nils-herrmann/clean_scirepeval huggingface dataset:
Neo-adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource-poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo-adjuvant therapy for breast cancer have been conducted in resource-rich countries. We chose Nigeria, a resource-poor country, as the major site for a phase II feasibility open-label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo-adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m(2) twice daily (2,000 mg/m(2) total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11-59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20-70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand-foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo-adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.
Endoscopic sclerotherapy for esophageal varices

Sclerotherapy for esophageal varices is now well established as a method of treatment for varices which have bled initially and then have been controlled by medical means. The long term outcome of such treatment is now under study. The value of sclerotherapy for acutely bleeding varices or as a prophylactic measure in patients with varices that have not bled is more controversial and its role awaits the outcome of additional controlled trials.
Insulin Resistance Change and Antiretroviral Therapy Exposure in HIV-Infected and Uninfected Rwandan Women: A Longitudinal Analysis

We longitudinally assessed predictors of insulin resistance (IR) change among HIV-uninfected and HIV-infected (ART-initiators and ART-non-initiators) Rwandan women.



HIV-infected (HIV+) and uninfected (HIV-) women provided demographic and clinical measures: age, body mass index (BMI) in Kg/(height in meters)2, Fat-Mass (FMI) and Fat-Free-Mass (FFMI) index, fasting serum glucose and insulin. Homeostasis Model Assessment (HOMA) was calculated to estimate IR change over time in log10 transformed HOMA measured at study enrollment or prior to ART initiation in 3 groups: HIV- (n = 194), HIV+ ART-non-initiators (n=95) and HIV+ ART-initiators (n=371). ANCOVA linear regression models of change in log10-HOMA were fit with all models included the first log10 HOMA as a predictor.



Mean±SD log10-HOMA was -0.18±0.39 at the 1st and -0.21±0.41 at the 2nd measure, with mean change of 0.03±0.44. In the final model (all women) BMI at 1st HOMA measure (0.014; 95% CI=0.006-0.021 per kg/m2; p<0.001) and change in BMI from 1st to 2nd measure (0.024; 95% CI=0.013-0.035 per kg/m2; p<0.001) predicted HOMA change. When restricted to subjects with FMI measures, FMI at 1st HOMA measure (0.020; 95% CI=0.010-0.030 per kg/m2; p<0.001) and change in FMI from 1st to 2nd measure (0.032; 95% CI=0.020-0.043 per kg/m2; p<0.0001) predicted change in HOMA. While ART use did not predict change in log10-HOMA, untreated HIV+ women had a significant decline in IR over time. Use or duration of AZT, d4T and EFV was not associated with HOMA change in HIV+ women.



Baseline BMI and change in BMI, and in particular fat mass and change in fat mass predicted insulin resistance change over ~3 years in HIV-infected and uninfected Rwandan women. Exposure to specific ART (d4T, AZT, EFV) did not predict insulin resistance change in ART-treated HIV-infected Rwandan women.
Application and Revision of Montreal Cognitive Assessment in China's Military Retirees with Mild Cognitive Impairment.

In an effort to accommodate MOCA to better fit for the Chinese context, this study was designed to employ the MOCA criteria to screen mild cognitive impairment (MCI) and analyze associated risk factors in military retirees.



Three hundred and four retired military cadres were recruited using a random cluster sampling technique with information collected including personal, prevalence, MOCA scale, and related neuropsychiatry scale. Thirty retirees were randomly chosen to be further analyzed one month later using the revised MOCA scale.



①Our data indicated an incidence rate of 64.8% for mild cognitive impairment in retired military cadres. The incidence rate for MCI was significantly higher in those aged 80 or above compared with those 80 years of age or younger (P<0.05). The incidence rate of MCI was significantly higher in those with fewer than 6 years of education compared with those with over 7 years of education (P<0.05). The MCI incidence was higher for those with little exercise than those taking regular exercise (P<0.01). Moreover, the MCI incidence was higher in stroke patients than those who never had a stroke episode (P<0.05). ②There was a significant correlation between MOCA and MMSE scale scores (r = 0.81). MOCA scale scores were negatively correlated with ADL and CES-D scores (although not PSQI scores). ③ MOCA recension Cronbach's alpha value was 0.862. The related coefficient of MOCA and MOCA recension was 0.878(P<0.01). When the Score of cut-off -point of the MOCA recension was 28, the area in ROC curve analyses was 0.859, as well as the largest area.



Retired cadres exhibited a greater incidence of MCI (than general population), which was closely associated with age, level of education and physical exercise and cerebral apoplexy. Revised MOCA scale displays a better validity and reaction degree of reliability and is more suitable for screening and diagnosis of MCI in the elderly in China.
The influence of age at onset and duration of illness on long-term outcome in patients with obsessive-compulsive disorder: A report from the International College of Obsessive Compulsive Spectrum Disorders (ICOCS)

Several studies reported a negative effect of early onset and long duration of illness on long-term outcome in psychiatric disorders, including Obsessive-Compulsive Disorder (OCD). OCD is a prevalent, comorbid and disabling condition, associated with reduced quality of life and overall well-being for affected patients and related caregivers. The present multicenter naturalistic study sought to assess the influence of early onset and duration of illness on long-term outcome in a sample of 376 OCD out-patients worldwide, as part of the "International College of Obsessive-Compulsive Spectrum Disorders" (ICOCS) network. Binary logistic regressions were performed with age at the onset and duration of illness, as continuous independent variables, on a series of different outcome dependent variables, including lifetime number of hospitalizations and suicide attempts, poly-therapy and psychiatric comorbidity. Correlations in terms of disability (SDS) were analyzed as well. Results showed that a longer duration of illness (but not earlier age of onset) was associated with hospitalization (odds ratio=1.03, p=0.01), earlier age at onset with CBT (odds ratio=0.94, p<0.001) and both a later age at onset (odds ratio=1.05, p=0.02) and a shorter duration of illness (odds ratio=0.93, p=0.02) with panic disorder comorbidity. In addition, earlier age at onset inversely correlated with higher social disability (r=-0.12, p=0.048) and longer duration of illness directly correlated with higher disability in work, social and family life (r=0.14, p=0.017; r=0.13, p=0.035; r=0.14, p=0.02). The findings from the present large, multicenter study indicate early onset and long duration of illness as overall negative predictors of long-term outcome in OCD.
Neuropharmacological dissection of placebo analgesia: expectation-activated opioid systems versus conditioning-activated specific subsystems.

We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain. Different types of placebo analgesic responses were evoked by means of cognitive expectation cues, drug conditioning, or a combination of both. Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine. Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone. Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone. Morphine conditioning alone (without expectation cues) induced a naloxone-reversible placebo effect. By contrast, ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially. Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive. Therefore, we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or, otherwise, naloxone-insensitive, depending on the procedure used to evoke the placebo response. These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia, and this balance is crucial for the activation of opioid or nonopioid systems. Expectation triggers endogenous opioids, whereas conditioning activates specific subsystems. In fact, if conditioning is performed with opioids, placebo analgesia is mediated via opioid receptors, if conditioning is performed with nonopioid drugs, other nonopioid mechanisms result to be involved.
Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis.

Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs).



In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500.



Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men.



Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.
A rapid outcomes ascertainment system improves the quality of prognostic and pharmacogenetic outcomes from observational studies.

Case-control and observational studies are popular choices for evaluating molecular prognostic/pharmacogenetic outcomes, but data quality is rarely tested. Using clinical trial and epidemiologic methods, we assessed the quality of prognostic and outcomes data obtainable from a large case-control study of lung cancer.



We developed an explicit algorithm (set of standard operating procedures forming a rapid outcomes ascertainment system) that encompassed multiple tests of quality assurance, and quality of data for a range of prognostic and outcomes variables, in several cancers, across several centers and two countries were assessed. Based on these assessments, the algorithm was revised and physicians' clinical practice changed. We reevaluated the quality of outcomes after these revisions.



Development of an algorithm with internal quality controls showed specific patterns of data collection errors, which were fixable. Although the major discrepancy rate in retrospective data collection was low (0.6%) when compared with external validated sources, complete data were found in <50% of patients for treatment response rate, toxicity, and documentation of patient palliative symptoms. Prospective data collection and changes to clinical practice led to significantly improved data quality. Complete data on response rate increased from 45% to 76% (P = 0.01, Fisher's exact test), for toxicity data, from 26% to 56% (P = 0.02), and for palliative symptoms, from 25% to 70% (P < 0.05), in one large lung cancer case-control study.



Observational studies can be a useful source for studying molecular prognostic and pharmacogenetic outcomes. A rapid outcomes ascertainment system with strict ongoing quality control measures is an excellent means of monitoring key variables.
Opportunities for improving medication use and monitoring in gout.

To study patterns and predictors of medication use and laboratory monitoring in gout.



In a cohort of veterans with a diagnosis of gout prescribed allopurinol, colchicine or probenecid, quality of care was assessed by examining adherence to the following evidence-based recommendations: (1) whether patients starting a new allopurinol prescription (a) received continuous allopurinol, (b) received colchicine prophylaxis, (c) achieved the target uric acid level of <or=6 mg/dl; and (2) whether doses were adjusted for renal insufficiency. The association of sociodemographic characteristics, healthcare utilisation and comorbidity with the recommendations was examined by logistic/Poisson regression.



Of the 643 patients with gout receiving a new allopurinol prescription, 297 (46%) received continuous allopurinol, 66 (10%) received colchicine prophylaxis and 126 (20%) reached the target uric acid level of <or=6 mg/dl. During episodes of renal insufficiency, appropriate dose reduction/discontinuation of probenecid was done in 24/31 episodes (77%) and of colchicine in 36/52 episodes (69%). Multivariable regression showed that higher outpatient utilisation, more rheumatology care and lower comorbidity were associated with better quality of care; more rheumatology clinic or primary care visits were associated with less frequent allopurinol discontinuation; more total outpatient visit days or most frequent visits to a rheumatology clinic were associated with a higher likelihood of receiving colchicine prophylaxis; and a lower Charlson Comorbidity Index or more outpatient visit days were associated with higher odds of reaching the target uric acid level of <or=6 mg/dl.



Important variations were found in patterns of medication use and monitoring in patients with gout with suboptimal care. A concerted effort is needed to improve the overall care of gout.
Advanced glycation endproducts and their receptor in different body compartments in COPD.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic airway inflammation and emphysema, and is caused by exposure to noxious particles or gases, e.g. cigarette smoke. Smoking and oxidative stress lead to accelerated formation and accumulation of advanced glycation end products (AGEs), causing local tissue damage either directly or by binding the receptor for AGEs (RAGE). This study assessed the association of AGEs or RAGE in plasma, sputum, bronchial biopsies and skin with COPD and lung function, and their variance between these body compartments.



Healthy smoking and never-smoking controls (n = 191) and COPD patients (n = 97, GOLD stage I-IV) were included. SAF) was measured in the skin, AGEs (pentosidine, CML and CEL) and sRAGE in blood and sputum by ELISA, and in bronchial biopsies by immunohistochemistry. eQTL analysis was performed in bronchial biopsies.



COPD patients showed higher SAF values and lower plasma sRAGE levels compared to controls and these values associated with decreased lung function (p <0.001; adjusting for relevant covariates). Lower plasma sRAGE levels significantly and independently predicted higher SAF values (p < 0.001). One SNP (rs2071278) was identified within a region of 50 kB flanking the AGER gene, which was associated with the gene and protein expression levels of AGER and another SNP (rs2071278) which was associated with the accumulation of AGEs in the skin.



In COPD, AGEs accumulate differentially in body compartments, i.e. they accumulate in the skin, but not in plasma, sputum and bronchial biopsies. The association between lower sRAGE and higher SAF levels supports the hypothesis that the protective mechanism of sRAGE as a decoy-receptor is impaired in COPD.
Phase I evaluation and pharmacokinetic study of pyrazine-2-diazohydroxide administered as a single bolus intravenous injection in patients with advanced solid tumors.

The sodium salt of pyrazine-2-diazohydroxide (PZDH; NSC 361456) was identified as an active congener of the antitumor lead pyridine-2-diazotate with enhanced chemical stability under physiological conditions. In a phase I trial of PZDH administered as a single i.v. bolus injection, 19 patients with refractory solid tumors received 44 courses of therapy at dose levels ranging from 50 to 350 mg/m2. No objective responses to PZDH were noted. Myelosuppression characterized by prolonged, delayed onset leukopenia and thrombocytopenia was the dose limiting toxicity. A maximum tolerated dose of 350 mg/m2 was identified for this treatment schedule. Nonhematological toxicity was limited to severe nausea and vomiting, experienced by all patients treated at the lower doses, although reasonably well controlled when antiemetics were given prior to chemotherapy. The plasma pharmacokinetics of PZDH was evaluated following a single course of therapy in 16 patients. Drug levels were monitored using a specific capillary gas chromatographic assay with a 1-ng/ml lower limit of quantitation. In patients treated with doses greater than 50 mg/m2, the concentration of PZDH in plasma declined in a distinctly triexponential manner and remained above 1.5 ng/ml for at least 8 h. However, the initial decay phase, characterized by a harmonic mean half-life of 3.9 +/- 3.5 (SD) min (range, 2.2-6.3 min), was the primary determinant of drug disposition, as indicated by its 85.5-93.1% contribution to the area under the plasma concentration-time profiles from time zero to infinity. The harmonic mean terminal half-life increased with escalations in dose from 2.7 +/- 0.8 h (n = 2) at 100 mg/m2 to 8.5 +/- 3.0 h at 350 mg/m2 (n = 6). Total plasma drug clearance was very similar in patients treated with doses of 50-250 mg/m2, exhibiting a mean value of 42.5 +/- 7.8 liters/h/m2 (n = 10); however, it was significantly lower at the 350 mg/m2 dose level, 27.2 +/- 6.6 liters/h/m2 (n = 6; P < 0.002), denoting a departure from linear pharmacokinetic behavior. The rather low steady state apparent volume of distribution, which ranged from 6.0 +/- 1.5 (50 mg/m2, n = 2) to 12.7 +/- 8.0 (350 mg/m2, n = 6) liters/m2, was indicative of limited distribution of the drug into body tissue. The absence of objective antitumor effects should not discourage continued evaluation of PZDH against solid tumors selected for probable sensitivity as indicated by preclinical testing. A dose of 250 mg/m2 on a single i.v. bolus schedule is recommended for these phase II trials.
Early Clinical Outcomes After Transcatheter Aortic Valve Replacement Using a Novel Self-Expanding Bioprosthesis in Patients With Severe Aortic Stenosis Who Are Suboptimal for Surgery: Results of the Evolut R U.S. Study.

This study sought to evaluate this transcatheter aortic valve (TAV) bioprosthesis in patients who are poorly suitable for surgical aortic valve (AV) replacement.



A novel self-expandable TAV bioprosthesis was designed to provide a low-profile delivery system, conformable annular sealing, and the ability to resheath and reposition during deployment.



The Evolut R U.S. study included 241 patients with severe aortic stenosis who were deemed to be at least high risk for surgery treated at 23 clinical sites in the United States. Clinical outcomes at 30 days were evaluated using Valve Academic Research Consortium-2 criteria. An independent echocardiography laboratory was used to evaluate hemodynamic outcomes.



Patients were elderly (83.3 ± 7.2 years of age) and had high surgical risk (Society of Thoracic Surgeons predicted risk of mortality of 7.4 ± 3.4%). The majority of patients (89.5%) were treated by iliofemoral access. Resheathing or recapturing was performed in 22.6% of patients; more than 1 valve was required in 3 patients (1.3%). The 30-day outcomes included all-cause mortality (2.5%), disabling stroke (3.3%), major vascular complications (7.5%), life-threatening or disabling bleeding (7.1%), and new permanent pacemaker (16.4%). AV hemodynamics were markedly improved at 30 days: the mean AV gradient was reduced from 48.2 ± 13.0 mm Hg to 7.8 ± 3.1 mm Hg (p < 0.001) and AV area increased from 0.6 ± 0.2 cm2 to 1.9 ± 0.5 cm2 (p < 0.001). Moderate residual paravalvular leak was identified in 5.3% of patients.



We conclude that this novel self-expanding TAV bioprosthesis is safe and effective for the treatment of patients with severe aortic stenosis who are suboptimal for surgery. (Medtronic CoreValve Evolut R U.S. Clinical Study; NCT02207569).
Food label education does not reduce sodium intake in people with type 2 diabetes mellitus. A randomised controlled trial

Sodium intake is high in people with type 2 diabetes (T2DM). The aim of this study was to investigate whether urinary sodium excretion can be reduced by educating people with T2DM to read food labels and choose low sodium products.



In a 3 month randomised controlled trial, 78 men (n=49) and women (n=29) with T2DM were recruited from a Diabetes Centre at a University teaching hospital. The intervention group was educated in a single session to use the nutrition information panel on food labels to choose products which complied with the Food Standards Australia New Zealand (FSANZ) guideline of <120 mg sodium/100 g food. The control group continued on their usual diet. The primary outcome measure was 24h urinary sodium excretion which was performed at baseline and 3 months. Data was analysed using repeated measures analysis of variance, independent samples t-test and Pearson's correlations.



At 3 months mean urinary sodium excretion was unchanged in the intervention (174±13 mmol/24 h and 175±13 mmol/24 h) and control group (167±15mmol/24h and 161±13 mmol/24 h), and there was no between group difference (p>0.05).



Sodium excretion was not reduced following the label reading education provided to this group of people with T2DM.