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Standish K.,Sustainable science Institute | Kuan G.,Socrates | Aviles W.,Sustainable science Institute | Harris E.,University of California at Berkeley
PLoS Neglected Tropical Diseases | Year: 2010

Dengue is a major public health problem in tropical and subtropical regions; however, under-reporting of cases to national surveillance systems hinders accurate knowledge of disease burden and costs. Laboratory-confirmed dengue cases identified through the Nicaraguan Pediatric Dengue Cohort Study (PDCS) were compared to those reported from other health facilities in Managua to the National Epidemiologic Surveillance (NES) program of the Nicaraguan Ministry of Health. Compared to reporting among similar pediatric populations in Managua, the PDCS identified 14 to 28 (average 21.3) times more dengue cases each year per 100,000 persons than were reported to the NES. Applying these annual expansion factors to national-level data, we estimate that the incidence of confirmed pediatric dengue throughout Nicaragua ranged from 300 to 1000 cases per 100,000 persons. We have estimated a much higher incidence of dengue than reported by the Ministry of Health. A country-specific expansion factor for dengue that allows for a more accurate estimate of incidence may aid governments and other institutions calculating disease burden, costs, resource needs for prevention and treatment, and the economic benefits of drug and vaccine development. © 2010 Standish et al.


Gordon A.,University of California at Berkeley | Gordon A.,U.S. National Institutes of Health | Videa E.,Sustainable science Institute | Kuan G.,Socrates | Harris E.,University of California at Berkeley
Clinical Infectious Diseases | Year: 2010

Background. Little is known about the clinical presentation and epidemiology of influenza A H1N1 pdm in children in developing countries. We assessed the severity of influenza A H1N1 pdm in children in Nicaragua by comparing H1N1pdm cases to seasonal influenza cases in an ongoing cohort study. Methods. The Nicaraguan Influenza Cohort Study was established in June 2007 to study the burden and seasonality of pediatric influenza in a tropical developing country. During the period from June 2007 through November 2009, a total of 4391 children aged 2-14 years participated in the cohort. We examined the attack rate of clinical influenza and assessed symptoms at first presentation in febrile patients with H1N1pdm versus those with seasonal influenza A or B. Results. The estimated clinical attack rate of H1N1pdm in the cohort was 20.1%, compared to 11.7% and 15.1% for seasonal influenza A and 11.9% and 24.2% for seasonal influenza A and B in 2007 and 2008, respectively. Symptoms significantly associated with H1N1pdm cases versus seasonal influenza A cases were sore throat (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.5), wheezing (OR, 5.1; 95% CI, 1.3-19.0), rhonchi (OR, 4.6; 95% CI, 1.4-15.0), crepitations (OR, 16.2; 95% CI, 2.1-128.7), pneumonia (OR, 8.0; 95% CI, 1.7-37.3), nausea (OR, 2.8; 95% CI, 1.5-5.1), and loss of appetite (OR, 2.1; 95% CI, 1.4-3.1). In addition, 3 concurrent influenza and dengue virus coinfections were identified. Conclusions. Children with influenza A H1N1pdm presented with significantly more symptoms of lower respiratory infection and gastrointestinal symptoms than children with seasonal influenza. The clinical influenza attack rate was high in both pandemic and seasonal years. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Gordon A.,University of California at Berkeley | Kuan G.,Socrates | Gresh L.,Sustainable science Institute | Aviles W.,Sustainable science Institute | Harris E.,University of California at Berkeley
PLoS Neglected Tropical Diseases | Year: 2013

Dengue, caused by the four serotypes of dengue virus (DENV), is the most prevalent mosquito-borne viral disease of humans. To examine the incidence and transmission of dengue, the authors performed a prospective community-based cohort study in 5,545 children aged 2-14 years in Managua, Nicaragua, between 2004 and 2010. Children were provided with medical care through study physicians who systematically recorded medical consult data, and yearly blood samples were collected to evaluate DENV infection incidence. The incidence of dengue cases observed was 16.1 cases (range 3.4-43.5) per 1,000 person-years (95% CI: 14.5, 17.8), and a pattern of high dengue case incidence every other year was observed. The incidence of DENV infections was 90.2 infections (range 45.2-105.3) per 1,000 person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young children (<6 years old) were primary (60%) and the majority of infections in older children (≥9 years of age) were secondary (82%), as expected. The incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI: 102.7, 143.4) was significantly higher than the incidence rate of primary DENV infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous analytic methodology used in this study, including incidence reporting in person-years, allows comparison across studies and across different infectious diseases. This study provides important information for understanding dengue epidemiology and informing dengue vaccine policy. © 2013 Gordon et al.


Biswas H.H.,University of California at Berkeley | Ortega O.,Sustainable science Institute | Gordon A.,University of California at Berkeley | Standish K.,Sustainable science Institute | And 2 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: Tens of millions of dengue cases and approximately 500,000 life-threatening complications occur annually. New tools are needed to distinguish dengue from other febrile illnesses. In addition, the natural history of pediatric dengue early in illness in a community-based setting has not been well-defined. Methods: Data from the multi-year, ongoing Pediatric Dengue Cohort Study of approximately 3,800 children aged 2-14 years in Managua, Nicaragua, were used to examine the frequency of clinical signs and symptoms by day of illness and to generate models for the association of signs and symptoms during the early phase of illness and over the entire course of illness with testing dengue-positive. Odds ratios (ORs) and 95% confidence intervals were calculated using generalized estimating equations (GEE) for repeated measures, adjusting for age and gender. Results: One-fourth of children who tested dengue-positive did not meet the WHO case definition for suspected dengue. The frequency of signs and symptoms varied by day of illness, dengue status, and disease severity. Multivariable GEE models showed increased odds of testing dengue-positive associated with fever, headache, retro-orbital pain, myalgia, arthralgia, rash, petechiae, positive tourniquet test, vomiting, leukopenia, platelets ≤150,000 cells/mL, poor capillary refill, cold extremities and hypotension. Estimated ORs tended to be higher for signs and symptoms over the course of illness compared to the early phase of illness. Conclusions: Day-by-day analysis of clinical signs and symptoms together with longitudinal statistical analysis showed significant associations with testing dengue-positive and important differences during the early phase of illness compared to the entire course of illness. These findings stress the importance of considering day of illness when developing prediction algorithms for real-time clinical management. © 2012 Biswas et al.


HTLV-1 is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease observed in up to 5% of individuals infected with HTLV-1. However, infected individuals without the disease can present neurological complaints relating to sensory, motor or urinary manifestations. The aim of this study was to investigate the incidence of neurological manifestations among patients with HTLV-1.Method: HTLV-1 patients in Salvador, Bahia, Brazil, were enrolled into a cohort study.Results: Among 414 subjects, 76 had definite and 87 had possible or probable HAM/TSP at the baseline, whereas 251 subjects had no neurological signs or symptoms. Definite HAM/TSP developed in 5 patients (1.74%). The asymptomatic subjects were selected for analysis. The incidence rate expressed per 1,000 persons-year was calculated. It was 206 for hand numbness, 129 for nocturia and 126 for urinary urgency. In the neurological examination, leg hyperreflexia presented an average incidence rate of 76; leg paraparesis, 52; and Babinski sign, 36. Kaplan-Meyer curves categorized according to gender and proviral load showed that females and patients with proviral load of more than 100,000 copies per 106 peripheral blood mononuclear cells (PBMCs) presented higher risk.Conclusion: Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up. Female gender and high proviral load were risk factors for neurological disease. © 2015, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2016

ABSTRACT Significance Though highly effective in changing the course of the global HIV epidemic current Antiretroviral Therapy ART fails to eradicate the infection completely This had lead to the emergence of drug resistant mutant strains the phenomenon of latent disease and a number of adherence and toxicity issues associate with long term therapy Novel compounds that inhibit transcription from integrated viral genomes thereby preventing the production of viral particles from stable viral reservoirs present a valuable and differentiated therapeutic potential in the treatment of HIV Tat a potent transactivator of HIV gene expression essential for the synthesis of full length transcripts of the integrated viral genome by RNA polymerase II is a highly sought after transcription target for the treatment of HIV Innovation Didehydro cortistatin A dCA a representative of the cortistatin class of compounds has demonstrated significant potential as a potent inhibitor of Tat Preliminary Data dCA has been shown to inhibit acute HIV replication has demonstrated additive effect of viral inhibition when combined with ART and has been found to highly impact latent viremia in CD T cells of virally suppressed patients receiving ART for at least three years However dCA has been shown to have off target activity that impacts it s safety profile in HIV therapy including potent anti angiogenesis effect Specific Aims The goal of this proposal is the design of a lead cortistatin agent that retains Tat inhibition activity has drug like properties and has a desirable safety and tolerability profile including the reduction of off target antiangiogenesis activity Specific Aim Optimization of key coupling step to enable the large scale synthesis of dCA In the Baran total synthesis of dCA the final step involves a Stille coupling reaction using loading of palladium catalyst while only providing a yield of dCA Screening new palladium catalysts reaction temperatures solvents reaction times concentration and lowering catalyst loading will be carried out to increase the efficiency of this reaction Specific Aim A Discovery of Alternative Scaffolds by modification of Steroid Body The Cost of Goods COGS to produce large quantities of dCA is a significant limiting factor that could potentially derail the advancement of this compound into clinical trials It is therefore prudent to discover alternative Steroid Body chemical scaffolds that can be synthesized readily on large scales Specific Aim B Optimization of Drug metabolism Drug Drug Interactions and Oral Bioavailability All truncated analogs prepared above will be evaluated in microsomal stability assays metabolic soft spots will be identified using MS MS analysis and design optimization will be driven towards molecules that display potent TAT inhibition while being stable to liver microsomes low hepatic clearance At the end of this Phase I study we expect to a have highly efficient reaction conditions to carry out the key coupling reaction smoothly b identify second generation Steroid Body chemical scaffold displaying potent inhibition of acute HIV replication via Tat binding good oral bioavailability minimum drug interaction potential and ready for IND enabling studies Project Narrative Cortistatin Inspired agents for HIV Therapy Though highly effective in changing the course of the global HIV epidemic current Antiretroviral Therapy ART fails to eradicate the infection completely This had lead to the emergence of drug resistant mutant strains the phenomenon of latent disease and a number of adherence and toxicity issues associate with long term therapy Novel compounds that inhibit transcription from integrated viral genomes thereby preventing the production of viral particles from stable viral reservoirs present a valuable and differentiated therapeutic potential in the treatment of HIV Tat a potent transactivator of HIV gene expression essential for the synthesis of full length transcripts of the integrated viral genome by RNA polymerase II is a highly sought after transcription target for the treatment of HIV Innovation Didehydro cortistatin A dCA a representative of the cortistatin class of compounds has demonstrated significant potential as a potent inhibitor of Tat


Patent
Socrates and University Hospitals Of Cleveland | Date: 2015-11-30

Systems, methods and computer readable media that facilitate providing clinically informed financial decisions that improve healthcare performance are provided. In an aspect, a system includes a performance evaluation component configured to identify groups of patients having received healthcare service by a healthcare organization and associated with a common healthcare service parameter and uncommon healthcare service parameters. The system further includes a scoring component configured to determine performance scores for respective groups of patients, wherein the performance scores reflect clinical and financial performance of the healthcare organization in association with provision of the healthcare service to the respective groups of patients. A comparison component further compare the respective groups of patients based on the performances scores respectively associated therewith to facilitate identifying one or more of the uncommon healthcare service parameters that are responsible for variance between at least a subset of performance scores.


Trademark
Socrates | Date: 2014-01-30

Providing on-line, non-downloadable software for medical services and clinics to track costs and billing, monitor quality of care, and provide profitability analysis.


Trademark
Socrates | Date: 2014-01-30

Providing on-line, non-downloadable software for medical services and clinics to track costs and billing, monitor quality fo care, and provide profitability analysis.


Trademark
Socrates | Date: 2016-12-02

Downloadable computer application software for mobile communication devices, including cellphones and tablets, to provide information and facilitate interactions in the field of entertainment, cultural, family, business, political, and sporting events. An Internet website portal to provide information and facilitate interactions in the field of entertainment, cultural, family, business, political, and sporting events.

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