New option for management of HIV-1 infection in treatment-naive patients: once-daily, fixed-dose combination of rilpivirine-emtricitabine-tenofovir

Fixed-dose combination tablets have become an important therapy option for patients infected with the human immunodeficiency virus. Fixed-dose combination rilpivirine-tenofovir-emtricitabine is a recently approved therapy option that has been extensively studied within the treatment-naïve population. When compared with efavirenz-based therapy, improved tolerability with rilpivirine-based therapy was balanced by higher rates of virologic failure to provide similar overall efficacy rates within the intention-to-treat analysis. As a result, providers will need to balance the potential for improved tolerability with fixed-dose combination rilpivirine-tenofovir-emtricitabine against a higher potential for virologic failure, particularly among patients with baseline viral loads above 100,000 copies/mL. Current treatment guidelines have recommended that fixed-dose combination rilpivirine-tenofovir-emtricitabine be an alternative therapy option for treatment-naïve patients and advise caution in those patients with high viral loads at baseline. Similar to other non-nucleoside reverse transcriptase inhibitor-based regimens, there are a number of drug interaction concerns with fixed-dose combination rilpivirine-tenofovir-emtricitabine that will necessitate monitoring and, in some cases, appropriate management. Additionally, the emergence of drug resistance to fixed-dose combination rilpivirine-tenofovir-emtricitabine has been well documented in clinical studies and close attention will be necessary in order to protect current and future therapy options. Overall, fixed-dose combination rilpivirine-tenofovir-emtricitabine is poised to provide an important therapy option for patients when appropriately applied

Desirable Characteristics of Hepatitis C Treatment Regimens: A Review of What We Have and What We Need.

There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens

Effect of Concomitant 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor Therapy on Creatine Phosphokinase Levels and Mortality Among Patients Receiving Daptomycin: Retrospective Cohort Study.

IntroductionThe prescribing information for daptomycin recommends discontinuing statin therapy during receipt of daptomycin. The literature supporting this recommendation is sparse. The objectives of this study were to examine the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on creatine phosphokinase (CPK) elevations and mortality among patients receiving daptomycin therapy.MethodsA retrospective cohort study was performed among daptomycin recipients in the Upstate New York Veterans' Healthcare Administration from September 15, 2003 to July 1, 2013. Inclusion criteria were: (1) daptomycin for ≥48 h, (2) availability of baseline CPK value and (3) >1 CPK level measurement taken while on therapy. The following were extracted from medical records: demographics, comorbidities, laboratory data, medication history (daptomycin, statins and concomitant drugs known to increase CPK), Acute Physiology and Chronic Health Evaluation (APACHE)-II score and vital status at 30 days. The exposure of interest was use of statins. The primary outcome was CPK elevation defined as a CPK value ≥3 times the upper limit of normal (ULN) if baseline CPK was normal, and ≥5 times ULN if baseline CPK was elevated. The secondary outcome was death within 30 days of commencing daptomycin.ResultsA total of 233 patients were included in this analysis. Among these patients, 53 received concomitant statin therapy. Most baseline clinical characteristics were similar between statin recipients and non-recipients. Five (2.1%) patients experienced a CPK elevation; 3/53 (5.7%) were statin recipients and 2/180 (1.1%) received daptomycin alone (p = 0.08). All patients with CPK elevations had normal baseline CPK values. No effect modification was observed by use of other concomitant medications known to increase CPK values. Death was observed more frequently among statin non-recipients (17.2%) than recipients (9.4%).ConclusionsAmong patients receiving daptomycin, no significant difference was observed in frequency of CPK elevation between statin recipients and non-recipients

Urban dwelling environments : Ahmedabad, India

Thesis (M.Arch.A.S.)--Massachusetts Institute of Technology, Dept. of Architecture, 1976.MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCHBibliography: p. 118.by Nimish Patel.M.Arch.A.S

A Cross-Sectional Study Comparing the Frequency of Drug Interactions After Adding Simeprevir- or Sofosbuvir-Containing Therapy to Medication Profiles of Hepatitis C Monoinfected Patients.

INTRODUCTION:This study compares the expected occurrence of contraindicated drug-drug interactions (XDDIs) when simeprevir (SIM)- or sofosbuvir (SOF)-containing therapy is added to medication profiles of patients with hepatitis C (HCV) monoinfection to quantify, in relative terms, the population-based risk of XDDIs. Second, this study identified the predictors of XDDIs when HCV therapies are added to medication profiles. METHODS:A cross-sectional study was performed among Veterans' Affairs patients. Inclusion criteria were: (1) age ≥18 years, (2) HCV infection, and (3) availability of a medication list. Patients with human immunodeficiency virus were excluded. Demographics, comorbidities, year of HCV diagnosis, and most recent medication list were collected from medical records. The primary outcome was the presence of XDDIs involving HCV therapy and the medications in the patient's home medication list after the addition of either SIM- or SOF-containing regimens. To define XDDIs, Lexi-Interact drug interaction software was used. RESULTS:4,251 patients were included. The prevalence of XDDIs involving SIM- or SOF-containing therapy were 12.6% and 4.7% (p < 0.001), respectively. In multivariable analyses examining the predictors of XDDIs involving SIM-containing therapy, the only medication-related predictor was use of ≥6 home medications (odds ratio OR 4.58, 95% confidence interval CI 3.54-5.20, p < 0.001). Similarly, use of ≥6 home medications was also the only variable associated with an increased probability of XDDI involving SOF-containing therapy (OR 3.83, 95% CI 2.57-5.70, p < 0.001). CONCLUSIONS:Sofosbuvir-containing therapy had a lower frequency of XDDIs than SIM-containing therapy. Polypharmacy with various classes of home medications predicted XDDIs involving SIM- or SOF-containing therapy

Vancomycin 24-Hour Area under the Curve/Minimum Bactericidal Concentration Ratio as a Novel Predictor of Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

While previous studies have examined the association between vancomycin (VAN) exposure and MIC with regard to outcomes in methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B), none have explored if a relationship exists with the VAN minimum bactericidal concentration (MBC). The objective of this study was to evaluate the VAN 24-h area under the curve (AUC24)/MBC ratio as a pharmacodynamic predictor of mortality. This retrospective cohort study included patients treated with VAN for MRSA-B with the primary outcome of 30-day all-cause mortality. Data collected included patient demographics, comorbidities, antimicrobial treatment data, therapeutic drug levels, and laboratory and microbiological data. Vancomycin MICs and MBCs were determined by Etest (MIC only) and broth microdilution (BMD). The vancomycin AUC24 was determined by pharmacokinetic maximum a posteriori probability Bayesian (MAP-Bayesian) analysis. The most significant breakpoint for 30-day mortality was determined by classification and regression tree (CART) analysis. The association between pharmacodynamic parameters (VAN AUC24/MICBMD, VAN AUC24/MICEtest, and AUC24/MBCBMD) and mortality were determined by χ2 and multivariable Poisson regression. Overall mortality in this cohort (n = 53) was 20.8% (n = 11/53), and all corresponding MRSA blood isolates were VAN susceptible (MIC range, 0.5 to 2 μg/ml; MIC50, 1 μg/ml; MIC90, 1 μg/ml). The CART-derived breakpoints for mortality were 176 (VAN AUC24/MBC) and 334 (VAN AUC24/MICBMD). In multivariable analysis, the association between a VAN AUC24/MBC of ≥176 and survival persisted, but VAN AUC24/MICBMD values (≥334 or ≥400) were not associated with improved mortality. In conclusion, VAN AUC24/MBC was a more important predictor of 30-day mortality than VAN AUC24/MIC for MRSA-B

Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia

Vancomycin-resistant Enterococcus faecium bloodstream infections (VREF-BSI) cause significant mortality, highlighting the need to optimize their treatment. We compared the effectiveness and safety of daptomycin (DAP) and linezolid (LZD) as continuous or sequential therapy for VREF-BSI in a national, retrospective, propensity score (PS)-matched cohort study of hospitalized Veterans Affairs patients (2004 to 2014). We compared clinical outcomes and adverse events among patients treated with continuous LZD, continuous DAP, or sequential LZD followed by DAP (LZD-to-DAP). Secondarily, we analyzed the impact of infectious diseases (ID) consultation and source of VREF-BSI. A total of 2,630 patients were included in the effectiveness analysis (LZD [n = 1,348], DAP [n = 1,055], LZD-to-DAP [n = 227]). LZD was associated with increased 30-day mortality versus DAP (risk ratio [RR], 1.11; 95% confidence interval [CI], 1.01 to 1.22; P = 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26; P = 0.015). LZD-to-DAP switchers had lower mortality than those remaining on LZD (RR, 1.29; 95% CI, 1.03 to 1.63; P = 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a ≥50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11; P = 0.001). DAP was associated with lower mortality than was LZD in patients with endocarditis (RR, 1.20; 95% CI, 1.02 to 1.41; P = 0.024); however, there was no statistically significant association between treatment group and mortality with regard to other sources of infection. Therefore, source of infection appears to be important in selection of patients most likely to benefit from DAP over LZD

Bacteriological analysis of bile in cholecystectomy patients

Background: Cholecystectomy is currently a frequently performed operation. The presence of gallstones within either the gallbladder or biliary tree is associated with the bacterial colonization of the bile. Acute cholangitis spans a continuous clinical spectrum and can progress from a local biliary infection to advanced disease with sepsis and multiple organ dysfunction syndrome. Therefore, it is important to know the microbiological flora of the gallbladder before prophylactic antibiotics are given. Aims & objectives: To evaluate the microbiological profile of bile from gall bladder in patients undergoing cholecystectomy. To determine the appropriate antibiotic for preoperative prophylaxis in cholecystectomy patients based on the microbiological profile of bile.Methods: The study was a prospective study carried out in SSG Hospital. A total of 78 patients undergone cholecystectomy who met the inclusion criteria were included in the study. 3cc bile was aspirated from all patients, this collected bile from gallbladder before cholecystectomy was transported to the laboratory in sterile test-tube. The specimen was evaluated to find out whether it is sterile or has any bacteria present. The types of bacteria are determined and whether the amount of isolate is significant or not. And sensitivity to antibacterial agents against antibiotics was determined.Results: 19 patients showed positive bile culture in which Escherichia coli was the most common isolated bacteria (63.16% among positive bile culture and 15.38% among all patients) and bile was sterile in 59 patients (75.64%). Other organisms isolated were Pseudomonas (3.85%), Klebsiella (2.56%), coagulase negative Staphylococcus and Staphylococcus viridans (1.28%). Positive bile culture was a more common finding (50% of patients were bile culture positive) in patients with acute cholecystitis in this study. Post-operative wound infection is more common (15.79%) in group of patients with isolated organism from bile. There is a strong correlation between bile culture and wound culture (75%).  Conclusions: It was found that sensitivity to third- and fourth-generation cephalosporins was higher as compared to aminoglycoside in acute as well as chronic cholecystitis. In this study levofloxacin also shows good sensitivity against isolated organism from bile. Piperacilin and tazobactum also shows good sensitivity against isolated organism from bile and they are more effective against pseudomonas. The resistance to second-generation cephalosporins and aminoglycoside has increased. For preoperative prophylaxis third and fourth-generation cephalosporins and levofloxacin show better promise and may be used as the first line of preoperative prophylaxis in operations for acute and chronic cholecystitis undergoing cholecystectomy.

Study of operative results of fracture acetabulum in adults

Background: Acetabular fractures are relatively rare intra-articular fractures and due to its complex anatomy, require absolute stability in the form of articular reduction and rigid fixation. Specific approaches need to be taken to operate such fractures and planned protocol needs to be followed to mobilize those patients postoperatively. Aims and Objectives: Primary objective of the study is to analyze the operative results of fracture acetabulum in terms of the operative technique used, clinico-radiological outcome, post-operative range of motion achieved, and time taken for mobilization. Secondary objective is to estimate early and late complication encountered related to technique, implants and to compare our study to other published studies. Materials and Methods: This study is a retrospective study of 26 patients with acetabular fractures operated at our institute from the period of May 2019 to May 2022. All patients who gave consent have been included in our study. Results: There was an improvement in functional and radiological outcomes of all the patients. Twenty-four patients showed excellent to good according to the Merle’d Aubigne Postel scoring in our study. Twenty-five patients achieved excellent to good according to Harris hip score. About 90% of patients in our study returned to their pre fracture work in 4 months. Conclusion: The quality of reduction and fixation is strongly associated with clinical results. In acetabular surgery, for fixing the fracture if we follow established protocols we can get good to excellent outcome in patients

Clinical Outcomes in Patients with Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Bloodstream Infection

The prevalence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infections varies in the literature, a problem complicated by the lack of routine screening procedures; however, limited data suggest that hVISA has been associated with persistent bloodstream infections (BSI) and vancomycin failure, yet these studies have been confounded by design issues. We conducted this study to compare the characteristics of patients with BSI caused by hVISA with those with vancomycin-susceptible Staphylococcus aureus (VSSA) treated with vancomycin. This retrospective, multicenter matched (1:1) cohort study compared the clinical characteristics and outcomes of hVISA and VSSA. Patients with hVISA methicillin-resistant Staphylococcus aureus (MRSA) BSI from 2004 to 2012 were matched to VSSA-MRSA BSI patients. The primary outcome was failure of vancomycin treatment, defined as a composite of persistent bacteremia (≥7 days), persistent signs and symptoms, change of MRSA antibiotic, recurrent BSI, or MRSA-related mortality. We identified 122 matched cases. The overall vancomycin failure rate was 57% (82% hVISA versus 33% VSSA; P \u3c 0.001). The individual components of failure in hVISA versus VSSA were persistent bacteremia, 59% versus 21% (P \u3c 0.001); change in MRSA therapy, 54% versus 25% (P = 0.001); MRSA-related mortality, 21% versus 10% (P = 0.081); and recurrence of BSI, 26% versus 2% (P \u3c 0.001). Using logistic regression analysis and adjusting for covariates, hVISA (adjusted odds ratio [aOR], 11.1; 95% confidence interval [CI], 4.3 to 28.7) and intensive care unit (ICU) admission (aOR, 4.5; 95% CI, 1.8 to 11.6) were still independently associated with vancomycin failure. Relative to VSSA BSI, patients with hVISA were more likely to experience failure of vancomycin treatment, including persistent bacteremia and recurrence. Our results indicate that hVISA was responsible for considerable morbidity