nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy of wrist working splints in patients with rheumatoid arthritis: a randomized controlled study.

To investigate the efficacy of wrist working splints after a period of splinting in patients with rheumatoid arthritis (RA).



We performed a 4-week randomized controlled trial among 33 RA patients with wrist arthritis. Patients were randomly allocated to the splinting group (n = 17) or the control group (n = 16). Patients in the splinting group received a prefabricated wrist working splint and were instructed to use this splint as much as possible during the day. The primary outcome measure was average wrist pain during the past week, measured using a visual analog scale (VAS). Secondary outcome measures were grip strength and functional ability. The latter was measured using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the short version of the Sequential Occupational Dexterity Assessment. Measurements were performed at baseline and after 4 weeks. Performance tests were performed without splint. Differences in change scores between the splinting and the control group were analyzed using analysis of covariance. To indicate the magnitude of the treatment effects, effect sizes were calculated.



A large and highly significant treatment effect on wrist pain was found. VAS pain scores decreased by 32% in the splinting group and increased by 17% in the control group. Small and nonsignificant treatment effects were found with regard to nonsplinted grip strength and functional ability.



Prefabricated wrist working splints are highly effective in reducing wrist pain after 4 weeks of splint wearing in RA patients with wrist arthritis.
Incorporation of a laser range scanner into image-guided liver surgery: surface acquisition, registration, and tracking.

As image guided surgical procedures become increasingly diverse, there will be more scenarios where point-based fiducials cannot be accurately localized for registration and rigid body assumptions no longer hold. As a result, procedures will rely more frequently on anatomical surfaces for the basis of image alignment and will require intraoperative geometric data to measure and compensate for tissue deformation in the organ. In this paper we outline methods for which a laser range scanner may be used to accomplish these tasks intraoperatively. A laser range scanner based on the optical principle of triangulation acquires a dense set of three-dimensional point data in a very rapid, noncontact fashion. Phantom studies were performed to test the ability to link range scan data with traditional modes of image-guided surgery data through localization, registration, and tracking in physical space. The experiments demonstrate that the scanner is capable of localizing point-based fiducials to within 0.2 mm and capable of achieving point and surface based registrations with target registration error of less than 2.0 mm. Tracking points in physical space with the range scanning system yields an error of 1.4 +/- 0.8 mm. Surface deformation studies were performed with the range scanner in order to determine if this device was capable of acquiring enough information for compensation algorithms. In the surface deformation studies, the range scanner was able to detect changes in surface shape due to deformation comparable to those detected by tomographic image studies. Use of the range scanner has been approved for clinical trials, and an initial intraoperative range scan experiment is presented. In all of these studies, the primary source of error in range scan data is deterministically related to the position and orientation of the surface within the scanner's field of view. However, this systematic error can be corrected, allowing the range scanner to provide a rapid, robust method of acquiring anatomical surfaces intraoperatively.
Use of sequential quadrupling dose regimens to study efficacy of inhaled corticosteroids in asthma.

Inhaled corticosteroids are widely used to treat asthma. There is a need to be able to compare different inhaled corticosteroids and different doses of an inhaled corticosteroid to determine potency and dose equivalence, but measuring efficacy in a dose related manner is difficult because of their slow onset of action. There is uncertainty about the role of sequential dosing regimens and the best end point for such studies. We have explored the use of sequential quadrupling dose regimens and a range of end points to assess the response to budesonide in subjects with asthma.



21 subjects with mild asthma, aged 18-65, took part in a randomised three way crossover study comparing two sequential and one non-sequential regimen, separated by at least 3 weeks. The sequential regimens consisted of increasing doses of inhaled budesonide (100, 400 1600 microg/day) with each dose being given for 1 or 2 weeks; the non-sequential regimen consisted of 1600 microg/day for 2 weeks with end points measured after 1 and 2 weeks. The end points studied included the provocative dose of adenosine monophosphate causing a 20% fall in forced expiratory volume in 1 second (PD20AMP), lung function, symptoms, and bronchodilator use.



There was a dose related increase in PD20AMP with both sequential dose regimens. The increase in PD20AMP ranged from 1.49 doubling doses (DD) following the lowest dose (100 microg/day) to 3.1 DD following the highest dose (1600 microg/day) in the 1 week sequential regimen and from 1.98 to 4.03 DD in the 2 week sequential regimen; standard deviations (SD) for the changes in PD20AMP ranged from 1.3 to 2.6 DD. Changes in forced expiratory volume in 1 second (FEV1) and morning peak expiratory flow rate (PEFR) were dose related but small and more variable (maximum change in FEV1=148 ml, SD 228 ml), while changes in evening PEFR, symptoms, and bronchodilator use were small and not dose related. Change in PD20AMP after budesonide 1600 microg did not differ significantly between regimens.



Combining PD20AMP measurements with a sequential regimen of three quadrupling doses of an inhaled corticosteroid given for 1 or 2 weeks provides clear dose-response curves for comparative studies. PD20AMP is a more sensitive end point for this purpose than FEV1, PEFR, symptoms, or relief inhaler use.
Improved virologic outcomes over time for HIV-infected patients on antiretroviral therapy in a cohort from Rio de Janeiro, 1997–2011

Previous cohort studies have demonstrated the beneficial effects of antiretroviral therapy (ART) on viral load suppression. We aimed to examine the factors associated with virologic suppression for HIV-infected patients on ART receiving care at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation in Rio de Janeiro, Brazil.



HIV-1 RNA levels and CD4+ T-cell counts at the date closest to midyear (1 July) were evaluated for 1,678 ART-naïve patients ≥ 18 years of age initiating ART between 1997 and 2010. The odds ratios (OR) and 95% confidence intervals (CI) for having an undetectable viral load (≤ 400 copies/mL) were estimated using generalized estimating equations regression models adjusted for clinical and demographic factors. Time-updated covariates included age, years since HIV diagnosis, hepatitis C diagnosis and ART interruptions.



Between 1997 and 2011, the proportion of patients with an undetectable viral load increased from 6% to 78% and the median [interquartile range] CD4+ T-cell count increased from 207 [162, 343] to 554 [382, 743] cells/μL. Pre-treatment median CD4+ T-cell count significantly increased over the observation period from 114 [37, 161] to 237 [76, 333] cells/μL (p < .001). The per-year adjusted OR (aOR) for having undetectable viral load was 1.18 (95% CI = 1.16-1.21). ART interruptions >1 month per calendar significantly decreased the odds [aOR = 0.32 (95% CI = 0.27-0.38)] of having an undetectable viral load. Patients initiating on a protease inhibitor (PI)-based first-line regimen were less likely to have undetectable viral load [aOR = 0.72 (95% CI = 0.63-0.83)] compared to those initiating on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen.



Our results demonstrate significant improvements in virologic outcomes from 1997 to 2011, which persisted after adjusting for other factors. This may in part be due to improvements in care and new treatment options. NNRTI- versus PI-based first-line regimens were found to be associated with increased odds of having an undetectable viral load, consistent with previous studies. Treatment interruptions were found to be the most important determinant of not having an undetectable viral load. Studies are needed to characterize the reasons for treatment interruptions and to develop subsequent strategies for improving adherence to ART.
Randomized Study of Persistent Atrial Fibrillation Ablation: Ablate in Sinus Rhythm Versus Ablate Complex-Fractionated Atrial Electrograms in Atrial Fibrillation.

Achieving long-term successful outcomes with ablation of persistent atrial fibrillation (AF) remains a clinical and procedural challenge. We aimed to assess 2 ablation strategies for persistent AF: pulmonary vein antral isolation (PVAI) in sinus rhythm after direct current cardioversion versus PVAI and ablation targeting complex-fractionated atrial electrograms while in AF.



Between June 2009 and July 2013, patients with continuous persistent AF for ≥3 months were prospectively randomized to either direct current cardioversion before PVAI and posterior wall/septum ablation while in sinus rhythm (group 1), versus same ablation in group 1 in addition to complex-fractionated atrial electrogram ablation while in AF (group 2). The procedural profiles and clinical outcomes of the 2 strategies were compared. Ninety patients were randomized to group 1 (n=46) or group 2 (n=44). There were no differences in baseline characteristics between groups. Over 365 days of follow-up after the index procedure, 16 patients (35%) in group 1 and 13 patients (30%) in group 2 remained arrhythmia-free off antiarrhythmic medications. Over long-term follow-up (median, 867 days), arrhythmia-free survival off antiarrhythmic medications was more likely in group 1 than in group 2 in Kaplan-Meier analysis (Log Rank P=0.04). Group 1 ablation was associated with significantly shorter procedural duration and fluoroscopy time (231±72 versus 273±76 min; P=0.008 and 54 [Q1-Q3: 46-67] versus 66 (Q1-Q3: 53-83] min; P=0.018, respectively).



In patients with persistent AF, PVAI in sinus rhythm after direct current cardioversion is associated with higher success and shorter procedural and fluoroscopy times compared with PVAI in AF with additional complex-fractionated atrial electrogram ablation.
Reduction of dietary sodium in Western Society. Benefit or risk?

THERE is widespread interest in relationships between dietary electrolyte intake and arterial pressure. Attention has been directed to potassium, calcium, and magnesium, but the predominant discussion has been of the possible role of dietary sodium in determining the level of blood pressure in Western society. Experts viewing information from animal research, from intraand interpopulation studies, and from manipulations of sodium intake in hypertensive and normotensive individuals have joined two opposing camps. Dialogue between the two has often been heated. In one camp are the "enthusiasts" who consider the evidence sufficient for encouraging Western society as a whole to restrict dietary sodium intake. Such dietary change would, they feel, lower arterial pressure overall, prevent the onset of hypertension in many, and most likely reduce the complications of high blood pressure. Unlike antihypertensive drug therapy, diet modification would have few if any undesirable effects; thus, for those in whom no benefit was seen at least no harm would result. The contrary camp houses the "skeptics." They claim the evidence is insufficient to justify attempts at lowering dietary sodium for the whole of Western society or even for all mild hypertensive patients. Skeptics emphasize that reports are conflicting on relationships between the level of sodium intake and blood pressure in both animals and humans; that the effects of short-term reductions in dietary sodium on arterial pressure in humans are disputed; that there is little information on the effects of sodium restriction over prolonged periods; and that there is no evidence that the complications of hypertension can be avoided by diet modification. Further, the skeptics are unwilling to accept that dietary changes may necessarily be harmless.
Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.
Sequencing topotecan and etoposide plus cisplatin to overcome topoisomerase I and II resistance: a pharmacodynamically based Phase I trial.

Resistance to topoisomerase (TOP) 1 and 2 inhibitors is a potentially important reason for treatment failure, and may be related, in part, to a down-regulation of the specific TOP target. Investigators in our laboratories previously noted such a down-regulation of the target, along with a reciprocal up-regulation of the alternate TOP. Therefore, sequencing TOP inhibitors may provide a means for overcoming resistance to the TOP I and II inhibitors. Furthermore, point mutations in TOP I, which confer resistance to TOP I inhibitors, were associated with collateral sensitivity to cisplatin.



A dose escalating Phase I trial of topotecan (at doses of 0.75 to 1.0 mg/m(2)/day) on days 1 to 3 with etoposide (70-80 mg/m(2)/day) and cisplatin (20-25 mg/m(2)/day) on days 8 to 10. The timing of the drug sequence was based on the prior Phase I pharmacokinetic and pharmacodynamic studies of camptothecin and etoposide, and the level of the TOP targets in peripheral blood monocytes.



Fifteen patients (7 males and 8 females) received 40 courses of therapy across three dose levels. The median age was 56 (range, 39-77), and the median performance status was 1 (range, 0-2). The diagnoses included: non-small cell lung cancer (7), head and neck cancer (2), cancer of unknown primary (2), and 1 each of ovarian cancer, prostate cancer, gastric cancer, and renal cancer. Level 1 (topotecan 1.0 mg/m(2)/day; etoposide 80 mg/m(2)/day; and cisplatin 25 mg/m(2)/day) produced severe and prolonged febrile neutropenia in the first patient treated, and the subsequent patients were then entered onto a reduced dose level (cohort 2: topotecan 0.75 mg/m(2)/day; etoposide 70 mg/m(2)/day; and cisplatin 20 mg/m(2)/day). Three of 6 patients on cohort 2 experienced grade IV neutropenia >5 days, and a decision was then made to add filgrastim at 5 micro g/kg rather than additionally reduce the dosages (cohort 3). Eight patients were then treated on cohort 3, and 1 of the 8 patients experienced a grade 4 neutropenia. Thus, cohort level three was considered the recommended dose for Phase II studies. Twelve of the 15 patients had disease assessable for response to therapy. Seven achieved stable disease for >/==" BORDER="0">2 months, whereas 5 showed continued progression of their disease.



These data show that sequencing TOP 1 and 2 inhibitors is feasible, and topotecan 0.75 mg/m(2)/day days 1-3; etoposide 70 mg/m(2)/day days 8-10; and cisplatin 20 mg/m(2)/day days 8-10 with filgrastim at 5 micro g/kg is an appropriate dose and schedule to test the concept of modulating TOP levels by sequencing the administration of the respective TOP inhibitors.
Delivering an Optimised Behavioural Intervention (OBI) to people with low back pain with high psychological risk; results and lessons learnt from a feasibility randomised controlled trial of Contextual Cognitive Behavioural Therapy (CCBT) vs. Physiotherapy

Low Back Pain (LBP) remains a common and costly problem. Psychological obstacles to recovery have been identified, but psychological and behavioural interventions have produced only moderate improvements. Reviews of trials have suggested that the interventions lack clear theoretical basis, are often compromised by low dose, lack of fidelity, and delivery by non-experts. In addition, interventions do not directly target known risk mechanisms. We identified a theory driven intervention (Contexual Cognitive Behavioural Therapy, CCBT) that directly targets an evidence-based risk mechanism (avoidance and ensured dose and delivery were optimised. This feasibility study was designed to test the credibility and acceptability of optimised CCBT against physiotherapy for avoidant LBP patients, and to test recruitment, delivery of the intervention and response rates prior to moving to a full definitive trial.



A randomised controlled feasibility trial with patients randomised to receive CCBT or physiotherapy. CCBT was delivered by trained supervised psychologists on a one to one basis and comprised up to 8 one-hour sessions. Physiotherapy comprised back to fitness group exercises with at least 60 % of content exercise-based. Patients were eligible to take part if they had back pain for more than 3 months, and scored above a threshold indicating fear avoidance, catastrophic beliefs and distress.



89 patients were recruited. Uptake rates were above those predicted. Scores for credibility and acceptability of the interventions met the set criteria. Response rates at three and six months fell short of the 75 % target. Problems associated with poor response rates were identified and successfully resolved, rates increased to 77 % at 3 months, and 68 % at 6 months. Independent ratings of treatment sessions indicated that CCBT was delivered to fidelity. Numbers were too small for formal analysis. Although average scores for acceptance were higher in the CCBT group than in the group attending physiotherapy (increase of 7.9 versus 5.1) and change in disability and pain from baseline to 6 months were greater in the CCBT group than in the physiotherapy group, these findings should be interpreted with caution.



CCBT is a credible and acceptable intervention for LBP patients who exhibit psychological obstacles to recovery.
Phenylketonuric patients decades after diet

Nineteen early-treated phenylketonuric patients, whose diet was discontinued between 4.5 and 13 years of age, and who have been off the diet for 12–28 years, were reassessed in 1992–93. There was little change in mean IQ between end of diet and follow-up, less than one IQ point on the average, with no change for any individual exceeding 12 IQ points. Both prior and current IQ correlated slightly negatively with mean phenylalanine (Phe) concentration, and positively with parents' education. The phenylalanine level at follow-up was significantly lower on average by about 900 µmol/L. Five of the subjects (26%) have evidence of mental disease. However, the data suggest that the discontinuation of the diet did not cause intellectual deterioration. Nonetheless, the patients' intellect cannot be the only consideration for maintenance of diet. The occurrence of psychopathology among phenylketonuric patients and the possible unknown effects of toxic elevation of phenylalanine during their lifetime suggest the need to maintain the diet. The use of DNA for diagnostic and prognostic purposes might assist in decisions about dietary quality and duration, and in anticipation of psychopathology.
Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma.

We used genome-wide methylation microarrays to analyze differences in CpG methylation patterns in cells relevant to the pathogenesis of myeloma plasma cells (B cells, normal plasma cells, monoclonal gammopathy of undetermined significance [MGUS], presentation myeloma, and plasma cell leukemia). We show that methylation patterns in these cell types are capable of distinguishing nonmalignant from malignant cells and the main reason for this difference is hypomethylation of the genome at the transition from MGUS to presentation myeloma. In addition, gene-specific hypermethylation was evident at the myeloma stage. Differential methylation was also evident at the transition from myeloma to plasma cell leukemia with remethylation of the genome, particularly of genes involved in cell-cell signaling and cell adhesion, which may contribute to independence from the bone marrow microenvironment. There was a high degree of methylation variability within presentation myeloma samples, which was associated with cytogenetic differences between samples. More specifically, we found methylation subgroups were defined by translocations and hyperdiploidy, with t(4;14) myeloma having the greatest impact on DNA methylation. Two groups of hyperdiploid samples were identified, on the basis of unsupervised clustering, which had an impact on overall survival. Overall, DNA methylation changes significantly during disease progression and between cytogenetic subgroups.
Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study.

Controversy exists with regard to the influence of APOE polymorphisms on coronary heart disease development and on the efficacy of statin treatment. we investigated the relationship between apoe, mortality and the response to treatment in Mediterranean myocardial infarction (mi) survivors.



We analysed 3304 Italian patients with MI randomized to pravastatin or no treatment in the GISSI-Prevenzione study, with a mean follow-up time of 23.0 +/- 6.7 months (median 24.3 months). Mortality curves were calculated using Kaplan-Meier method, and differences in survival were tested using the log-rank test. There were 109 deaths during follow-up. Patients treated with pravastatin showed a significant decrease in mortality compared with non-treated patients (HR 0.67, 95% confidence interval 0.45-0.97, P = 0.038). Among the 3304 patients, 554 (16.8%) were epsilon4 carriers and 2750 (83.2%) were non-epsilon4 carriers. No significant difference in terms of mortality was observed between the epsilon4 and the non-epsilon4 carriers (3.61% vs. 3.24%, P = 0.67). However, although in non-epsilon4 carriers no significant difference in mortality was observed between patients treated with pravastatin and non-treated (2.81% vs. 3.67%, P = 0.21), among the epsilon4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated (1.85% vs. 5.28%, P = 0.023).



We found that epsilon4 allele is a determinant of pravastatin response in terms of survival. Though in the entire population investigated,we found a beneficial effect of pravastatin in terms of survival, only the epsilon4 carriers seemed to have gained a significant benefit from this treatment. We suggest that the effect of statins is of particular interest in this fraction of the population. Genetic markers can help in identifying patients that benefit more from statin treatment.