Recent trends in early stage response to combination antiretroviral therapy in Australia.

BACKGROUND: There have been improvements in combination antiretroviral therapy (cART) over the past 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. METHODS: Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4(+) T-cell count and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. RESULTS: A total of 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy and 72% initiated treatment ≥1996 using cART (30% 1996-1999, 12% 2000-2003, 11% 2004-2007 and 19% ≥2008). Overall CD4(+) T-cell count response improved by later era of initiation (P<0.001), although 2000-2003 CD4(+) T-cell count response was less than that for 1996-1999 (P=0.007). The average proportion with detectable viral load from 2 to 4 years post-treatment commencement by era was: <1996 mono/duo 0.69 (0.67-0.71), 1996-1999 cART 0.29 (0.28-0.30), 2000-2003 cART 0.22 (0.20-0.24), 2004-2007 cART 0.09 (0.07-0.10) and ≥2008 cART 0.04 (0.03-0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996-1999 to 29% after 2008 (P<0.001). CONCLUSIONS: Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4(+) T-cell count) and also increased durability of first-line ART regimens.

High rates of sexually transmissible infections in HIV-positive patients in the Australian HIV Observational Database: a prospective cohort study.

UNLABELLED: Background In HIV-positive people, sexually transmissible infections (STIs) probably increase the infectiousness of HIV. METHODS: In 2010, we established a cohort of individuals (n=554) from clinics in the Australian HIV Observational Database (AHOD). We calculated retrospective rates for four STIs for 2005-10 and prospective incidence rates for 2010-11. RESULTS: At baseline (2010), patient characteristics were similar to the rest of AHOD. Overall incidence was 12.5 per 100 person-years. Chlamydial infections increased from 3.4 per 100 person-years (95% confidence interval (CI): 1.9-5.7) in 2005 to 6.7 per 100 person-years (95% CI: 4.5-9.5) in 2011, peaking in 2010 (8.1 per 100 person-years; 95% CI: 5.6-11.2). Cases were distributed among rectal (61.9%), urethral (34%) and pharyngeal (6.3%) sites. Gonococcal infections increased, peaking in 2010 (4.7 per 100 person-years; 95% CI: 5.6-11.2; Ptrend=0.0099), distributed among rectal (63.9%), urethral (27.9%) and pharyngeal (14.8%) sites. Syphilis showed several peaks, the largest in 2008 (5.3 per 100 person-years; 95% CI: 3.3-8.0); the overall trend was not significant (P=0.113). Genital warts declined from 7.5 per 100 person-years (95% CI: 4.8-11.3) in 2005 to 2.4 per 100 person-years (95% CI: 1.1-4.5) in 2011 (Ptrend=0.0016). CONCLUSIONS: For chlamydial and gonococcal infections, incidence was higher than previous Australian estimates among HIV-infected men who have sex with men, increasing during 2005-2011. Rectal infections outnumbered infections at other sites. Syphilis incidence remained high but did not increase; that of genital warts was lower and decreased.

Determinants of viremia copy-years in people with HIV/AIDS after initiation of antiretroviral therapy.

BACKGROUND: Recent studies suggest higher cumulative HIV viremia exposure measured as viremia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (1) report the association between VCY and all-cause mortality and (2) assess associations between common patient characteristics and VCY. METHODS: Analyses were based on patients recruited to the Australian HIV Observational Database (AHOD) who had received ≥24 weeks of antiretroviral therapy (ART). We established VCY after 1, 3, 5, and 10 years of ART by calculating the area under the plasma viral load time series. We used survival methods to determine the association between high VCY and all-cause mortality. We used multivariable mixed-effect models to determine predictors of VCY. We compared a baseline information model with a time-updated model to evaluate discrimination of patients with high VCY. RESULTS: Of the 3021 AHOD participants who initiated ART, 2073 (69%), 1667 (55%), 1267 (42%), and 638 (21%) were eligible for analysis at 1, 3, 5, and 10 years of ART, respectively. Multivariable-adjusted hazard ratio association between all-cause mortality and high VCY was statistically significant, hazard ratio 1.52 (1.09, 2.13), P = 0.01. Predicting high VCY after 1 year of ART for a time-updated model compared with a baseline information model, the area under the sensitivity/specificity curve was 0.92 vs. 0.84; and at 10 years of ART, area under the sensitivity/specificity curve was 0.87 vs. 0.61, respectively. CONCLUSION: A high cumulative measure of viral load after initiating ART is associated with increased risk of all-cause mortality. Identifying patients with high VCY is improved by incorporating time-updated information.

High-voltage leak detection of a parenteral proteinaceous solution product packaged in form-fill-seal plastic laminate bags. Part 2. Method performance as a function of heat seal defects, product-package refrigeration, and package plastic laminate lot.

Part 1 of this three-part research series detailed the development and validation of a high-voltage leak detection test (HVLD, also known as an electrical conductivity and capacitance test) for verifying the container-closure integrity of a small-volume laminate plastic bag containing an aqueous solution formulation of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. Leak detection capability was verified using positive controls each with a single laser-drilled hole in the bag film face. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect weaknesses and/or gaps in the bag heat seal. Study 2 checked the HVLD detection of bag holes in packages stored 4 days at ambient conditions followed by 17 days at refrigeration. Study 3 examined HVLD test results for packages tested when cold. Study 4 compared HVLD test results as a function of bag plastic film lots. The final Part 3 of this series will report the impact of HVLD exposure on product visual appearance and chemical stability. LAY ABSTRACT: In Part 1 of this three-part series, a leak test method based on electrical conductivity and capacitance, also called high-voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with a solution for injection of the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®) by Novo Nordisk A/S, Bagsværd, Denmark. In this Part 2, HVLD leak detection capability was further explored in four separate studies. Study 1 investigated the ability of HVLD to detect bag heat seal leaks. Study 2 checked HVLD's ability to detect bag holes after a total of 21 days at ambient plus refrigerated temperatures. Study 3 looked to see if HVLD results changed for packages tested when still cold. Study 4 compared HVLD results for multiple bag plastic film lots. The final Part 3 of this series will report any evidence of drug component degradation caused by HVLD exposure.

High-voltage leak detection of a parenteral proteinaceous solution product packaged in form-fill-seal plastic laminate bags. Part 1. Method development and validation.

In Part 1 of this three-part research series, a leak test performed using high-voltage leak detection (HVLD) technology, also referred to as an electrical conductivity and capacitance leak test, was developed and validated for container-closure integrity verification of a small-volume laminate plastic bag containing an aqueous solution for injection. The sterile parenteral product is the rapid-acting insulin analogue, insulin aspart (NovoRapid®/NovoLog®, by Novo Nordisk A/S, Bagsværd, Denmark). The aseptically filled and sealed package is designed to preserve product sterility through expiry. Method development and validation work incorporated positive control packages with a single hole laser-drilled through the laminate film of each bag. A unique HVLD method characterized by specific high-voltage and potentiometer set points was established for testing bags positioned in each of three possible orientations as they are conveyed through the instrument's test zone in each of two possible directions-resulting in a total of six different test method options. Validation study results successfully demonstrated the ability of all six methods to accurately and reliably detect those packages with laser-drilled holes from 2.5-11.2 µm in nominal diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product physico-chemical stability. LAY ABSTRACT: In this Part 1 of a three-part research series, a leak test method based on electrical conductivity and capacitance, called high voltage leak detection (HVLD), was used to find leaks in small plastic bags filled with an insulin pharmaceutical solution for human injection by Novo Nordisk A/S (Bagsværd, Denmark). To perform the test, the package is electrically grounded while being conveyed past an electrode linked to a high-voltage, low-amperage transformer. The instrument measures the current that passes from the transformer to the electrode, through the packaged product and along the package walls, to the ground. Plastic packages without defect are relatively nonconductive and yield a low voltage reading; a leaking package with electrically conductive solution located in or near the leak triggers a spike in voltage reading. Test methods were optimized and validated, enabling the detection of leaking packages with holes as small as 2.5 µm in diameter. Part 2 of this series will further explore HVLD test results as a function of package seal and product storage variables. The final Part 3 will report the impact of HVLD exposure on product stability.

Trends in detectable viral load by calendar year in the Australian HIV observational database.

BACKGROUND: Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART. METHODS: Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up. RESULTS: Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009. CONCLUSIONS: Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia.

Vacuum decay container closure integrity leak test method development and validation for a lyophilized product-package system.

A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated for container-closure integrity verification of a lyophilized product in a parenteral vial package system. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity check, and for testing product stored on stability in lieu of sterility tests. Method development and optimization challenge studies incorporated artificially defective packages representing a range of glass vial wall and sealing surface defects, as well as various elastomeric stopper defects. Method validation required 3 days of random-order replicate testing of a test sample population of negative-control, no-defect packages and positive-control, with-defect packages. Positive-control packages were prepared using vials each with a single hole laser-drilled through the glass vial wall. Hole creation and hole size certification was performed by Lenox Laser. Validation study results successfully demonstrated the vacuum decay leak test method's ability to accurately and reliably detect those packages with laser-drilled holes greater than or equal to approximately 5 µm in nominal diameter. All development and validation studies were performed at Whitehouse Analytical Laboratories in Whitehouse, NJ, under the direction of consultant Dana Guazzo of RxPax, LLC, using a VeriPac 455 Micro Leak Test System by Packaging Technologies & Inspection (Tuckahoe, NY). Bristol Myers Squibb (New Brunswick, NJ) fully subsidized all work. LAY ABSTRACT: A leak test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method was developed and validated to detect defects in stoppered vial packages containing lyophilized product for injection. This nondestructive leak test method is intended for use in manufacturing as an in-process package integrity check, and for testing product stored on stability in lieu of sterility tests. Test method validation study results proved the method capable of detecting holes laser-drilled through the glass vial wall greater than or equal to 5 µm in nominal diameter. Total test time is less than 1 min per package. All method development and validation studies were performed at Whitehouse Analytical Laboratories in Whitehouse, NJ, under the direction of consultant Dana Guazzo of RxPax, LLC, using a VeriPac 455 Micro Leak Test System by Packaging Technologies & Inspection (Tuckahoe, NY). Bristol Myers Squibb (New Brunswick, NJ) fully subsidized all work.

AIDS-related and non-AIDS-related mortality in the Asia-Pacific region in the era of combination antiretroviral treatment.

OBJECTIVE: Although studies have shown reductions in mortality from AIDS after the introduction of combination antiretroviral treatment (cART), little is known about cause-specific mortality in low-income settings in the cART era. We explored predictors of AIDS and non-AIDS mortality and compared cause-specific mortality across high-income and low-income settings in the Asia-Pacific region. METHODS: We followed patients in the Asia Pacific HIV Observational Database from the date they started cART (or cohort enrolment if cART initiation was identified retrospectively), until the date of death or last follow-up visit. Competing risks methods were used to estimate the cumulative incidence, and to investigate predictors, of AIDS and non-AIDS mortality. RESULTS: Of 4252 patients, 215 died; 89 from AIDS, 97 from non-AIDS causes and 29 from unknown causes. Age more than 50 years [hazard ratio 4.29; 95% confidence interval (CI) 2.10-8.79] and CD4 cell counts less than or equal to 100 cells/microl (hazard ratio 8.59; 95% CI 5.66-13.03) were associated with an increased risk of non-AIDS mortality. Risk factors for AIDS mortality included CD4 cell counts less than or equal to 100 cells/microl (hazard ratio 34.97; 95% CI 18.01-67.90) and HIV RNA 10 001 or more (hazard ratio 4.21; 95% CI 2.07-8.55). There was some indication of a lower risk of non-AIDS mortality in Asian high-income, and possibly low-income, countries compared to Australia. CONCLUSION: Immune deficiency is associated with an increased risk of AIDS and non-AIDS mortality. Older age predicts non-AIDS mortality in the cART era. Less conclusive was the association between country-income level and cause-specific mortality because of the relatively high proportion of unknown causes of death in low-income settings.

Poor baseline immune function predicts an incomplete immune response to combination antiretroviral treatment despite sustained viral suppression.

OBJECTIVES: To determine the prevalence and predictors of an incomplete immune response in patients with sustained viral suppression after starting their first or second combination antiretroviral treatment (cART) regimen. METHODS: All patients were recruited to the Australian HIV Observational Database (AHOD) by March 2006. Data were analyzed to assess the prevalence of an incomplete immune response (<350 cells/microL) in the 12-24 months after starting the first or second cART regimen. Factors associated with an incomplete immune response were assessed using logistic regression and time to AIDS/death was assessed using survival analysis. RESULTS: Of the 2493 patients recruited to AHOD by March 2006, 590 were eligible for the analysis. Twenty-eight percent of patients with a baseline CD4 count <350 cells per microliter had an incomplete immune response 12-24 months after starting their first or second cART regimen. Lower baseline CD4 count before starting the cART regimen was predictive of an incomplete immune response. There was a nonsignificant trend toward faster AIDS or death in incomplete immune responders. CONCLUSIONS: An incomplete immune response in patients with sustained viral suppression is associated with poorer immune function before starting cART. Type of cART or individual antiretroviral drug was not associated with an incomplete immune response.

Vacuum decay container/closure integrity testing technology. Part 2. Comparison to dye ingress tests.

Part 1 of this series demonstrated that a container closure integrity test performed according to ASTM F2338-09 Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method using a VeriPac 325/LV vacuum decay leak tester by Packaging Technologies & Inspection, LLC (PTI) is capable of detecting leaks > or = 5.0 microm (nominal diameter) in rigid, nonporous package systems, such as prefilled glass syringes. The current study compared USP, Ph.Eur. and ISO dye ingress integrity test methods to PTI's vacuum decay technology for the detection of these same 5-, 10-, and 15-microm laser-drilled hole defects in 1-mL glass prefilled syringes. The study was performed at three test sites using several inspectors and a variety of inspection conditions. No standard dye ingress method was found to reliably identify all holed syringes. Modifications to these standard dye tests' challenge conditions increased the potential for dye ingress, and adjustments to the visual inspection environment improved dye ingress detection. However, the risk of false positive test results with dye ingress tests remained. In contrast, the nondestructive vacuum decay leak test method reliably identified syringes with holes > or = 5.0 microm.

Trends in antiretroviral treatment use and treatment response in three Australian states in the first decade of combination antiretroviral treatment.

OBJECTIVES: To determine if there were any differences in antiretroviral treatment (ART) use across the three eastern states of Australia, New South Wales (NSW), Victoria and Queensland, during the period 1997 to 2006. METHODS: We used data from a clinic-based cohort, the Australian HIV Observational Database (AHOD), to determine the proportion of HIV-infected patients on ART in selected clinics in each state and the proportion of treated patients with an undetectable viral load. Data from the national Highly Specialised Drugs program and AHOD were used to estimate total numbers of individuals on ART and the proportion of individuals living with HIV on ART nationally and by state. Data from the HIV Futures Survey and the Gay Community Periodic Survey were used to determine the proportion of community-based men who have sex with men on ART. The proportion of patients with primary HIV infection (PHI) who commenced ART within 1 year of diagnosis was obtained from the Acute Infection and Early Disease Research Program (AIEDRP) CORE01 protocol and Primary HIV and Early Disease Research: Australian Cohort (PHAEDRA) cohorts. RESULTS: We estimated that the numbers of individuals on ART increased from 3181 to 4553 in NSW, 1309 to 1926 in Victoria and 809 to 1615 in Queensland between 2000 and 2006. However, these numbers may reflect a lower proportion of individuals living with HIV on ART in NSW compared with the other states (37% compared with 49 and 55% in 2000). We found similar proportions of HIV-positive men who have sex with men participants were on ART in all three states over the study period in the clinic-based AHOD cohort (81-92%) and two large, community-based surveys in Australia (69-85% and 49-83%). Similar proportions of treated patients had an undetectable viral load across the three states, with a consistently increasing trend over time observed in all states. We found that more PHI patients commenced treatment in the first year following HIV diagnosis in NSW compared with Victoria; however, the sample size was very small. CONCLUSIONS: For the most part, patterns of ART use were similar across NSW, Victoria and Queensland using a range of available data from cohort studies, community surveys and national prescription databases in Australia. However, there may be a lower proportion of individuals living with HIV on ART in NSW compared with the other states, and there is some indication of a more aggressive treatment approach with PHI patients in NSW compared with Victoria.

A "fishy" cough: hepatobronchial fistula due to a pyogenic liver abscess.

A hepatobronchial fistula is an anatomic communication between the liver parenchyma and the bronchial tree. Major causes of such fistulae include inflammatory conditions resulting from obstruction of the biliary tract and infectious processes, such as pyogenic liver abscesses, amoebiasis, and hydatid cysts. We report a rare case of a patient (with a chronic, recurrent hepatic abscess) who suffered a persistent, productive cough resulting from a hepatobronchial fistula.

Risk factors for HIV infection in a gynaeco-obstetric population in Vietnam--a case-control study.

BACKGROUND: Vietnam has an emerging HIV epidemic, particularly in male drug injectors. Data on HIV infections in women in the general population, and their risk factors, are scanty. METHODS: A case-control study was performed in a large gynaeco-obstetric hospital in Haiphong city in 1998-2001. The sample was 22000 attendees. The medical records of 58 HIV-seropositive cases were compared with 422 randomly chosen HIV-seronegative controls for potential risk factors. RESULTS: A multivariate analysis found that HIV infection was associated with young age, past/current history of sexually transmitted infections (STI) and being unemployed. Patients aged 21-30 years were 10-fold less likely to be infected than women aged <20 years (OR 0.11, 95% CI 0.04-0.33). Women with a past/current history of STI had over 20 times the risk of those who did not (95% CI 6.7-62.3). Unemployed women had at least twice the risk of infection of any other occupational group. CONCLUSIONS: We have identified risk factors in women that have not been highlighted previously in Vietnam. Our study suggests that all antenatal women, especially those who are young or unemployed (or, with a current/past history of STI), should be offered free HIV tests, counselling and management.

Meta-analysis: computed tomographic colonography.

BACKGROUND: Computed tomographic (CT) colonography, also called virtual colonoscopy, is an evolving technology under evaluation as a new method of screening for colorectal cancer. However, its performance as a test has varied widely across studies, and the reasons for these discrepancies are poorly defined. PURPOSE: To systematically review the test performance of CT colonography compared to colonoscopy or surgery and to assess variables that may affect test performance. DATA SOURCES: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Controlled Trials Register were searched for English-language articles published between January 1975 and February 2005. STUDY SELECTION: Prospective studies of adults undergoing CT colonography after full bowel preparation, with colonoscopy or surgery as the gold standard, were selected. Studies had to have used state-of-the-art technology, including at least a single-detector CT scanner with supine and prone positioning, insufflation of the colon with air or carbon dioxide, collimation smaller than 5 mm, and both 2-dimensional and 3-dimensional views during scan interpretation. The evaluators of the colonogram had to be unaware of the findings from use of the gold standard test. Data on sensitivity and specificity overall and for detection of polyps less than 6 mm, 6 to 9 mm, and greater than 9 mm in size were abstracted. Sensitivities and specificities weighted by sample size were calculated, and heterogeneity was explored by using stratified analyses and meta-regression. DATA SYNTHESIS: 33 studies provided data on 6393 patients. The sensitivity of CT colonography was heterogeneous but improved as polyp size increased (48% [95% CI, 25% to 70%] for detection of polyps <6 mm, 70% [CI, 55% to 84%] for polyps 6 to 9 mm, and 85% [CI, 79% to 91%] for polyps >9 mm). Characteristics of the CT colonography scanner, including width of collimation, type of detector, and mode of imaging, explained some of this heterogeneity. In contrast, specificity was homogenous (92% [CI, 89% to 96%] for detection of polyps <6 mm, 93% [CI, 91% to 95%] for polyps 6 to 9 mm, and 97% [CI, 96% to 97%] for polyps >9 mm). LIMITATIONS: The studies differed widely, and the extractable variables explained only a small amount of the heterogeneity. In addition, only a few studies examined the newest CT colonography technology. CONCLUSIONS: Computed tomographic colonography is highly specific, but the range of reported sensitivities is wide. Patient or scanner characteristics do not fully account for this variability, but collimation, type of scanner, and mode of imaging explain some of the discrepancy. This heterogeneity raises concerns about consistency of performance and about technical variability. These issues must be resolved before CT colonography can be advocated for generalized screening for colorectal cancer.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is an important medical condition and there is great public health concern related to its increasing incidence and potential implications for the development of end-stage liver disease. NASH represents a progression beyond simple lipid deposition in the liver parenchyma, requiring histologic evidence for hepatocyte injury such as ballooning degeneration, Mallory bodies, and/or pericellular fibrosis that can potentially lead to progressive liver injury and eventually cirrhosis. It is believed that several insults contribute to the evolution of hepatic injury such as insulin dysregulation, lipid deposition, oxidative free radicals, and lipid perioxidation. Initial treatment protocols for NASH focus on various aspects of injury in an attempt to control insulin imbalances, improve lipid regulation, reduce free radicals, and ameliorate the inflammatory process. No therapy is conclusively beneficial in all individuals, but preliminary data suggest several approaches that hold promise.

Perceived versus actual medication regimens among internal medicine patients.

Exchange of accurate information between patients and medical providers is imperative for appropriate medication prescribing. We performed an evaluation of medication regimens of patients with information obtained independently from patient-completed surveys and nursing and provider interviews. The actual medication regimen was determined after the clinic encounter via mail-in forms or telephone interviews with patients reporting current medications directly from prescription bottles. Two hundred thirteen patients taking an average of 3.8 prescription medications were enrolled. Patients, nurses, and primary care providers were modestly accurate in reporting the number of medications being taken (kappa, 0.57,0.51, and 0.58, respectively); however, they performed poorly in reporting complete medication regimens as defined by the correct names, doses, and frequencies with 100% accuracy (34%, 26.7%, and 29.3%, respectively). Patients who created their own lists were more accurate than those who relied on memory, lists provided by providers, or discharge summaries. These findings indicate a significant difference between intended versus actual medication regimens at home.

Forty-two-year-old active duty Marine presents with hematemesis.

A 42-year-old active duty marine presented to the emergency room with hematemesis. This article describes the appropriate step-by-step management for this individual with an upper gastrointestinal bleed, and we discuss potential differential diagnoses and update readers on the current aspects of managing his final diagnosis. Through questions and discussions, we will cover various diagnostic modalities and management strategies related to this case and provide some insight on the military relevance of his final condition.