Antiretroviral Treatment Gaps and Adherence Among People with HIV in the U.S. Medicare Program.

Approximately one-quarter of people with HIV (PWH) in the U.S. receive coverage through the Medicare program; however, no prior real-world study has examined antiretroviral therapy (ART) gaps and adherence and associated factors in this population. This retrospective cohort analysis used 2013-2018 national Medicare fee-for-service claims data to identify all PWH initiated on a new ART regimen including protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTIs], or integrase strand transfer inhibitors [INSTIs] between 1/1/2014 and 12/31/2017. Study outcomes included ART adherence (based on proportion of days covered [PDC]), continuous treatment gaps ranging from 1 to 6 days to ≥ 180 days, and discontinuation (continuous gap ≥ 90 days) in the 12-month follow-up period. Multivariable regressions were used to assess factors associated with ART adherence and discontinuation. The final sample included 48,627 PWH (mean age: 54.5 years, 74.4% male, 47.5% White, 89.8% disabled). Approximately 53.0% of PWH had a PDC ≥ 0.95, 30.2% had a PDC between 0.70 and < 0.95, and 16.8% had PDC < 0.70. Treatment gaps of at least ≥ 7-days (55.2%) and ≥ 30-days (26.2%) were common and 10.1% PWH discontinued treatment. Younger age, female sex, Black race, higher comorbidity score, mental health conditions, and substance use disorder were associated with higher odds of lower adherence and discontinuation (all p-values < 0.05). In conclusion, suboptimal adherence and treatment gaps in ART use were commonly observed among PWH in Medicare. Interventions and policies to mitigate barriers to adherence are urgently needed in this population to both improve their survival and increase the potential for ending the HIV epidemic in the US.

Prevalence, incidence, and risk factors for hepatitis C virus infection in hemodialysis patients.

Hepatitis C virus (HCV) infection is common in dialysis patients and is associated with increased morbidity and mortality. We used the Dialysis Outcomes and Practice Patterns Study (DOPPS, 1996-2015) to assess trends in the prevalence, incidence, and risk factors for HCV infection as defined by a documented diagnosis or antibody positivity. Among prevalent hemodialysis patients, HCV prevalence was nearly 10% in 2012-2015. Prevalence ranged from 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. HCV prevalence decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had recently (<4 months) initiated dialysis. The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced 3 or more cases over a median of 1.1 years. High HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates. Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population. Combined with a high prevalence of HCV infection among patients with Stage 5 CKD, high rates of HCV seroconversion in a subset of hemodialysis units may contribute to this disparity.

Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir.

PURPOSE: People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. PATIENTS AND METHODS: PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. RESULTS: There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. CONCLUSION: This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. CLINICALTRIALSGOV IDENTIFIER: NCT02358044.

Kidney Function Decline in Patients with CKD and Untreated Hepatitis C Infection.

BACKGROUND AND OBJECTIVES: Studies evaluating the role of hepatitis C viral (HCV) infection on the progression of CKD are few and conflicting. Therefore, we evaluated the association of untreated HCV on kidney function decline in patients with stage 3-5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included members of Kaiser Permanente Southern California and Kaiser Permanente Mid-Atlantic States aged ≥18 years, with incident HCV and CKD diagnoses from January 1, 2004 to December 31, 2014. We used generalized estimating equations to compare the rate of change in eGFR between those with HCV and CKD versus CKD alone, adjusting for covariates. Cox proportional hazards models compared the risk of 25% decrease in eGFR and ESKD (defined as progression to eGFR<15 ml/min per 1.73 m2 on two or more occasions, at least 90 days apart) in those with HCV and CKD versus CKD alone, adjusting for covariates. RESULTS: We identified 151,974 patients with CKD only and 1603 patients with HCV and CKD who met the study criteria. The adjusted annual decline of eGFR among patients with HCV and CKD was greater by 0.58 (95% confidence interval [95% CI], 0.31 to 0.84) ml/min per 1.73 m2, compared with that in the CKD-only population (HCV and CKD, -1.61; 95% CI, -1.87 to -1.35 ml/min; CKD only, -1.04; 95% CI, -1.06 to -1.01 ml/min). Adjusted for covariates, the hazard for a 25% decline in eGFR and for ESKD were 1.87 (95% CI, 1.75 to 2.00) and 1.93 (95% CI, 1.64 to 2.27) times higher among those with HCV and CKD, respectively, compared with those with CKD only. CONCLUSIONS: Untreated HCV infection was associated with greater kidney function decline in patients with stage 3-5 CKD.

HCV treatment initiation in persons with chronic kidney disease in the directly acting antiviral agents era: Results from ERCHIVES.

BACKGROUND: Newer direct acting antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether approval of newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. METHODS: We identified HCV+ persons in ERCHIVES between October 1999 and July 2016. We excluded HIV+ and HBsAg+ and those with missing baseline HCV RNA and baseline eGFR data. We identified persons initiated on any approved DAA-regimen through July 2016, by CKD stage. Logistic regression analyses were used to determine factors associated with treatment initiation. RESULTS: Among 83 706 evaluable persons, 21.1% initiated treatment. Rates differed significantly by CKD stage: 22.1% for eGFR>90 mL/min/1.73 m2 and CKD stage-2; 14.9% for CKD stage 3; and 8.0% for CKD stage-4/5. Those with CKD stage-3 were 33% less likely and those with CKD stage-4/5 were 60% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90 mL/min/1.73 m2 . Treatment initiation was less likely in HCV genotype 2 (OR 0.59; 95%CI 0.53,0.66) or 3 (OR 0.53; 95%CI 0.47,0.61) and those with diabetes (OR 0.87, 95% CI 0.81,0.94), cardiovascular disease (OR 0.77, 95% CI 0.70,0.84), alcohol abuse or dependence (OR 0.74, 95% CI 0.70,0.79) or cirrhosis (OR 0.86, 95% CI 0.80,0.92) at baseline. CONCLUSIONS: Persons with more advanced CKD are less likely to receive treatment for HCV despite recent data on safety and efficacy. Strategies are needed to improve treatment rates in the HCV/CKD population.

Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: In the C-SURFER study, therapy with the all-oral elbasvir plus grazoprevir regimen for 12 weeks in patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease resulted in a high rate of virological cure compared with placebo. Here, we report sustained virological response (SVR), safety data, health-related quality-of-life (HRQOL), and virological resistance analyses in patients in C-SURFER who received immediate antiviral therapy or who received placebo before therapy. METHODS: In this phase 3, multicentre, randomised, placebo-controlled study, we randomly assigned adults with HCV genotype 1 infection and stage 4-5 chronic kidney disease enrolled at 68 centres worldwide to either elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks (immediate treatment group) or placebo for 12 weeks followed by elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks beginning at week 16 (deferred treatment group). The primary safety and efficacy endpoints for the immediate treatment group and placebo phase of the deferred treatment group have been reported previously. Here, we report safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-Item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs). SVR at 12 weeks (SVR12) was assessed in the modified full analysis set (FAS), defined as all patients excluding those who did not receive at least one dose of study drug, who died, or who discontinued the study before the end of treatment for reasons determined to be unrelated to HCV treatment. This trial is registered with ClinicalTrials.gov, Number NCT02092350. FINDINGS: Between March 30 and Nov 28, 2014, 235 patients were enrolled and received at least one dose of study drug. The modified FAS included 116 patients assigned to immediate treatment and 99 assigned to deferred treatment. 115 (99·1%; 95% CI 95·3-100·0) of 116 assigned to immediate treatment achieved SVR12 compared with 97 (98·0%; 92·9-99·7) of 99 assigned to deferred treatment. In patients with genotype 1a infections, SVR12 was achieved by 11 (84·6%) of 13 patients with detectable baseline NS5A RASs and in 98 (100%) of 98 without. HRQOL did not differ at week 12 between immediate treatment and the placebo phase of deferred treatment. Safety was generally similar between patients receiving immediate treatment and those receiving placebo in the deferred treatment group. One serious adverse event during deferred treatment (interstitial nephritis) and one during the placebo phase of deferred treatment (raised lipase concentration) were deemed related to study drug. Four patients died, one who received immediate treatment (cardiac arrest) and three who received deferred treatment (aortic aneurysm, pneumonia, and unknown cause); all four deaths were considered unrelated to study drugs. Of the three deaths in the deferred treatment group, one occurred during placebo treatment and two occurred before starting active treatment. There were no notable differences in aminotransferase elevations in the deferred treatment group compared with the immediate treatment group, and no patients in the deferred treatment group had total bilirubin elevations. INTERPRETATION: These data add to the growing body of clinical evidence for the fixed-dose combination regimen of elbasvir plus grazoprevir for 12 weeks and support use of this therapy in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. FUNDING: Merck Sharp & Dohme.

Impact of Renal Disease on Patients with Hepatitis C: A Retrospective Analysis of Disease Burden, Clinical Outcomes, and Health Care Utilization and Cost.

BACKGROUND/AIMS: Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. METHODS: This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. RESULTS: In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. CONCLUSIONS: Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs.

Staphylococcus aureus infections following knee and hip prosthesis insertion procedures.

BACKGROUND: Staphylococcus aureus is the most common and most important pathogen following knee and hip arthroplasty procedures. Understanding the epidemiology of invasive S. aureus infections is important to quantify this serious complication. METHODS: This nested retrospective cohort analysis included adult patients who had undergone insertion of knee or hip prostheses with clean or clean-contaminated wound class at 11 hospitals between 2003-2006. Invasive S. aureus infections, non-superficial incisional surgical site infections (SSIs) and blood stream infections (BSIs), were prospectively identified following each procedure. Prevalence rates, per 100 procedures, were estimated. RESULTS: 13,719 prosthetic knee (62%) and hip (38%) insertion procedures were performed. Of 92 invasive S. aureus infections identified, SSIs were more common (80%) than SSI and BSI (10%) or BSI alone (10%). The rate of invasive S. aureus infection/100 procedures was 0.57 [95% CI: 0.43-0.73] for knee insertion and 0.83 [95% CI: 0.61-1.08] for hip insertion. More than half (53%) were methicillin-resistant. Median time-to-onset of infection was 34 and 26 days for knee and hip insertion, respectively. Infection was associated with higher National Healthcare Safety Network risk index (p ≤ 0.0001). CONCLUSIONS: Post-operative invasive S. aureus infections were rare, but difficult-to-treat methicillin-resistant infections were relatively common. Optimizing preventative efforts may greatly reduce the healthcare burden associated with S. aureus infections.

Naturally occurring IgG antibody levels to the Staphylococcus aureus protein IsdB in humans.

Staphylococcus aureus is a well-recognized, clinically important cause of nosocomial infections, and as such, a vaccine to prevent S. aureus infections would be an important achievement. A Phase IIB/III study of V710, a vaccine containing iron-regulated surface determinant B (IsdB), demonstrated significant sero-conversion rates in cardiovascular surgery patients following a single pre-surgery immunization. However, the vaccine was not efficacious in preventing bacteremia or deep sternal wound infection post-surgery, thus raising the possibility that IsdB might not be available for immune recognition during infection. The purpose of the work described herein was to evaluate and quantify the naturally occurring anti-IsdB levels at baseline and over time during infection, to understand whether IsdB is expressed during a S. aureus infection in hospitalized non-vaccinated patients. We evaluated baseline and follow-up titers in 3 populations: (1) healthy subjects, (2) hospitalized patients with non-S. aureus infections, and (3) hospitalized patients with S. aureus infections. Baseline anti-IsdB levels generally overlapped between the 3 groups, but were highly variable within each group. In healthy subjects, baseline and follow-up levels were highly correlated (Spearman's rho = 0.93), and the geometric mean fold-rise (GMFR) in anti-IsdB levels between study entry and last value was 0.9-fold (95% confidence interval (CI): 0.8 to 1.0 ; p = 0.09), showing no trend over time. The convalescent GMFR in anti-IsdB levels from baseline was 1.7-fold (95% CI: 1.3 to 2.2, p = 0.0008) during S. aureus infection, significantly different from the 1.0-fold GMFR (95% CI: 0.9-1.2, p = 0.60) in non-S. aureus infection, p = 0.005. Additionally, S. aureus isolates (51) obtained from the hospitalized patient group expressed the IsdB protein in vitro. Collectively, these data suggest that IsdB expression levels rise substantially following infection with S. aureus, but not with other pathogens, and IsdB is likely well-conserved across S. aureus strains.

Distribution of hepatitis C virus genotypes in a diverse US integrated health care population.

Hepatitis C virus (HCV) genotypes influence response to therapy, and recently approved direct-acting antivirals are genotype-specific. Genotype distribution information can help to guide antiviral development and elucidate infection patterns. HCV genotype distributions were studied in a diverse cross-section of patients in the Northern California Kaiser Permanente health plan. Associations between genotype and race/ethnicity, age, and sex were assessed with multivariate logistic regression models. The 10,256 patients studied were median age 56 years, 62% male, 55% White non-Hispanic. Overall, 70% were genotype 1, 16% genotype 2, 12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5 [3.8-5.5]) and Asians (OR 1.2 [1.0-1.4]) were more likely to have genotype 1 than 2/3 versus non-Hispanic Whites. Women less likely had genotype 1 versus 2/3 than did men (OR 0.86 [0.78-0.94]). Versus non-Hispanic Whites, Asians (OR 0.38 [0.31-0.46]) and Blacks (OR 0.73 [0.63-0.84]) were less likely genotype1a than 1b; Hispanics (OR 1.3 [1.1-1.5]) and Native Americans (OR 1.9 [1.2-2.8]) more likely had genotype 1a than 1b. Patients age ≥65 years less likely had genotype 1a than 1b versus those age 45-64 (OR 0.34 [0.29-0.41]). The predominance of genotype 1 among all groups studied reinforces the need for new therapies targeting this genotype. Racial/ethnic variations in HCV genotype and subtype distribution must be considered in formulating new agents and novel strategies to successfully treat the diversity of hepatitis C patients.

Epidemiology and outcome of major postoperative infections following cardiac surgery: risk factors and impact of pathogen type.

BACKGROUND: Major postoperative infections (MPIs) are poorly understood complications of cardiac surgery. We examined the epidemiology, microbiology, and outcome of MPIs occurring after cardiac surgery. METHODS: The study cohort was drawn from the Society of Thoracic Surgeon National Cardiac Database and comprised adults who underwent cardiac surgery at 5 tertiary hospitals between 2000 and 2004. We studied the incidence, microbiology, and risk factors of MPI (bloodstream or chest wound infections within 30 days after surgery), as well as 30-day mortality. We used multivariate regression analyses to evaluate the risk of MPI and mortality. RESULTS: MPI was identified in 341 of 10,522 patients (3.2%). Staphylococci were found in 52.5% of these patients, gram-negative bacilli (GNB) in 24.3%, and other pathogens in 23.2%. High body mass index, previous coronary bypass surgery, emergency surgery, renal impairment, immunosuppression, cardiac failure, and peripheral/cerebrovascular disease were associated with the development of MPI. Median postoperative duration of hospitalization (15 days vs 6 days) and mortality (8.5% vs 2.2%) were higher in patients with MPIs. Compared with uninfected individuals, odds of mortality were higher in patients with S aureus MPIs (adjusted odds ratio, 3.7) and GNB MPIs (adjusted odds ratio, 3.0). CONCLUSIONS: Staphylococci accounted for the majority of MPIs after cardiac surgery. Mortality was higher in patients with Staphylococcus aureus- and GNB-related MPIs than in patients with MPIs caused by other pathogens and uninfected patients. Preventive strategies should target likely pathogens and high-risk patients undergoing cardiac surgery.

Incidence and predictors of human papillomavirus-6, -11, -16, and -18 infection in young norwegian women.

BACKGROUND: Natural history data on human papillomavirus (HPV) incidence and its risk factors have not been reported on from young women in Norway. We report on incidence and predictors of HPV-6, 11, 16, and 18; 6 or 11; 16 or 18; or all 4. METHODS: A 48-month prospective study enrolled 898 women aged 16 to 24 between 1998 and 2000. HPV DNA polymerase chain reaction testing of genital tract specimens was performed and risk data collected every 6 months and HPV serology and genital Chlamydia trachomatis testing performed every 12 months. Cumulative incidence was estimated using the Kaplan-Meier method and covariates evaluated in Cox models. RESULTS: Among the women who were HPV DNA- and serology-negative at entry, 48-month cumulative incidences (95% confidence interval) were as follows: HPV-6: 20.0% (17.1-23.4), HPV-11: 2.2% (1.3-3.5), HPV-16: 25.0% (21.7-28.8), HPV-18: 13.6% (11.3-16.4), HPV-6 or -11: 21.5% (18.5-25.0), HPV-16 or -18: 30.4% (26.7-34.5), and HPV-6, -11, -16, or -18: 37.8% (33.6-42.3). Younger age at first intercourse, being single, having no regular partner, reporting new partners, and genital C. trachomatis infection were independent risk factors of incident HPV. CONCLUSIONS: Proxies measuring new partnerships and genital C. trachomatis infection predicted incident HPV-6, -11, -16, or -18. Incidence of HPV-6, -11, -16, or -18 in young Norwegian women is high, with more than one-third becoming infected over 48 months.

Variation in the type and frequency of postoperative invasive Staphylococcus aureus infections according to type of surgical procedure.

OBJECTIVE: To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study. SETTING: Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia. PATIENTS: Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures. METHODS: We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate. RESULTS: In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures. CONCLUSION: The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

Incidence of and preoperative risk factors for Staphylococcus aureus bacteremia and chest wound infection after cardiac surgery.

OBJECTIVE: Staphylococcus aureus infections after cardiac surgery result in significant morbidity and mortality. Identifying patients at elevated risk for these infections preoperatively could facilitate efforts to reduce infection rates. The objectives of this study were to estimate the incidence of postoperative S. aureus infections in cardiac surgery patients, to identify preoperative risk factors for these infections, and to establish a patient risk profile by means of data available to clinicians prior to surgery. DESIGN: Cohort study. SETTING: Eight medical centers that participate in the Society of Thoracic Surgeons National Cardiac Database. PATIENTS: Patients who were undergoing elective cardiac surgery during the period January 1, 2000 through December 31, 2004. METHODS: Clinical and microbiological data from 16,386 patients were combined. Multivariable stepwise logistic regression analysis was performed to predict S. aureus infection, which was defined by culture results. RESULTS: Of the 16,386 patients, 205 (1.3%) developed S. aureus bloodstream or chest wound infection within 90 days after surgery. On multivariable analysis, bootstrap-validated preoperative risk factors for S. aureus bloodstream or chest wound infection included a body mass index greater than 40 (adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.1-3.2]), chronic renal failure (aOR, 1.8 [95% CI, 1.1-2.9]), and chronic lung disease (aOR, 1.4 [95% CI, 1.0-2.0]). Only 8 patients had all 3 risk factors. CONCLUSIONS: Although preoperative risk factors can be easily identified, the majority of patients who developed S. aureus infections after cardiac surgery did not have any risk factors. Preventive measures should not be restricted to a select group of cardiac surgery patients and should rather address the entire patient population.

Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma.

PURPOSE: To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes. PATIENTS AND METHODS: Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated. RESULTS: Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE. CONCLUSION: Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

Response to montelukast among subgroups of children aged 2 to 14 years with asthma.

BACKGROUND: Determining who responds to asthma therapies, particularly leukotriene modifiers, continues to be explored. OBJECTIVE: We sought to identify patient characteristics predictive of response to montelukast. METHODS: We used data from 2 clinical trials in which children with asthma received either montelukast or placebo. Symptoms, beta-agonist use, and unanticipated health resource use caused by asthma were recorded in validated daily diaries for children 2 to 5 (n = 689) and 6 to 14 (n = 336) years old. We defined primary end points of days without asthma in 2- to 5-year-old patients (24 hours without symptoms, beta-agonist use, or asthma attack) and change in percent predicted FEV(1) in 6- to 14-year-old children. Asthma attack was defined by the use of rescue oral corticosteroids or by an unscheduled visit to a medical provider. Patients were grouped according to baseline characteristics, such as family history of asthma, personal history of allergy, frequency of asthma symptoms, eosinophilia, and concomitant use of inhaled corticosteroids or cromolyn. We examined the stratum-specific effects of montelukast on the percentage of days without asthma, change in percent predicted FEV(1), asthma attack, and a variety of secondary symptom and FEV(1) end points. RESULTS: We did not identify characteristics that predicted response to montelukast in either preschool or 6- to 14-year-old children. These findings were consistent across all symptom and FEV(1) outcomes. There was also no differential response to montelukast in either age group when asthma attack was the outcome. CONCLUSION: The patient characteristics studied do not appear to provide an indication of who will benefit most from treatment with montelukast.