Search

Background & aimsA comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs.MethodsPROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment.ResultsOf 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements.ConclusionsIn real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities.Lay summaryPatients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.

BackgroundSymptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables.Methods and findingsPROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not.ConclusionsThis large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication.Trial registration(Clinicaltrial.gov: NCT02601820).

Introduction: Triage of patients is critical to patient safety, yet no clear information exists as to the utility of initial vital signs in identifying critically ill older emergency department (ED) patients. The objective of this study is to evaluate a set of initial vital sign thresholds as predictors of severe illness and injury among older adults presenting to the ED.Methods: We reviewed all visits by patients aged 75 and older seen during 2007 at an academic ED serving a large community of older adults. Patients’ charts were abstracted for demographic and clinical information including vital signs, via automated electronic methods. We used bivariate analysis to investigate the relationship between vital sign abnormalities and severe illness or injury, defined as intensive care unit (ICU) admission or ED death. In addition, we calculated likelihood ratios for normal and abnormal vital signs in predicting severe illness or injury.Results: 4,873 visits by patients aged 75 and above were made to the ED during 2007, and of these 3,848 had a complete set of triage vital signs. For these elderly patients, the sensitivity and specificity of an abnormal vital sign taken at triage for predicting death or admission to an ICU were 73% (66,81) and 50% (48,52) respectively (positive likelihood ratio 1.47 (1.30,1.60); negative likelihood ratio 0.54 (0.30,0.60).Conclusion: Emergency provider assessment and triage scores that rely primarily on initial vital signs are likely to miss a substantial portion of critically ill older adults. [West J Emerg Med. 2013;14(5):453–460.]

PurposeCancer cachexia is a devastating and understudied illness in patients with head and neck squamous cell carcinoma (HNSCC). The primary objective was to identify clinical characteristics and serum levels of cytokines and cachexia-related factors in patients with HNSCC. The secondary objective was to detect the occurrence of cytokine and cachexia-related factor gene expression in HNSCC tumors.Experimental designFor the primary objective, cross-sectional data were obtained from prospectively recruited patients identified as cachexia cases and matching cachexia-free controls. For the secondary objective, a retrospective cohort design with matched controls was used.ResultsClinical characteristics associated with cancer cachexia in HNSCC were T(4) status (P = 0.01), increased C-reactive protein (P = 0.01), and decreased hemoglobin (P < 0.01). Exploratory multiplex analysis of serum cytokine levels found increased interleukin (IL)-6 (P = 0.04). A highly sensitive ELISA confirmed the multiplex result for increased IL-6 in cachectic patients (P = 0.02). Quality of life was substantially reduced in patients with cachexia compared with noncachectic patients (P < 0.01). All tumors of HNSCC patients both with and without cachexia expressed RNA for each cytokine tested and the cachexia factor lipid-mobilizing factor. There were no statistically significant differences between the cytokine and cachexia factor RNA expression of cachectic and noncachectic patients (each P > 0.05). No tumors expressed the cachexia factor proteolysis-inducing factor.ConclusionWe have identified clinical characteristics and pathophysiologic mechanisms associated with cancer cachexia in a carefully defined population of patients with HNSCC. The data suggest that the acute-phase response and elevated IL-6 are associated with this complex disease state. We therefore hypothesize that IL-6 may represent an important therapeutic target for HNSCC patients with cancer cachexia.

Objectives. We examined the use of voluntary HIV testing among state prisoners in the North Carolina prison system. Methods. We calculated system-wide and facility-specific proportions and rates of adult inmates tested for HIV and estimated associations between testing status and inmate characteristics for prisoners in North Carolina. Results. Of the 54016 inmates who entered prison between January 2004 and May 2006, 20 820 (38%) were tested for HIV; of those tested, 18 574 (89%) were tested at admission. Across the 8 intake prisons, more than 80% of inmates in both female facilities but less than 15% of inmates in 4 of 6 male facilities were tested. Prisoners with a documented history of heroin use, crack or cocaine use, conventional HIV risk behavior, or tuberculosis were at least 10% more likely to be tested than were inmates without these characteristics. However, more than 60% of men reporting conventional risk behaviors were not tested. Before covariate adjustment, Black men were 30% less likely than White men to be tested; in the multivariable regression model, this difference was attenuated to 13%. Conclusions. Rates of HIV testing varied widely across intake prisons, and many male inmates with documented risk of infection were never tested. (Am J Public Health. 2009;99:S452-S459. DOI: 10.2105/AJPH.2007.133124)

Objectives. We identified factors associated with testing HIV positive in a prison system performing voluntary HIV testing on inmates and estimated the number of undetected HIV cases to evaluate the efficacy of risk-factor-based HIV testing. Methods. We used logistic regression to estimate associations between HIV serostatus and HIV risk behaviors, mental health, coinfection status, and sociodemographic characteristics for prisoners entering the North Carolina Department of Correction from January 2004 through May 2006. We estimated the number of undetected HIV cases on the basis of age-, gender-, and race-specific HIV prevalences among prisoners and in the state. Results. Nearly 3.4% (718/21 419) of tested prisoners were HIV positive. The strongest risk factors for infection among men were having sex with men (odds ratio [OR]=8.0), Black race (OR=6.2), other non-White race (OR=7.4), and being aged 35 to 44 years (OR = 4.1). The strongest risk factor among women was Black race (OR=3.8). Among HIV-positive prisoners, 65% were coinfected with HCV. We estimated that between 24% (223) and 61% (1101) of HIV cases remained undetected. Conclusions, The associations between HIV serostatus and a variety of factors highlight the potential limitations of risk-factor-based HIV testing in prisons, as do the high number of potential undetected HIV cases. doi: 10.2105/AJPH.2007.133389)

A study was conducted to characterize the incidence and magnitude of serum alanine aminotransferase (ALT) elevations in healthy participants receiving 4g of acetaminophen daily, either alone or in combination with selected opioids, as compared with participants treated with placebo. It was found that initiation of recurrent dally intake of 4g acetaminophen in healthy adults is associated with ALT elevations and concomitant treatment with opioids does not increase this effect.

Discovery of novel drug delivery systems to the brain remains a key task for successful treatment of neurodegenerative disorders. Herein, the biodistribution of immunocyte‐based carriers, peripheral blood mononuclear cells (PBMCs), and monocyte‐derived EVs are investigated in adult rhesus macaques using longitudinal PET/MRI imaging. 64Cu‐labeled drug carriers are introduced via different routes of administration: intraperitoneal (IP), intravenous (IV), or intrathecal (IT) injection. Whole body PET/MRI (or PET/CT) images are acquired at 1, 24, and 48 h post injection of 64Cu‐labeled drug carriers, and standardized uptake values (SUVmean and SUVmax) in the main organs are estimated. The brain retention for both types of carriers increases based on route of administration: IP < IV < IT. Importantly, a single IT injection of PBMCs produces higher brain retention compared to IT injection of EVs. In contrast, EVs show superior brain accumulation compared to the cells when administered via IP and IV routes, respectively. Finally, a comprehensive chemistry panel of blood samples demonstrates no cytotoxic effects of either carrier. Overall, living cells and EVs have a great potential to be used for drug delivery to the brain. When identifying the ideal drug carrier, the route of administration could make big differences in CNS drug delivery. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that women with a history of sexual abuse more likely to become pregnant as adolescents than nonabused peers. We examined a cohort of 734 mothers ages 12 to 42 selected form 1985 to 1987 for participation in a longitudinal investigation for any relationship between sexual abuse prior to age 18 and childbearing characteristics, including their age at the birth of their first child as well as parity. Thirty-two percent reported sexual abuse. After controlling for poverty, race, maternal education, marital status, and age, there was no significant difference between the abused and nonabused mothers in their age at first birth; how ever, parity was higher for the sexually abused group. Fifty-five percent of mothers with a sexual abuse history had had more than one child as opposed to 39% of the nonabused mothers (p [is less than] 0.0001)., Sexual abuse and teenage pregnancy are each a significant and increasingly recognized public health problem in our society. Increased risk of teenage pregnancy as a consequence of sexual abuse (whether [...]

Objective: The purpose of this research was to determine whether risk factors for a maltreatment report in the first year of life, especially the interaction of life event stress and social support, persist into the second and third years of life. Method: Predominantly low income mothers who had been interviewed shortly after the birth of infants in a longitudinal cohort were re-interviewed around the infants' first birthdays, and reports to North Carolina's Central Registry of Child Abuse and Neglect were tracked for substantiated maltreatment reports. Results: Variables significantly associated with a substantiated maltreatment report in the second or third year of life (p < .01) were first year maltreatment reports and participation in Medicaid. Three interactions between a stressful life event indicator variable and a social support indicator variable were significant predictors of substantiated second or third year reports (p < .05). Conclusions: Even in the presence of significant risk factors from the first year of life, life event stress can increase the risk of a substantiated maltreatment report in the second or third years of life, but social support may moderate the effect of life events. Key Words - Child abuse, Child neglect. Life change events, Stress, Psychological, Social support.