28 research outputs found
Metal ion–humic acid nanoparticle interactions: role of both complexation and condensation mechanisms
Distribution Channels in International Markets: A Comparative Analysis of the Distribution of New Zealand Tourism in Australia, Great Britain and the USA
Intraparticulate speciation analysis of soft nanoparticulate metal complexes. The impact of electric condensation on the binding of Cd 2+
Effect of recombinant zoster vaccine on incidence of Herpes zoster after autologous stem cell transplantation : a randomized clinical trial
IMPORTANCE Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster.
OBJECTIVE To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients.
DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT.
INTERVENTIONS Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n=922) or placebo (n=924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter.
MAIN OUTCOMES AND MEASURES The primary end point was occurrence of confirmed herpes zoster cases.
RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P<.001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P=.02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P=.02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P=.01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points.
CONCLUSIONS AND RELEVANCE Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0161041
Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation A Randomized Clinical Trial
IMPORTANCE Herpes zoster, a frequent complication following autologous
hematopoietic stem cell transplantation (HSCT), is associated with
significant morbidity. A nonlive adjuvanted recombinant zoster vaccine
has been developed to prevent posttransplantation zoster.
OBJECTIVE To assess the efficacy and adverse event profile of the
recombinant zoster vaccine in immunocompromised autologous HSCT
recipients.
DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded
study conducted in 167 centers in 28 countries between July 13, 2012,
and February 1, 2017, among 1846 patients aged 18 years or older who had
undergone recent autologous HSCT.
INTERVENTIONS Participants were randomized to receive 2 doses of either
recombinant zoster vaccine (n=922) or placebo (n=924) administered into
the deltoid muscle; the first dose was given 50 to 70 days after
transplantation and the second dose 1 to 2 months thereafter.
MAIN OUTCOMES AND MEASURES The primary end point was occurrence of
confirmed herpes zoster cases.
RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688
[37%] women) who received 1 vaccine or placebo dose, 1735 (94%)
received a second dose and 1366 (74%) completed the study. During the
21-month median follow-up, at least 1 herpes zoster episode was
confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94
per 1000 person-years, respectively), an incidence rate ratio (IRR) of
0.32 (95% CI, 0.22-0.44; P<.001), equivalent to 68.2% vaccine
efficacy. Of 8 secondary end points, 3 showed significant reductions in
incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR,
0.1; 95% CI, 0.00-0.78; P=.02) and of other prespecified herpes
zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22;
95% CI, 0.04-0.81; P=.02) and in duration of severe worst herpes
zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days;
hazard ratio, 0.62; 95% CI, 0.42-0.89; P=.01). Five secondary
objectives were descriptive. Injection site reactions were recorded in
86% of vaccine and 10% of placebo recipients, of which pain was the
most common, occurring in 84% of vaccine recipients (grade 3: 11%).
Unsolicited and serious adverse events, potentially immune-mediated
diseases, and underlying disease relapses were similar between groups at
all time points.
CONCLUSIONS AND RELEVANCE Among adults who had undergone autologous
HSCT, a 2-dose course of recombinant zoster vaccine compared with
placebo significantly reduced the incidence of herpes zoster over a
median follow-up of 21 months.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0161041
Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation A Randomized Clinical Trial
IMPORTANCE Herpes zoster, a frequent complication following autologous
hematopoietic stem cell transplantation (HSCT), is associated with
significant morbidity. A nonlive adjuvanted recombinant zoster vaccine
has been developed to prevent posttransplantation zoster.
OBJECTIVE To assess the efficacy and adverse event profile of the
recombinant zoster vaccine in immunocompromised autologous HSCT
recipients.
DESIGN, SETTING, AND PARTICIPANTS Phase 3, randomized, observer-blinded
study conducted in 167 centers in 28 countries between July 13, 2012,
and February 1, 2017, among 1846 patients aged 18 years or older who had
undergone recent autologous HSCT.
INTERVENTIONS Participants were randomized to receive 2 doses of either
recombinant zoster vaccine (n=922) or placebo (n=924) administered into
the deltoid muscle; the first dose was given 50 to 70 days after
transplantation and the second dose 1 to 2 months thereafter.
MAIN OUTCOMES AND MEASURES The primary end point was occurrence of
confirmed herpes zoster cases.
RESULTS Among 1846 autologous HSCT recipients (mean age, 55 years; 688
{[}37\%] women) who received 1 vaccine or placebo dose, 1735 (94\%)
received a second dose and 1366 (74\%) completed the study. During the
21-month median follow-up, at least 1 herpes zoster episode was
confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94
per 1000 person-years, respectively), an incidence rate ratio (IRR) of
0.32 (95\% CI, 0.22-0.44; P<.001), equivalent to 68.2\% vaccine
efficacy. Of 8 secondary end points, 3 showed significant reductions in
incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR,
0.1; 95\% CI, 0.00-0.78; P=.02) and of other prespecified herpes
zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22;
95\% CI, 0.04-0.81; P=.02) and in duration of severe worst herpes
zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days;
hazard ratio, 0.62; 95\% CI, 0.42-0.89; P=.01). Five secondary
objectives were descriptive. Injection site reactions were recorded in
86\% of vaccine and 10\% of placebo recipients, of which pain was the
most common, occurring in 84\% of vaccine recipients (grade 3: 11\%).
Unsolicited and serious adverse events, potentially immune-mediated
diseases, and underlying disease relapses were similar between groups at
all time points.
CONCLUSIONS AND RELEVANCE Among adults who had undergone autologous
HSCT, a 2-dose course of recombinant zoster vaccine compared with
placebo significantly reduced the incidence of herpes zoster over a
median follow-up of 21 months.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0161041
Management of coronary disease in patients with advanced kidney disease
BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction
Health status after invasive or conservative care in coronary and advanced kidney disease
BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy