nils-herrmann/clean_scirepeval huggingface dataset:
Analysis of active surveillance uptake for low-risk localized prostate cancer in Canada: a Canadian multi-institutional study

Although the uptake of active surveillance (AS) appears to be increasing in published series, the uptake in most geographic regions remains largely unknown. Our aim was to examine practice patterns around the use of AS in low-risk prostate cancer in Canada. In addition, we examined regional variations in AS uptake, predictors of AS uptake, and persistent use for 12 months. This is a retrospective multicentre review of low-risk patients who underwent a prostate biopsy in 2010 in six centres in four provinces (BC, QC, MB and ON). AS was identified based on chart review and required a minimum of 6 months of follow-up after diagnosis without any active treatment. Of 986 patients, 781 patients (mean age 64 years) were incident cases and over three-quarters (77.3 %) chose AS at diagnosis. There were significant differences in uptake of AS by centre (range 65.0–98.0 %, p ≤ 0.05). Key multivariate predictors of pursuing AS included older age (OR 1.34, p = 0.044), centre (p = 0.021), lower number of cores (OR 1.09, p = 0.025), lower number of positive biopsy cores (OR 0.52, p < 0.001), and lower percent core involvement (OR 0.84, p < 0.001). In total, 516 (85.4 %) men remained on AS over 12 months. Maintenance with AS over 12 months differed by centre, ranging from 64.1 to 93.9 % (p = 0.001). Predictors of maintenance with AS over 12 months included older age, centre, and lower number of positive cores. Active surveillance is widely practiced across Canada, but important regional differences were observed. Further analyses are required to understand the root causes of differences and to determine whether AS uptake is changing over time.
The anti-ischemic mechanism of action of ranolazine in stable ischemic heart disease.

The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply.



In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated.



Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise.



Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001).



The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia.
Physician and pharmacist collaboration to improve blood pressure control.

Studies have demonstrated that blood pressure (BP) control can be improved when clinical pharmacists assist with patient management. The objective of this study was to evaluate if a physician and pharmacist collaborative model in community-based medical offices could improve BP control.



This was a prospective, cluster randomized, controlled clinical trial with clinics randomized to a control group (n = 3) or to an intervention group (n = 3). The study enrolled 402 patients (mean age, 58.3 years) with uncontrolled hypertension. Clinical pharmacists made drug therapy recommendations to physicians based on national guidelines. Research nurses performed BP measurements and 24-hour BP monitoring.



The mean (SD) guideline adherence scores increased from 49.4 (19.3) at baseline to 53.4 (18.1) at 6 months (8.1% increase) in the control group and from 40.4 (22.6) at baseline to 62.8 (13.5) at 6 months (55.4% increase) in the intervention group (P = .09 for adjusted between-group comparison). The mean BP decreased 6.8/4.5 mm Hg in the control group and 20.7/9.7 mm Hg in the intervention group (P < .05 for between-group systolic BP comparison). The adjusted difference in systolic BP was -12.0 (95% confidence interval [CI], -24.0 to 0.0) mm Hg, while the adjusted difference in diastolic BP was -1.8 (95% CI, -11.9 to 8.3) mm Hg. The 24-hour BP levels showed similar effect sizes. Blood pressure was controlled in 29.9% of patients in the control group and in 63.9% of patients in the intervention group (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1; P < .001).



A physician and pharmacist collaborative intervention achieved significantly better mean BP and overall BP control rates compared with a control group. Additional research should be conducted to evaluate efficient strategies to implement team-based chronic disease management.
Strong Agreement of Nationally Recommended Retention Measures from the Institute of Medicine and Department of Health and Human Services

We sought to quantify agreement between Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) retention indicators, which have not been compared in the same population, and assess clinical retention within the largest HIV cohort collaboration in the U.S.



Observational study from 2008-2010, using clinical cohort data in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).



Retention definitions used HIV primary care visits. The IOM retention indicator was: ≥2 visits, ≥90 days apart, each calendar year. This was extended to a 2-year period; retention required meeting the definition in both years. The DHHS retention indicator was: ≥1 visit each semester over 2 years, each ≥60 days apart. Kappa statistics detected agreement between indicators and C statistics (areas under Receiver-Operating Characteristic curves) from logistic regression analyses summarized discrimination of the IOM indicator by the DHHS indicator.



Among 36,769 patients in 2008-2009 and 34,017 in 2009-2010, there were higher percentages of participants retained in care under the IOM indicator than the DHHS indicator (80% vs. 75% in 2008-2009; 78% vs. 72% in 2009-2010, respectively) (p<0.01), persisting across all demographic and clinical characteristics (p<0.01). There was high agreement between indicators overall (κ = 0.83 in 2008-2009; κ = 0.79 in 2009-2010, p<0.001), and C statistics revealed a very strong ability to predict retention according to the IOM indicator based on DHHS indicator status, even within characteristic strata.



Although the IOM indicator consistently reported higher retention in care compared with the DHHS indicator, there was strong agreement between IOM and DHHS retention indicators in a cohort demographically similar to persons living with HIV/AIDS in the U.S. Persons with poorer retention represent subgroups of interest for retention improvement programs nationally, particularly in light of the White House Executive Order on the HIV Care Continuum.
Phase I and pharmacokinetic trial of PTC299 in pediatric patients with refractory or recurrent central nervous system tumors: a PBTC study

PTC299 is a novel, orally-bioavailable small molecule that selectively inhibits vascular endothelial growth factor receptor protein synthesis at the post-transcriptional level. Based on promising preclinical results, we conducted a pediatric phase I study to estimate the maximum tolerated dose, describe dose-limiting toxicities (DLT) and characterize the pharmacokinetic profile of PTC299 in children with recurrent CNS tumors. PTC299 was administered orally twice or three times daily, depending on the regimen. Four regimens were evaluated using the rolling 6 design, starting with 1.2 mg/kg/dose twice daily and escalating to 2 mg/kg/dose three times daily. Pharmacokinetic studies were performed during the first two courses. Twenty-seven children (14 male, median age 11.2, range 5.5–21 years) with recurrent brain tumors were treated; 21 were fully evaluable for toxicity assessment. Therapy was well-tolerated, and the only DLT was grade 3 hyponatremia. Grade three and grade four toxicities were uncommon in subsequent cycles. Median AUC0–Tlast values at the 2 mg/kg were similar to those observed in adults. The study was terminated while patients were being treated at the highest planned dose, due to hepatotoxicity encountered in the ongoing adult phase I studies. No complete or partial responses were observed. Two patients with low-grade gliomas were noted to have minor responses, and at the time of the study’s closure, 5 children with low-grade gliomas had been on therapy for 8 or more courses (range 8–16). PTC299 was well-tolerated at the highest dose level tested (2 mg/kg/dose TID) in children with recurrent brain tumors and prolonged disease stabilization was seen in children with low-grade gliomas.
Multicenter evaluation of Tosoh glycohemoglobin analyzer.

We describe an Anglo-French evaluation of a new analyzer.



The Tosoh HLC-723 GHb V, A1c2.2 glycohemoglobin analyzer is an HPLC instrument with primary blood tube sampling, bar-code reading, cap piercing, and the ability to chromatographically separate labile hemoglobin A1c (HbA1c). We evaluated two analytical protocols, 2.2 and 3.0 min, and compared results for blood samples collected from diabetic and nondiabetic subjects with those obtained with Bio-Rad Diamat and Variant analyzers.



Within- and between batch-imprecision (CVs) was <2% with linearity to at least 15.9% HbA1c. Although some hemoglobinopathies were detected in the 2. 2-min chromatography, clearer evidence of abnormality was visible in the 3.0-min version. Comparison with established methods showed good correlation (r = 0.993; n = 316 with Diamat; and r = 0.995; n = 133 with Variant) but highlighted calibration differences.



The problems of manual blood sample preparation, labile HbA1c, and carbamylated hemoglobin interference associated with the older instruments have been eliminated in the new Tosoh analyzer. The 3. 0-min protocol is preferred for routine use.
Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery?

Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supernatant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.
Mortality and cancer in patients with new musculoskeletal episodes: a cohort study.

The risk of serious outcome in persons presenting to primary care with common regional musculoskeletal problems is unknown.



To determine the risk of mortality and cancer in older patients presenting with new musculoskeletal problems.



Cohort study.



One hundred and seventy-nine general practices contributing to the General Practice Research Database.



Cases were 48,206 people aged > or =50 years, with a recorded musculoskeletal problem in 1996 but none during the previous 2 years. Cases were allocated to groups based on problem location (for example, the back). A total of 40,254 controls had no musculoskeletal consultation during 1996 or during the previous 2 years. Outcome measures were mortality and recorded malignant and pre-malignant neoplasms 1 and 10 years after baseline consultation.



Mortality rates in the first year of follow-up were higher for cases (373 per 10,000 person-years) than controls (244). The hip (standardised mortality ratio 2.36; 95% confidence interval [CI] = 1.99 to 2.77 compared to controls) and back (2.07; 95% CI = 1.87 to 2.28) groups had the highest 1-year rates. Ten-year mortality rates were closer between groups. Higher cancer rates were found for the back, hip, and neck groups. The first-year excess mortality in cases was only partly explained by cancer and other comorbidity (hip hazard ratio 1.72; 95% CI = 1.43 to 2.07; back 1.68; 95% CI = 1.49 to 1.90).



New consulting episodes of musculoskeletal problems in the back or hip are associated with higher subsequent cancer rates and increased mortality risk in older people. Unexpected cancer and death in these patients remains rare but the ability of clinical signs and symptoms to identify persons at risk needs to be confirmed.
Predictors of dropout from community clinic child CBT for anxiety disorders.

The aim was to investigate predictors of treatment dropout among 182 children (aged 8-15 years) participating in an effectiveness trial of manual-based 10-session individual and group cognitive behavior therapy (CBT) for anxiety disorders in community clinics. The dropout rate was 14.4%, with no significant difference between the two treatment conditions. We examined predictors for overall dropout (n=26), early (≤session 4, n=15), and late dropout (≥session 5, n=11). Overall dropout was predicted by low child and parent rated treatment credibility, and high parent self-rated internalizing symptoms. Low child rated treatment credibility predicted both early and late dropout. High parent self-rated internalizing symptoms predicted early dropout, whereas low parent rated treatment credibility predicted late dropout. These results highlight the importance of addressing treatment credibility, and to offer support for parents with internalizing symptoms, to help children and families remain in treatment.
Preliminary clinical results of a biphasic waveform and an RV lead system.

Biphasic defibrillation waveforms have provided a reduction in defibrillation thresholds in transvenous ICD systems. Although a variety of biphasic waveforms have been tested, the optimal pulse durations and tilts have yet to be identified. A multicenter clinical study was conducted to evaluate the performance of a new ICD biphasic waveform and new RV active fixation steroid eluting lead system. Fifty-three patients were entered into the study. Mean age was 63 years with a mean ejection fraction of 36.8%. Primary indication for implantation was monomorphic ventricular tachycardia alone (54.7%). Forty-eight patients (90.6%) were implanted with an RV shocking lead and active can alone as the anodal contact. The ICD can was the cathode. In four cases (7.5%), an additional SVC or CS lead was used due to a high DFT with the RV lead alone. In an additional case, a chronic SVC lead was used although the RV-Can DFT was acceptable. DFT for all cases at implant was 9.8 +/- 3.7 J. Repeat testing at 3 months for a subset of patients showed a reduction in DFT (7.4 +/- 3.0 J), P value = 0.03. Sensing and pacing characteristics of the RV lead system remained excellent during the study period (acute 0.047 +/- 0.005 ms at 5.4 V and 9.9 +/- 6.2 mV R wave; chronic 0.067 +/- 0.11 ms at 5.4 V and 9.3 +/- 5.4 mV R wave). It is concluded that this lead system provides good acute and chronic sensing and pacing characteristics with good DFT values in combination with this waveform.
Recombinate study

In the Recombinate study of previously treated patients, we have followed 67 patients (the majority of them were adults or adolescents) for as long as 5.5 years, although a majority of patients have been on study for a shorter period of time. As part of the research protocol, T-cell phenotype analyses have been carried out prospectively from baseline through to the present time. A superficial analysis had been carried out on this data some time back, but now a somewhat more detailed analysis has been done. Overall there are 67 individuals, with a mean age of 26.5 years. There were 23 HIV negatives, the rest being HIV positive. At the time of entry no patients were moving towards end-stage HIV-disease; a positive prognosis was a criterion for enrollment. There were 59 patients tested for CD4s at baseline. Testing was done by local laboratories rather than at a central lab. Of this group 19 HIV-negative patients were studied, but they are not the subject of this paper. There were 40 HIVpositive patients analyzed, with mean CD4s at baseline of 428 and a range in absolute numbers as wide as 271136. Looking at the group of 40 patients as a whole, there was a general change, a drop in CD4 numbers over the period of the study. CD8s tended to increase very slightly, and the CD4/CD8 ratio tended to be the most stable of these three parameters monitored. However, on looking at this in more detail it became apparent that age is a co-factor for HIV disease progression; we know that children and adolescents move more slowly through the HIV disease process, and that elderly individuals move more rapidly this has been reported by a number of groups. In addition, it appears that CD4 numbers may also be associated with rapidity of progression. We therefore decided to look at our numbers and compare them with those reported by de Biasi and his group in the October, 1991, issue of Blood. They had selected their patients, 20 individuals, according to age and CD4 numbers at entry, and then randomized them to receive either the Hemofil-M high-purity product or an intermediate-purity concentrate. So we had a look at our HIV-positive Recombinate patients, particular patients between 12 and 36 years of age: there were 32,
Outcome of distal radius fractures in relation to bone mineral density.

The purpose of this study was to determine whether osteoporosis influenced the clinical results of distal radius fractures in women above the age of 40 years. Forty patients underwent bone mineral densitometry of the distal forearm, hip and lumbar spine. Radiographs of both wrists were taken at the time of fracture healing and the difference in ulnar variance, palmar tilt and radial inclination with the contralateral wrist was measured. Wrist mobility, grip strength and pain relief were determined in 35 patients with a follow-up of more than one year. We found that the clinical results correlated better with bone mineral density than with the radiological parameters. Osteoporosis may be one of the factors affecting the outcome of distal radius fractures.
Viral and Host Factors in Determining Response of Relapsers with Chronic Hepatitis C to Retreatment with Interferon

In chronic hepatitis C the rate of relapse afteran end-of-treatment response to interferon may exceed50%. The usefulness of retreatment of relapsers withinterferon in obtaining a complete sustained response and the role of clinical, virological andimmunological features in determining long-term efficacyof retreatment are unclear. We aimed to assess theefficacy of interferon retreatment in obtaining acomplete sustained response, to evaluate whetherincreasing the dose may enhance responsiveness, and toidentify possible predictors of sustained response. Weenrolled 42 patients with biopsy-proven chronichepatitis C without cirrhosis who had previouslyresponded to a six-month course ofInterferon-α2b (total dose: group A, 22patients, 234 MU; group B, 20 patients, 468 MU) and thenrelapsed. All, except one, were HCV-RNA negative at the end of first cycle ofinterferon; most (31/42, 74%) were infected by HCV 1b.Subjects were randomly allocated to receive anothercycle of interferon either at the original dose (group A1: 234 MU, 11 patients; groupB 468 MU, 10 patient) or twice the original dose (groupA2: 468 MU, 11 patients; group B : 936 MU, 10patients). At the end of the second cycle of interferon,24 subjects (57%) had normal ALT and were HCV-RNAnegative, and 16 (39%) had normal ALT, but were HCV-RNApositive. A complete sustained response was obtained ineight patients (19%), at a similar rate in all treatment groups. Complete sustainedresponders were different from the other patients interms of age (35.9 ± 10.4 vs 44.1 ± 8.8,P = 0.027), rate of infection with non-1b HCV (6/8 vs5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428median copies/ml, P = 0.037) and serum levels of90K/MAC-2 BP (5.76 ± 3.01 vs 10.25 ± 5.16units/ml, P = 0.02), an N-glycoprotein implicated incellular defense functions. Multivariate logistic analysisvalidated age and HCV genotype as independent predictorsof CSR. Among noncirrhotic relapsers who received atotal interferon dose ≥234 MU in the first cycle,retreatment usually induced end-of-treatment response. Acomplete sustained response was obtained in only one ofevery five subjects. Increasing the dose of interferonabove that of the first cycle did not enhance the rate of sustained response. In conclusionwe might assert that young subjects infected by non-1bHCV and with low levels of HCV-RNA and of 90K/MAC-2 BPare the best candidates for retreatment.