. Culture contamination may obscure underlying uropathogens, leading to pyelonephritis or potential neonatal infection if untreated. Conversely, overtreatment of false positive bacteriuria could lead to adverse effects from antibiotics and increased risk for antibiotic resistance. As nurses play a prominent role in patient education, diagnostic stewardship interventions may want to utilize nurses' educational capabilities to improve urine culture collection. TWEETABLE ABSTRACT: 55 % of urine cultures collected in primary care clinics were contaminated, revealing a major opportunity for nurse-driven diagnostic stewardship interventions.

Implementing peer recovery coaching and improving outcomes for substance use disorders in underserved communities.

INTRODUCTION: The Peer Recovery Expansion Project (PREP) was designed to expand outreach and deliver enhanced treatment services via peer-recovery coaches for individuals with substance use disorder (SUD) and limited access to healthcare. METHODS: PREP was implemented in low-socioeconomic areas with historic challenges to accessing SUD treatment. Services were provided to 153 clients through tailored cultural responsiveness, use of peer-based recovery coaching, and development of a Recovery Support Network. Outcome data were collected using the Government Performance and Reporting Act tool at intake and at 6-month follow-up for coaches and clients. RESULTS: The vast majority of peer-recovery coaches were satisfied with the overall quality of the training and their training experience (96.8%). Around 95% agreed that the training enhanced their skills in the topic area and 93% agreed that the training was relevant to substance use disorder treatment at the 6-month post training survey. Majority of clients were from low-income, minority demographics that had a high prevalence history of incarceration, homelessness, and inconsistent employment. At 6-month follow-up, they reported a 22% increase in stable housing and a 25% increase in full-time/part-time employment/training program enrollment. They also demonstrated a significant decline in reported depression, anxiety, and prescribed medication use at 6-month follow-up when compared to baseline. CONCLUSIONS: Clients enrolled in a tailored evidence based peer-led program decreased their psychiatric symptoms and increased their housing stability and employment. Study outcomes support the use of an integrated peer-led support for increasing engagement in care for adults experiencing substance use disorders.

US Hospitalizations and 60-Day Readmission Rates Associated With Herpes Simplex Virus Encephalitis: Analysis of All Cause Readmissions and Encephalopathy Associated Readmissions.

BACKGROUND: Herpes simplex encephalitis (HSE) is the most common cause of encephalitis hospitalizations. We sought to describe and analyze features associated with all cause readmissions and encephalopathy associated readmissions amongst HSE cases. METHODS: HSE hospitalizations and 60-day rehospitalizations were assessed in a retrospective cohort using linked hospitalizations from the Healthcare Utilization Project (HCUP) National Readmission Database (NRD) from 2010 through 2017. Risk factors for all-cause readmissions and encephalopathy associated readmissions were assessed with a weighted logistic regression model. RESULTS: There were 10 272 HSE cases in the US between 2010 and 2017, resulting in a national rate of 4.95 per 100 000 hospitalizations. A total of 23.7% were readmitted at least once within 60-days. Patients that were readmitted were older (mean age 62.4 vs 57.9, P < .001), had a greater number of procedures at the index hospitalization (adjusted odds ratio [aOR] 1.03, P < .001) and have a higher Charlson comorbidity score (aOR 1.11, P < .001). Among those readmitted, 465 (16.5%) had an encephalopathy related diagnosis. Over 8 years, the rate of encephalopathy associated readmissions increased from 0.12 to 0.20. Encephalopathy specific readmissions were found to be associated with greater age (mean age 65.9 vs 61.7, P = .004) and findings of cerebral edema at index hospitalization (aOR 2.16, P < .001). CONCLUSIONS: HSE readmissions are relatively common, particularly among older and sicker individuals. However, early signs and symptoms of neurological disease at index were correlated with encephalopathic specific readmissions.

Salary Differences Between Schools of Medicine and Schools of Public Health for Nonclinical PhD Faculty: A Case Study of One Large Multicampus University System.

There are no evidence-based findings to assist professionals with advanced public health and social science degrees in choosing the appropriate academic location. A cross-sectional case study in 2019 was conducted using publicly available online data of full-time, nonclinical, doctoral-level academic faculty in schools of public health (SOPHs) and schools of medicine (SOMs), within one large university system. Analyses included descriptive statistics and generalized linear regression models comparing salaries between school types by academic rank, after gender and race/ethnicity adjustment. The study included 181 faculty members, 35.8% assistant, 34.1% associate, and 30.1% full professors. After accounting for race/ethnicity and gender, SOM assistant and associate professors had 9% (P = .03) and 14% (P = .008) higher mean salaries than SOPH counterparts. Findings suggest slight salary advantages for SOM faculty for early- to mid-career PhDs in one university system. Factors such as start-up packages, time to promotion, and grant funding need further exploration.

Adjunctive steroids in adults with encephalitis: a propensity score analysis.

OBJECTIVE: Adjuvant steroids have been used for the treatment of encephalitis, although there is limited data regarding its benefit. We described the use and impact of adjunctive steroids on adverse clinical outcomes (ACO) in adults with encephalitis. METHODS: Retrospective observational study of 230 adults with encephalitis at two tertiary care hospital systems in Houston, Texas, between August 2008 and September 2017. An ACO was assessed at the time of death or discharge and defined as a Glasgow Outcome Scale 1-4. A propensity score analysis was performed. RESULTS: Out of 230 adult encephalitis patients enrolled, 121 (52.6%) received steroids. Adjunctive steroids were given more frequently to those who had focal neurological deficits (P = 0.01), required mechanical ventilation (MV) (P = 0.01), had intensive care unit admission (P < 0.001), had white matter abnormalities (P = 0.01) or cerebral edema on magnetic resonance imaging of the brain (P = 0.003). An ACO was seen in 135 (58.7%) of patients. The use of adjunctive steroids did not impact ACOs (P = 0.52) on univariate analyses or after propensity score matching. Predictors for an ACO in logistic regression analyses included a Glasgow Coma Score (GCS) < 8, fever, MV, and cerebral edema. INTERPRETATION: Adjunctive steroids are used more frequently in sicker patients and are not associated with improved clinical outcomes.

Predicting Inpatient Mortality Among Encephalitis Patients: A Novel Admission Risk Score.

BACKGROUND: Identifying underlying commonalities among all-cause encephalitis cases can be extraordinarily useful in predicting meaningful risk factors associated with inpatient mortality. METHODS: A retrospective cohort of patients with encephalitis was derived from a clinical chart review of adult patients (age ≥18 years) across 16 different hospitals in Houston, Texas, between January 2005 and July 2015. Clinical features at admission were assessed for their correlation with inpatient mortality and used to derive a final risk score prediction tool. RESULTS: The study included a total of 273 adult patients with all-cause encephalitis, 27 (9.9%) of whom died during hospitalization. A limited number of clinical features were substantially different between patients who survived and those who died (Charlson score, Glasgow coma scale [GCS], immunosuppression, fever on admission, multiple serologic studies, and abnormal imaging). A final multivariable logistic model was derived with the following risk factors, which were transformed into a scoring system: 1 point was assigned to the presence of a Charlson score >2, thrombocytopenia, or cerebral edema, and 2 points for a GCS value <8. Patients were then classified into different risk groups for inpatient mortality: 0 points (0%), 1 point (7%), 2 points (10.9%), 3 points (36.8%), and ≥4 points (81.8%). CONCLUSIONS: The risk score developed from this study shows a high predictive value. This can be highly beneficial in alerting care providers to key clinical risk factors associated with in-hospital mortality in adults with encephalitis.

Estimating the obstetric co-morbidity burden using administrative data: The impact of the pregnancy-related assessment window.

BACKGROUND: Despite increased research using large administrative databases to identify determinants of maternal morbidity and mortality, the extent to which these databases capture obstetric co-morbidities is unknown. OBJECTIVE: To evaluate the impact that the time window used to assess obstetric co-morbidities has on the completeness of ascertainment of those co-morbidities. METHODS: We conducted a five-year analysis of inpatient hospitalisations of pregnant women from 2010-2014 using the Nationwide Readmissions Database. For each woman, using discharge diagnoses, we identified 24 conditions used to create the Obstetric Comorbidity Index. Using various assessment windows for capturing obstetric co-morbidities, including the delivery hospitalisation only and all weekly windows from 7 to 280 days, we calculated the frequency and rate of each co-morbidity and the degree of underascertainment of the co-morbidity. Under each scenario, and for each co-morbidity, we also calculated the all-cause, 30-day readmission rate. RESULTS: There were over 3 million delivery hospitalisations from 2010 to 2014 included in this analysis. Compared with a full 280-day window, assessment of obstetric co-morbidities using only diagnoses made during the delivery hospitalisation would result in failing to identify over 35% of cases of chronic renal disease, 28.5% cases in which alcohol abuse was documented during pregnancy, and 23.1% of women with pulmonary hypertension. For seven other co-morbidities, at least 1 in 20 women with that condition would have been missed with exclusive reliance on the delivery hospitalisation for co-morbidity diagnoses. Not only would reliance on delivery hospitalisations have resulted in missed cases of co-morbidities, but for many conditions, estimates of readmission rates for women with obstetric co-morbidities would have been underestimated. CONCLUSIONS: An increasing proportion of maternal and child health research is based on large administrative databases. This study provides data that facilitate the assessment of the degree to which important obstetric co-morbidities may be underascertained when using these databases.

Clinical Epidemiology, Risk Factors, and Outcomes of Encephalitis in Older Adults.

BACKGROUND: Encephalitis is associated with significant morbidity and mortality, with unknown etiologies in the majority of patients. Large prognostic studies evaluating elderly patients are currently lacking. METHODS: We performed a retrospective cohort of encephalitis cases in 19 hospitals from New Orleans, Louisiana, and Houston, Texas, between the years 2000 and 2017. RESULTS: A total of 340 adult (aged ≥17 years) patients with confirmed encephalitis were enrolled, and 194 (57%) had unknown etiologies. A cerebrospinal fluid polymerase chain reaction (PCR) for herpes simplex virus (HSV) and varicella zoster virus was done in 237 (69%) and 82 (24%) patients, respectively. Furthermore, an arboviral serology was done in 169 (49%) patients and measurements of anti-N-methyl-D-aspartate receptor antibodies were taken in 49 (14%) patients. A total of 172 out of 323 patients (53%) had adverse clinical outcomes (ACOs) at discharge. Older individuals (>65 years of age) had a lower prevalence of human immunodeficiency virus, had a higher number of comorbidities, were less likely to receive adjuvant steroids, were more likely to have a positive arbovirus serology, were more likely to have a positive HSV PCR, were more likely to have abnormal computerized tomography findings, and were more likely to have to have an ACO (all P values < .05). Prognostic factors independently associated with an ACO were age ≥65, fever, Glasgow Coma Scale (GCS) score <13, and seizures (all P values ≤0.01). CONCLUSIONS: Encephalitis in adults remain with unknown etiologies and adverse clinical outcomes in the majority of patients. Independent prognostic factors include age ≥65 years, fever, GCS score <13, and seizures.

Exploring classification of birth defects severity in national hospital discharge databases compared to an active surveillance program.

OBJECTIVE: To explore the extent to which the severity of birth defects could be differentiated using severity of illness (SOI) and risk of mortality (ROM) measures available in national discharge databases. METHODS: Data from the 2012-14 National Inpatient Sample (NIS) was used to identify hospitalizations with one or more major birth defects reported annually to the National Birth Defects Prevention Network using the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Each hospitalization also contained a 4-level SOI and 4-level ROM classification measure. For each birth defect and for each individual birth defect-related ICD-9-CM code, we calculated mean and median SOI and ROM, the proportion of hospitalizations in each level of SOI and ROM, the inpatient mortality rate, and level of agreement between various existing or derived severity proxies in the NIS and the Texas Birth Defects Registry (TBDR). RESULTS: Mean SOI ranged from 1.5 (cleft lip alone) to 3.7 (single ventricle), and mean ROM ranged from 1.1 (cleft lip alone) to 3.9 (anencephaly). As a group, critical congenital heart defects had the highest average number of co-occurring defects, mean SOI, and ROM, whereas orofacial and genitourinary defects had the lowest SOI and ROM. We found strong levels of agreement between TBDR severity classifications and NIS severity classifications defined using Level 3 or 4 SOI or ROM Level 3 or 4. CONCLUSIONS: This preliminary investigation demonstrated how severity indices of birth defects could be differentiated and compared to a severity algorithm of an existing surveillance program.

Adolescent vaccine co-administration and coverage in New York City: 2007-2013.

OBJECTIVES: To investigate adolescent vaccination in New York City, we assessed tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal conjugate (MCV4), and human papillomavirus (HPV) vaccine uptake, vaccine co-administration, and catch-up coverage over time. METHODS: We analyzed data from the Citywide Immunization Registry, a population-based immunization information system, to measure vaccine uptake and co-administration, defined as a Tdap vaccination visit where MCV4 or HPV vaccine was co-administered, among 11-year-olds. Catch-up vaccinations were evaluated through 2013 for adolescents born 1996 to 2000, by birth cohort. HPV vaccination among boys included data from 2010 to 2013. RESULTS: Adolescent vaccine administration was greatest during the back-to-school months of August to October and was highest for Tdap. Although MCV4 uptake improved over the study years, HPV vaccine uptake among girls stagnated; boys achieved similar uptake of HPV vaccine by 2012. By 2013, 65.4% had MCV4 co-administered with Tdap vaccine, whereas 28.4% of girls and 25.9% of boys had their first dose of HPV vaccine co-administered. By age 17, Tdap and MCV4 vaccination coverage increased to 97.5% and 92.8%, respectively, whereas ≥1-dose and 3-dose HPV vaccination coverage were, respectively, 77.5% and 53.1% for girls and 49.3% and 21.6% for boys. Age-specific vaccination coverage increased with each successive birth cohort (P < .001). CONCLUSIONS: From 2007 to 2013, there were greater improvements in Tdap and MCV4 vaccination than HPV vaccination, for which co-administration with Tdap vaccine and coverage through adolescence remained lower. Parent and provider outreach efforts should promote timely HPV vaccination for all adolescents and vaccine co-administration.

An image-based algorithm for precise and accurate high throughput assessment of drug activity against the human parasite Trypanosoma cruzi.

We present a customized high content (image-based) and high throughput screening algorithm for the quantification of Trypanosoma cruzi infection in host cells. Based solely on DNA staining and single-channel images, the algorithm precisely segments and identifies the nuclei and cytoplasm of mammalian host cells as well as the intracellular parasites infecting the cells. The algorithm outputs statistical parameters including the total number of cells, number of infected cells and the total number of parasites per image, the average number of parasites per infected cell, and the infection ratio (defined as the number of infected cells divided by the total number of cells). Accurate and precise estimation of these parameters allow for both quantification of compound activity against parasites, as well as the compound cytotoxicity, thus eliminating the need for an additional toxicity-assay, hereby reducing screening costs significantly. We validate the performance of the algorithm using two known drugs against T.cruzi: Benznidazole and Nifurtimox. Also, we have checked the performance of the cell detection with manual inspection of the images. Finally, from the titration of the two compounds, we confirm that the algorithm provides the expected half maximal effective concentration (EC50) of the anti-T. cruzi activity.

Reaching children never previously vaccinated for influenza through a school-located vaccination program.

OBJECTIVES: We determined the success of the school-located vaccination (SLV) program, implemented in 2009 in New York City to deliver pandemic influenza A (H1N1) monovalent vaccine (pH1N1), versus provider offices in reaching children who had never previously received influenza vaccine. METHODS: We compared the immunization history of children vaccinated in school versus provider offices. We included records in the Citywide Immunization Registry with pH1N1 administered between October 2009 and March 2010 to elementary school-aged children. RESULTS: In total, 96,524 children received pH1N1 vaccine in schools, and 102,933 children received pH1N1 vaccine in provider offices. Of children vaccinated in schools, 34% had never received seasonal influenza vaccination in the past, compared with only 10% of children vaccinated at provider offices (P < .001). Children vaccinated in schools were more likely to have received a second dose of pH1N1 in 2009-2010 than those vaccinated in provider offices (80% vs 45%). CONCLUSIONS: The SLV program was more successful at reaching children who had never received influenza immunization in the past and should be considered as a strategy for delivering influenza vaccine in routine and emergency situations.

Identification of novel compounds inhibiting chikungunya virus-induced cell death by high throughput screening of a kinase inhibitor library.

Chikungunya virus (CHIKV) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415), one pyrrolopyridine (CND0545) and one thiazol-carboxamide (CND3514) inhibited CHIKV-associated cell death in a dose-dependent manner, with EC50 values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against CHIKV having a novel antiviral activity--inhibition of virus-induced CPE--likely by targeting kinases involved in apoptosis.