Development and Use of a Web-based Data Management System for a Randomized Clinical Trial of Adolescents and Young Adults

Recent advances in technology provide support for multi-site, web-based data entry systems and the storage of data in a centralized location, resulting in immediate access to data for investigators, reduced participant burden and human entry error, and improved integrity of clinical trial data. The purpose of this paper is to describe the development of a comprehensive, web-based data management system for a multi-site randomized behavioral intervention trial. Strategies used to create this study-specific data management system included interdisciplinary collaboration, design mapping, feasibility assessments, and input from an advisory board of former patients with characteristics similar to the targeted population. The resulting data management system and development strategies provide a template for other behavioral intervention studies

Viewpoint: A Pragmatic Approach to Constructing a Minimum Data Set for Care of Patients with HIV in Developing Countries

Providing quality health care requires access to continuous patient data that developing countries often lack. A panel of medical informatics specialists, clinical human immunodeficiency virus (HIV) specialists, and program managers suggests a minimum data set for supporting the management and monitoring of patients with HIV and their care programs in developing countries. The proposed minimum data set consists of data for registration and scheduling, monitoring and improving practice management, and describing clinical encounters and clinical care. Data should be numeric or coded using standard definitions and minimal free text. To enhance accuracy, efficiency, and availability, data should be recorded electronically by those generating them. Data elements must be sufficiently detailed to support clinical algorithms/guidelines and aggregation into broader categories for consumption by higher level users (e.g., national and international health care agencies). The proposed minimum data set will evolve over time as funding increases, care protocols change, and additional tests and treatments become available for HIV-infected patients in developing countrie

CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre

Objective: Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design: We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods: We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?” Results: Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naïve estimates depending on assumptions about access to care among lost patients. Conclusions: Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it

Evaluating the Impact of a HIV Low-Risk Express Care Task-Shifting Program: A Case Study of the Targeted Learning Roadmap

In conducting studies on an exposure of interest, a systematic roadmap should be applied for translating causal questions into statistical analyses and interpreting the results. In this paper we describe an application of one such roadmap applied to estimating the joint effect of both time to availability of a nurse-based triage system (low risk express care (LREC)) and individual enrollment in the program among HIV patients in East Africa. Our study population is comprised of 16;513 subjects found eligible for this task-shifting program within 15 clinics in Kenya between 2006 and 2009, with each clinic starting the LREC program between 2007 and 2008. After discretizing followup into 90-day time intervals, we targeted the population mean counterfactual outcome (i.e. counterfactual probability of either dying or being lost to follow up) at up to 450 days after initial LREC eligibility under three fixed treatment interventions. These were (i) under no program availability during the entire follow-up, (ii) under immediate program availability at initial eligibility, but non-enrollment during the entire follow-up, and (iii) under immediate program availability and enrollment at initial eligibility. We further estimated the controlled direct effect of immediate program availability compared to no program availability, under a hypothetical intervention to prevent individualenrollment in the program. Targeted minimum loss-based estimation was used to estimate the mean outcome, while Super Learning was implemented to estimate the required nuisance parameters. Analyses were conducted with the ltmle R package; analysis code is available at an online repository as an R package. Results showed that at 450 days, the probability of in-care survival for subjects with immediate availability and enrollment was 0:93 (95% CI: 0.91, 0.95) and 0:87 (95% CI: 0.86, 0.87) for subjects with immediate availability never enrolling. For subjects without LREC availability, it was 0:91 (95% CI: 0.90, 0.92). Immediate program availability without individualenrollment, compared to no program availability, was estimated to slightly albeit significantly decrease survival by 4% (95% CI 0.03,0.06, p\u3c 0:01). Immediately availability and enrollment resulted in a 7% higher in-care survival compared to immediate availability with non-enrollment after 450 days (95% CI -0.08,-0.05, p\u3c 0:01). The results are consistent with a fairly small impact of both availability and enrollment in the LREC program on in-care survival

Influencing functional outcomes: a look at role performance and satisfaction with life following liver transplant

Abstract 572 The success of orthotopic liver transplantation (OLT), originally measured as survival, now extends to quality of the life saved. Return to work (RTW) is also a desired outcome. Our AIM was to explore the relationship between 5 pre-OLT factors & 5 post-OLT quality of life (QOL) domains with life satisfaction and primary productive role to better understand how to improve both. METHODS: Patients (pts)1-3 yrs post-OLT filled QOL form during follow-up clinic visits between 7/04 to 6/05. The Liver transplantation Database-Quality of life (LTD-QOL) form yielded data on 5 domains: measure of disease (MOD), psychological distress/well-being (PDW), personal function (PF), social/role function (SRF) & general health perception (GHP). Results: 229 pts were first categorized as satisfied overall with life (79%), or dissatisfied, and then assigned to groups based on primary productive role (51%), no primary productive role, or retired. Pre-OLT variables were age, gender, marital status, education, & etiology of liver disease; HCV (33%), alcohol liver disease (ALD)(11%), HCV+ALD (10%), & others (46%). Marital status & age were not significantly related to the outcome variables. Etiology of liver disease, education, and time since OLT and 5 post-OLT QOL domains were significantly associated with both outcome variables; satisfaction and primary productive role (p<.0001).To understand the differences, the 5 physical & men-tal QOL domains were regressed on primary productive role and satisfaction. Pts (mean age 54 yrs (19-74 yrs), males, 70%) fell into the category of primary productive role rates (51%). Pts transplanted for ALD were significantly (p<.05) more likely to be satisfied with life, whereas individuals with HCV±ALD, had lowest satisfaction and were most likely to be unable/uninterested in work. Stepwise logistical regression analysis of satisfaction demonstrated that GHP and SRF correlated most highly. Although satisfaction was significant in bivariate analysis, regression analysis of the influence of domains of QOL, as well as employment, demonstrated that SRF & GHP correlated most highly with life satisfaction. CONCLUSIONS: SRF and GHP correlate with good QOL post OLT. HCV patients have low levels of satisfaction whereas the highest level of satisfaction is in the ALD group. Further studies should address methods to improve satisfaction in those with HCV

A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count &gt;350&nbsp;cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years

Declining Tuberculosis Incidence Among People Receiving HIV Care and Treatment Services in East Africa, 2007–2012

Background: Antiretroviral therapy (ART) reduces the risk of Tuberculosis (TB) among people living with HIV (PLWH). With ART scale-up in sub-Saharan Africa over the past decade, incidence of TB among PLWH engaged in HIV care is predicted to decline. Methods: We conducted a retrospective analysis of routine clinical data from 168,330 PLWH receiving care at 35 facilities in Kenya, Tanzania, and Uganda during 2003–2012, participating in the East African region of the International Epidemiologic Databases to Evaluate AIDS. Temporal trends in facility-based annual TB incidence rates (per 100,000 person years) among PLWH and country-specific standardized TB incidence ratios using annual population-level TB incidence data from the World Health Organization were computed between 2007 and 2012. We examined patient-level and facility-level factors associated with incident TB using multivariable Cox models. Results: Overall, TB incidence rates among PLWH in care declined 5-fold between 2007 and 2012 from 5960 to 985 per 100,000 person years [P = 0.0003] (Kenya: 7552 to 1115 [P = 0.0007]; Tanzania: 7153 to 635 [P = 0.0025]; Uganda: 3204 to 242 [P = 0.018]). Standardized TB incidence ratios significantly decreased in the 3 countries, indicating a narrowing gap between incidence rates among PLWH and the general population. We observed lower hazards of incident TB among PLWH on ART and/or isoniazid preventive therapy and receiving care in facilities offering TB treatment onsite. Conclusions: Annual TB incidence rates among PLWH significantly declined during ART scale-up but remained higher than the general population. Increasing access to ART and isoniazid preventive therapy and co-location of HIV and TB treatment may further reduce TB incidence among PLWH

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy