Prognosis in acute pancreatitis associated with HIV infection.

BACKGROUND: This prospective study compared scoring systems in predicting adverse outcomes in HIV associated acute pancreatitis (HIV+ve AP) METHODS: Systemic inflammatory response syndrome (SIRS), Glasgow criteria, C-reactive protein (CRP), bedside index of severity in acute pancreatitis (BISAP) and APACHE II scores using standard cut-off values were used to predict the endpoint of moderate and severe disease in HIV-ve and HIV+ve patients and in CD4 counts above and below 200 cells/mm3. RESULTS: Ninety (38%) of 238 patients with AP were HIV+ve. Fifteen had organ failure, 33 local complications and 12 patients died. Advanced age was not associated with severe disease. The APACHE II was the best predictor of severe disease in HIV+ve (AUC 0.88) and HIV-ve patients (AUC 0.81) and CRP was the poorest predictor (AUC 0.59) in HIV+ve patients. In HIV+ve patients with CD4 counts greater and less than 200 cells/mm3 the Glasgow and APACHE II scores were the best prognosticators (AUC > 0.8) and BISAP in patients with CD4 > 200 cells/mm3 (AUC 0.90). CONCLUSION: The APACHE II score was most effective irrespective of HIV status whereas the BISAP scores was better in CD4 > 200 cells/mm3.

Phylogenomic analyses recover a clade of large-bodied decapodiform cephalopods.

Phylogenetic relationships among the squids and cuttlefishes (Cephalopoda:Decapodiformes) have resisted clarification for decades, despite multiple analyses of morphological, molecular and combined data sets. More recently, analyses of complete mitochondrial genomes and hundreds of nuclear loci have yielded similarly ambiguous results. In this study, we re-evaluate hypotheses of decapodiform relationships by increasing taxonomic breadth and utilizing higher-quality genome and transcriptome data for several taxa. We also employ analytical approaches to (1) identify contamination in transcriptome data, (2) better assess model adequacy, and (3) account for potential biases. Using this larger data set, we consistently recover a clade comprising Myopsida (closed-eye squid), Sepiida (cuttlefishes), and Oegopsida (open-eye squid) that is sister to a Sepiolida (bobtail and bottletail squid) clade. Idiosepiida (pygmy squid) is consistently recovered as the sister group to all sampled decapodiform lineages. Further, a weighted Shimodaira-Hasegawa test applied to one of our larger data matrices rejects all alternatives to these ordinal-level relationships. At present, available nuclear genome-scale data support nested clades of relatively large-bodied decapodiform cephalopods to the exclusion of pygmy squids, but improved taxon sampling and additional genomic data will be needed to test these novel hypotheses rigorously.

Spiralian Genomes Reveal Gene Family Expansions Associated with Adaptation to Freshwater.

The colonization of freshwater habitats by marine-adapted organisms represents a major transition that has only occurred a few times in the evolution of animals. Only around half of the extant animal phyla have representatives in both marine and freshwater environments and even within those phyla some major clades are restricted to marine environments. Moving from marine to freshwater environments can create severe osmotic and ionic stresses and the mechanisms that animals have used to adapt to those stresses are still not well understood. In this study, we downloaded amino acid sequence data from 11 spiralian animal genomes (four freshwater taxa representing four different phyla as well as 7 marine taxa) and identified a number of gene family expansions that have occurred exclusively in the freshwater lineages. Further investigation of these gene families and the timing and nature of their expansions will illuminate one of the major evolutionary transitions in the history of life on Earth.

The grass squid Pickfordiateuthis pulchella is a paedomorphic loliginid.

The wide disparity in adult body size observed both within and among animal taxa has long attracted widespread interest, with several general rules having been proposed to explain trends in body size evolution. Adult body size disparity among the cephalopod mollusks is remarkable, with adult body sizes ranging from a few centimeters to several meters. Some of the smallest cephalopods are found within Pickfordiateuthis, a group comprising three described species of squid found in the western Atlantic and tropical eastern Pacific. Pickfordiateuthis pulchella, the type species of the genus, was initially proposed to be closely related to the loliginid squids (Loliginidae), with subsequent descriptions of additional species supporting a placement within Loliginidae. Pickfordiateuthis is remarkable in that all species reach sexual maturity at about one-fifth to one-tenth the size seen in most loliginid species. To date, no phylogenetic analyses have included representatives of Pickfordiateuthis. To infer the phylogenetic position of Pickfordiateuthis and explore its implications for body size evolution, we collected specimens of Pickfordiateuthis pulchella from Brazilian waters and sequenced regions of two loci-the mitochondrial large ribosomal subunit (rrnL a.k.a. 16S) gene and the nuclear gene rhodopsin. Maximum likelihood and Bayesian analyses of these sequences support a placement of Pickfordiateuthis pulchella as sister to a clade comprising the Western Hemisphere loliginid genera Doryteuthis and Lolliguncula. Analyses of body size evolution within Loliginidae suggest that a shift to a smaller body size optimum occurred along the lineage leading to P. pulchella, with some evidence of shifts toward larger sizes in the ancestors of Loligo and Sepioteuthis; these inferences seem to be robust to phylogenetic uncertainty and incomplete taxon sampling. The small size and juvenile-like morphological traits seen in adult Pickfordiateuthis (e.g., sepiolid-like fins and biserial sucker arrangement in the tentacles) may be due to paedomorphosis.

Na+ /K+ -ATPase gene duplications in clitellate annelids are associated with freshwater colonization.

Major habitat transitions, such as those from marine to freshwater habitats or from aquatic to terrestrial habitats, have occurred infrequently in animal evolution and may represent a barrier to diversification. Identifying genomic events associated with these transitions can help us better understand mechanisms that allow animals to cross these barriers and diversify in new habitats. Study of the Capitella telata and Helobdella robusta genomes allows examination of one such habitat transition (marine to freshwater) in Annelida. Initial examination of these genomes indicated that the freshwater leech H. robusta contains many more copies (12) of the sodium-potassium pump alpha-subunit (Na+ /K+ -ATPase) gene than does the marine polychaete C. telata (2). The sodium-potassium pump plays a key role in maintenance of cellular ionic balance and osmoregulation, and Na+ /K+ -ATPase duplications may have helped annelids invade and diversify in freshwater habitats. To assess whether the timing of Na+ /K+ -ATPase duplications coincided with the marine-to-freshwater transition in Clitellata, we used transcriptomic data from 18 annelid taxa, along with the two genomes, to infer a species phylogeny and identified Na+ /K+ -ATPase gene transcripts in order to infer the timing of gene duplication events using tree-based methods. The inferred timing of Na+ /K+ -ATPase duplication events is consistent with the timing of the initial marine-to-freshwater transition early in the history of clitellate annelids, supporting the hypothesis that gene duplications may have played a role in the annelid diversification into freshwater habitats.

Inflorescence evolution in Santalales: integrating morphological characters and molecular phylogenetics.

PREMISE OF THE STUDY: The sandalwood order (Santalales) includes members that present a diverse array of inflorescence types, some of which are unique among angiosperms. This diversity presents not only interpretational challenges but also opportunities to test fundamental concepts in plant morphology. Here we used modern phylogenetic approaches to address the evolution of inflorescences in the sandalwood order. METHODS: Phylogenetic analyses of two nuclear and three chloroplast genes were conducted on representatives of 146 of the 163 genera in the order. A matrix was constructed that scored nine characters dealing with inflorescences. One character, "trios", that encompasses any grouping of three flowers (i.e., both dichasia and triads) was optimized on samples of the posterior distribution of trees from the Bayesian analysis using BayesTraits. Three nodes were examined: the most recent common ancestors of (A) all ingroup members, (B) Loranthaceae, and (C) Opiliaceae, Santalaceae s.l., and Viscaceae. KEY RESULTS: The phylogenetic analysis resulted in many fully resolved nodes across Santalales with strong support for 18 clades previously named as families. The trios character was not supported for nodes A and C, whereas it was supported for node B where this partial inflorescence type is best described as a triad. CONCLUSIONS: Essentially every major inflorescence type can be found in Santalales; however, the dichasium, a type of partial inflorescence, is rarely seen and is not plesiomorphic for the order. In the family Erythropalaceae, inflorescences are mostly in small, axillary fascicles or cymes. Successive families show both cymose and racemose types and compound systems (e.g., thyrses). Inflorescences in Amphorogynaceae and Viscaceae are not dichasial and in general are difficult to compare to "standard" inflorescences.

Clarifying the phylogenetic relationships and taxonomy of Stenonema, Stenacron and Maccaffertium, three common eastern North American mayfly genera.

Stenonema, Stenacron, and Maccaffertium are three closely related genera of mayflies (Ephemeroptera:Heptageniidae) commonly found across North America. Due to their primarily aquatic life history and sensitivity to aquatic pollutants, these mayflies are often used as water quality indicators. However, there is little morphological variation within these genera, leading to difficulties in identification and rampant taxonomic confusion, limiting their utility as bioindicators. In an attempt to resolve the phylogenetic relationships of Stenonema, Stenacron, and Maccaffertium, and to clarify their higher-level classifications, we sequenced regions of two mitochondrial genes (cytochrome oxidase subunit 1 (cox1) and 16S ribosomal RNA (rrnl)) and two nuclear genes (Wingless (Wg) and histone H3) from 60 individuals representing most of the described species in these genera and included data from representatives of three heptageniid genera (Kageronia, Macdunnoa and Pseudiron) proposed in previous studies to be closely related to our focal taxa as well as two more distantly related heptageniid genera (Epeorus and Heptagenia) to root the phylogenies. Maximum likelihood and Bayesian analysis were conducted on single-gene and concatenated multi-gene data sets and species tree methods were utilized to resolve relationships. These analyses resolved Stenacron as a monophyletic group sister to a clade comprising Macdunnoa, Maccaffertium and Stenonema. Maccaffertium was found to be paraphyletic, with Stenonema femoratum resolved within Maccaffertium as sister to M. mexicanum. Many relationships remained unresolved or varied across analyses, making revision of the classification based on phylogenetic considerations challenging. To minimize confusion while naming clades and acknowledging uncertainty in our phylogenetic conclusions, we redefine Stenonema to include Maccaffertium and propose three subgenera-Stenonema, Maccaffertium and Lewisa- for key well-supported clades.

Assessing the utility of transcriptome data for inferring phylogenetic relationships among coleoid cephalopods.

Historically, deep-level relationships within the molluscan class Cephalopoda (squids, cuttlefishes, octopods and their relatives) have remained elusive due in part to the considerable morphological diversity of extant taxa, a limited fossil record for species that lack a calcareous shell and difficulties in sampling open ocean taxa. Many conflicts identified by morphologists in the early 1900s remain unresolved today in spite of advances in morphological, molecular and analytical methods. In this study we assess the utility of transcriptome data for resolving cephalopod phylogeny, with special focus on the orders of Decapodiformes (open-eye squids, bobtail squids, cuttlefishes and relatives). To do so, we took new and previously published transcriptome data and used a unique cephalopod core ortholog set to generate a dataset that was subjected to an array of filtering and analytical methods to assess the impacts of: taxon sampling, ortholog number, compositional and rate heterogeneity and incongruence across loci. Analyses indicated that datasets that maximized taxonomic coverage but included fewer orthologs were less stable than datasets that sacrificed taxon sampling to increase the number of orthologs. Clades recovered irrespective of dataset, filtering or analytical method included Octopodiformes (Vampyroteuthis infernalis + octopods), Decapodiformes (squids, cuttlefishes and their relatives), and orders Oegopsida (open-eyed squids) and Myopsida (e.g., loliginid squids). Ordinal-level relationships within Decapodiformes were the most susceptible to dataset perturbation, further emphasizing the challenges associated with uncovering relationships at deep nodes in the cephalopod tree of life.

Completing the Maternal Care Team: OB/GYN Expertise at Rural District Hospitals in Ghana, a Qualitative Study.

Introduction To provide a qualitative perspective on the changes that occurred after newly placed OB/GYNs began working at district hospitals in Ashanti, Ghana. Methods Structured interviews of healthcare professionals were conducted at eight district hospitals located throughout the Ashanti district of Ghana, four with and four without a full-time OB/GYN on staff. Individuals interviewed include: medical superintendents, medical officers, district hospital administrators, OB/GYNs (where applicable), and nurse-midwives. Interviews were transcribed verbatim and content analysis was performed to identify common themes. Characteristics quotes were identified to illustrate principal interview themes. Quotes were verified in context by researchers for accuracy. Results Interviews with providers revealed four areas most impacted by an OB/GYN's leadership and expertise at district hospitals: patient referral patterns, obstetric protocol and training, facility management and organization, and hospital reputation. Discussion OB/GYNs are uniquely positioned to add clinical capacity and care quality to established maternal care teams at district hospitals-empowering district hospitals as reliable care centers throughout rural Ghana for women's health. Coordinated efforts between government, donors and OBGYN training institutions to provide complete obstetric teams is the next step to achieve the global goal of eliminating preventable maternal mortality by 2030.

Phylogenomic analyses of Crassiclitellata support major Northern and Southern Hemisphere clades and a Pangaean origin for earthworms.

BACKGROUND: Earthworms (Crassiclitellata) are a diverse group of annelids of substantial ecological and economic importance. Earthworms are primarily terrestrial infaunal animals, and as such are probably rather poor natural dispersers. Therefore, the near global distribution of earthworms reflects an old and likely complex evolutionary history. Despite a long-standing interest in Crassiclitellata, relationships among and within major clades remain unresolved. METHODS: In this study, we evaluate crassiclitellate phylogenetic relationships using 38 new transcriptomes in combination with publicly available transcriptome data. Our data include representatives of nearly all extant earthworm families and a representative of Moniligastridae, another terrestrial annelid group thought to be closely related to Crassiclitellata. We use a series of differentially filtered data matrices and analyses to examine the effects of data partitioning, missing data, compositional and branch-length heterogeneity, and outgroup inclusion. RESULTS AND DISCUSSION: We recover a consistent, strongly supported ingroup topology irrespective of differences in methodology. The topology supports two major earthworm clades, each of which consists of a Northern Hemisphere subclade and a Southern Hemisphere subclade. Divergence time analysis results are concordant with the hypothesis that these north-south splits are the result of the breakup of the supercontinent Pangaea. CONCLUSIONS: These results support several recently proposed revisions to the classical understanding of earthworm phylogeny, reveal two major clades that seem to reflect Pangaean distributions, and raise new questions about earthworm evolutionary relationships.

Community-based surveillance of maternal deaths in rural Ghana.

OBJECTIVE: To examine the feasibility and effectiveness of community-based maternal mortality surveillance in rural Ghana, where most information on maternal deaths usually comes from retrospective surveys and hospital records. METHODS: In 2013, community-based surveillance volunteers used a modified reproductive age mortality survey (RAMOS 4+2) to interview family members of women of reproductive age (13-49 years) who died in Bosomtwe district in the previous five years. The survey comprised four yes-no questions and two supplementary questions. Verbal autopsies were done if there was a positive answer to at least one yes-no question. A mortality review committee established the cause of death. FINDINGS: Survey results were available for 357 women of reproductive age who died in the district. A positive response to at least one yes-no question was recorded for respondents reporting on the deaths of 132 women. These women had either a maternal death or died within one year of termination of pregnancy. Review of 108 available verbal autopsies found that 64 women had a maternal or late maternal death and 36 died of causes unrelated to childbearing. The most common causes of death were haemorrhage (15) and abortion (14). The resulting maternal mortality ratio was 357 per 100 000 live births, compared with 128 per 100 000 live births derived from hospital records. CONCLUSION: The community-based mortality survey was effective for ascertaining maternal deaths and identified many deaths not included in hospital records. National surveys could provide the information needed to end preventable maternal mortality by 2030.

Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease.

BACKGROUND & AIMS: Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone. METHODS: In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50. RESULTS: Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated. CONCLUSIONS: The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment with prednisone. ClincialTrials.gov number, NCT00132899.

The public health impact of training physicians to become obstetricians and gynecologists in Ghana.

OBJECTIVES: We assessed the public health effect of creating and sustaining obstetrics and gynecology postgraduate training in Ghana, established in 1989 to reverse low repatriation of physicians trained abroad. METHODS: All 85 certified graduates of 2 Ghanaian university-based postgraduate training programs from program initiation in 1989 through June 2010 were identified and eligible for this study. Of these, 7 were unable to be contacted, inaccessible, declined participation, or deceased. RESULTS: Of the graduates, 83 provide clinical services in Ghana and work in 33 sites in 8 of 10 regions; 15% were the first obstetrician and gynecologist at their facility, 25% hold clinical leadership positions, 50% practice in teaching hospitals, and 14% serve as academic faculty. CONCLUSIONS: Creating capacity for university-based postgraduate training in obstetrics and gynecology is effective and sustainable for a comprehensive global approach to reduce maternal and neonatal morbidity and mortality. Policies to support training and research capacity in obstetrics and gynecology are an integral part of a long-term national plan for maternal health.

Use of amylase and alanine transaminase to predict acute gallstone pancreatitis in a population with high HIV prevalence.

BACKGROUND: The etiology of acute pancreatitis can be difficult to determine early in the course of the disease. The aim of the present study was to determine the relationship between biochemical parameters and the cause of acute pancreatitis. METHODS: A prospectively collected database of patients admitted with acute pancreatitis between 2001 and 2008 was analyzed. The relationships between etiology and age, sex, admission serum amylase level, and admission alanine transaminase (ALT) level were evaluated. RESULTS: Acute pancreatitis was diagnosed in 464 patients. The disease was related to alcohol in 275 cases, gallstones in 81 cases, HIV in 49 cases, dyslipidemia in 42 cases, and it was idiopathic in 17 cases. Alcoholic pancreatitis was more common in men, whereas the other identifiable causes were more common in women (P < 0.001). Mean age at presentation was 39 years with no difference in age in relation to etiology (P = 0.057). When compared to patients with non-biliary causes of pancreatitis, patients with gallstone pancreatitis had greater median (range) serum amylase activity [1,423 U/l (153-7,500 U/l) versus 589 U/l (58-11,144 U/l); P < 0.001] and ALT activity [153 U/l (8-13,233 U/l) versus 31 U/l (6-421 U/l); P < 0.001]. No significant differences in amylase or ALT activity were found between non-biliary etiologies (P > 0.05). Alanine transaminase was the only factor independent of sex to predict gallstone etiology, with activity >150 U/l having a specificity of 97 %. CONCLUSIONS: In patients with acute gallstone pancreatitis, the serum amylase and ALT activities were more than double those of other etiologies. An ALT level of >150 U/l was highly predictive of gallstone etiology independent of gender. Neither amylase nor ALT could differentiate non-biliary etiologies. The combination of amylase and ALT offered no improvement in predicting etiology over each alone.

Potentially under-recognized late-stage physical and psychosexual complications of non-therapeutic neonatal penile circumcision: a qualitative and quantitative analysis of self-reports from an online community forum.

The removal of non-pathogenic foreskin from the penis of healthy neonates and infants for non-religious reasons is routinely practiced in many parts of the world. High level data from well-designed randomized controlled trials of circumcision in neonates and infants does not guide clinical practice. Reliable counts of immediate and short term circumcision complications are difficult to estimate. Emerging evidence suggests routine neonatal circumcision could lead to long term psychological, physical, and sexual complications in some men. The stigma associated with discussing circumcision complications creates a prevalence paradox where the presence of significant circumcision complications is higher than reported. Prior to the Internet, there were very few forums for men from diverse communities, who were troubled about their circumcision status, to discuss and compare stories. To investigate the long term consequences of circumcision, we reviewed 135 posts from 109 individual users participating in a circumcision grief subsection of Reddit, an internet discussion board. We identified three major categories of complications: physical such as pain during erections and lost sensitivity, psychological such as anxiety and violation of autonomy, and sexual such as feeling that the sexual experience was negatively altered or being unable to complete a sexual experience. We also identified a "discovery process" where some men described coming into awareness of their circumcision status. These findings suggest that neonatal circumcision can have significant adverse consequences for adult men. The removal of normal foreskin tissue should be limited to adult men who choose the procedure for cosmetic reasons or when medically indicated.

Growth model for international academic medicine partnerships: Qualitative analysis of Ghana postgraduate Ob/Gyn training program.

This study aims to detail the capacity strengthening process of the Ghana Ob/Gyn postgraduate training program in order to inform a model by which international academic medicine partnerships can form, grow, and effectively tackle development challenges. A qualitative analysis with grounded theory methodological approach was utilized. Convenience and purposive sampling were used to select certified Ob/Gyn training program graduates. Interviews were conducted face-to-face in in Accra, Kumasi, Cape Coast, and Tamale, Ghana between June 21 to August 20, 2017. An additional data analysis of 48 semi-structured interviews previously collected for another study were examined for factors pertinent to graduate career development. Coded data were grouped according to themes and subthemes. Emerging themes demonstrated that graduates further complete the maternal care team and facilitate collaboration amongst healthcare workers. Themes also included graduates' pursuit of subspecialty training and research. Graduates cited the training program as key to their professional development. Graduates assume leadership roles in hospital management and operations, teaching, mentoring, interprofessional maternal care team, and knowledge-sharing. Graduates expressed eagerness to subspecialize and to advance their research training and skills. The results suggest a growth model of international academic medicine partnerships from basic obstetric training to advanced training. The model is developed for adaptability in other SSA countries and low-resource settings so that it may effectively strengthen health workforce capacity. We hope that this program can serve as a model for other partnerships in medical specialties.

Patient time costs and out-of-pocket costs in hepatitis C.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with substantial costs to patients, their caregivers and society. AIMS: We evaluated time costs (time spent seeking healthcare) and out-of-pocket (OOP) costs for patients with HCV and their caregivers. METHODS: We measured costs for 738 HCV outpatients in a tertiary-care clinic using a patient-completed questionnaire. Time and OOP costs were compared across disease stages and sociodemographic categories. We examined the association between cost and disease stage using linear regression adjusting for age, gender, marital status, education, income and Index of Coexistent Disease (ICED) comorbidity score. Costs were expressed in 2007 Canadian dollars. RESULTS: The mean annual time cost per patient was $2136 (98 h), and ranged from $281 (18 h) in individuals who had cleared the virus to $9416 in transplant recipients (420 h). Caregiver costs were reported in 10% of patients. The mean annual OOP cost per patient was $1326. Patients receiving active treatment and those with late-stage disease spent $2500-2800 per year on HCV-related healthcare, approximately 7% of their annual income. Patients who had cleared the virus had the lowest time and OOP costs. Low income and unemployed patients had higher costs. CONCLUSIONS: In HCV-infected individuals, OOP and time costs represent a significant economic burden and fall disproportionately upon those least able to afford them. The lower cost burden among those who were successfully treated suggests that wider use of antiviral therapy may reduce economic burden in addition to improving health outcomes.

Health utilities and psychometric quality of life in patients with early- and late-stage hepatitis C virus infection.

BACKGROUND AND AIM: Hepatitis C virus (HCV) infection is associated with impairment in health-related quality of life (HRQOL). The purpose of this study was to evaluate HRQOL across the HCV disease spectrum using preference-based (utility) and non-preference-based (psychometric) methods, adjusting for sociodemographic factors and co-morbidity. METHODS: Hepatitis C virus patients (n = 751) were recruited from several tertiary care settings in Vancouver, Canada for this observational, cross-sectional cohort study. Patients completed the Health Utilities Index Mark 2/3, a self-administered time trade-off utility instrument, and the Hepatitis Quality of Life Questionnaire (SF-36 with HCV-specific items). We examined the association between HRQOL and disease stage using linear regression adjusting for age, education, marital status, income, and co-morbidities. RESULTS: Utility scores were low across disease stage and instrument, ranging from 0.51 to 0.80. On the SF-36, the mean Physical Component Summary score ranged from 37.2 to 49.2 across disease stage, and the Mental Component Summary score ranged from 39.7 to 45.7 (United States norms = 50). In general, patients with viral clearance had the highest scores, and those with late-stage disease (cirrhosis, liver cancer) had the lowest. Multivariable linear regression showed that the effect of disease stage was modest overall. Increasing age, lower income, unattached marital status, and high comorbidity were strongly associated with impairment in HRQOL. CONCLUSIONS: The effect of stage of disease on HRQOL is modest, although viral clearance is associated with higher HRQOL. HCV patients' HRQOL is strongly associated with concomitant illness and sociodemographic factors.