In routine clinical practice, few physicians use early viral kinetics to guide HCV dual therapy treatment decisions.

BACKGROUND & AIMS: PROPHESYS is a large, multinational, non-interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on-treatment virological response (VR). METHODS: This PROPHESYS subanalysis is restricted to treatment-naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono-infected patients who received peginterferon alfa-2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria. RESULTS: The likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non-RVR/EVR patients with HCV RNA>400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB-4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa-2a dose, but a high proportion received a higher-than-recommended ribavirin dose. CONCLUSIONS: Despite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.

Knowledge and perceptions about community-acquired staphylococcal infections among health care workers in Hawai'i.

Since the early 1990s, national rates of methicillin-resistant Staphylococcus aureus (MRSA) infections have increased dramatically.1,2 Initially identified in health care settings, community-acquired MRSA is now a major public health concern. With Hawai'i's expanding S. aureus and MRSA epidemic closely approximating the national trend in inpatient and outpatient settings,7,8 a high level of knowledge and awareness among health care workers is essential to successfully control this evolving epidemic. Health care and related workers were surveyed to assess their knowledge and perceptions about staphylococcal and MRSA infections. Knowledge was estimated by demonstrated ability to correctly identify risk factors including diabetes and obesity, as well as to demonstrate awareness of a growing staphylococcal and MRSA epidemic.9,10 Perceptions were estimated by level of concern of antibiotic resistance as well as of the severity of the staphylococcal and MRSA epidemic. Variations in knowledge and perception concerning basic principles associated with S. aureus infections as well as characteristics of the evolving S. aureus and MRSA epidemic were observed among various occupations (advance clinical practitioners, nurses, public health professionals, athletic trainers, and non-medical workers) as well as work locations (hospital, community, and non-clinical community). Overall, health care and related workers in community settings demonstrated disparities in knowledge regarding S. aureus and MRSA infections. They were also more likely to misperceive this growing threat. These findings provide support for focused educational interventions targeting community health care and related workers to improve awareness of staphylococcal infections in order to successfully address and combat this evolving epidemic.

Changes in fasting plasma glucose levels with ribavirin and pegylated interferon treatment in normal and impaired glucose tolerant patients with chronic hepatitis C.

BACKGROUND: Patients with Hepatitis C Virus (HCV) infection have increased rates of glucose intolerance, and studies have shown the improvement of fasting plasma glucose (FPG) levels after clearance of HCV infection with standard ribavirin plus pegylated interferon treatment. The purpose of this study was to examine glycemic changes with standard HCV treatment in patients with impaired fasting glucose (IFG) and normal fasting glucose (NFG). METHODS: A retrospective study of FPG changes in HCV patients with IFG and NFG treated with standard HCV therapy was conducted. Baseline characteristics and viral responses were assessed; FPG levels before treatment, at the end of treatment, and more than one-month post treatment were compared. RESULTS: The mean FPG levels increased by 8.68 mg/dl at the end of treatment in the NFG group but decreased by 9.0 mg/dl in the IFG group, a statistically significant difference (P=0.019). The change in FPG levels remained significantly different after adjusting for weight change (P=0.009) and weight changes and initial weight (P=0.039). FPG change from baseline at more than one month after treatment were similar in both groups (P=0.145). The change in FPG levels was not associated with sustained viral response. CONCLUSIONS: In HCV-infected patients, standard ribavirin plus pegylated interferon treatment reduced FPG levels in patients with IFG and increased FPG levels in NFG individuals; independent of initial weight, weight change, or viral response. Standard HCV treatment modulates fasting plasma glucose levels which supports the need for a prospective study to determine the clinical significance of this finding.

A probe-based method for confirmation of methicillin-resistant Staphylococcus aureus and detection of Panton-Valentine leukocidin and tst virulence genes.

Probe-based detection of mecA, lukS/F-PV (Panton-Valentine leukocidin), and tst virulence genes in 435 isolates of Staphylococcus aureus had comparable sensitivity and specificity to end-point polymerase chain reaction as a reference standard.

Albinterferon Alfa-2b was not inferior to pegylated interferon-α in a randomized trial of patients with chronic hepatitis C virus genotype 1.

BACKGROUND & AIMS: The current standard of care for patients with chronic hepatitis C virus (HCV) genotype 1 is once-weekly pegylated interferon-α (Peg-IFNα) plus daily ribavirin for 48 weeks. We evaluated the efficacy/safety of albinterferon alfa-2b (albIFN), a novel, long-acting, genetic fusion polypeptide of albumin and IFNα-2b. METHODS: In the phase 3 ACHIEVE-1 trial, 1331 patients were assigned equally to 3 open-label, 48-week treatment groups: Peg-IFNα-2a 180 µg every week, or albIFN 900 or 1200 µg every 2 weeks administered subcutaneously, with weight-based oral ribavirin 1000-1200 mg/day. During the study, the data monitoring committee recommended dose modification for all patients receiving albIFN 1200 µg to 900 µg because of increased pulmonary adverse events (AEs) in the 1200-µg arms of both ACHIEVE studies. Main outcome measure was sustained virologic response (SVR; undetectable serum HCV RNA at week 72). RESULTS: Intention-to-treat SVR rates were 51.0% (225/441), 48.2% (213/442), and 47.3% (208/440) with Peg-IFNα-2a, and albIFN 900 and 1200 µg, respectively. The primary objective of showing noninferiority of albIFN 900 µg (P < .001) and 1200 µg (P = .003) vs Peg-IFNα-2a for SVR was achieved. Multivariate modeling indicated consistency of treatment effect across subgroups. Serious/severe AE rates were 23.1%, 24.0%, 28.2%; treatment discontinuation rates because of AEs were 4.1%, 10.4%, 10.0%; discontinuation rates because of respiratory AEs were 0%, 0.9%, 1.6%; with Peg-IFNα-2a, and albIFN 900 and 1200 µg, respectively. Hematologic abnormality rates were comparable across the Peg-IFNα-2a and albIFN 900-µg groups. CONCLUSIONS: albIFN 900 µg every 2 weeks showed comparable efficacy, with similar serious/severe AE rates, although with a higher discontinuation rate, vs Peg-IFNα-2a in patients with chronic HCV genotype 1.

Viral hepatitis in Hawai'i--differing perspectives.

This publication contains information from a conference titled "Individual Perspectives on the Silent Epidemic of Viral Hepatitis in Hawai'i" held in October of 2007 with updates and additional contributions from annual conferences in 2008 and 2009. These conferences were sponsored by the Hepatitis Support Network of Hawai'i and held in Honolulu, Hawai'i at the Queen's Conference Center. The primary objectives of the conferences have been to heighten awareness of viral hepatitis in Hawai'i and to bring together health care professionals to learn about these infections and to help them respond to the challenges they bring to the people of Hawai'i. The initial conference was oriented to present the unique and individual perspectives of patients, physicians, and other healthcare providers specific to the complex issues of hepatitis in an effort to help them understand their role in the context of others and to develop a team approach in responding to this epidemic.

Prevention of community-associated methicillin-resistant Staphylococcus aureus infection among Asian/Pacific Islanders: a qualitative assessment.

BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been increasingly reported over the past decade, including in Asian/Pacific Islanders (A/PIs). METHODS: We conducted ethnographic interviews in O'ahu and Kaua'i, Hawai'i, with 10 Asian/Pacific Islanders identified as having a history of CA-MRSA infections. RESULTS: Most (7/10) thought skin infections were not a new problem in Hawai'i. Most (8/9) attempted to self-treat the infection prior to seeking medical care with a range of home remedies and store- bought solutions. Most respondents did not initially comprehend the severity of their infection and only sought medical treatment after concern from family, unbearable pain, and/or other symptoms of illness. CONCLUSION: Clinicians should be aware of the reportedly frequent use of home remedies by this population, as it may potentially contribute to interactions when treatments are combined. If clinicians and public health professionals do not address perceptions and misperceptions of how MRSA is acquired, it will be very difficult to prevent infection, and may also delay individuals from seeking treatment.

Quantitation of Staphylococcus aureus in seawater using CHROMagar SA.

A microbiological algorithm has been developed to analyze beach water samples for the determination of viable colony forming units (CFU) of Staphylococcus aureus (S. aureus). Membrane filtration enumeration of S. aureus from recreational beach waters using the chromogenic media CHROMagar SA alone yields a positive predictive value (PPV) of 70%. Presumptive CHROMagar SA colonies were confirmed as S. aureus by 24-hour tube coagulase test. Combined, these two tests yield a PPV of 100%. This algorithm enables accurate quantitation of S. aureus in seawater in 72 hours and could support risk-prediction processes for recreational waters. A more rapid protocol, utilizing a 4-hour tube coagulase confirmatory test, enables a 48-hour turnaround time with a modest false negative rate of less than 10%.

Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment.

OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). METHODS: A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. RESULTS: Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 10(3) cells/microl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. CONCLUSION: Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.

Risk factors for community-associated methicillin-resistant Staphylococcus aureus cellulitis--and the value of recognition.

OBJECTIVES: To identify the risk factors for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) cellulitis. METHODS: A review of risk factors for CA-MRSA skin and soft tissue infection in previously published literature was first performed. A retrospective cohort study was then conducted in a teaching ambulatory-care clinic of a tertiary medical center in Honolulu, Hawaii. RESULTS: Of 137 cases with cellulitis diagnosed from January 2005 to December 2007, MRSA was recovered from 85 (62%) of patients who presented with either abscesses or skin ulcers. The recovery of MRSA was significantly associated with obesity (p=0.01), presence of abscesses (p=0.01), and lesions involving the head and neck (p=0.04). Independent risk factors by multivariate logistic regression analysis included the presence of abscesses [adjusted odds ratio (aOR) 2.72; 95% confidence interval (CI) 1.27-5.83; p=0.01] and obesity (aOR 2.33; 95%; CI 1.10-4.97; p%0.03). Patients with CA-MRSA were less likely to receive an appropriate antibiotic (p=0.04) and were more likely to require antibiotic change at evaluation in one week (p=0.04) compared with patients infected with non-MRSA bacteria. CONCLUSIONS: The presence of abscesses and obesity were significantly associated with CA-MRSA cellulitis. Empiric therapy with antibiotics active against MRSA should be guided by these risk factors.

Investigating approaches to improving appropriate antibiotic use among higher risk ethnic groups.

A field study with follow up investigations sought to: 1. determine whether cold packs (over-the-counter symptomtic treatments), coupled with in-office education, improve antibiotic-related knowledge, attitudes and behaviors more than in-office education alone in patient populations with high percentages of Asian Americans and Hawaiian/Pacific Islanders; 2. identify possible reasons for intervention outcomes as described by physicians who participated in the field study; and 3. explore potential future directions based on a large sample survey of physicians in the field study's highly ethnic county. The intervention resulted in a pre- to post-consultation decrease in perceived need for and an increase in knowledge about antibiotic risks but had no impact on frequency of reported receipt of an antibiotic prescription. Unexpectedly, in-office education alone was more effective in increasing knowledge than in-office education plus the cold pack. In-depth interviews of field study physicians and a large scale physician survey suggest that cold pack interventions targeting patient populations with high percentages of Asian Americans and Hawaiian/Pacific Islanders may be more likely to succeed if accompanied by mass public education regarding risks and physician training regarding effective ways to talk to patients. Use of in-office education with cold packs alone may not achieve desired results.

Viral hepatitis in a homeless shelter in Hawai'i.

It is estimated that as many as 21,000 people in the state of Hawai'i may be infected with HCV Most of those infected with viral hepatitis are unaware they are infected. Complications from viral hepatitis include liver cirrhosis and hepatocellular carcinoma. Hawai'i has the highest incidence of hepatocellular carcinoma in the United States. In 2003 there were over 6000 homeless and over 155,000 people at-risk of becoming homeless living in the state of Hawai'i. Risk factors for hepatitis, such as drug use, tattoos, sexual contact, and sharing of personal hygiene equipment are more prevalent in the homeless population. To determine the incidence of hepatitis B and C among a population of homeless individuals, a health fair was held at a Honolulu area homeless shelter with approximately 200 residents. The incidence of hepatitis B and C was determined by anti-HCV and HBsAg blood tests. A survey was also conducted regarding risk factors and basic demographics. Fifty-nine homeless adults volunteered for testing and took the survey. Thirty-one (52%) volunteers were born in Micronesia, twenty-four (41%) were born in the United States, two (3%) were born in Samoa, one (2%) was born in the Philippines, and one (2%) was born in the Marshall Islands. Forty adults were tested for Hepatitis C antibody, three of which tested positive. The primary risk factor among this group was jail time (100%), followed by illegal drug injection (67%), tattoos (67%), ear/body piercing (67%), snorting drugs (33%), blood transfusions (33%), and a sex partner with hepatitis (33%). Forty adults were also tested for HBsAg, One of which tested positive. This was a recent immigrant from Micronesia. Homeless people in Hawai'i are more likely to have hepatitis B or C because risk factors are common among this population. Additionally a large proportion of Hawai'i's homeless people come from the Pacific Islands, where the prevalence of hepatitis B is one of the highest in the world. In addition there are significant risks of hepatitis spread among the homeless and into the general population as many homeless do not realize they are infected. The health fair approach was an effective means for screening homeless people for hepatitis B and C. Our preliminary information suggests homeless shelters may be a good place for education, screening, and possibly interventions as well.

Efficacy and safety of peginterferon alfa-2a/ribavirin in methadone maintenance patients: randomized comparison of direct observed therapy and self-administration.

BACKGROUND: Adherence to chronic hepatitis C (CHC) treatment may be particularly challenging in methadone maintenance patients. We assessed the safety, tolerability, and efficacy of peginterferon alfa-2a/ribavirin treatment in methadone maintenance patients previously untreated for CHC. METHODS: Patients were randomized 1:1 to direct observed therapy (DOT) or self-administration (SA) of peginterferon alfa-2a. DOT patients were seen weekly at methadone clinics; SA patients were seen less frequently, only at investigative sites. Genotype 1-infected patients were treated for 48 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (1,000/1,200 mg/day); genotypes 2- and 3-infected patients were treated for 24 wk with peginterferon alfa-2a (180 microg/wk)/ribavirin (800 mg/day). RESULTS: Based on defined efficacy stopping rules, 77% (37/48) completed their targeted length of treatment, and 44% (21/48) achieved sustained virologic response (SVR). Two DOT and 3 SA patients were withdrawn for safety reasons and 6 and 9, respectively, for nonsafety reasons. Over 60% and 50% of each group were >80% compliant with the planned cumulative doses of peginterferon alfa-2a and ribavirin, respectively, and over 60% with overall treatment duration. SVR rates were 54% (13/24) for DOT and 33% (8/24) for SA; 23% (3/13) and 38% (6/16), respectively, for genotype 1 and 91% (10/11) and 25% (2/8), respectively, for genotypes 2 and 3. Stepwise logistic regression analysis, showed that DOT (vs SA; OR 3.27, 95% CI 0.90-11.91, P = 0.073) and Caucasian race (vs Other; OR 13.31, 95% CI 1.42-124.71, P = 0.023) were predictors of SVR. CONCLUSION: Peginterferon alfa-2a/ribavirin can be used safely and successfully in CHC patients receiving methadone maintenance.

Survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage in healthy college students, Hawai'i.

Currently, the carriage rate for Community-Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA) is unknown in Hawai'i. This survey focuses on a healthy population of 95 college students and 5 faculty who completed a survey related to possible risk factors for colonization of Staphylococcus aureus and were sampled for S. aureus from their anterior nares. Thirty-three (33%) subjects were carrying Staphylococcus aureus and of those, 3 (3%) carried MRSA. There was no significant association between Staphylococcus aureus carriage and ethnicity, gender exposure to seawater, prior Staphylococcus aureus infections, recent antibiotic use, or pets. Additional testing of a larger group of healthy individuals would be beneficial in assessing factors associated with CA-MRSA and Methicillin-susceptible Staphylococcus aureus (MSSA) carriage in Hawai'i.

Culturally sensitive strategies designed to target the silent epidemic of hepatitis B in a Filipino community.

Hepatitis B is frequent in the Philippines. A high rate of immigration to the United States has brought many Filipinos with infections who are asymptomatic yet will go on to develop liver cancer and cirrhosis unless diagnose and evaluated. Interventions are necessary to educate this ethnic community, identify those infected, and offer therapy. In an effort to reach this high risk population in Hawai'i an intervention program was designed to address the silent epidemic of hepatitis. Ethnic barriers were crossed through involvement of trusted, key stakeholders and individuals within the Filipino health care and church communities, along with groups that had joint missions to address viral hepatitis. After extensive planning and meetings with faith-based organizations and health care providers in the Filipino community, it was decided to hold a community health fair in the Filipino community to provide culturally appropriate health information and services. More than 500 individuals attended the health fair; 167 participated in a survey and were tested for hepatitis B. Significant knowledge gaps were found in relation to risk factors, prevention strategies, and transmission. Five individuals tested positive; all were immigrants and did not know of their disease. The objective to educate people and test them for hepatitis was successful through utilizing ethnic community leaders, religious organizations, health care professionals, and a collaborative health fair.

Comparative costs of ertapenem and piperacillin-tazobactam in the treatment of diabetic foot infections.

PURPOSE: To evaluate potential cost savings, trial data were used to determine the clinical outcomes for i.v. ertapenem given once daily and i.v. piperacillin-tazobactam given every six hours daily in treating diabetic foot infections. METHODS: A cost-minimization analysis (CMA) was conducted on the drug-dosing data of the subset of patients enrolled in a recent double-blind randomized trial who were treated solely as inpatients and were clinically evaluable at fi nal assessment (n = 99). Cost per dose was calculated from (a) average hospital acquisition price per dose for ertapenem ($40.52) or piperacillin-tazobactam ($13.58), (b) average U.S. wages and benefits for labor, based on nine published time-and-motion studies of i.v. antibiotic preparation and administration ($3.10), and (c) consumable supplies, using a 40% discount off the manufacturer list price ($2.90). For each patient, the actual number of antibiotic doses given was multiplied by total cost per dose. RESULTS: There were no significant differences between antibiotic groups with respect to patient demographics, percentage with a severe wound, and mean days of i.v. therapy. Compared with piperacillin-tazobactam, patients treated with ertapenem received significantly fewer mean doses (25.5 versus 7.5; p < 0.0001) and lower antibiotic-related costs ($502.76 versus $355.55, respectively; p < 0.001). The $147.21 difference between groups accounts for approximately 3% of total hospital Medicare reimbursements for these infections. CONCLUSION: A CMA of treatment of diabetic foot infections showed that, compared with piperacillin-tazobactam given four times daily i.v., ertapenem given once daily i.v. was associated with lower drug acquisition and supply costs and less time and labor devoted to preparation and administration of i.v. therapy.