nils-herrmann/clean_scirepeval huggingface dataset:
A phase II study of gefitinib in patients with metastatic melanoma.

Gefitinib is an inhibitor of the epidermal growth factor receptor, which is frequently expressed on both choroidal and nonchoroidal melanoma cells. We evaluated the clinical efficacy of gefitinib in patients with metastatic melanoma. Patients with stage IV or unresectable stage III melanoma and Zubrod performance status of less than or equal to 2 were eligible. Previous systemic treatment for metastatic disease was required. The dose of oral gefitinib was 250 mg administered daily, and tumor response was evaluated every 6 weeks. Forty-six patients with nonchoroidal melanoma and six with choroidal melanoma were treated, and 48 were evaluable for response. The median age was 62.5 years. Forty-one patients (79%) had stage M1c disease. There were no drug-related grade 4 or 5 adverse events, and fatigue was the only grade 3 adverse event that occurred in more than 5% of patients. Two patients (4%) had partial responses and 13 patients (27%) had disease stabilization. The two responders had a median duration of response of 10.9 months. The median overall progression-free survival was 1.4 months and the median overall survival was 9.7 months. Among the patients with sufficient tissues obtained before and 6 weeks after starting gefitinib administration, there were no notable trends in the changes of the tumoral expression of p-ERK1/2, p-AKT, PAK1, and serum levels of vascular endothelial growth factor or IL-8 with treatment. We concluded that gefitinib was well tolerated but had minimal clinical efficacy as a single-agent therapy for unselected patients with metastatic melanoma.
Communication and Low Mood (CALM): a randomized controlled trial of behavioural therapy for stroke patients with aphasia

The aim was to evaluate behavioural therapy as a treatment for low mood in people with aphasia.



A randomized controlled trial comparing behavioural therapy plus usual care with a usual care control. Potential participants with aphasia after stroke were screened for the presence of low mood. Those who met the criteria and gave consent were randomly allocated.



Participants were recruited from hospital wards, community rehabilitation, speech and language therapy services and stroke groups.



Of 511 people with aphasia identified, 105 had low mood and were recruited.



Behavioural therapy was offered for up to three months. Outcomes were assessed three and six months after random allocation.



Stroke Aphasic Depression Questionnaire, Visual Analog Mood Scales 'sad' item, and Visual Analogue Self-Esteem Scale.



Participants were aged 29 to 94 years (mean 67.0, SD 13.5) and 66 (63%) were men. Regression analysis showed that at three months, when baseline values and communication impairment were controlled for, group allocation was a significant predictor of the Stroke Aphasic Depression Questionnaire (P < 0.05), visual analogue 'sad' (P = 0.03), and Visual Analogue Self-Esteem Scale (P < 0.01). At six months, group alone was a significant predictor of the Stroke Aphasic Depression Questionnaire (P < 0.05), and remained significant when baseline values were controlled for (P = 0.02). Mean Stroke Aphasic Depression Questionnaire 10-item hospital version scores decreased from baseline to six months by six points in the intervention group as compared with an increase of 1.9 points in the control group.



Behavioural therapy seemed to improve the mood of people with aphasia.
Value of Risk Stratification to Increase the Predictive Validity of HbA1c in Screening for Undiagnosed Diabetes in the US Population

Opportunistic screening using hemoglobin A1c (HbA1c) may improve detection of undiagnosed diabetes but remains controversial. To evaluate the predictive validity of HbA1c as a screening test for undiagnosed diabetes in a risk-stratified sample of the US population. Weighted cross-sectional analysis of diabetes risk factors, HbA1c, and fasting plasma glucose (FPG) in National Health and Nutrition Examination Survey (NHANES), 1999–2004. Six thousand seven hundred and twenty-three NHANES participants from morning examination session, aged ≥18 years and without prior physician-diagnosed diabetes. HbA1c and undiagnosed diabetes defined by FPG ≥ 7.0 mmol/l (126 mg/dl). The estimated prevalence of undiagnosed diabetes in the US population was 2.8% (5.5 million people). HbA1c had strong correlation with undiagnosed diabetes, with an area under the receiver-operating characteristic curve of 0.93. Independent predictors of undiagnosed diabetes were older age, male sex, black race, hypertension, elevated waist circumference, elevated triglycerides, and low high-density lipoprotein cholesterol. We derived a risk score for undiagnosed diabetes and stratified participants into low (0.44% prevalence), moderate (4.1% prevalence), and high (11.1% prevalence) risk subgroups. In moderate and high risk groups, a threshold HbA1c value ≥ 6.1% identified patients requiring confirmatory FPG; HbA1c ≤ 5.4% identified patients for whom diabetes could be reliably excluded. Intermediate HbA1c (5.5–6.0%) may exclude diabetes in moderate, but not high risk groups). Risk stratification improves the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. Although opportunistic screening with HbA1c would improve detection of undiagnosed diabetes, cost-effectiveness studies are needed before implementation of specific screening strategies using HbA1c.
Ultraviolet index and location are important determinants of vitamin D status in people with human immunodeficiency virus.

This study aimed to document the vitamin D status of HIV-infected individuals across a wide latitude range in one country and to examine associated risk factors for low vitamin D. Using data from patients attending four HIV specialist clinics across a wide latitude range in Australia, we constructed logistic regression models to investigate risk factors associated with 25(OH)D < 75 nmol L(-1). 1788 patients were included; 87% were male, 76% Caucasian and 72% on antiretroviral therapy. The proportion with 25(OH)D < 50 nmol L(-1) was 27%, and <75 nmol L(-1) was 54%. Living in Melbourne compared with Cairns (adjusted odds ratio (aOR) 3.30; 95% CI 2.18, 4.99, P < 0.001) and non-Caucasian origin (aOR 2.82, 95% CI 2.12, 3.75, P < 0.001) was associated with an increased risk, while extreme UV index compared with low UV index was associated with a reduced risk (aOR 0.33; 95% CI 0.20, 0.55, P < 0.001) of 25(OH)D < 75 nmol L(-1). In those with biochemistry available (n = 1117), antiretroviral therapy was associated with 25(OH)D < 75 nmol L(-1); however, this association was modified by serum cholesterol status. Location and UV index were the strongest factors associated with 25(OH)D < 75 nmol L(-1). Cholesterol, the product of an alternative steroid pathway with a common precursor steroid, modified the effect of antiretroviral therapy on serum 25(OH)D.
Can a short film impact HIV-related risk and stigma perceptions? Results from an experiment in Abuja, Nigeria.

HIV/AIDS-related stigma is believed to result in negative social consequences for people with the disease and to be a deterrent to HIV serostatus testing. The ability of communicators to change people's stigma perceptions and subsequently impact decisions to test, however, is not well understood. Based on the entertainment-education approach, this article presents the results of a field experiment conducted in Abuja, Nigeria, testing a mediated intervention designed to reduce HIV-related stigma and risk perceptions. The results indicate that the intervention was effective relative to a control in impacting perceptions of the severity of HIV and some stigma-related attitudes, particularly for male participants; and that for this sample, risk and stigma perceptions significantly impact intentions to test for HIV. It also showed that severity perceptions mediated the relationship between viewing the film and testing intent.
Follow-up Cost of Breast Cancer Patients with Localized Disease After Primary Treatment: a Randomized Trial

We studied the cost of follow-up of 472 breast cancer patients without distant metastasis after primary treatment in four different schedules in a randomized trial. The mean follow-up was 4.2 years. The four schedules differed in frequency of follow-up visits (every third or sixth month) and in intensity of diagnostic examinations (routine or on clinical grounds). Neither the frequency of visits nor the intensity of diagnostic examinations had any effect on disease-free or overall survival of patients. The total costs of follow-up, however, were different in the four follow-up schedules and varied between arms per patient from 1050 to 2269€ and per detected recurrence from 4166 to 9149€. Outpatient visits every third month compared to every sixth month and routine examinations in the follow-up of asymptomatic primary breast cancer patients do not improve patient disease-free or overall survival, but increase the costs of follow-up 2.2 times.
Phase I and pharmacological study of a new camptothecin derivative, exatecan mesylate (DX-8951f), infused over 30 minutes every three weeks.

A Phase I study of exatecan, a new water-soluble camptothecin derivative, was conducted to determine the maximum tolerated dose and a recommended dose, according to an internationally standardized core protocol. Pharmacological profiles of lactone and total (lactone + carboxylate) exatecan were also investigated.



Fifteen patients with advanced solid malignancies were treated with 3, 5, and 6.65 mg/m(2) of exatecan infused over 30 min every 3 weeks. Concentrations of lactone, total drug, and a metabolite in plasma and urine were determined during the first course.



Dose-limiting neutropenia and liver dysfunction were observed in two of six patients at 6.65 mg/m(2), but no grade 3 or worse diarrhea was observed. Emesis was moderate, and no grade 3 or worse nausea and vomiting were observed at a recommended dose of 5 mg/m(2), with prophylactic use of granisetron. Pharmacokinetics were linear and had moderate variability; clearances of lactone and total drug were 6.8 +/- 2.8 and 2.1 +/- 1.1 (mean +/- SD) l/h/m(2), respectively. The ratio of lactone concentration to total drug concentration in plasma decreased from 0.81 +/- 0.06 at the end of infusion to 0.15 +/- 0.06 10 h after the infusion. The lactone:total ratio of drug exposure was 0.30 +/- 0.08, ranging from 0.16 to 0.43. Neutropenia was related to the drug exposure of both lactone and total drug.



The recommended dose of exatecan infused over 30 min every 3 weeks is 5 mg/m(2), with a favorable toxicity profile of mild and infrequent diarrhea. Interpatient variability of pharmacokinetics was similar to or smaller than that with other camptothecin derivatives.
Outcomes after Pylorus-preserving Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Trial

The aim of the present study was to compare in a prospective, multicenter trial the results early and late after pylorus-preserving gastrectomy (PPG) versus conventional distal gastrectomy (CDG) with Billroth I anastomosis for early gastric cancer. Eighty-one patients with early gastric cancer were randomized and then underwent either PPG or CDG. Duration of operation, intraoperative blood loss, days until removal of the nasogastric tube, days until start of oral intake, and decrease in body weight were studied as parameters for outcomes early after the surgery. Late results were studied in patients followed for longer than 3 years. Change in body weight, status of oral intake, symptoms suggesting early dumping syndrome, and overall satisfaction were addressed in the questionnaire. The presence of gallstones was examined with ultrasonography. There were no differences in early results between PPG and CDG. The incidence of early dumping syndrome was lower in PPG (8%) than in CDG (33%). Other late results including the incidence of gallstones were not different between the 2 groups. These results indicate that PPG is as safe as CDG and has an advantage in terms of early dumping syndrome.
Efficacy of a Metalloproteinase Inhibitor in Spinal Cord Injured Dogs

Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured cord.
The Imperial College Cambridge Manchester (ICCAM) platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part A: Study description.

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development. Addiction studies typically involve small samples because of recruitment difficulties and attrition. We established the platform in three centres to assess the feasibility of a multisite approach to address these issues. Pharmacological modulation of reward, impulsivity and emotional reactivity were investigated in a monetary incentive delay task, an inhibitory control task, and an evocative images task, using selective antagonists for µ-opioid, dopamine D3 receptor (DRD3) and neurokinin 1 (NK1) receptors (naltrexone, GSK598809, vofopitant/aprepitant), in a placebo-controlled, randomised, crossover design. In two years, 609 scans were performed, with 155 individuals scanned at baseline. Attrition was low and the majority of individuals were sufficiently motivated to complete all five sessions (n=87). We describe herein the study design, main aims, recruitment numbers, sample characteristics, and explain the test hypotheses and anticipated study outputs.
Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression.

Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls.



Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression.



The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004).



This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.
The Protective Effect of Carnitine in Human Diphtheric Myocarditis

Carnitine, an important cofactor in the transport of fatty acids to the interior of cell mitochondria, is depleted in myocardial tissue of guinea pigs submitted to diphtheric toxin administration. Mortality rates were reduced in these animals by supplying exogenous amounts of carnitine. The accumulation of fatty acids in the cytoplasm of human heart cells reported in cases of diphtheria suggests that carnitine might possibly be depleted in human myocardium as well.For the purpose of studying the effect of carnitine administration, 132 diphtheric patients were randomly divided into two groups, one of them (carnitine-treated group, n =73) receiving DL-carnitine, 100 mg/kg/day during 4 days after admission, in addition to routine treatment, which was prescribed for this and the control group (n =59). The presence of myocardial damage was evaluated by clinical, electrocardiographic, radiological, and enzymatic criteria. Carnitine administration resulted in decreased incidence of heart failure (P =0.0475), of pacemaker implants (P =0.0256), and of lethality indexes due to myocarditis (P =0.013). We suggest that carnitine can play an important role in the treatment of diphtheric patients.
Running nurse-led secondary prevention clinics for coronary heart disease in primary care: qualitative study of health professionals' perspectives.

A randomised trial of nurse-led secondary prevention clinics for coronary heart disease resulted in improved secondary prevention and significantly lowered all-cause mortality at 4-year follow-up. This qualitative trial was conducted to explore the experience of health professionals that had been involved in running the clinics.



To identify the barriers and facilitators to establishing secondary prevention clinics for coronary heart disease within primary care.



Semi-structured audiotaped telephone interviews with GPs and nurses involved in running clinics.



A stratified, random sample of 19 urban, suburban, and rural general practices in north-east Scotland.



Semi-structured telephone interviews with 19 GPs and 17 practice-based nurses involved in running nurse-led clinics for the secondary prevention of coronary heart disease.



Eight practices had run clinics continuously and 11 had stopped, with eight subsequently restarting. Participants accounted for these patterns by referring to advantages and disadvantages of the clinics in four areas: patient care, development of nursing skills, team working, and infrastructure. Most practitioners perceived benefits for patients from attending secondary prevention clinics, but some, from small rural practices, thought they were unnecessary. The extended role for nurses was welcomed, but was dependent on motivated staff, appropriate training and support. Clinics relied on, and could enhance, team working, however, some doctors were wary of delegating. With regard to infrastructure, staff shortages (especially nurses) and accommodation were as problematic as lack of funds.



Nurse-led secondary prevention clinics were viewed positively by most healthcare professionals that had been involved in running them, but barriers to their implementation had led most to stop running them at some point. Lack of space and staff shortages are likely to remain ongoing problems, but improvements in funding training and communication within practices could help clinics to be put into practice and sustained.
“Looking back to my family”: Indigenous Australian patients’ experience of hemodialysis

In common with Indigenous populations elsewhere, Indigenous Australians have higher incidence of end-stage kidney disease (ESKD), but lower transplantation rates than their non-Indigenous counterparts. Understanding how the demands of dialysis impact on, and are impacted by, the lives of Indigenous patients may provide important insight into treatment pathways and decision-making.



We conducted semi-structured interviews in 2005-06 with 146 Indigenous and 95 non-Indigenous patients from nine hospital renal wards and 17 associated dialysis centres, which together treat the majority of Indigenous Australian ESKD patients.



Factors influencing treatment experience included: the impacts of late diagnosis; family separations associated with relocating for treatment; the physical and psychosocial demands of hemodialysis; and ineffective communication between health care providers and patients. Although not unique to them, Indigenous patients were more likely to experience the combined effect of all factors.



Social/situational circumstances profoundly affect Indigenous Australian dialysis patients' ability to fully engage with treatment. This may ultimately affect their likelihood of receiving optimal treatment, including transplantation. Areas for improvement include: earlier diagnosis; improved linkages between specialist renal services and primary care in regional settings; more effective communication and patient education; and more systematic, transparent approaches to patient "compliance" in transplant and home dialysis guidelines.