Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
613
result(s) for
"Betts, Robert"
Sort by:
Early Removal of Central Venous Catheter in Patients with Candidemia Does Not Improve Outcome: Analysis of 842 Patients from 2 Randomized Clinical Trials
Background. Patients with candidemia frequently have a central venous catheter (CVC) in place, and its early removal is considered the standard of care. Methods. We performed a subgroup analysis of 2 phase III, multicenter, double-blind, randomized, controlled trials of candidemia to examine the effects of early CVC removal (within 24 or 48 h after treatment initiation) on the outcomes of 842 patients with candidemia. Inclusion criteria were candidemia, age >16 years, CVC at diagnosis, and receipt of ≥1 dose of the study drug. Six outcomes were evaluated: treatment success, rates of persistent and recurrent candidemia, time to mycological eradication, and survival at 28 and 42 days. Univariate and multivariate analyses were performed, controlling for potential confounders. Results. In univariate analysis, early CVC removal did not improve time to mycological eradication or rates of persistent or recurrent candidemia but was associated with better treatment success and survival. These benefits were lost in multivariate analysis, which failed to show any beneficial effect of early CVC removal on all 6 outcomes and identified Acute Physiology and Chronic Health Evaluation II score, older age, and persistent neutropenia as the most significant variables. Our findings were consistent across all outcomes and time points (removal within 24 or 48 h and survival at 28 and 42 days). The median time to eradication of candidemia was similar between the 2 study groups. Conclusions. In this cohort of 842 adults with candidemia followed up prospectively, early CVC removal was not associated with any clinical benefit. These findings suggest an evidence-based re-evaluation of current treatment recommendations.
Journal Article
Efficacy, Safety, and Tolerability of Herpes Zoster Vaccine in Persons Aged 50—59 Years
Background. Herpes zoster (HZ) adversely affects individuals aged 50—59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50—59 years. Methods. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50—59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. Results. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1—80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. Conclusions. In subjects aged 50—59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. Clinical Trials Registration. NCT00534248.
Journal Article
A Multicenter, Double-Blind Trial of a High-Dose Caspofungin Treatment Regimen versus a Standard Caspofungin Treatment Regimen for Adult Patients with Invasive Candidiasis
Background. The standard caspofungin treatment regimen (50 mg/day after a 70-mg dose on day 1) is effective and well tolerated for the treatment of invasive candidiasis, but experience with higher doses of caspofungin is limited. We evaluated the safety and efficacy of caspofungin at 3 times the standard dosing regimen. Methods. Patients with proven invasive candidiasis were randomized to receive a standard or high-dose (150 mg/day) caspofungin treatment regimen. Safety was assessed in all patients as treated. Efficacy was assessed as a secondary objective in a full-analysis-set population. A favorable overall response was defined as symptom resolution and microbiological clearance at the end of caspofungin therapy. Results. A total of 204 patients were included in the safety analysis (104 received the standard regimen, and 100 received the high-dose regimen), and 197 were included in the efficacy analysis (102 and 95 in the standard and high-dose treatment groups, respectively). Patient demographic characteristics, neutropenia status (6.7% and 8.0% had neutropenia, respectively), and Acute Physiology and Chronic Health Evaluation II scores (mean, 16.5 and 17, respectively) were similar between treatment groups. Significant drug-related adverse events occurred in 1.9% of patients receiving the standard regimen and 3.0% of patients receiving the high-dose regimen (difference, 1.1%; 95% confidence interval, −4.1% to 6.8%). The most-common drug-related adverse events in the standard and high-dose treatment groups were phlebitis (3.8% and 2.0%, respectively), increased alkaline phosphatase level (6.9% and 2.0%, respectively), and increased aspartate transaminase level (4.0% and 2.0%, respectively). Overall, 71.6% of patients who received the standard regimen and 77.9% of patients who received the high-dose regimen had favorable overall responses (difference, 6.3%; 95% confidence interval, −5.9% to 18.4%; not statistically significant). Mortality at 8 weeks after therapy was similar between groups. Conclusions. Both caspofungin dosing regimens were effective and well tolerated in patients with invasive candidiasis. No safety concerns were found for caspofungin at a dosage of 150 mg/day.
Journal Article
Micafungin versus Caspofungin for Treatment of Candidemia and Other Forms of Invasive Candidiasis
Background. Invasive candidiasis is an important cause of morbidity and mortality among patients with health care–associated infection. The echinocandins have potent fungicidal activity against most Candida species, but there are few data comparing the safety and efficacy of echinocandins in the treatment of invasive candidiasis. Methods. This was an international, randomized, double-blind trial comparing micafungin (100 mg daily) and micafungin (150 mg daily) with a standard dosage of caspofungin (70 mg followed by 50 mg daily) in adults with candidemia and other forms of invasive candidiasis. The primary end point was treatment success, defined as clinical and mycological success at the end of blinded intravenous therapy. Results. A total of 595 patients were randomized to one the treatment groups and received at least 1 dose of study drug. In the modified intent-to-treat population, 191 patients were assigned to the micafungin 100 mg group, 199 to the micafungin 150 mg group, and 188 to the caspofungin group. Demographic characteristics and underlying disorders were comparable across the groups. Approximately 85% of patients had candidemia; the remainder had noncandidemic invasive candidiasis. At the end of blinded intravenous therapy, treatment was considered successful for 76.4% of patients in the micafungin 100 mg group, 71.4% in the micafungin 150 mg group, and 72.3% in the caspofungin group. The median time to culture negativity was 2 days in the micafungin 100 mg group and the caspofungin group, compared with 3 days in the micafungin 150 mg groups. There were no significant differences in mortality, relapsing and emergent infections, or adverse events between the study arms. Conclusions. Dosages of micafungin 100 mg daily and 150 mg daily were noninferior to a standard dosage of caspofungin for the treatment of candidemia and other forms of invasive candidiasis.
Journal Article
Recommendations for the Management of Herpes Zoster
The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.
Journal Article
Safety and Immunogenicity of Heat-Treated Zoster Vaccine (ZVHT) in Immunocompromised Adults
Background. Safety and immunogenicity of heat-treated zoster vaccine (ZV HT ) were assessed in immunocompromised adults. Methods. In a randomized, double-blind, placebo–controlled, multicenter study, 4 doses ZV HT or placebo were administered approximately 30 days apart to adults with either solid tumor malignancy (STM); hematologic malignancy (HM); human immunodeficiency virus (HIV) with CD4⁺ ≤200; autologous hematopoietic stem-cell transplant (HCT) or allogeneic-HCT recipients. Varicella-zoster virus (VZV) T-cell responses by interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) and VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and approximately 28 days after each dose. Results. No safety signals were found in any group. IFN-γ ELISPOT geometric mean fold rises (GMFR) after dose 4 in STM, HM, HIV, and autologous-HCT patients were 3.00 (P<.0001), 2.23 (P = .004), 1.76 (P = .026), and 9.01 (P = NA), respectively. Similarly, antibody GMFR were 2.35 (P<. 0001), 1.28 (P = . 003), 1.37 (P = .017), and 0.90 (P = NA), respectively. T-cell and antibody responses were poor after 4 doses of ZV HT m allogeneic-HCT patients. Conclusion. ZV HT was generally safe and immunogenic through 28 days post-dose 4 in adults with STM, HM, and HIV. Autologous-HCT but not allogeneic-HCT patients had a rise in T-cell response; antibody responses were not increased in either HCT population. Study identification. V212-002 Clinical Trials Registration. NCT00535236
Journal Article
Comparison of Caspofungin and Amphotericin B for Invasive Candidiasis
Caspofungin is a new echinocandin drug that has activity against the cell wall of candida species. This double-blind trial evaluated whether caspofungin is as effective as amphotericin B, which has substantial toxicity. Among 224 patients with invasive candidiasis, the outcomes were successful in 73.4 percent of those treated with caspofungin and in 61.7 percent of those treated with amphotericin B. The frequency of nephrotoxic effects was lower with caspofungin than with amphotericin B.
The optimal first-line treatment for serious candida infections is a controversial issue. Amphotericin B has served as standard treatment for five decades,
1
–
3
but toxic effects often limit its use.
2
Fluconazole has a role in the treatment of candidemia.
4
–
10
Prospective, randomized studies have shown that fluconazole is as effective as amphotericin B, with superior safety, for the treatment of candidemia in patients without neutropenia.
11
–
13
However, certain non-albicans candida species, which account for over half the cases of candidemia, are less susceptible to fluconazole.
14
–
18
The need remains for new agents to treat serious candida infections. One alternative is . . .
Journal Article
Outbreak of Mycobacterium chelonae Infection Associated with Tattoo Ink
An outbreak of cutaneous Mycobacterium chelonae infection associated with tattooing was traced to contaminated, premixed tattoo ink. An associated Perspective article discusses the public health implications.
Since 2003, a growing number of published case reports have linked tattooing with localized infections due to atypical mycobacteria.
1
–
13
Mycobacterium chelonae
is a rapidly growing form of nontuberculous mycobacteria; overall, it is an uncommon cause of cutaneous infections.
14
We describe an investigation of an outbreak involving 19 persons with presumed
M. chelonae
infection after receiving a tattoo from a single artist who used a premixed ink that was contaminated before distribution. Previous outbreaks were associated with dilution and contamination of ink at the tattoo parlor.
Methods
Index Patient
On January 4, 2012, we and colleagues at the Monroe County . . .
Journal Article
The immunogenicity and safety of different formulations of a novel Staphylococcus aureus vaccine (V710): Results of two Phase I studies
► V710 is a S. aureus vaccine containing the highly conserved IsdB surface protein. ► V710 was immunogenic in healthy subjects in a liquid, adjuvanted vaccine. ► V710 was immunogenic in healthy subjects in a lyophilized vaccine. ► All formulations were immunogenic within 14 days in healthy subjects. ► All formulations were well-tolerated.
Merck V710 is a novel vaccine that contains the highly conserved Staphylococcus aureus iron surface determinant B (IsdB) protein. V710 has induced positive immune responses in healthy subjects. The purpose of the two studies described herein was to evaluate the immunogenicity and safety of two different formulations of V710. Both studies were randomized, controlled, double-blind, parallel-group trials. Study 1 compared liquid, aluminum-adjuvanted V710 (30μg) with liquid, non-adjuvanted V710 (30μg) in a 1:1 ratio in 64 healthy adults (18–70 years). Study 2 compared non-adjuvanted lyophilized V710 (60μg) with saline placebo in a 4:1 ratio in 51 healthy adults (18–80 years). Blood was collected at screening and up to Day 360 postvaccination in Study 1, and at screening and up to Day 84 postvaccination in Study 2. Sera were analyzed for IsdB-specific antibodies using a total IgG assay. The primary endpoints in Study 1 were the proportion of patients with a positive immune response (≥2-fold rise in IsdB-specific IgG antibody level) the geometric mean concentration (GMC), and the geometric mean-fold rise (GMFR), all from baseline at Day 14. The primary endpoint in Study 2 was the GMFR in IsdB-specific IgG antibody concentration from baseline at Day 14. In Study 1, 84.4% responded in the adjuvanted V710 group, and 71.9% in the non-adjuvanted V710 group. The GMC was 115.4μg/mL in the adjuvanted group and 99.1μg/mL in the nonadjuvanted group. The GMFR in antibody concentration in the group receiving aluminum-adjuvanted V710 was 4.5 and the GMFR in the group receiving non-adjuvanted V710 was 4.0. In Study 2, the GMFR in antibody concentration in the V710 group was 5.3, and 80.5% had a positive immune response. None responded in the placebo group. Positive immune response was seen in the active treatment groups over the full duration of each study. There were no serious adverse experiences (AE) in either study, and no patients discontinued due to an AE. There were no clinically meaningful differences in AEs between groups in either study. In conclusion, V710, both with and without aluminum adjuvant, and in both liquid and lyophilized formulations, was immunogenic within 14 days of vaccination. All treatments showed similar safety profiles.
Journal Article