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Search Results: 1 - 10 of 148917 matches for " John T. Brooks "
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Measured Dynamic Social Contact Patterns Explain the Spread of H1N1v Influenza
Ken T. D. Eames ,Natasha L. Tilston,Ellen Brooks-Pollock,W. John Edmunds
PLOS Computational Biology , 2012, DOI: 10.1371/journal.pcbi.1002425
Abstract: Patterns of social mixing are key determinants of epidemic spread. Here we present the results of an internet-based social contact survey completed by a cohort of participants over 9,000 times between July 2009 and March 2010, during the 2009 H1N1v influenza epidemic. We quantify the changes in social contact patterns over time, finding that school children make 40% fewer contacts during holiday periods than during term time. We use these dynamically varying contact patterns to parameterise an age-structured model of influenza spread, capturing well the observed patterns of incidence; the changing contact patterns resulted in a fall of approximately 35% in the reproduction number of influenza during the holidays. This work illustrates the importance of including changing mixing patterns in epidemic models. We conclude that changes in contact patterns explain changes in disease incidence, and that the timing of school terms drove the 2009 H1N1v epidemic in the UK. Changes in social mixing patterns can be usefully measured through simple internet-based surveys.
Alteration of Gene Expression Signatures of Cortical Differentiation and Wound Response in Lethal Clear Cell Renal Cell Carcinomas
Hongjuan Zhao, Zongming Ma, Robert Tibshirani, John P. T. Higgins, B?rje Ljungberg, James D. Brooks
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006039
Abstract: Clear cell renal cell carcinoma (ccRCC) is the most common malignancy of the adult kidney and displays heterogeneity in clinical outcomes. Through comprehensive gene expression profiling, we have identified previously a set of transcripts that predict survival following nephrectomy independent of tumor stage, grade, and performance status. These transcripts, designated as the SPC (supervised principal components) gene set, show no apparent biological or genetic features that provide insight into renal carcinogenesis or tumor progression. We explored the relationship of this gene list to a set of genes expressed in different anatomical segments of the normal kidney including the cortex (cortex gene set) and the glomerulus (glomerulus gene set), and a gene set expressed after serum stimulation of quiescent fibroblasts (the core serum response or CSR gene set). Interestingly, the normal cortex, glomerulus (part of the normal renal cortex), and CSR gene sets captured more than 1/5 of the genes in the highly prognostic SPC gene set. Based on gene expression patterns alone, the SPC gene set could be used to sort samples from normal adult kidneys by the anatomical regions from which they were dissected. Tumors whose gene expression profiles most resembled the normal renal cortex or glomerulus showed better survival than those that did not, and those with expression features more similar to CSR showed poorer survival. While the cortex, glomerulus, and CSR signatures predicted survival independent of traditional clinical parameters, they were not independent of the SPC gene list. Our findings suggest that critical biological features of lethal ccRCC include loss of normal cortical differentiation and activation of programs associated with wound healing.
Retention in an antiretroviral therapy programme during an era of decreasing drug cost in Limbe, Cameroon
Mosoko Jembia J,Akam Wilfred,Weidle Paul J,Brooks John T
Journal of the International AIDS Society , 2011, DOI: 10.1186/1758-2652-14-32
Abstract: Background In 2002, Cameroon initiated scale up of antiretroviral therapy (ART); on 1 October 2004, a substantial reduction in ART cost occurred. We assessed the impact of this event and other factors on enrolment and retention in care among HIV-infected patients initiating ART from February 2002 to December 2005 at the single ART clinic serving the Southwest Region in Limbe, Cameroon. Methods We retrospectively analyzed clinical and pharmacy payment records of HIV-infected patients initiating ART according to national guidelines. We compared two cohorts of patients, enrolled before and after 1 October 2004, to determine if price reduction was associated with enhanced enrolment. We assessed factors associated with retention and survival by Cox proportional hazards models. Retention in care implied patients who had contact with the healthcare system as of 31 December 2005 (including those who were transferred to continue care in other ART centres), although these patients may have interrupted therapy at some time. A patient who was not retained in care may have dropped out (lost to follow up) or died. Results Mean enrolment rates for 2920 patients who initiated ART before and after the price reduction were 46.5 and 95.5 persons/month, respectively (p < 0.001). The probabilities of remaining alive and in care were 0.66 (95% CI 0.64-0.68) at six months, 0.58 (95% CI 0.56-0.60) at one year, 0.47 (95% CI 0.45-0.49) at two years and 0.35 (95% CI 0.32-0.38) at three years; they were not significantly different between the two cohorts of patients enrolled before and after the price reduction over the first 15 months of comparable follow up (hazard ratio 1.1; 95% CI 0.9-1.2, p = 0.27). In multivariable analysis using multiple imputations to compensate for missing values, factors associated with dropping out of care or dying were male gender (HR 1.33 [1.18-1.50], p = 0.003), treatment paid by self, family or partly by other (HR 3.05 [1.99-4.67], p < 0.001), and, compared with residents of Limbe, living more than 150 km from Limbe (HR 1.41 [1.18-1.69], p < 0.001), or being residents of Douala (HR 1.51 [1.16-1.98], p < 0.001). Conclusions Reducing the cost of ART increased enrolment of clients in the programme, but did not change retention in care. In a system where most clients pay for ART, an accessible clinic location may be more important than the cost of medication for retention in care. Decentralizing ART clinics might improve retention and survival among patients on ART.
CD4 Cell Counts at HIV Diagnosis among HIV Outpatient Study Participants, 2000–2009
Kate Buchacz,Carl Armon,Frank J. Palella,Rose K. Baker,Ellen Tedaldi,Marcus D. Durham,John T. Brooks
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/869841
Abstract: Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS participants diagnosed with HIV infection ≤6 months prior to entry into care during 2000–2009. We assessed the correlates of CD4 count <200 cells/mm3 at HIV diagnosis (late HIV diagnosis) by logistic regression. Results. Of 1,203 eligible patients, 936 (78%) had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm3 and did not significantly improve over time ( ). Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis ( ). Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ≥35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions. There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment. 1. Introduction Recent HIV surveillance data suggest that approximately 33% of HIV-infected persons in the United States present for HIV testing late and have AIDS (CD4+ cell count <200?cells/mL or an AIDS-defining illness) within one year after HIV diagnosis [1, 2]. Patients are less likely to experience the full benefits of highly active combination antiretroviral (cART) therapy if they enter HIV care and initiate treatment at a CD4 count <350?cells/mm3 [3, 4]; the clinical cost is even more profound when the CD4 count is <200?cells/mm3 or the patient has already developed clinical AIDS [5–8]. In addition, persons who remain unaware of their HIV-positive status (estimated 21% to 25% of infected persons in the USA in recent years) [9, 10] may not only miss the benefits of earlier cART treatment, but are also more likely to remain chronically viremic and are thereby more likely to transmit HIV to their sexual and needle-sharing partners [9]. The CDC has been promoting strategies to encourage more widespread HIV screening to diagnose infected persons earlier in the course of their illness, including by releasing in 2006 the guidelines for implementing routine universal opt-out testing in healthcare settings [11]. Yet, the latest HIV surveillance data [1, 2] and epidemiologic studies in multiple US populations indicate that the proportion of persons who are diagnosed late in the course of HIV infection [2, 12, 13] or present late for HIV care [14, 15] remains unacceptably high. Stable or worsening
Implementing an Information System Strategy: A Cost, Benefit, and Risk Analysis Framework for Evaluating Viable IT Alternatives in the US Federal Government  [PDF]
Sofia E. Espinoza, Joan S. Brooks, John Araujo
Int'l J. of Communications, Network and System Sciences (IJCNS) , 2018, DOI: 10.4236/ijcns.2018.116007
Abstract: In the US Federal government, an analysis of alternatives (AoA) is required for a significant investment of resources. The AoA yields the recommended alternative from a set of viable alternatives for the investment decision. This paper presents an integrated AoA and project management framework for analyzing new or emerging alternatives (e.g., Cloud computing), as may be driven by an information system strategy that incorporates a methodology for analyzing the costs, benefits, and risks of each viable alternative. The case study in this paper, about a business improvement project to provide public health and safety services to citizens in a US Federal agency, is a practical application of this integrated framework and reveals the benefits of this integrated approach for an investment decision. The decision making process in the framework—as an integrated, organized, and adaptable set of management and control practices—offers a defensible recommendation and provides accountability to stakeholders.
Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008
Kate Buchacz,Rose Baker,Douglas J. Ward,Frank J. Palella,Joan S. Chmiel,Benjamin Young,Bienvenido G. Yangco,Richard M. Novak,John T. Brooks
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/230290
Abstract: Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, ). Resistance to PIs decreased among PI-exposed patients (71% to 46%, ) as exposure to ritonavir-boosted PIs increased (6% to 81%, ). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs. 1. Introduction Highly active combination antiretroviral therapy (cART) has significantly improved survival and reduced the rates of AIDS-related complications among HIV-infected persons [1–3]. Emergence of HIV variants with reduced susceptibility to antiretroviral (ARV) medications can significantly limit the effectiveness and durability of treatment [3–8]. Use of ARV resistance testing to optimize cART selection has been associated with better virologic and clinical outcomes [9–11] and improved survival [12], and resistance testing is now generally recommended in the clinical management of HIV infection [13–15]. We have previously shown that use of genotypic and phenotypic testing increased in the HIV Outpatient Study (HOPS) during 1999–2006 and that the likelihood of testing varied by HIV disease severity and demographic characteristics [16]. Recent European and Canadian studies have suggested that both the prevalence [17, 18] and incidence [19, 20] of ARV resistance among HIV-infected persons have declined, due predominately to a decrease in the proportion of patients with pre-cART mono- or dual-ARV experience, and the increasing use and effectiveness of more tolerable and potent cART regimens that appear less likely to result in resistance mutations [18–22].
Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis
Vimalanand S. Prabhu,Paul G. Farnham,Angela B. Hutchinson,Sada Soorapanth,James D. Heffelfinger,Matthew R. Golden,John T. Brooks,David Rimland,Stephanie L. Sansom
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0019936
Abstract: Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations.
A Mathematical Model of Comprehensive Test-and-Treat Services and HIV Incidence among Men Who Have Sex with Men in the United States
Stephen W. Sorensen, Stephanie L. Sansom, John T. Brooks, Gary Marks, Elizabeth M. Begier, Kate Buchacz, Elizabeth A. DiNenno, Jonathan H. Mermin, Peter H. Kilmarx
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029098
Abstract: Background Early diagnosis and treatment of HIV infection and suppression of viral load are potentially powerful interventions for reducing HIV incidence. A test-and-treat strategy may have long-term effects on the epidemic among urban men who have sex with men (MSM) in the United States and may achieve the 5-year goals of the 2010 National AIDS Strategy that include: 1) lowering to 25% the annual number of new infections, 2) reducing by 30% the HIV transmission rate, 3) increasing to 90% the proportion of persons living with HIV infection who know their HIV status, 4) increasing to 85% the proportion of newly diagnosed patients linked to clinical care, and 5) increasing by 20% the proportion of HIV-infected MSM with an undetectable HIV RNA viral load. Methods and Findings We constructed a dynamic compartmental model among MSM in an urban population (based on New York City) that projects new HIV infections over time. We compared the cumulative number of HIV infections in 20 years, assuming current annual testing rate and treatment practices, with new infections after improvements in the annual HIV testing rate, notification of test results, linkage to care, initiation of antiretroviral therapy (ART) and viral load suppression. We also assessed whether five of the national HIV prevention goals could be met by the year 2015. Over a 20-year period, improvements in test-and-treat practice decreased the cumulative number of new infections by a predicted 39.3% to 69.1% in the urban population based on New York City. Institution of intermediate improvements in services would be predicted to meet at least four of the five goals of the National HIV/AIDS Strategy by the 2015 target. Conclusions Improving the five components of a test-and-treat strategy could substantially reduce HIV incidence among urban MSM, and meet most of the five goals of the National HIV/AIDS Strategy.
MCM2 - a promising marker for premalignant lesions of the lung: a cohort study
Dong-Feng Tan, Joel A Huberman, Andrew Hyland, Gregory M Loewen, John SJ Brooks, Amy F Beck, Ivan T Todorov, Gerold Bepler
BMC Cancer , 2001, DOI: 10.1186/1471-2407-1-6
Abstract: Parallel sections were stained with antibodies against MCM2 and Ki-67, and the frequencies of staining were independently measured by two investigators. Differences were evaluated statistically using the two-sided correlated samples t-test and Wilcoxon rank sum test.For each of the 41 specimens, the average frequency of staining by anti-MCM2 (39%) was significantly (p < 0.001) greater than by anti-Ki-67 (16%). In metaplastic lesions anti-MCM2 frequently detected cells near the epithelial surface, while anti-Ki-67 did not.We conclude that MCM2 is detectable in 2-3 times more proliferating premalignant lung cells than is Ki-67. The promise of MCM2 as a sensitive marker for premalignant lung cells is enhanced by the fact that it is present in cells at the surface of metaplastic lung lesions, which are more likely to be exfoliated into sputum. Future studies will determine if use of anti-MCM2 makes possible sufficiently early detection to significantly enhance lung cancer survival rates.The 5-year survival rate for patients with lung cancer is approximately 15%, and it has changed only marginally in the last 30 years [1]. Tumor stage is the most significant prognostic parameter for 5-year survival, but even patients with non-small cell lung cancer (non-SCLC) in pathologic stage IA disease (a tumor of less than 3 cm diameter located in one lobe of the lung and more than 2 cm from the carina without visceral pleural involvement, atelectasis, or pneumonitis, and absence of metastatic spread to regional lymph nodes) have a 33% chance of recurrence within 5 years after complete surgical resection (lobectomy with mediastinal lymph node dissection) [2]. In this group of patients, the tumor most frequently recurs at distant sites, including the bone, liver, adrenal glands, and brain [3], and the size of the primary tumor does not appear to impact on survival [4]. This suggests that even small and seemingly resectable lung cancers metastasize early. Data from randomized screenin
Validation of the individualised neuromuscular quality of life for the USA with comparison of the impact of muscle disease on those living in USA versus UK
Reza Sadjadi, Kelly A Vincent, Alison J Carr, Jessica Walburn, Victoria L Brooks, Shree Pandya, John T Kissel, Carlayne E Jackson, Michael R Rose, Muscle Study Group
Health and Quality of Life Outcomes , 2011, DOI: 10.1186/1477-7525-9-114
Abstract: We conducted a postal survey of QoL issues in US adults with muscle disease using an agreed translation, from UK to US English, of the same questionnaire as was used in the original construction of INQoL. This questionnaire included an opportunity for free text comments on any aspects of QoL that might not have been covered by the questionnaire. We examined the responses using both quantitative and qualitative approaches. The frequency of the responses in US versus UK populations was compared using appropriate correlation tests and Rasch analysis. A phenomenological approach was used to guide the qualitative analysis and facilitate the exploration of patients' perceptions and experiences.The US survey received 333 responses which were compared with 251 UK survey responses.We found that INQoL domains covered all the issues raised by US subjects with no additional domains required. The experiences of those with muscle disease were remarkably similar in the US and UK but there were differences related to the impact of muscle disease on relationships and on employment which was greater for those living in the United States. The greater impact on employment was associated with a higher importance rating given to employment in the US. This may reflect the lower level of financial support for those who are unemployed, and the loss of employment related health benefits.INQoL is appropriate for use in US population but there may be differences in the importance that US subject attach to certain aspects of QoL that could be the basis for further study.If these differences are confirmed then this may have implications for the interpretation of QoL outcomes in multi-national trials.Muscle diseases (MD) are a group of conditions that can be acquired or genetic and which result in progressive shrinking and weakness of the skeletal muscle such as to cause varying degrees of disability. The individual muscle diseases differ in their age of onset, their rate of progression and their
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