Pharmacokinetic Interaction between Ritonavir and Indinavir in Healthy Volunteers

The pharmacokinetic interaction between indinavir and ritonavir was evaluated in five groups of healthy adult volunteers to explore the potential for twice-daily (b.i.d.) dosing of this combination. All subjects received 800 mg of indinavir every 8 h (q8h) on day 2. In addition, subjects in group I received one dose of 800 mg of indinavir on day 1 and 800 mg of indinavir q8h on day 17. Subjects in Groups II and IV each received one dose of 600 mg of indinavir on days 1 and 17, and subjects in groups III and V each received one dose of 400 mg of indinavir on days 1 and 17. During days 3 to 17, ritonavir placebo or ritonavir at 200, 300, 300, or 400 mg q12h was given to groups I, II, III, IV, and V, respectively. Ritonavir at steady state probably inhibited the cytochrome P-450 3A metabolism of indinavir and substantially increased plasma indinavir concentrations, with the area under the plasma concentration-time curve (AUC) increasing up to 475% and the peak concentration in serum (C_max) increasing up to 110%. The C_max/trough concentration ratio decreased from 50 in standard q8h regimens to less than 14 when indinavir was administered with ritonavir. For a constant indinavir dose, an increase in the ritonavir dose yielded similar indinavir AUCs, C_maxs, and concentrations at 12 h (C₁₂s). For a constant ritonavir dose, an increase in the indinavir dose resulted in approximately proportional increases in the indinavir AUC, less than proportional increases in C_max, and slightly more than proportional increases in C₁₂. Ritonavir reduced between-subject variability in the indinavir AUC and trough concentrations and did not affect indinavir renal clearance. With the altered pharmacokinetic profile, indinavir likely could be given as a b.i.d. combination regimen with ritonavir. This could potentially improve patient compliance and thereby reduce treatment failures.     

Urinary biomarker of oxidative stress correlating with outcome in critically septic patients

Objective To determine whether urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), an in vivo parameter of oxidative stress, is correlated with the outcome of critically septic patients. Design and setting Clinical outcome study in an adult medical ICU. Patients Eighty-five consecutive septic patients: 59 men and 26 women. Measurements and results Urinary 8-OHdG was analyzed using isotope-dilution liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality in these 85 septic patients was 25.9% (n = 22) and hospital mortality 38.8% (n = 33). APACHE II scores of survivors on day 1, on day 3, and the difference between them differed significantly from those of nonsurvivors (day 1, 21.0 ± 7.1 vs. 25.9 ± 8.0; day 3, 15.0 ± 5.8 vs. 23.2 ± 8.3; difference, 6.0 ± 5.5 vs. 1.7 ± 6.6). Urinary 8-OHdG was significantly lower in survivors than in nonsurvivors on day 1 (1.8 ± 2.4 vs. 3.0 ± 2.4). The area under receiver operating characteristic curve analysis for the association between day 1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon discharge from hospital revealed similar results. Conclusions This is a preliminary study. The excretion of the urinary 8-OHdG, as measured using isotope-dilution LC/MS/MS, as the APACHE II score, were correlated with the outcome of critically septic patients in medical ICU. An erratum to this article can be found at     

Management of cirrhotic patients with blunt abdominal trauma: analysis of risk factor of postoperative death with the Model for End-Stage Liver Disease score

IntroductionThe aim of this retrospective study is to analyse the risk factors of mortality in cirrhotic patients with blunt abdominal trauma (BAT) underwent laparotomy and the value of the Model for End-Stage Liver Disease (MELD) score to predict postoperative death is determined.Materials and methodsFrom July 1993 to June 2005, 34 cirrhotic patients with BAT were reviewed. Data are presented as mean ± standard deviation (SD), frequency (percentage), or Pearson correlation coefficient. Predictors were compared by uni- and multiple logistic regression analysis and results were considered statistically significant if P < 0.05. The prognostic value of the MELD score in predicting postoperative death was assessed using receiver operating characteristic (ROC) curve analysis.ResultsOf the 34 patients (27 men, 7 women; mean age, 49 years), the Injury Severity Score (ISS) ranged from 4 to 43 (mean: 14). Of the 34 patients, 12 were treated with nonoperative management (NOM) initially and 4 succeeded and 30 patients (88.2%) eventually required laparotomy. Of the 30 operative patients, 7 died of haemorrhagic shock and the other 6 died of multiple organ failure with a 43.3% mortality rate. Of the 17 survivors after laparotomy, 4 developed intra-abdominal complication, and 3 developed extra-abdominal complication with a 41.2% morbidity rate. On univariate analysis, the significant predictors of surgical mortality were shock at emergency department, damage control laparotomy, ISS and MELD score. On multiple logistic regression analysis, the significant predictors of operative mortality were shock at ED (P = 0.021) and MELD score (P = 0.012). Analysis by ROC curve identified cirrhotic patients with a MELD score equal to or above 17 as the best cut-off value for predicting postoperative death.ConclusionsLiver cirrhosis with BAT has a high operative rate, low salvage rate of NOM, high surgical mortality and morbidity rate. The MELD score can accurately predict postoperative death and a MELD score equal to or above 17 of our data is at high risk of postoperative death.     

The Renin-Angiotensin-aldosterone system in podocytes

The renin-angiotensin-aldosterone system (RAAS) plays a critical role in kidney function and its inhibition reduces proteinuria and preserves kidney function in patients with chronic kidney disease. Recent studies have shown that podocytes generate many components of the RAAS and they express receptors of RAAS, including angiotensin II, mineralocorticoid, and prorenin receptors. Crucial functions of podocytes, such as contraction, apoptosis, autophagocytosis, and cytoskeletal organization, have been shown to be regulated by the angiotensin II type 1 receptors. An activation of the glomerular RAAS and protection from podocyte injury by RAAS inhibitors have been shown in many glomerular diseases. Exploring the interaction between the local RAAS and the signaling involved in RAAS activation in podocytes will lead to new therapeutic strategies of podocyte protection.     

Factors influencing consumer adoption of USB-based Personal Health Records in Taiwan

ABSTRACT: BACKGROUND: Usually patients receive healthcare services from multiple hospitals, and consequently their healthcare data are dispersed over many facilities' paper and electronic-based record systems. Therefore, many countries have encouraged the research on data interoperability, access, and patient authorization. This study is an important part of a national project to build an information exchange environment for cross-hospital digital medical records carried out by the Department of Health (DOH) of Taiwan in May 2008. The key objective of the core project is to set up a portable data exchange environment in order to enable people to maintain and own their essential health information.This study is aimed at exploring the factors influencing behavior and adoption of USB-based Personal Health Records (PHR) in Taiwan. METHODS: Quota sampling was used, and structured questionnaires were distributed to the outpatient department at ten medical centers which participated in the DOH project to establish the information exchange environment across hospitals. A total of 3000 questionnaires were distributed and 1549 responses were collected, out of those 1465 were valid, accumulating the response rate to 48.83%. RESULTS: 1025 out of 1465 respondents had expressed their willingness to apply for the USB-PHR. Detailed analysis of the data reflected that there was a remarkable difference in the "usage intention" between the PHR adopters and non-adopters (chi2 =182.4, p < 0.001). From the result of multivariate logistic regression analyses, we found the key factors affecting patients' adoption pattern were Usage Intention (OR, 9.43, 95%C.I., 5.87-15.16), Perceived Usefulness (OR, 1.60; 95%C.I., 1.11-2.29) and Subjective Norm (OR, 1.47; 95%C.I., 1.21-1.78). CONCLUSIONS: Higher Usage Intentions, Perceived Usefulness and Subjective Norm of patients were found to be the key factors influencing PHR adoption. Thus, we suggest that government and hospitals should promote the potential usefulness of PHR, and physicians should encourage patients' to adopt the PHR.     

Community Outbreak of Adenovirus,Taiwan, 2011

In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14–October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008–2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the People’s Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.     

bla(OXA-181)-positive Klebsiella pneumoniae, Singapore

TO THE EDITOR: Nordmann et al. (1) raised concern over the global spread of carbapenemase-producing Enterobacteriaceae. In their article, they called attention to the oxacillinase-48 (OXA-48) type carbapenemases because bacteria that produce these enzymes do not have a distinctive antimicrobial drug susceptibility profile, and there is less awareness of this mechanism of carbapenem resistance. We report the recent isolation of bla(OXA-181)-positive Klebsiella pneumoniae from 2 patients from Bangladesh who were admitted to separate hospitals in Singapore within a short period of each other.     

Factors affecting personal exposure to thoracic and fine particles and their components

Central monitoring site (CMS) concentrations have been used to represent population-based personal exposures to particulate matter (PM) of ambient origin. We investigated the associations of the concentrations of PM(2.5) and PM(10) and their elemental components for elderly clinic patients with chronic obstructive pulmonary disease in two cities with different PM compositions, that is, New York City (NYC) and Seattle. Daily measurements of CMS, outdoor residential, and indoor PM(10) and PM(2.5) concentrations, as well as personal PM(10), were made concurrently for 12-consecutive winter days at 9 NYC and 15 Seattle residences, as well for 9 NYC residences in summer. Filters were analyzed for elemental components using X-ray fluorescence (XRF), and for black carbon (BC) by light reflectance, and outdoor-indoor-personal relationships of PM components were examined using mixed-effect models. Using sulfur (S) as a tracer of PM of ambient origin, the mean contributions of outdoor PM(2.5) was 55.2% of the indoor concentrations in NYC, and 80.0% in Seattle, and outdoor PM(2.5) in NYC and Seattle were 19.7 and 18.5% of personal PM(2.5) concentration. S was distributed homogeneously in both cities (R(2)=0.65), whereas nickel (R(2)=0.23) was much more spatially heterogeneous. Thus, CMS measurements can adequately reflect personal exposures for spatially uniform components, such as sulfate, but they are not adequate for components from more local sources.