BACKGROUND:Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied.METHODS:We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications.RESULTS:We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78-0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78-0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission.CONCLUSIONS:In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

Few studies evaluated the effects of pentoxifylline on hard endpoints in patients with predialysis stage 5 chronic kidney disease (CKD). Thus, we tried to explore the effects of pentoxifylline and its interaction with renin-angiotensin-aldosterone system (RAAS) blockade on the development of endstage renal disease (ESRD) and mortality. This nationwide cohort study retrospectively included patients who had a serum creatinine level of >6 mg/dL and received erythropoiesis-stimulating agents (ESAs) between 2000 and 2010. We analyzed 7,366 pentoxifylline users and 7,366 propensity score-matched nonusers. Using Cox proportional hazard models, pentoxifylline reduced the risks of ESRD and the composite renal outcome but not that of mortality. In terms of the risks of developing ESRD, pentoxifylline alone exerted a comparable beneficial effect to combined therapy with an RAAS inhibitor and greater renoprotection than RAAS inhibitor monotherapy. This study suggests pentoxifylline is efficacious in slowing progression to ESRD in patients with predialysis stage 5 CKD.

Summary Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (Pis). Whether the HIV-1 from these patients with virological failure to first-generation Pls remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation Pls in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 Pls. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation Pls.

BACKGROUND:Proteinuria reflects disrupted renal function in which enhanced immuno-inflammation activity plays a key role. So far, information concerning the relations between proteinuria and peripheral different leucocyte counts is limited. We thereby conducted this study aiming to obtain comprehensive information of the issue. METHODS:Study subjects were participants of a health check programme from 2000 to 2002. Additional two enrolment criteria were (i) leucocyte analysis was checked with a same blood cell counter and (ii) urinalysis showed no pyuria or haematuria. Data of subjects were retrospectively collected and analysed by using sas program. RESULTS:Higher neutrophil and monocyte counts, but not lymphocyte count, were significantly associated with both the presence and the severity of proteinuria (all P < 0.0001, n= 12 225). Such associations maintained significant after adjustments of age, sex, body mass index, mean blood pressure and blood levels of glycosylated hemoglobin (HbA1c), total cholesterol, triglycerides and creatinine (all P< or = 0.001, n= 12 225). There was a sharp increase in the incidence of proteinuria in association with a neutrophil count > or =4.50 x 10(9)/L (P< or = 0.0001). CONCLUSION:Our study showed that in apparently normal adults the presence and the severity of proteinuria could be reflected by the peripheral neutrophil and monocyte counts, but not the lymphocyte count. These findings, together with the documented inflammatory basis of proteinuria and the diverse pathophysiological roles of differential leucocytes, suggest that peripheral differential leucocyte counting may be useful in predicting the course of an existing proteinuria. Perspective longitudinal follow-up studies are needed to test this presumption.

Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV-infected patients receiving combination antiretroviral therapy (CART) in Taiwan.Incident cases of DM were identified among HIV-infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case-control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV-infected patients.In 824 HIV-infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person-years of follow-up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209-5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159-8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186-5.389).Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV-infected patients receiving CART in Taiwan.

Background Although many studies have been carried out on pulmonary diseases in HIV‐infected patients, studies specifically investigating the aetiologies of cavitary lung lesions are rare. Methods HIV‐infected patients enrolled in a cohort study who presented with cavitary lung lesions by radiography were identified between June 1994 and March 2008. Medical records and radiological and microbiological data for these patients were retrospectively reviewed using a standardized case collection form. Results During the 14‐year study period, 73 episodes of cavitary lung lesions were diagnosed in 66 of 1790 (3.7%) HIV‐infected patients. At the diagnosis of cavitary lung lesions, the median CD4 count was 25 cells/μL (range 1–575 cells/μL). Eighty‐one pathogens were considered causative, with fungi being the most common aetiology (42.0%), followed by bacteria (29.6%) and mycobacteria (25.9%). Of the fungal pneumonias, 19 (55.9%) were caused by Penicillium marneffei , 11 (32.4%) by Cryptococcus neoformans , two (5.9%) by Pneumocystis jirovecii , and two (5.9%) by Aspergillus species. During the study period, 11 of 205 patients (5.4%) who were diagnosed as having tuberculosis presented with cavitary lung lesions, compared with 19 of 36 patients (52.8%) with penicilliosis and 11 of 64 patients (17.2%) with cryptococcosis ( P <0.0001). The median CD4 count of patients with cavitary lung lesions resulting from tuberculosis (115 cells/μL) was significantly higher than that of patients with cavitary lung lesions resulting from penicilliosis (4 cells/μL) and cryptococcosis (29.5 cells/μL). Conclusions Our findings suggest that invasive infections attributable to endemic fungi were the leading cause of cavitary lung lesions among patients in the late stage of HIV infection, and were more common than infections attributable to bacteria and mycobacteria.

Purpose To assess the efficacy of oral azithromycin in the treatment of chlamydial conjunctivitis. Methods We performed a retrospective study in patients with clinically suspected chlamydial conjunctivitis who underwent conjunctival swab sampling for Chlamydia direct fluorescent antibody (DFA) tests between 1 January 2006 and 31 December 2006. Patients with positive DFA results were orally administered azithromycin once a week for 2 consecutive weeks. If DFA examinations still showed positive results after 4 weeks, additional azithromycin was orally administered once. The DFA tests were repeated 4 weeks later, and this was continued until the DFA tests showed negative results. Results Among the 67 suspected patients, 45 (67.2%) showed positive results from the DFA tests, of whom 42 received treatment. After the first 2 weeks, only 27 patients returned to the clinic and completed the treatment. The test results of 19 (70.4%) patients became negative after the treatment with two weekly doses of oral azithromycin. Among the remaining eight patients, four (14.8%) needed an additional dose of oral azithromycin, and the other four (14.8%) required two additional doses. All 27 patients tolerated the treatment well, with an adverse event of mild gastritis in only one patient. Conclusions Two weekly doses of oral azithromycin were effective and well tolerated in the treatment of chlamydial conjunctivitis. However, more than one course of treatment was necessary in some patients.

Quinolones are broad spectrum antibiotics that are intensively used and can induce immediate- and delayed-type hypersensitivity reactions, either IgE or T-cell mediated, in about 2–3% of treated patients. Objective: To better understand how T cells interact with quinolones to produce the hypersensitivity and to describe the possible prevention of the reactions. Methods: We search in PubMed for quinolones and adverse reactions naming each one of the therapeutics in use and the possible hypersensitivity reactions e.g., anaphylaxis, drug-induced delayed reactions, and hypersensitivity syndrome reactions. We also performed a search on organ-specific hypersensitivity reactions including cutaneous reactions, hepatic reactions, and renal reactions. Results: Our data show that T cells are involved in delayed immune reactions to quinolones and that cross-reactivity among the different quinolones is frequent. The predictive tests for quinolone-induced hypersensitivity should be used in patients before they are given the medication. Conclusions: Early identification of the mechanism of toxicity, quantitative assessment using laboratory tests, analysis of risk factors for patient susceptibility to the quinolones, and possible drug-drug interactions may lead to appropriate patient selection for therapy, monitoring the injury early and discontinuation of the therapeutic agent.

This study compared the clinical presentations of 58 episodes of cryptococcosis in 50 patients and 26 episodes of penicillosis in 25 patients infected with human immunodeficiency virus (HIV) between June 1994 and June 2004, and assessed the safety of discontinuation of secondary prophylaxis for endemic fungal infections in those patients responding to highly active anti-retroviral therapy (HAART). Neurological symptoms were seen more commonly in patients with cryptococcosis, whereas respiratory symptoms, lymphadenopathy, hepatomegaly and/or splenomegaly, and non-thrush-related oral presentations were seen more commonly in patients with penicillosis. Patients with penicillosis were more likely to have abnormal chest radiography results and radiographic presentations of interstitial lesions, cavitations, fibrotic lesions and mass lesions. At the end of the study, maintenance antifungal therapy had been discontinued in 27 patients with cryptococcosis and in 18 patients with penicillosis in whom the median CD4 count had increased to 186 cells/microL (range, 9-523 cells/microL) and 95 cells/microL (range, 15-359 cells/microL), respectively, after HAART. Only one episode of penicillosis recurred (a relapse rate of 1.72/100 person-years; 95% CI, 1.44-2.10/100 person-years) after a median follow-up duration of 35.3 months (range, 2.6-91.6 months). No relapses occurred in patients with cryptococcosis after a median follow-up duration of 22.3 months (range, 1-83.4 months). These findings suggest that there are differences in the clinical presentations between endemic cryptococcosis and penicillosis in patients with HIV infection, and that it is safe to discontinue secondary antifungal prophylaxis for cryptococcosis and penicillosis in patients responding to HAART.

Spontaneous renal or peri-renal bleeding or so-called Wunderlich's syndrome is a rare but potentially life-threatening condition. Most reported cases are Caucasian and caused by ruptured renal tumors, either benign or malignant. The syndrome has never been documented in Orientals with underlying autoimmune diseases. We report 3 cases of spontaneous renal bleeding with concurrent systemic lupus erythematosus and vasculitis presenting with flank or abdominal pain, anemia, leukocytosis, and a high C-reactive protein. All were diagnosed by computerized tomography, magnetic resonance imaging or angiography, and treated successfully with glucocorticoids and cytotoxic agents without surgical intervention.

We assessed the seroprevalence of Toxoplasma gondii infection and incidence of toxoplasma encephalitis (TE) in 844 non-haemophiliac HIV-infected patients in Taiwan between June 1994 and April 2003. Approximately 70% (69.3%) of them had a baseline CD4+ lymphocyte count of 200 × 106/L or less, and more than 70% (73.9%) having initiated highly active antiretroviral therapy. The seroprevalence of T. gondii infection was 10.2%, which did not differ with sex, age, route of transmission, birth inside or outside of Taiwan, or CD4+ lymphocyte stratifications. After a median observation duration of 603 days (range, 1–3264 days), 10 (1.2%) patients developed 11 episodes of TE after a median interval of 30 days (range, 1–941 days) between enrolment and diagnosis of TE, with an incidence of 0.59 per 100 person-years (PY) (95% confidence interval, 0.56–0.63 per 100 PY). We concluded that the incidence of TE of HIV-infected patients in Taiwan was lower than that reported in western countries because of a lower seroprevalence of T. gondii infection and use of antimicrobial prophylaxis and antiretroviral therapy, although most of the patients were at the late stage of HIV infection.

Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.

Lupus cystitis was rare but frequently resulted in obstructive uropathy and had a strong association with gastrointestinal(GI) symptoms. We treated six patients with systemic lupus erythematosus(SLE) and obstructive uropathy from January 1996 to December 2001 in a university hospital. Evidence of cystitis was obtained from cystoscopic biopsy or the presence of thickened bladder wall in image study. Similar to other reports, five patients had GI manifestations such as abdominal pain, nausea/vomiting, diarrhoea or ileus. In addition, mesenteric lymphadenopathy or pancreatitis was noted in three patients. Two patients had been treated for idiopathic thrombocytopenic purpura (ITP), four and 20 years ago, respectively. All six patients had antibodies to double-stranded DNA ( dsDNA). Five patients each had antibodies to cardiolipin (IgG aCL) or SSA. The high prevalence of anti-SSA had also been reported in Chinese lupus patients with intestinal pseudo-obstruction, a clinical manifestation frequently associated with bilateral ureterohydronephrosis. Two patients died of intractable infection after the surgical procedures for persistent ureterohydronephrosis and both patients had antibodies to ribosomal P proteins. Lupus cystitis might not be so rare in Chinese patients with SLE. The diagnosis should be kept in mind when lupus patients have urinary and/or GI symptoms.

We estimated the cost needed to provide lifetime HAART for Taiwanian HIV-infected patients. The 1998-2002 survival curve of Taiwan National HIV Cohort was analyzed and extrapolated beyond the follow-up limit using a Monte Carlo simulation method. The lifetime cost of HAART was estimated by the cumulative sum of average drug cost multiplied by the expected probability of survival, adjusted by a 3% annual discount rate. If the average annual drug cost is at the level of US$10,000 per patient, the estimated cost of providing lifetime HAART is US$67,290 +/- 7,863 per patient if treatment is started after the development of AIDS (estimated life expectancy 10.8 +/- 3.8 yrs). If treatment is started immediately after diagnosis of asymptomatic HIV infection (estimated life expectancy 17.8 +/- 3.3 yrs), US$109,210 +/- 6,325 per patient will be required.

Background and Purpose: Nosocomial bloodstream infection (NBSI) is common in patients with human immuno-deficiency virus (HIV) infection. This study evaluated the incidence, causative pathogens, and outcome of NBSIs in hospitalized HIV-infected patients at a university hospital in Taiwan.Methods: The medical records of all HIV-infected patients who developed NBSIs from June 1994 to June 2003 were retrospectively reviewed. A standardized case record form was used to collect demographic, clinical, laboratory, and microbiologic data.Results: During the study period, 57 episodes of NBSIs occurred in 51 HIV-infected patients whose median age was 37 years (range, 23 to 60 years). All of the patients were at HIV infection stage C. The incidence of NBSIs was 2.3 per 1000 person-days of hospitalization (41.4 per 1000 discharges). More than three-fourths of the 57 episodes (77.2%) were classified as primary NBSIs. Other infection foci included respiratory tract (6 episodes), urinary tract (3), surgical site (2), and skin (2). Staphylococcus species were the leading pathogens (42.1 %). The crude and attributable mortality rates in patients with NBSIs during the study period were 38.6% and 26.1%, respectively. Multivariate analysis using a logistic regression model revealed that shock and hypoalbuminemia at the onset of NBSIs were the 2 factors predictive of mortality.Conclusions: NBSIs in hospitalized patients in the late stage of HIV infection were associated with a high attributable mortality rate. Staphylococcus species were the leading pathogen responsible for NBSIs. Presentations of shock and hypoalbuminemia were predictive of mortality.