V2O5 nanowires exhibit an intrinsic catalytic activity towards classical peroxidase substrates such as 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 3,3,5,5,‐tetramethylbenzdine ...(TMB) in the presence of H2O2. These V2O5 nanowires show an optimum reactivity at a pH of 4.0 and the catalytic activity is dependent on the concentration. The Michaelis‐Menten kinetics of the ABTS oxidation over these nanowires reveals a behavior similar to that of their natural vanadium‐dependent haloperoxidase (V‐HPO) counterparts. The V2O5 nanowires mediate the oxidation of ABTS in the presence of H2O2 with a turnover frequency (kcat) of 2.5 × 103 s−1. The KM values of the V2O5 nanowires for ABTS oxidation (0.4 μM) and for H2O2 (2.9 μM) at a pH of 4.0 are significantly smaller than those reported for horseradish peroxidases (HRP) and V‐HPO indicating a higher affinity of the substrates for the V2O5 nanowire surface. Based on the kinetic parameters and similarity with vanadium‐based complexes a mechanism is proposed where an intermediate metastable peroxo complex is formed as the first catalytic step. The nanostructured vanadium‐based material can be re‐used up to 10 times and retains its catalytic activity in a wide range of organic solvents (up to 90%) making it a promising mimic of peroxidase catalysts.
V2O5 nanowires show an intrinsic catalytic activity towards classical peroxidase of substrates such as 2,2‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 3,3,5,5,‐tetramethylbenzadine (TMB) in the presence of H2O2. The Michaelis–Menten kinetics of the ABTS oxidation over these nanowires reveal behavior that is similar to that of their natural vanadium‐dependent haloperoxidase (V‐HPO) counterparts. The nanostructured vanadium‐based material can be re‐used up to 10 times and retains its catalytic activity making it a promising mimic of peroxidase catalysts.
Purpose
To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure.
...Methods
The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h.
Results
Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8–57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08–2.77;
p
= 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1–1.01;
p
= 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (
p
< 0.001) and mechanical ventilation (
p
< 0.001) for longer and had longer intensive care unit stays (
p
< 0.001) and greater mortality (25.9 vs. 1.7 %;
p
< 0.001) than patients who did not.
Conclusions
Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.
Summary Background The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but ...screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. Methods ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. Findings With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 1·58–1·69 including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). Interpretation In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Funding Each centre had its own funding responsibility.
Abstract Background The complications of prostate needle biopsy (PNB) are important when considering the benefits and harms of prostate cancer screening. Studies from the United States and Canada ...have recently reported increasing numbers of hospitalizations for infectious complications after PNB. Objective Examine the risk of infectious complications and hospital admissions after PNB in a European screening trial. Design, setting, and participants From 1993 to 2011, 10 474 PNBs were performed in the European Randomized Study of Screening for Prostate Cancer (Rotterdam section). Prophylaxis originally consisted of trimethoprim-sulfamethoxazole. Beginning in 2008, it was changed to ciprofloxacin. Measurements Febrile complications and hospital admissions were assessed by questionnaires 2 wk after PNB. Logistic regression was used to identify risk factors for biopsy-related fever and hospital admission. Results and limitations Fever and hospital admission were reported on 392 of 9241 questionnaires (4.2%) and 78 of 9198 questionnaires (0.8%), respectively. Although most fevers were managed on an outpatient basis, 81% of hospital admissions were for infection. Of the 56 available blood cultures, 34 were positive with Escherichia coli as the predominant organism. On multivariable analysis, prostate enlargement and diabetes were significantly associated with an increased risk of fever after PNB, whereas later year of biopsy was the only factor significantly associated with an increased risk of hospital admission. Conclusions In a European screening trial, <5% PNBs resulted in febrile complications. Significant risk factors included diabetes and prostatic enlargement. Although most fevers were managed on an outpatient basis, infection remained the leading cause of hospital admission after PNB. Consistent with prior international reports, the frequency of hospital admissions after PNB significantly increased over time. Nevertheless, the absolute frequency of hospital admissions related to PNB was low and should not dissuade healthy men who would benefit from early prostate cancer diagnosis from undergoing biopsy when clinically indicated.
Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European ...Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up.
The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer.
After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval CI, 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality.
Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).
Abstract Background Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing ...interest as an alternative to radical treatment of low-risk PCa. Objective To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) ≤10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score ≤6. PSA was measured every 3–6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy–free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized. Trial registration The current program is registered at the Dutch Trial Register with ID NTR1718 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1718 ).
The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from ...prostate cancer.
We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006.
In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval CI, 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90).
PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)
Abstract Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have ...assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk–benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Objective Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. Evidence acquisition A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Evidence synthesis Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone–releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Conclusions Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk–benefit ratio.
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