nils-herrmann/clean_scirepeval huggingface dataset:
Health effect of the New Nordic Diet in adults with increased waist circumference: a 6-mo randomized controlled trial.

The regional Mediterranean Diet has been associated with lower risk of disease.



We tested the health effects of the New Nordic Diet (NND), which is a gastronomically driven regional, organic, and environmentally friendly diet, in a carefully controlled but free-living setting.



A total of 181 centrally obese men and women, with a mean (range) age of 42 y (20-66 y), body mass index (in kg/m(2)) of 30.2 (22.6-47.3), and waist circumference of 100 cm (80-138 cm) were randomly assigned to receive either the NND (high in fruit, vegetables, whole grains, and fish) or an average Danish diet (ADD) for 26 wk. Participants received cookbooks and all foods ad libitum and free of charge by using a shop model. The primary endpoint was the weight change analyzed by both completer and intention-to-treat analyses.



A total of 147 subjects [81% (NND 81%; ADD 82%)] completed the intervention. A high dietary compliance was achieved, with significant differences in dietary intakes between groups. The mean (±SEM) weight change was -4.7 ± 0.5 kg for the NND compared with -1.5 ± 0.5 kg for the ADD (adjusted difference: -3.2 kg; 95% CI: -4.6, -1.8 kg; P < 0.001) for the completer analysis, and the difference was -3.0 kg (95% CI: -4.0, -2.1 kg) for the intention-to-treat analysis. The NND produced greater reductions in systolic blood pressure (adjusted difference: -5.1 mm Hg; 95% CI: -8.2, -2.1 mm Hg) and diastolic blood pressure (adjusted difference: -3.2 mm Hg; 95% CI: -5.7, -0.8 mm Hg) than did the ADD.



An ad libitum NND produces weight loss and blood pressure reduction in centrally obese individuals.
Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit

Cholinesterase (ChE) inhibition represents the most efficacious treatment approach for Alzheimer's disease (AD) to date. This multiple-dose study has examined the relationship between inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in the cerebrospinal fluid (CSF) and cognitive change (measured by the Computerised Neuropsychological Test Battery [CNTB]) following administration of the ChE inhibitor, rivastigmine (Exelon®). In 18 patients with mild to moderate AD, CNTB scores, activities of AChE and BuChE in the CSF, and plasma BuChE activity were determined prior to treatment with rivastigmine. Doses of rivastigmine were then titrated (1 mg b.i.d./week) to final doses of 1, 2, 3, 4, 5 or 6 mg b.i.d. (n = 3 per dose). Following treatment with the target dose of rivastigmine for at least 3 days, CNTB scores were re-determined. CSF samples were continuously collected together with plasma samples prior to and for 12 hours after the final dose of rivastigmine, and AChE and BuChE activities determined. AChE in CSF and BuChE in plasma were dose-dependently inhibited by rivastigmine treatment. The inhibition of BuChE in CSF was not clearly dose-dependent. A statistically significant correlation was observed between the change in CNTB summary score and inhibition of AChE activity (r =−0.56, p < 0.05) and BuChE activity (r =−0.65, p < 0.01) in CSF. Improvement in speed-, attention- and memory-related subtests of the CNTB correlated significantly with inhibition of BuChE but not AChE activity in CSF. Weak or absent correlation with change in cognitive performance was noted for inhibition of plasma BuChE. These results indicate that cognitive improvement with rivastigmine in AD is associated with central inhibition of ChEs and support a role for central BuChE in addition to AChE inhibition in modulating cholinergic function in AD.
Elevated rates of intracerebral hemorrhage in individuals from a US clinical care HIV cohort.

To compare rates of intracerebral hemorrhage (ICH) in HIV-infected and uninfected individuals in a large clinical care cohort and to assess risk factors associated with ICH.



We identified incident ICH in HIV-infected and uninfected control cohorts from the Partners Health Care system using ICD-9-CM codes. We constructed Cox proportional hazards models to estimate adjusted hazard ratios for HIV infection and other predictors of ICH.



The incidence rate of ICH was 2.29 per 1,000 person-years in HIV-infected individuals compared with 1.23 per 1,000 person-years in uninfected individuals, with an unadjusted incidence rate ratio of 1.85 (95% confidence interval 1.37-2.47, p < 0.001). In a multivariable model, HIV infection was independently associated with a higher hazard of ICH, although its effect diminished with increasing age. Female sex was associated with a lower hazard of ICH in the uninfected cohort but not in the HIV cohort. CD4 count <200 × 10(6) cells/L and anticoagulant use were predictive of ICH.



HIV infection conferred an increased adjusted hazard of ICH, which was more pronounced in young patients and in women.
Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a Phase III Trial of the Gynecologic Cancer Intergroup.

To determine if incorporation of an additional cytotoxic agent improves overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma who receive carboplatin and paclitaxel.



Women with stages III to IV disease were stratified by coordinating center, maximal diameter of residual tumor, and intent for interval cytoreduction and were then randomly assigned among five arms that incorporated gemcitabine, methoxypolyethylene glycosylated liposomal doxorubicin, or topotecan compared with carboplatin and paclitaxel. The primary end point was OS and was determined by pairwise comparison to the reference arm, with a 90% chance of detecting a true hazard ratio of 1.33 that limited type I error to 5% (two-tail) for the four comparisons.



Accrual exceeded 1,200 patients per year. An event-triggered interim analysis occurred after 272 events on the reference arm, and the study closed with 4,312 women enrolled. Arms were well balanced for demographic and prognostic factors, and 79% of patients completed eight cycles of therapy. There were no improvements in either PFS or OS associated with any experimental regimen. Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup.



Compared with standard paclitaxel and carboplatin, addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction. Dual-stage, multiarm, phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm. The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC.
A polysomnographic study in young psychiatric inpatients: major depression, anorexia nervosa, bulimia nervosa.

The baseline EEG sleep patterns of 10 young depressed patients, 20 patients with anorexia nervosa, 10 patients with bulimia nervosa, and 10 healthy subjects were found to be indistinguishable, except for an increased REM density in the depressed patients. In eating disorder patients, a concomitant major depressive episode had no influence on EEG sleep. The results of the cholinergic REM sleep induction test revealed a significantly faster induction of REM sleep in the depressed patients when compared with the eating disorder patients and the control subjects. This indicates a subthreshold hypersensitivity of the REM sleep triggering cholinergic transmitter system in depressives, but not in eating disorder patients.
A Randomized, Double-Blind, Placebo-Controlled Trial: The Efficacy of Multispecies Probiotic Supplementation in Alleviating Symptoms of Irritable Bowel Syndrome Associated with Constipation 

The efficacy of supplementation treatment with two multispecies probiotic formulates on subjects diagnosed with IBS-C and the assessment of their gut microbiota were investigated.  A randomized, double-blind, three-arm parallel group trial was carried out on 150 IBS-C subjects divided into three groups (F_1, F_2, and F_3). Each group received a daily oral administration of probiotic mixtures (for 60 days) F_1 or F_2 or placebo F_3, respectively. Fecal microbiological analyses were performed by species-specific qPCR to assess the different amount of probiotics.  The percentage of responders for each symptom was higher in the probiotic groups when compared to placebo group during the treatment period (t60) and was maintained quite similar during the follow-up period (t90). Fecal analysis demonstrated that probiotics of the formulations increased during the times of treatment only in fecal DNA from subjects treated with F_1 and F_2 and not with F_3, and the same level was maintained during the follow-up period.  Multispecies probiotic supplementations are effective in IBS-C subjects and induce a different assessment in the composition of intestinal microbiota. This clinical study is registered with the clinical study registration number ISRCTN15032219.
Effects of a long-term aerobic exercise intervention on institutionalized patients with dementia.

Long-term interventions aimed at analyzing the impact of physical exercise on important health markers in institutionalized individuals with dementia are relatively scarce. This longitudinal study intends to identify the effects of a physical exercise program on cognitive decline, memory, depression, functional dependence and neuropsychiatric disturbances in institutionalized individuals with dementia.



Randomized controlled trial.



Homecare residents with dementia were assigned to an exercise (EG) or to a control group (CG). Participants in the EG cycled for at least 15min daily during 15 months, while those in the CG performed alternative sedentary recreational activities. The Mini-Mental State Examination (MEC), the Timed "Up & Go" Test, the Neuropsychiatric Inventory, the Katz Index, the Cornell Scale for Depression in Dementia and the Fuld Object Memory Evaluation were administered before and after the intervention.



Sixty-three individuals in the CG and 51 individuals in the EG completed the intervention. A statistically significant decline in cognitive function was observed in individuals included in the CG (p=0.015), while a slight improvement was observed in those included in the EG. Significant improvement was observed in the neuropsychiatric symptoms (p=0.020), memory function (p=0.028) and functional mobility (p=0.043) among those who exercised. Exercise seemed to have a greater effect in those suffering from severe cognitive impairment.



This study provides evidence that aerobic physical exercise has a significant impact on improving cognitive functioning, behavior, and functional mobility in institutionalized individuals with dementia.
Placebo treatment in acute stroke trials : benefit or harm to patients?

Some stroke patients and their families express reservations about participating in trials of experimental therapies for acute stroke. Among many reasons given for this is the concern that by participating, patients may be deprived of some component of routine care. We sought to determine the effect on outcome of participating in a clinical stroke trial while being treated with placebo.



Prospective clinical information was collected for all patients admitted with acute ischemic stroke between July 1995 and July 1996. A subgroup of these patients was enrolled in a clinical trial of acute stroke therapy and had been randomly assigned to the placebo group. The control group was selected from concurrent stroke patients who were not enrolled in any clinical trial. The National Institutes of Health Stroke Scale (NIHSS) was performed on admission and on day 7 after admission. The Glasgow Outcome Scale (GOS) was also performed at discharge. Stroke severity was classified as "severe" if NIHSS was >/=9 or GOS >/=3. Group comparisons were performed with chi(2) tests.



One hundred twenty-six patients were evaluated. Forty-seven were placebo patients, and 79 were selected as control subjects. There were no significant differences between the groups with respect to age, sex, hematocrit, blood glucose level, history of hypertension, diabetes, smoking, or initial NIHSS. In addition, there was no difference between groups in terms of the frequency of baseline stroke subtype. Among our controls, 55 patients (70%) were on antithrombotic treatment during hospitalization, whereas none of our placebo patients were on any antithrombotic treatment. For the GOS at follow-up, a good outcome was attained by 76% of the control subjects and 72% of placebo patients (not significant). A severe NIHSS (>9) at follow-up, however, was documented in 15% of controls and 59% of placebo patients (P<0.001). There was a trend toward a higher ("worse") mean follow-up NIHSS among placebo patients (mean NIHSS, 11) versus controls (mean NIHSS, 6) (P=0.09).



Patients enrolled in the placebo arms of some acute clinical stroke trials have similar functional outcomes but more severe neurological deficits at 1 week than did a control group. These findings might be partially explained by the withholding of antithrombotic medication and the exclusion criteria inherent in most trials. Vigilance is required to ensure that all patients participating in stroke studies be guaranteed optimal known medical therapy.
Long Term Effects on Risk Factors for Cardiovascular Disease after 12-Months of Aerobic Exercise Intervention - A Worksite RCT among Cleaners

Occupational groups exposed to high occupational physical activity have an increased risk for cardiovascular disease (CVD). This may be explained by the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces the relative aerobic workload. Thus, the aim was to evaluate the 12-months effects of worksite aerobic exercise on risk factors for CVD among cleaners.



One hundred and sixteen cleaners aged 18-65 years were randomized to a group performing aerobic exercise and a reference group receiving lectures. Outcomes were collected at baseline and after 12-months. A repeated measures 2×2 multi-adjusted mixed-model design was applied to compare the between-group differences using intention-to-treat analysis.



Between-group differences (p<0.05) were found favouring the aerobic exercise group: cardiorespiratory fitness 2.15 (SE 1.03) mlO2/min/kg, aerobic workload -2.15 (SE 1.06) %HRR, resting HR -5.31 (SE 1.61) beats/min, high sensitive C-reactive protein -0.65 (SE 0.24) μg/ml. The blood pressure was unaltered. Stratified analyses on relative aerobic workload at baseline revealed that those with relative aerobic workloads ≥30% of HRR seems to impose a notable adverse effect on resting and ambulatory blood pressure.



This long-term worksite aerobic exercise intervention among cleaners led to several beneficial effects, but also potential adverse effects among those with high relative aerobic workloads.
Prehospital treatment with continuous positive airway pressure in patients with acute respiratory failure: a regional observational study

Patients with acute respiratory failure are at risk of deterioration during prehospital transport. Ventilatory support with continuous positive airway pressure (CPAP) can be initiated in the prehospital setting. The objective of the study is to evaluate adherence to treatment and effectiveness of CPAP as an addition to standard care.



In North Denmark Region, patients with acute respiratory failure, whom paramedics assessed as suffering from acute cardiopulmonary oedema, acute exacerbation of chronic obstructive pulmonary disease or asthma were treated with CPAP using 100 % O2 from 1 March 2014 to 3 May 2015. Adherence to treatment was evaluated by number of adverse events and discontinuation of treatment. Intensive care admissions and mortality were reported in this cohort. Effectiveness was evaluated by changes in peripheral oxygen saturation (SpO2) and respiratory rate during transport and compared to a historical control (non-CPAP) group treated with standard care only. Values were compared by hypothesis testing and linear modelling of SpO2 on arrival at scene and ΔSpO2 stratified according to treatment group.



In fourteen months, 171 patients were treated with CPAP (mean treatment time 35 ± 18 min). Adverse events were reported in 15 patients (9 %), hereof six discontinued CPAP due to hypotension, nausea or worsening dyspnoea. One serious adverse event was reported, a suspected pneumothorax treated adequately by an anaesthesiologist called from a mobile emergency care unit. Among CPAP patients, 45 (27 %) were admitted to an intensive care unit and 24 (14 %) died before hospital discharge. The non-CPAP group consisted of 739 patients. From arrival at scene to arrival at hospital, CPAP patients had a larger increase in SpO2 than non-CPAP patients (87 to 96 % versus 92 to 96 %, p < 0.01) and a larger decrease in respiratory rate (32 to 25 versus 28 to 24 breaths/min, p < 0.01). In a linear model, CPAP was superior to non-CPAP in patients with initial SpO2 ≤90 % (p < 0.05). One CPAP patient (0.6 %) and eight non-CPAP patients (1.1 %) were intubated in the prehospital setting.



The study design reflects the daily prehospital working environment including long transport timesand paramedics educated in treating symptoms of acute respiratory failure, rather than treating one specific diagnosis. The study population was included consecutively and few patients were lost to follow-up. However, the study was too small to allow assessment of any effect of prehospital CPAP on mortality, nor could the effectiveness in specific disease conditions be examined.



In an emergency medical service including physician backup, adherence to CPAP treatment administered by paramedics was high and treatment was effective in patients with acute respiratory failure.
Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment.



AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study).



Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain.



The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease.
Effect of atorvastatin on the incidence of acute kidney injury following valvular heart surgery: a randomized, placebo-controlled trial

Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to reduce acute kidney injury (AKI) after cardiac surgery through their pleiotropic properties. Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery. Two-hundred statin-naïve patients were randomly allocated to receive either statin or placebo. Atorvastatin was administered orally to the statin group according to a dosage schedule (80 mg single dose on the evening prior to surgery; 40 mg on the morning of surgery; three further doses of 40 mg on the evenings of postoperative days 0, 1, and 2). AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria. The incidence of AKI was similar in the statin and control groups (21 vs. 26 %, respectively, p = 0.404). Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups. The statin group required significantly less norepinephrine and vasopressin during surgery, and fewer patients in the statin group required vasopressin. There were no significant differences in postoperative outcomes. Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery.
Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy.

The antibody-drug conjugate trastuzumab-DM1 (T-DM1) combines the biologic activity of trastuzumab with targeted delivery of a potent antimicrotubule agent, DM1, to human epidermal growth factor receptor 2 (HER2)-overexpressing cancer cells. Based on results from a phase I study that showed T-DM1 was well tolerated at the maximum-tolerated dose of 3.6 mg/kg every 3 weeks, with evidence of efficacy, in patients with HER2-positive metastatic breast cancer (MBC) who were previously treated with trastuzumab, we conducted a phase II study to further define the safety and efficacy of T-DM1 in this patient population.



This report describes a single-arm phase II study (TDM4258g) that assessed efficacy and safety of intravenous T-DM1 (3.6 mg/kg every 3 weeks) in patients with HER2-positive MBC who had tumor progression after prior treatment with HER2-directed therapy and who had received prior chemotherapy.



With a follow-up of ≥ 12 months among 112 treated patients, the objective response rate by independent assessment was 25.9% (95% CI, 18.4% to 34.4%). Median duration of response was not reached as a result of insufficient events (lower limit of 95% CI, 6.2 months), and median progression-free survival time was 4.6 months (95% CI, 3.9 to 8.6 months). The response rates were higher among patients with confirmed HER2-positive tumors (immunohistochemistry 3+ or fluorescent in situ hybridization positive) by retrospective central testing (n = 74). Higher response rates were also observed in patients whose tumors expressed ≥ median HER2 levels by quantitative reverse transcriptase polymerase chain reaction for HER2 expression, compared with patients who had less than median HER2 levels. T-DM1 was well tolerated with no dose-limiting cardiotoxicity. Most adverse events (AEs) were grade 1 or 2; the most frequent grade ≥ 3 AEs were hypokalemia (8.9%), thrombocytopenia (8.0%), and fatigue (4.5%).



T-DM1 has robust single-agent activity in patients with heavily pretreated, HER2-positive MBC and is well tolerated at the recommended phase II dose.