nils-herrmann/clean_scirepeval huggingface dataset:
Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain.

The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity.



In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days.



In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, -0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13).



Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.
Rifaximin therapy for patients with irritable bowel syndrome without constipation.

Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.



In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.



Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.



Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools.
Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia

Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities.



The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts.



Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%).



DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms--the sensory profile--is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies.
Mesothelin expression is associated with poor outcomes in breast cancer

Mesothelin is a potential therapeutic target and prognostic marker in breast cancer. However, results on its prognostic value in breast cancer have been equivocal and warranted further evaluation. We analyzed clinical data from two breast cancer patient cohorts comprising of 141 patients treated at our institution (discovery cohort) and 844 patients from The Cancer Genome Atlas (TCGA) (validation cohort). Mesothelin expression was quantified by immunohistochemistry or by RNA transcript levels as measured by whole-transcriptome sequencing in the discovery and validation cohorts respectively. Univariate analyses of data from the discovery cohort demonstrated that tumor size [hazard ratio (HR) = 1.30, 95 % confidence interval (CI) 1.11–1.51], positive (+) axillary lymph nodes (HR = 3.34; 95 % CI 1.51–7.39), and mesothelin expression (HR = 2.03; 95 % CI 1.10–3.74) were associated with disease-specific survival. Multivariate analyses demonstrated that mesothelin expression was significantly associated with worse survival (HR = 3.06, 95 % CI 1.40–6.68) after adjusting for (+) axillary lymph nodes and tumor size. Using TCGA cohort as validation dataset, mesothelin-expressing tumors were indeed significantly associated with worse overall survival with HR = 1.46; 95 % CI 1.05–2.03 and HR = 1.69; 95 % CI 1.17–2.42 in univariate and multivariate analyses respectively. Our results suggest that mesothelin is a prognostic breast tumor marker whose expression is highly enriched in triple negative breast cancer (TNBC) tumors. As there is no existing targeted therapy for TNBC, mesothelin may be a promising drug target for TNBC. Future work is needed to evaluate the efficacy of mesothelin directed targeted therapy in the treatment of breast cancer.
Cardiorespiratory response to exercise after renal sympathetic denervation in patients with resistant hypertension.

This study sought to investigate the effects of interventional renal sympathetic denervation (RD) on cardiorespiratory response to exercise.



RD reduces blood pressure at rest in patients with resistant hypertension.



We enrolled 46 patients with therapy-resistant hypertension as extended investigation of the Symplicity HTN-2 (Renal Denervation With Uncontrolled Hypertension) trial. Thirty-seven patients underwent bilateral RD and 9 patients were assigned to the control group. Cardiopulmonary exercise tests were performed at baseline and 3-month follow-up.



In the RD group, compared with baseline examination, blood pressure at rest and at maximum exercise after 3 months was significantly reduced by 31 ± 13/9 ± 13 mm Hg (p < 0.0001) and by 21 ± 20/5 ± 14 mm Hg (p < 0.0001), respectively. Achieved work rate increased by 5 ± 13 W (p = 0.029) whereas peak oxygen uptake remained unchanged. Blood pressure 2 min after exercise was significantly reduced by 29 ± 17/8 ± 15 mm Hg (p < 0.001 for systolic blood pressure; p = 0.002 for diastolic blood pressure). Heart rate at rest decreased after RD (4 ± 11 beats/min; p = 0.028), whereas maximum heart rate and heart rate increase during exercise were not different. Heart rate recovery improved significantly by 4 ± 7 beats/min after renal denervation (p = 0.009). In the control group, there were no significant changes in blood pressure, heart rate, maximum work rate, or ventilatory parameters after 3 months.



RD reduces blood pressure during exercise without compromising chronotropic competence in patients with resistant hypertension. Heart rate at rest decreased and heart rate recovery improved after the procedure.
Is a targeted and planned GP intervention effective in cardiovascular disease prevention? A randomized controlled trial

The optimal intensity and duration of the intervention to achieve sustained risk reduction in patients at high and very high cardiovascular (CV) risk still need to be established. The aim of this study was to evaluate the impact of general practitioner's (GP's) systematic and planned intervention on total CV risk reduction and a change in individual CV risk factors.



This was a cluster-randomized trial (ISRCTN31857696) including 64 practices and 3245 patients aged ≥40. The participating GPs and their examinees were randomized into an intervention or to a control group (standard care). Intervention group practitioners followed up their examinees during 1, 3, 6, 12, and 18 months. The main outcome measures were change in proportion of patients with low, moderate, high, and very high CV risk, and change in individual CV risk factors from the first to the second registration.



The proportion of patients with very high CV risk was lower in the intervention group, the same as of patients with high blood pressure, total and LDL cholesterol, and increased intake of alcohol. The mean systolic (-1.49 mmHg) and diastolic (-1.57 mmHg) blood pressure, triglycerides (-0.18 mmol/L), body mass index (-0.22), and waist (-0.4 cm) and hip circumference (-1.08 cm) was reduced significantly in the intervention group. There was no additional impact in the intervention group of other tested CV risk factors.



Systematic and planned GP's intervention in CVD prevention reduces the number of patients with very high total CV risk and influences a change in lifestyle habits.
Translation, cultural adaptation and reproducibility of the Oxford Shoulder Score questionnaire for Brazil, among patients with rheumatoid arthritis.

Although shoulder questionnaires validated for Brazil do exist, none of them are aimed at populations with rheumatic disease. We believe that the Oxford Shoulder Score (OSS) may be useful in this population. The objective of this study was to translate the OSS, adapt it to Brazilian culture and test its reproducibility.  Validation study conducted in university outpatient clinics.  The OSS was translated into Portuguese by two English teachers and was then retranslated into English by two native English teachers. These translations were reviewed by a committee to establish the version of OSS-Brazil to be administered to 30 patients with rheumatoid arthritis (RA) and shoulder pain, in order to test the cultural adaptation. The validity and reproducibility was tested among another 30 patients with RA and shoulder pain, of both genders and aged 18 to 65 years. The internal consistency and reproducibility were analyzed. The following instruments were evaluated: OSS-Brazil; a numerical scale for shoulder pain; DASH; HAQ and SF-36.  The internal consistency was 0.957 and the intra and inter-rater reproducibility was 0.917 and 0.861, respectively. A high level of correlation was found between OSS-Brazil and the following: HAQ (-0.663), DASH (-0.731) and the SF-36 domains of functional capacity (0.589), physical aspects (0.507), pain (0.624), general state of health (0.444), vitality (0.634) and mental health (0.578).  OSS-Brazil was successfully translated and adapted, and this version exhibited good internal consistency, reliability and construct validity.
Outcome of totally implantable venous-access port-related infections.

We aimed to study factors associated with the outcome of totally implantable venous-access port (TIVAP)-related infections.



We conducted a prospective and observational cohort study of patients presenting with a solid tumor and TIVAP-related infection.



We monitored 97 patients for 12weeks. The case fatality at 12weeks was high (54%). Factors associated with case fatality at week 12 included patients' underlying cancer (metastatic status, parenteral nutrition, home care). Infectious complications (local abscess, hematogenous metastases, infection recurrence, septic shock) were frequently observed (48%). The delay in TIVAP removal was the only variable significantly associated with complications (TIVAP removed more than a week after removal decision, P=0.001, or more than a week after onset of clinical symptoms, P=0.002). On the basis of IDSA guidelines, we also observed that 25% of patients whose TIVAP had been removed could have benefited from a conservative treatment. Infections occurring within a month of TIVAP implantation were significantly associated with a Staphylococcus aureus infection (P=0.008).



Case fatality is high in this population of patients due to the poor status of patients. TIVAP should be promptly removed when appropriate but the patient's poor status might delay or even prevent its removal. Some patients could instead benefit from a conservative treatment. There is currently no recommendation for this therapeutic option and studies are needed to clarify its efficacy. Additionally, infection occurring within a month of TIVAP insertion could be a supplementary criterion for removal as S. aureus is associated with early infection.
Cluster randomised trial of the effectiveness of motivational interviewing for universal prevention.

The prevention of initiation of tobacco, alcohol and drug use is a major societal challenge, for which the existing research literature is generally disappointing. This study aimed to test the effectiveness of adaptation of Motivational Interviewing (MI) for universal prevention purposes, i.e. to prevent initiation of new substance use among non-users, and to reduce risks among existing users.



Cluster randomised trial with 416 students aged 16-19 years old recruited in 12 London Further Education colleges without regard to substance use status. Individualised MI was compared with standard practice classroom-delivered Drug Awareness intervention, both delivered over the course of one lesson. Prevalence, initiation and cessation rates for the 3 target behaviours of cigarette smoking, alcohol consumption and cannabis use, along with reductions in use and harm indicators after both 3 and 12 months were assessed.



This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome. Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition.



This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study.
Study in Parkinson disease of exercise (SPARX): translating high-intensity exercise from animals to humans.

A burgeoning literature suggests that exercise has a therapeutic benefit in persons with Parkinson disease (PD) and in animal models of PD, especially when animals exercise at high intensity. If exercise is to be prescribed as "first-line" or "add-on" therapy in patients with PD, we must demonstrate its efficacy and dose-response effects through testing phases similar to those used in the testing of pharmacologic agents. The SPARX Trial is a multicenter, randomized, controlled, single-blinded, Phase II study that we designed to test the feasibility of using high-intensity exercise to modify symptoms of PD and to simultaneously test the nonfutility of achieving a prespecified change in patients' motor scores on the Unified Parkinson Disease Rating Scale (UPDRS). The trial began in May 2102 and is in the process of screening, enrolling, and randomly assigning 126 patients with early-stage PD to 1 of 3 groups: usual care (wait-listed controls), moderate-intensity exercise (4 days/week at 60%-65% maximal heart rate [HRmax]), or high-intensity exercise (4 days/week at 80%-85% HRmax). At 6-month follow-up, the trial is randomly reassigning usual care participants to a moderate-intensity or high-intensity exercise group for the remaining 6 months. The goals of the Phase II trial are to determine if participants can exercise at moderate and high intensities; to determine if either exercise yields benefits consistent with meaningful clinical change (nonfutility); and to document safety and attrition. The advantage of using a non-futility approach allows us to efficiently determine if moderate- or high-intensity exercise warrants further large-scale investigation in PD.
Five-year clinical course associated with DSM-IV alcohol abuse or dependence in a large group of men and women.

The prognostic validity of the DSM-IV diagnoses of alcohol abuse and alcohol dependence was evaluated by examining the 5-year clinical course associated with those diagnoses in a large group of predominantly blue-collar men and women.



Personal semistructured interviews were carried out 5 years after an initial evaluation with 1,346 (75%) of the approximately 1,800 men and women participating in the Collaborative Study on the Genetics of Alcoholism who were eligible for follow-up.



About two-thirds of the 298 subjects with DSM-IV alcohol dependence at baseline maintained that diagnosis during the 5-year study period. Fifty-five percent of the 288 subjects with DSM-IV alcohol abuse at baseline continued to meet one or more of the 11 DSM-IV abuse/dependence criteria, and 3.5% went on to meet the criteria for dependence at follow-up. Among the 760 subjects with no alcohol diagnosis at baseline, 2.5% met the criteria for alcohol dependence and 12.8% for alcohol abuse at follow-up. Baseline characteristics that predicted the occurrence of any of the 11 DSM-IV abuse/dependence criteria during the 5-year interval included male gender, lack of marital stability, presence of several of the criteria for dependence, and history of illicit drug use.



The data suggest that over 5 years the DSM-IV diagnosis of alcohol dependence predicts a chronic disorder with a relatively severe course, while DSM-IV alcohol abuse predicts a less persistent, milder disorder that does not usually progress to dependence.
The current state of introduction of HPV vaccination into national immunisation schedules in Europe: results of the VENICE 2008 survey.

Three surveys have been undertaken in European Union (EU) member states since January 2007, within the European Commission funded Vaccine European New Integrated Collaboration Effort (VENICE) project, to monitor the decision status regarding the introduction of human papillomavirus (HPV) vaccination into national immunisation schedules. A web-based questionnaire was developed and completed online by the 28 countries participating in VENICE. According to the last update (31st December 2008), 15 countries have decided to introduce HPV vaccination into their national immunisation schedule, while another six have started the decision-making process with a recommendation favouring introduction. Varying target populations have been selected by the countries which have introduced vaccination. The number of countries which have made a decision or recommendation has increased from 12 to 21 between October 2007 and December 2008. This survey demonstrates the rapidly evolving nature of HPV vaccine introduction in Europe. A further update should be available in the second half of 2009.
Alcohol intake increases high-grade prostate cancer risk among men taking dutasteride in the REDUCE trial.

Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5α-reductase inhibitor (5-ARI) finasteride.



Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride.



Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PCa status at 2 yr and 4 yr of follow-up.



Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa.



Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking dutasteride. In contrast, men randomized to dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa (p=0.01). Among alcohol abstainers, dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38-0.90), but dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67-1.45).



Alcohol consumption negated a protective association between dutasteride and high-grade PCa.



We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.