To evaluate the relationship between regional body composition and liver disease (fibrosis or steatosis) in HIV/HCV co-infected individuals.
Whole body dual-energy X-ray absorptiometry (DXA) was performed in 173 HIV/HCV co-infected persons within 12 months of a liver biopsy. Significant fibrosis was defined as a METAVIR stage greater than 1. Steatosis was graded as: 0, none; 1, steatosis involving less than 5% of hepatocytes; 2, 5–29%; 3, 30–60%; 4 greater than 60%, and was defined as more than 0. Poisson regression with robust variance was used to estimate prevalence ratios of the outcome measures.
The population was 62% male and 84% black with a median body mass index of 25.2 kg/m2 (interquartile range 22.5, 29.3 kg/m2). No differences in regional body fat or fat distribution were observed in 42 patients with significant fibrosis compared to others with less fibrosis. However, the 77 individuals (45%) with steatosis had greater central fat than those without steatosis [prevalence ratio 1.04 per kg trunk fat; 95% confidence interval (CI) 1.04, 1.11], after adjusting for hepatic fibrosis (prevalence ratio 1.77; 95% CI 1.29, 2.42), uncontrolled HIV replication (viral load >400 copies/ml) (prevalence ratio 1.57; 95% CI 1.12, 2.22), age, sex, race and diabetes mellitus.
In HIV/HCV co-infected individuals, measures of regional body fat or fat distribution were not associated with hepatic fibrosis. In contrast, increased central adiposity by DXA, as well as concomitant fibrosis and uncontrolled HIV, were associated with hepatic steatosis. The extent to which weight loss and effective antiretroviral therapy can reduce the risk of steatosis deserves further investigation.
body composition; hepatic fibrosis; hepatitis C; HIV; steatosis
Data from 6 human immunodeficiency virus clinics showed improvements in clinic attendance after versus before a clinic-wide intervention (7% on short-term measure; 3% on longer-term measure). Several subgroups showed larger improvements: younger patients, new or reengaging patients, and patients with elevated viral loads.
Background. Retention in care for human immunodeficiency virus (HIV)–infected patients is a National HIV/AIDS Strategy priority. We hypothesized that retention could be improved with coordinated messages to encourage patients' clinic attendance. We report here the results of the first phase of the Centers for Disease Control and Prevention/Health Resources and Services Administration Retention in Care project.
Methods. Six HIV-specialty clinics participated in a cross-sectionally sampled pretest-posttest evaluation of brochures, posters, and messages that conveyed the importance of regular clinic attendance. 10 018 patients in 2008–2009 (preintervention period) and 11 039 patients in 2009–2010 (intervention period) were followed up for clinic attendance. Outcome variables were the percentage of patients who kept 2 consecutive primary care visits and the mean proportion of all primary care visits kept. Stratification variables were: new, reengaging, and active patients, HIV RNA viral load, CD4 cell count, age, sex, race or ethnicity, risk group, number of scheduled visits, and clinic site. Data were analyzed by multivariable log-binomial and linear models using generalized estimation equation methods.
Results. Clinic attendance for primary care was significantly higher in the intervention versus preintervention year. Overall relative improvement was 7.0% for keeping 2 consecutive visits and 3.0% for the mean proportion of all visits kept (P < .0001). Larger relative improvement for both outcomes was observed for new or reengaging patients, young patients and patients with elevated viral loads. Improved attendance among the new or reengaging patients was consistent across the 6 clinics, and less consistent across clinics for active patients.
Conclusion. Targeted messages on staying in care, which were delivered at minimal effort and cost, improved clinic attendance, especially for new or reengaging patients, young patients, and those with elevated viral loads.
To compare the early mortality pattern and causes of death among patients starting HAART in Brazil and the United States.
We analyzed the combined data from two clinical cohorts followed at the Johns Hopkins AIDS Service in Baltimore, United States, and the Evandro Chagas Clinical Research Institute AIDS Clinic in Rio de Janeiro, Brazil. Participants included those who entered either cohort between 1999 and 2007 and were antiretroviral naive. Follow-up was at 1 year since HAART initiation. Cox proportional hazards regression analysis was used to assess the role of the city on the risk of death.
A total of 859 and 915 participants from Baltimore and Rio de Janeiro, respectively, were included. In Rio de Janeiro, 64.7% of deaths occurred within 90 days of HAART initiation; in Baltimore, 48.9% occurred between 180 and 365 days. AIDS-defining illness (61.8%) and non-AIDS-defining illness (55.6%) predominated as causes of death in Rio de Janeiro and Baltimore, respectively. Risk of death was similar in both cities (hazard ratio 1.04; P value=0.95) after adjusting for CD4+ T cell count, age, sex, HIV risk group, prior AIDS-defining illness, and Pneumocystis jirovecii pneumonia and Mycobacterium avium prophylaxis. Individuals with CD4+ T cell count less than or equal to 50 cells/μl (hazard ratio 4.36; P = 0.001) or older (hazard ratio, 1.03; P = 0.03) were more likely to die.
Although late HIV diagnosis is a problem both in developed and developing countries, differences in the timing and causes of deaths clearly indicate that, besides interventions for early HIV diagnosis, different strategies to curb early mortality need to be tailored in each country.
antiretroviral therapy; causes of death; cohort; early mortality; HIV/AIDS
Fractures and cirrhosis are major causes of morbidity and mortality among HIV–HCV-coinfected individuals. It is not known whether vitamin D deficiency is associated with these outcomes.
Between 2005 and 2007, 116 HIV–HCV- coinfected individuals underwent dual-energy X-ray absorptiometry within 1 year of a liver biopsy. 25-Hydroxy-vitamin D (25OHD) and parathyroid hormone were measured from archived samples. Low bone mineral density (BMD) was defined as BMD≥2 standard deviations lower than age-, sex- and race-matched controls (Z-score ≤−2.0) at the total hip, femoral neck or lumbar spine. Histological fibrosis staging was assessed according to the METAVIR system (0 [no fibrosis] to 4 [cirrhosis]).
The cohort was 87% African-American and 63% male. The median age (IQR) was 49.9 years (46.5–53.3). A total of 89% had a CD4+ T-cell count >200 cells/mm3 and 64% were receiving HAART. The median 25OHD was 19 ng/ ml (IQR 11.0–26.0). Hypovitaminosis D (25OHD≤15 ng/ml) was present in 41% and secondary hyperparathyroidism, defined by parathyroid hormone >65 pg/ml, was present in 24%. In total, 27% had low BMD (Z-score ≤−2) at the spine, femoral neck or total hip, and 39% had significant hepatic fibrosis (METAVIR≥2). In multivariate analysis, vitamin D deficiency was not associated with significant fibrosis or with BMD at any site.
Vitamin D deficiency was highly prevalent in this mostly African-American HIV–HCV-coinfected population, but was not related to BMD or liver disease severity. These data suggest that efforts to increase vitamin D levels in this population may not improve bone or liver outcomes.
To determine whether tenofovir disoproxil fumarate (TDF) is associated with renal dysfunction when used as part of an initial antiretroviral regimen and to assess the effect of ritonavir-boosted protease inhibitor (PI/r) coadministration on renal function in TDF-treated patients.
Analysis from a prospective observational cohort.
We compared all antiretroviral-naive patients with an estimated glomerular filtration rate (eGFR) of more than 50 ml/min per 1.73 m2 (modification of diet in renal disease equation) who initiated either TDF (n = 201) or any alternative nucleoside reverse transcriptase inhibitor (NRTI) (n = 231) after 1 January 2002.
Patients taking both TDF and NRTIs experienced an initial decline in eGFR during the first 180 days of therapy, but eGFR stabilized between 180 and 720 days. There was no difference between TDF and NRTI use in 25 or 50% decline in eGFR at 1 or 2 years or in change in eGFR at 6, 12, or 24 months. Those taking TDF and a PI/r had a greater median decline in eGFR than those taking TDF and a non-NRTI at 6 months (P = 0.01), with trends at 12 (P = 0.08) and 24 months (P = 0.08). There was no difference in median GFR decline between those on an NRTI and PI/r vs. an NRTI and non-NRTI.
Our data are consistent with results of clinical trials, which have shown no evidence of renal toxicity when TDF is used as part of an initial regimen. Our results support the use of TDF as a component of the initial antiretroviral regimen, and suggest that the eGFR should be monitored more closely when TDF is used with a PI/r.
antiretroviral; kidney; nephrotoxicity; nucleoside analog reverse transcriptase inhibitor; protease inhibitor; renal; tenofovir
As a first step in understanding the role that health care providers may play in observed gender disparities in HIV care in the United States, we sought to examine whether HIV providers' perceptions of and attitudes toward female and male patients differ. We used data from the Enhancing Communication to Improve HIV Outcomes (ECHO) study, a multisite, cross-sectional study focused on the role of the patient–provider relationship in disparities in HIV care conducted from October 2006 to June 2007. Using separate scales, we assessed HIV providers' perceptions about their patients (e.g., intelligence, compliance, responsibility) as well as providers' attitudes toward their patients (e.g., like, respect, frustrate). We used multivariable linear regression with generalized estimating equations to compare provider scores for female and male patients. Our sample comprised 37 HIV providers and 317 patients. Compared with male patients, HIV-infected females were less likely to be highly educated or employed, and more likely to report nonadherence to antiretroviral medications and depressive symptoms. In unadjusted and adjusted analyses, there was a significant difference in providers' perceptions of female and male patients, with providers having more negative perceptions of female patients. However, there was no significant difference in HIV providers' attitudes toward female and male patients in unadjusted or adjusted analyses. Further study is needed to elucidate the role of providers' perceptions and attitudes about female and male patients in observed gender disparities in HIV care.
To examine the association between early HIV viremia and mortality after HIV-associated lymphoma.
Multicenter observational cohort study.
Center for AIDS Research Network of Integrated Clinical Systems cohort.
HIV-infected patients with lymphoma diagnosed between 1996 and 2011, who were alive 6 months after lymphoma diagnosis and with ≥2 HIV RNA values during the 6 months after lymphoma diagnosis.
Cumulative HIV viremia during the 6 months after lymphoma diagnosis, expressed as viremia copy-6-months.
Main outcome measure
All-cause mortality between 6 months and 5 years after lymphoma diagnosis.
Of 224 included patients, 183 (82%) had non-Hodgkin lymphoma (NHL) and 41 (18%) had Hodgkin lymphoma (HL). At lymphoma diagnosis, 105 (47%) patients were on antiretroviral therapy (ART), median CD4 count was 148 cells/µlL (IQR 54– 322), and 33% had suppressed HIV RNA (<400 copies/mL). In adjusted analyses, mortality was associated with older age [adjusted hazard ratio (AHR) 1.37 per decade increase, 95% CI 1.03–1.83], lymphoma occurrence on ART (AHR 1.63, 95% CI 1.02– 2.63), lower CD4 count (AHR 0.75 per 100 cell/µL increase, 95% CI 0.64–0.89), and higher early cumulative viremia (AHR 1.35 per log10copies × 6-months/mL, 95% CI 1.11–1.65). The detrimental effect of early cumulative viremia was consistent across patient groups defined by ART status, CD4 count, and histology.
Exposure to each additional 1-unit log10 in HIV RNA throughout the 6 months after lymphoma diagnosis, was associated with a 35% increase in subsequent mortality. These results suggest that early and effective ART during chemotherapy may improve survival.
AIDS; Burkitt lymphoma; diffuse large B-cell lymphoma; HIV; Hodgkin lymphoma; lymphoma; non-Hodgkin lymphoma
Prior research has documented sociodemographic disparities in the use of antiretroviral therapy (ART). Recent therapeutic developments and changing epidemiological profiles may have altered such disparities. We examine the extent to which socio-demographic differences in prescribed ART have changed between 2002 and 2008.
We analyzed data abstracted from medical records at 13 US sites participating in the Human Immunodeficiency Virus Research Network. Prescription of ART was assessed for each year in care for each patient. A total of 14,092 patients were followed up for 39,251 person-years. We examined ART use as a function of sex, race/ethnicity, human immunodeficiency virus risk group, age, and CD4 history (no test <500 cells/mm3, one or more tests between 500 and 350 cells/mm3, 1 test ≤350 cells/mm3, and 2 or more tests ≤350 cells/mm3). Using multiple logistic regression, we ascertained interactions between each of these variables and calendar year.
The overall percentage prescribed ART increased from 60% to 80% between 2002 and 2008. Among those with 2 or more CD4 tests ≤350 cells/mm3, the percentage increased from 82% to 92%. ART rates were higher for those with lower CD4 counts but increased over time for all CD4 groups and for all demographic groups. Nevertheless, sex and racial/ethnic disparities persisted. Significant interactions were obtained for CD4 history by year, age by year, and age by CD4 history.
Although prescription of ART became more widespread from 2002 to 2008, patients who were female, black, or younger still had lower ART rates than male, white, or older patients.
ART; disparities; time trends; utilization; sociodemographic differences
Studies have repeatedly found that providers miss 70-90% of opportunities to express empathy. Our study sought to characterize provider responses to patients’ emotions, with the overall goal of better understanding reasons for lack of empathic response.
We analyzed 47 visits between patients and their providers. We defined empathic opportunities as instances where patients expressed a strong negative emotion. We then developed thematic categories to describe provider response.
We found a total of 29 empathic opportunities within 21 visits. Provider responses were categorized as ignore, dismiss, elicit information, problem-solve, or empathize. An empathic statement occurred at some point in the response sequence in 13/29 opportunities (45%). When problem-solving was the initial response, empathic statements rarely occurred in subsequent dialogue. Among the 16 instances with no empathic statements, providers engaged in problem-solving in 8 (50%).
Similar to other studies, we found providers missed most opportunities to respond empathically to patient emotion. Yet contrary to common understanding, providers often addressed the problem underlying the emotion, especially when the problem involved logistical or biomedical issues, as opposed to grief.
With enhanced awareness, providers may better recognize situations where they can offer empathy in addition to problem-solving.
Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers.
Antiretroviral therapy medication errors are common among hospitalized patients with human immunodeficiency virus (HIV) infection (29% of admissions on hospital day 1) but are quickly corrected (7% of admissions on hospital day 2). Compared with those admitted to the HIV/AIDS service, patients admitted to surgical services were at increased risk of errors.
Background. Antiretroviral therapy (ART) medication errors can lead to drug resistance, treatment failure, and death. Prior research suggests that ART medication errors are on the rise in US hospitals. This analysis provides a current estimate of inpatient antiretroviral prescribing errors.
Methods. Retrospective review of medication orders during the first 48 hours of hospitalization for patients with human immunodeficiency virus (HIV) infection admitted to the Johns Hopkins Hospital between 1 January and 31 December 2009. Errors were classified as (1) incomplete regimen, (2) incorrect dosage, (3) incorrect schedule, and (4) nonrecommended drug-drug combinations. Multivariable regression was used to identify factors associated with errors.
Results. A total of 702 admissions occurred in 2009. Of these, 380 had ART medications prescribed on the first day and 308 on the second day of hospitalization. A total of 145 ART medication errors in 110 admissions were identified on the first day (29%), and 22 errors were identified in 21 admissions on the second day (7%). The most common errors were incomplete regimen and incorrect dosage or schedule. Protease inhibitors accounted for the majority of dosing and scheduling errors (71%–73%). Compared with patients admitted to the HIV/AIDS service, those admitted to surgical services were at increased risk of errors (adjusted odds ratio, 3.10; 95% confidence interval, 1.18–8.18).
Conclusions. ART medication errors are common among hospitalized HIV-infected patients on the first day of admission, but most are corrected within 48 hours. Interventions are needed to safeguard patients and prevent serious complications of ART medication errors especially during the first 24 hours of hospitalization.
Genomic profiling has identified a subtype of high-risk B-progenitor acute lymphoblastic leukemia (B-ALL) with alteration of IKZF1, a gene expression profile similar to BCR-ABL1-positive ALL and poor outcome (Ph-like ALL). The genetic alterations that activate kinase signaling in Ph-like ALL are poorly understood. We performed transcriptome and whole genome sequencing on 15 cases of Ph-like ALL, and identified rearrangements involving ABL1, JAK2, PDGFRB, CRLF2 and EPOR, activating mutations of IL7R and FLT3, and deletion of SH2B3, which encodes the JAK2 negative regulator LNK. Importantly, several of these alterations induce transformation that is attenuated with tyrosine kinase inhibitors, suggesting the treatment outcome of these patients may be improved with targeted therapy.
Chimeric transcripts, including partial and internal tandem duplications (PTDs, ITDs) and gene fusions, are important in the detection, prognosis, and treatment of human cancers.
We describe Barnacle, a production-grade analysis tool that detects such chimeras in de novo assemblies of RNA-seq data, and supports prioritizing them for review and validation by reporting the relative coverage of co-occurring chimeric and wild-type transcripts. We demonstrate applications in large-scale disease studies, by identifying PTDs in MLL, ITDs in FLT3, and reciprocal fusions between PML and RARA, in two deeply sequenced acute myeloid leukemia (AML) RNA-seq datasets.
Our analyses of real and simulated data sets show that, with appropriate filter settings, Barnacle makes highly specific predictions for three types of chimeric transcripts that are important in a range of cancers: PTDs, ITDs, and fusions. High specificity makes manual review and validation efficient, which is necessary in large-scale disease studies. Characterizing an extended range of chimera types will help generate insights into progression, treatment, and outcomes for complex diseases.
Transcriptome assembly; Chimeric transcripts; Fusion; Partial tandem duplication; PTD; Internal tandem duplication; ITD; RNA-seq; Transcriptome
Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.
HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.
We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.
In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.
ClinicalTrails.gov NCT00279110 NCT00279110?term = NCT00279110&rank = 1
For optimal clinical benefit, HIV-infected patients should receive periodic outpatient care indefinitely. However, initially establishing HIV care and subsequent retention in care are problematic. This study examines establishment, retention, and loss to follow-up (LTFU) in a large, multi-site cohort over a 2-8 year period.
Medical record data were reviewed for 22,984 adult HIV patients receiving care at 12 clinics in the HIV Research Network between 2001-2009. Three dichotomous outcome measures were based on each patient's history of outpatient visits. Establishment reflects whether the patient made outpatient visits for longer than 6 months after initial enrollment. The retention measure reflects whether the patient had at least 2 outpatient visits separated by 90 days in each year in care. LTFU reflects whether the patient had no outpatient visits for more than 12 months without returning. Multiple logistic regression examined demographic and clinical correlates of each outcome, as well as the combined outcome of meeting all three measures.
Overall, 21.7% of patients never established HIV care after an initial visit. Among established patients, 57.4% did not meet the retention criterion in all years, and 34.9% were LTFU. Only 20.4% of all patients met all three criteria. The odds of successfully meeting all three criteria were higher for women, for older patients, for Hispanics compared with whites, and for those with CD4 levels ≤50 cells/mm3.
These data highlight the need to improve establishment and retention in HIV care.
HIV; Loss to follow-up; retention in care; outpatient use
Medulloblastoma, the most common malignant pediatric brain tumour, is currently treated with non-specific cytotoxic therapies including surgery, whole brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, prior attempts to identify targets for therapy have been underpowered due to small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup enriched. The most common region of focal copy number gain is a tandem duplication of the Parkinson’s disease gene SNCAIP, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1 that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGFβ signaling in Group 3, and NF-κB signaling in Group 4 suggest future avenues for rational, targeted therapy.
Recent-infection testing assays/algorithms (RITAs) have been developed to exploit the titer and avidity of HIV antibody evolution following seroconversion for incidence estimation. The Vitros Anti-HIV 1+2 assay (Ortho-Clinical Diagnostics) was approved by the FDA to detect HIV-1 and HIV-2 infections. We developed a less-sensitive (LS) and an avidity-modified version of this assay to detect recent HIV infection. Seroconversion panels (80 subjects, 416 samples) were tested to calculate the mean duration of recent infection (MDR) for these assays. A panel from known long-term (2+ years) HIV-infected subjects on highly active antiretroviral therapy (HAART) (n = 134) and subjects with low CD4 counts (AIDS patients [n = 140]) was used to measure the false-recent rate (FRR) of the assays. Using a signal-to-cutoff ratio of 20 and the LS-Vitros assay gave a RITA MDR of 215 days (95% confidence interval [95% CI], ±65 days) and using an avidity index (AI) of 0.6 gave an MDR of 170 days (±44 days), while a combination of the two assays yielded a MDR of 146 days (±38.6) and an FRR of 8%. Misclassifying subjects with known long-term infection as recently infected occurred in 14% of AIDS patients and 29% (95% CI, 22, 38) of HAART subjects and 3% (95% CI, 0.8, 7.2) and 42% (95% CI, 33, 51), respectively, for the LS- and avidity-modified Vitros assays, with a misclassification rate of 15% (95% CI, 11, 20) overall using a dual-assay algorithm. Both modified Vitros assays can be used to estimate the length of time since seroconversion and in calculations for HIV incidence. Like other RITAs, they are subject to high FRR in subjects on HAART or with AIDS.
White spruce (Picea glauca) is a dominant conifer of the boreal forests of North America, and providing genomics resources for this commercially valuable tree will help improve forest management and conservation efforts. Sequencing and assembling the large and highly repetitive spruce genome though pushes the boundaries of the current technology. Here, we describe a whole-genome shotgun sequencing strategy using two Illumina sequencing platforms and an assembly approach using the ABySS software. We report a 20.8 giga base pairs draft genome in 4.9 million scaffolds, with a scaffold N50 of 20 356 bp. We demonstrate how recent improvements in the sequencing technology, especially increasing read lengths and paired end reads from longer fragments have a major impact on the assembly contiguity. We also note that scalable bioinformatics tools are instrumental in providing rapid draft assemblies.
Availability: The Picea glauca genome sequencing and assembly data are available through NCBI (Accession#: ALWZ0100000000 PID: PRJNA83435). http://www.ncbi.nlm.nih.gov/bioproject/83435.
Supplementary data are available at Bioinformatics online.
Chronic diseases may influence patients taking major life changing decisions (MLCDs) concerning for example education, career, relationships, having children and retirement. A validated measure is needed to evaluate the impact of chronic diseases on MLCDs, improving assessment of their life-long burden. The aims of this study were to develop a validated questionnaire, the “Major Life Changing Decision Profile” (MLCDP) and to evaluate its psychometric properties.
50 interviews with dermatology patients and 258 questionnaires, completed by cardiology, rheumatology, nephrology, diabetes and respiratory disorder patients, were analysed for qualitative data using Nvivo8 software. Content validation was carried out by a panel of experts. The first version of the MLCDP was completed by 210 patients and an iterative process of multiple Exploratory Factor Analyses and item prevalence was used to guide item reduction. Face validity and practicability was assessed by patients.
48 MLCDs were selected from analysis of the transcripts and questionnaires for the first version of the MLCDP, and reduced to 45 by combination of similar themes. There was a high intraclass correlation coefficient (0.7) between the 13 members of the content validation panel. Four more items were deleted leaving a 41-item MLCDP that was completed by 210 patients. The most frequently recorded MLCDs were decisions to change eating habits (71.4%), to change smoking/drinking alcohol habits (58.5%) and not to travel or go for holidays abroad (50.9%).
Factor analysis suggested item number reduction from 41 to 34, to 29, then 23 items. However after taking into account item prevalence data as well as factor analysis results, 32 items were retained. The 32-item MLCDP has five domains education (3 items), job/career (9), family/relationships (5), social (10) and physical (5). The MLCDP score is expressed as the absolute number of decisions that have been affected.
The 32-item (5 domains) MLCDP has been developed as an easy to complete generic tool for use in clinical practice and for quality of life and epidemiological research. Further validation is required.
Major life changing decisions; MLCD; Major life changing decision profile; MLCDP; Chronic disease impact; Long-term impact; Life events; Life course; Life decisions; Quality of life; Psychometric properties
In a large North American cohort study, anal cancer incidence rates were substantially higher for HIV-infected men who have sex with men, other men, and women compared with HIV-uninfected individuals. Rates increased from 1996–1999 to 2000–2003 but plateaued by 2004–2007.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men).
Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007.
Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
Hospitalization rates for comorbid conditions among persons living with HIV in the current HAART era are unknown.
Hospitalization data from 2001 – 2008 were obtained on 11,645 adults receiving longitudinal HIV care at 4 geographically diverse U.S. HIV clinics within the HIV Research Network. Modified clinical classification software from the Agency for Healthcare Research and Quality assigned primary ICD-9 codes into diagnostic categories. Analysis was performed with repeated measures negative binomial regression.
During 2001 – 2008, the rate of AIDS defining illness (ADI) hospitalizations declined from 6.7 to 2.7 per 100 person years (PY), incidence rate ratio per year, 0.89 [0.87, 0.91]. Among the other diagnostic categories with average rates > 2 per 100 PY, cardiovascular hospitalizations increased over time (1.07 [1.03, 1.11]), while non-AIDS defining infection (0.98 [0.96, 1.00]), psychiatric (0.96 [0.93, 1.00]), and gastrointestinal/liver (0.96 [0.92, 1.00]) were slightly decreasing or stable. While less frequent overall, renal and pulmonary admissions also increased over time in univariate and multivariate analyses. Of all diagnostic categories, ADI admissions had the longest mean length of stay, 10.5 days.
ADI hospitalizations have continued to decline in recent years but are still relatively frequent and potentially costly given long lengths of stay. Increases or stability in the rates of chronic end-organ disease admissions imply a need for broader medical knowledge among individual clinicians and/or teams who care for persons living with HIV and a need for long-term access to medications for these conditions.
Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus.
Preoperative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%.
Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125.
HE4 is elevated in all stages of endometrial cancer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.
Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass.
Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC.
Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2--80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8--89.3).
An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.