Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI<25 kg/m 2 ), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI >40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p<0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p<0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment

Men\u27s health supplement use and outcomes in men receiving definitive intensity-modulated radiation therapy for localized prostate cancer.

BACKGROUND: Approximately 50% of newly diagnosed cancer patients start taking dietary supplements. Men\u27s health supplements (MHSs), which we define as supplements that are specifically marketed with the terms men\u27s health and prostate health (or similar permutations), are often mislabeled as having potential anticancer benefits. OBJECTIVE: We evaluated the effects of MHSs on patient outcomes and toxicities in patients who were undergoing definitive intensity-modulated radiation therapy (IMRT) for localized prostate cancer. DESIGN: This retrospective analysis included patients who were being treated at a National Cancer Institute-designated comprehensive cancer center and consented to have information stored in a prospective database. MHSs were queried online. Outcome measures were freedom from biochemical failure (FFBF) (biochemical failure was defined with the use of the prostate-specific antigen nadir + 2-ng/mL definition), freedom from distant metastasis (FFDM), cancer-specific survival (CSS), and overall survival (OS) as well as toxicities. Kaplan-Meier analysis, log-rank tests, Fine and Gray competing-risk regression (to adjust for patient and lifestyle factors), and Cox models were used. RESULTS: From 2001 to 2012, 2207 patients were treated with IMRT with a median dose of 78 Gy, and a median follow-up of 46 mo. Of these patients, 43% were low risk, 37% were intermediate risk, and 20% were high risk; 10% used MHSs. MHSs contained a median of 3 identifiable ingredients (range: 0-78 ingredients). Patients who were taking an MHS compared with those who were not had improved 5-y OS (97% compared with 92%, respectively; P = 0.01), but there were no differences in the FFBF (94% compared with 89%, respectively; P = 0.12), FFDM (96% compared with 97%, respectively; P = 0.32), or CSS (100% compared with 99%, respectively; P = 0.22). The unadjusted association between MHS use and improved OS was attenuated after adjustment for patient lifestyle factors and comorbidities. There was no difference in toxicities between the 2 groups (late-grade 3-4 genitourinary CONCLUSION: The use of MHSs is not associated with outcomes or toxicities

Effects of Time to Treatment on Biochemical and Clinical Outcomes for Patients With Prostate Cancer Treated With Definitive Radiation.

INTRODUCTION: The purpose of this study was to evaluate if time to treatment (TTT) has an effect on outcomes for patients with localized prostate cancer treated with definitive external beam radiation therapy (EBRT). PATIENTS AND METHODS: We included 4064 patients (1549 low-risk, 1612 intermediate-risk, and 903 high-risk) treated with EBRT. For each National Comprehensive Cancer Network (NCCN) risk group, TTT (defined as the time between initial positive prostate biopsy and start of RT) was analyzed in 4 intervals: \u3c 3, 3-6, 6-9, and 9-24 months. We recorded the use of androgen deprivation therapy among patients with intermediate-risk and high-risk disease. RESULTS: The median TTT was 3.3 months (range, 0.6-23.5 months), and it was similar for each risk group (range, 3.3-3.4 months). The median follow up was 64 months. There were no significant differences in biochemical failure, distant metastasis, or overall survival for patients with TTT \u3c 3, 3-6, 6-9, or 9-24 months for each risk group. There were also no significant differences in the outcomes at 5 years when patients with TTT \u3e 3.3 months were compared with those with TTT ≤ 3.3 months for each risk group. For high-risk men, 328 of 450 (72.9%) with TTT \u3e 3.3 months were on androgen deprivation therapy (ADT) versus 299 of 453 (66%) with TTT ≤ 3.3 months. Among men with high-risk cancer treated without ADT, there remained no significant difference in outcomes between TTT \u3e 3.3 months and TTT ≤ 3.3 months. CONCLUSION: TTT was not associated with significant differences in outcomes among each risk group of men with localized prostate cancer treated with EBRT. Among the high-risk patients, there were no observed detriments in outcomes with TTT \u3e 3.3 months regardless of androgen deprivation therapy use

Cloning, expression and functional characterisation of a peroxiredoxin from the potato cyst nematode Globedera rostochiensis

We report the cloning, expression and functional characterisation of a peroxidase belonging to the peroxiredoxin family from the potato cyst nematode Globodera rostochiensis, the first molecule of this type from any nematode parasitic on plants. The G. rostochiensis peroxiredoxin catalyses the breakdown of hydrogen peroxide, but not cumene or t-butyl hydroperoxide, in a trypanosomatid reducing system comprising trypanothione reductase, trypanothione and tryparedoxin. In common with its homologues from Onchocerca volvulus and Brugia malayi, the G. rostochiensis enzyme is present on the surface of invasive and post-infective juveniles despite the apparent lack of a cleavable N-terminal signal peptide. The possibility that the G. rostochiensis peroxiredoxin plays a role in protection of the parasite from plant defence responses is discussed. (C) 2000 Elsevier Science B.V. All rights reserved.</p

Effects of interruptions of external beam radiation therapy on outcomes in patients with prostate cancer.

INTRODUCTION: To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa). METHODS: We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group. RESULTS: There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12-185.8). The median NTDR was 31% (range 23-71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR CONCLUSION: Unintentional treatment breaks during dose escalated external beam radiation therapy for PCa did not cause a significant difference in outcomes, although duration of follow up limits the strength of this conclusion

The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.

INTRODUCTION: To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era. MATERIALS AND METHODS: This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (\u3e= 23 months), or those with follow up \u3c 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates. RESULTS: Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS \u3e= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates. CONCLUSION: Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT

Long Term Results of a Phase III Randomized Prospective Trial of Erectile Tissue Sparing IMRT for Men with Clinically Localized Prostate Cancer

To determine if limiting the doses delivered to the penile bulb (PB) and corporal bodies (CB) with IMRT preserves erectile function compared to standard IMRT in men with prostate cancer. 117 patients with low-intermediate risk, clinical T1a-T2c prostate adenocarcinoma were enrolled to a single-institution, prospective, single blind, phase III randomized trial. All received definitive IMRT to 74-80 Gy in 37-40 fractions and standard IMRT (s-IMRT) or erectile tissue sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the PB and CB to ≤ 15 Gy and ≤ 7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function (IIEF) and PDE5 medication records. 62 patients received ETS-IMRT and 54 received s-IMRT; 1 patient did not receive radiation therapy. Prior to treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, p=0.53). Of 85 evaluable patients with IIEF and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (p=0.86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (p=0.54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-yr 91.8% vs 90.7%, respectively, p=0.77) with a median follow-up of 7.4 years. There were no differences in acute or late GI or GU toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, though power was limited by attrition and unplanned dosimetric crossover. Erectile tissue sparing IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited