Structural role of the tyrosine residues of cytochrome c

The tertiary structures of horse, tuna, Neurospora crassa, horse [Hse65,Leu67]- and horse [Hse65,Leu74]-cytochromes c were studied with high-resolution 1H n.m.r. spectroscopy. The amino acid sequences of these proteins differ at position 46, which is occupied by phenylalanine in the horse proteins but by tyrosine in the remaining two, and at positions 67, 74 and 97, which are all occupied by tyrosine residues in horse and tuna cytochrome c but in the other proteins are substituted by phenylalanine or leucine, though there is only one such substitution per protein. The various aromatic-amino-acid substitutions do not seriously affect the protein structure

Quality of data collection in a large HIV observational clinic database in sub-Saharan Africa: implications for clinical research and audit of care

<p>Abstract</p> <p>Background</p> <p>Observational HIV clinic databases are now widely used to answer key questions related to HIV care and treatment, but there has been no systematic evaluation of their quality of data. Our objective was to evaluate the completeness and accuracy of recording of key data HIV items in a large routine observational HIV clinic database.</p> <p>Methods</p> <p>We looked at the number and rate of opportunistic infections (OIs) per 100 person years at risk in the 24 months following antiretroviral therapy (ART) initiation in 559 patients who initiated ART in 2004-2005 and enrolled into a research cohort. We compared this with data in a routine clinic database for the same 559 patients, and a further 1233 patients who initiated ART in the same period. The Research Cohort database was considered as the reference "gold standard" for the assessment of data accuracy. A crude percentage of underreporting of OIs in the clinic database was calculated based on the difference between the OI rates reported in both databases.</p> <p>We reviewed 100 clinic patient medical records to assess the accuracy of recording of key data items of OIs, ART toxicities and ART regimen changes.</p> <p>Results</p> <p>The overall incidence rate per 100 person years at risk for the initial OI in the 559 patients in the research cohort and clinic databases was 24.1 (95% CI: 20.5-28.2) and 13.2 (95% CI: 10.8-16.2) respectively, and 10.4 (95% CI: 9.1-11.9) for the 1233 clinic patients. This represents a 1.8- and 2.3-fold higher rate of events in the research cohort database compared with the same 599 patients and 1233 patients in the routine clinic database, or a 45.1% and 56.8% rate of underreporting, respectively. The combined error rate of missing and incorrect items from the medical records' review was 67% for OIs, 52% for ART-related toxicities, and 83% and 58% for ART discontinuation and modification, respectively.</p> <p>Conclusions</p> <p>There is a high rate of underreporting of OIs in a routine HIV clinic database. This has important implications for the use and interpretation of routine observational databases for research and audit, and highlights the need for regular data validation of these databases.</p

Resource utilization in lung cancer diagnostic procedures:Current use and budget consequences

The main objective of this study is to determine the current use of lung cancer diagnostic procedures in two large hospitals in the Netherlands, to explore deviations in guideline adherence between the hospitals, and to estimate the budget impact of the diagnostic work-up as well as the over- and underutilization.A state transition model for the diagnostic pathway for lung cancer patients was developed using existing clinical practice guidelines (CPG) combined with a systematic literature. In addition to the CPGs depicting current practice, diagnostic utilization was gathered in two large hospitals representing an academic tertiary care hospital and a large regional teaching hospital for patients, who were selected from the Netherlands cancer registry.The total population consisted of 376 patients with lung cancer. Not in all cases the guideline was followed, for instance in the usage of MR brain with stage III lung cancer patients (n = 70). The state-transition model predicts an average budget impact for the diagnostic pathway per patient estimated of € 2496 in the academic tertiary care hospital and € 2191 in the large regional teaching hospital.The adherence to the CPG's differed between hospitals, which questions the adherence to CPG's in general. Adherence to CPG's could lead to less costs in the diagnostic pathway for lung cancer patients

An Empirical Approach to Defining Loss to Follow-up Among Patients Enrolled in Antiretroviral Treatment Programs

In many programs providing antiretroviral therapy (ART), clinicians report substantial patient attrition; however, there are no consensus criteria for defining patient loss to follow-up (LTFU). Data on a multisite human immunodeficiency virus (HIV) treatment cohort in Lusaka, Zambia, were used to determine an empirical “days-late” definition of LTFU among patients on ART. Cohort members were classified as either “in care” or LTFU as of December 31, 2007, according to a range of days-late intervals. The authors then looked forward in the database to determine which patients actually returned to care at any point over the following year. The interval that best minimized LTFU misclassification was described as “best-performing.” Overall, 33,704 HIV-infected adults on ART were included. Nearly one-third (n = 10,196) were at least 1 day late for an appointment. The best-performing LTFU definition was 56 days after a missed visit, which had a sensitivity of 84.1% (95% confidence interval (CI): 83.2, 85.0), specificity of 97.5% (95% CI: 97.3, 97.7), and misclassification of 5.1% (95% CI: 4.8, 5.3). The 60-day threshold performed similarly well, with only a marginal difference (<0.1%) in misclassification. This analysis suggests that ≥60 days since the last appointment is a reasonable definition of LTFU. Standardization to empirically derived definitions of LTFU will permit more reliable comparisons within and across programs

Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART