nils-herrmann/clean_scirepeval huggingface dataset:
Trazodone plus pregabalin combination in the treatment of fibromyalgia: a two-phase, 24-week, open-label uncontrolled study

Although trazodone is frequently used by fibromyalgia patients, its efficacy on this disease has not been adequately studied. If effective, pregabalin, whose beneficial effects on pain and sleep quality in fibromyalgia have been demonstrated, could complement the antidepressant and anxiolytic effects of trazodone. The aim of the present study was to assess the effectiveness of trazodone alone and in combination with pregabalin in the treatment of fibromyalgia.



 Trazodone, flexibly dosed (50-300 mg/day), was administered to 66 fibromyalgia patients during 12 weeks; 41 patients who completed the treatment accepted to receive pregabalin, also flexibly dosed (75-450 mg/day), added to trazodone treatment for an additional 12-week period. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index (PSQI), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), the Brief Pain Inventory (BPI), the Short-Form Health Survey (SF-36), and the Patients' Global Improvement scale (PGI). Emergent adverse reactions were recorded. Data were analyzed with repeated measures one-way ANOVA and paired Student's t test.



Treatment with trazodone significantly improved global fibromyalgia severity, sleep quality, and depression, as well as pain interference with daily activities although without showing a direct effect on bodily pain. After pregabalin combination additional and significant improvements were seen on fibromyalgia severity, depression and pain interference with daily activities, and a decrease in bodily pain was also apparent. During the second phase of the study, only two patients dropped out due to side effects.



Trazodone significantly improved fibromyalgia severity and associated symptomatology. Its combination with pregabalin potentiated this improvement and the tolerability of the drugs in association was good.
A phase 3 trial of extended release oral dalfampridine in multiple sclerosis.

A previous phase 3 study showed significant improvement in walking ability in multiple sclerosis (MS) patients treated with oral, extended-release dalfampridine (4-aminopyridine) 10mg twice daily. The current study was designed to confirm efficacy and further define safety and pharmacodynamics.



This was a 39-center, double-blind trial in patients with definite MS of any course type. Participants were randomized to 9 weeks of treatment with dalfampridine (10mg twice daily; n = 120) or placebo (n = 119). Response was defined as consistent improvement on the Timed 25-Foot Walk, with percentage of timed walk responders (TWRs) in each treatment group as the primary outcome. The last on-treatment visit provided data from 8 to 12 hours postdose, to examine maintenance of effect.



One patient from each group was excluded from the modified Intention to Treat population. The proportion of TWRs was higher in the dalfampridine group (51/119 or 42.9%) compared to the placebo group (11/118 or 9.3%, p < 0.0001). The average improvement in walking speed among dalfampridine-treated TWRs during the 8-week efficacy evaluation period was 24.7% from baseline (95% confidence interval, 21.0-28.4%); the mean improvement at the last on-treatment visit was 25.7%, showing maintenance of effect over the interdosing period. There were no new safety findings.



This interventional study provides class 1 evidence that dalfampridine extended-release tablets produce clinically meaningful improvement in walking ability in a subset of people with MS, with the effect maintained between doses.
Effect of early direct current cardioversion on the recurrence of atrial fibrillation in patients with persistent atrial fibrillation.

In patients with persistent atrial fibrillation (AF), the sinus rhythm (SR) can be restored by direct current cardioversion (DCC), although the recurrence of AF after successful DCC is common. We examined whether transesophageal echocardiography (TEE)-guided early DCC, compared with the conventional approach of DCC after 3 weeks of anticoagulation with dabigatran-etexilat, reduces the recurrence of AF. A total of 126 consecutive patients with persistent AF were randomly assigned to a TEE followed by early DCC (n = 65) or to a conventional treatment with dabigatran-etexilat for 3 weeks followed by DCC (n = 61). None of the patients received any antiarrhythmic treatment other than β blockers, and all the DCCs were successful. Forty-eight-hour Holter monitoring was performed at 28 days and at 3, 6, and 12 months after the DCC. The primary outcome was AF recurrence lasting ≥30 seconds. The analysis was stratified by AF duration <60 (n = 62) or >60 days (n = 64) before DCC. We observed a significant reduction in the AF recurrence risk (p = 0.003) in patients with persistent AF <60 days who received early DCC, but there was no significant benefit of early DCC (p = 0.456) in patients with persistent AF lasting >60 days. The recurrence-free survival probability at 28 days in patients with persistent AF <60 days was 0.27 (95% confidence interval 0.14 to 0.51) in the conventional treatment group compared with 0.69 (95% confidence interval 0.54 to 0.87; p = 0.006) in the early DCC group. A benefit of early DCC persisted throughout 12 months of follow-up. In conclusion, TEE-guided early DCC in patients with persistent AF <60 days results in a significant reduction of AF recurrence.
A multifaceted intervention to improve treatment of osteoporosis in postmenopausal women with wrist fractures: a cluster randomized trial

In a cluster randomized trial, we evaluated the effect of a multifaceted intervention (directed at both patient and primary care physician) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture. Compared to usual care, women in the intervention practices were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments. Postmenopausal women with wrist fractures are at increased risk of future fragility fractures, yet they frequently do not receive evaluation and treatment for osteoporosis. We set out to evaluate a multifaceted intervention designed to improve management of osteoporosis in older women with recent wrist fractures. Cluster randomized trial of 270 women cared for in 119 primary care practices. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario, Canada. Family practices were randomly assigned to either the intervention or usual care. The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician, in addition to an educational package and letter to the women. The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture. The mean age of women was 69(10.9) years. The intervention increased the proportion of women started on osteoporosis medications (28% vs. 10%) of controls, adjusted OR 3.45, 95% CI, 1.58–7.56, p = 0.002) and the proportion who had a bone mineral density (BMD) test (53.3% vs. 26%) of controls, OR 3.38, 95% CI, 1.83–6.26, p < 0.001). In addition to the intervention, having a female physician was a predictor of increased testing and treatment rates. A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures.
[Diagnostic and prognostic efficiency of 24-hour Holter monitoring in patients with syncope].

Syncope is a common condition and complex to diagnose. The yield of the 24h-Holter ECG in this context has not been clearly defined. The aim of this study was to evaluate its diagnostic and prognostic capacity in these patients.



Retrospective study of 6,006 consecutive patients sent to our unit for 24h-Holter ECG monitoring for syncope. We registered the diagnostic findings and abnormal findings potentially related to an arrhythmic cause of syncope. The prognostic endpoint was a combination of death or the need for device implantation (pacemaker or defibrillator) within one year.



242 patients (4%) presented diagnostic findings and 472 (7.9%) had some abnormal findings. In 328 cases device implantation was necessary within one year, but up to 66% of these patients did not have any relevant findings on the Holter monitoring. A total of 564 patients presented the combined event, including 36.8% of patients with diagnostic findings and 8.2% without them.



24h-Holter ECG monitoring presents a limited diagnostic and prognostic yield in unselected patients with syncope.
Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously.

To evaluate the safety, pharmacokinetics, and biological activity of suberoylanilide hydroxamic acid (SAHA) administered by 2-h i.v. infusion in patients with advanced cancer.



SAHA was administered for 3 days every 21 days in part A and 5 days for 1-3 weeks in part B. Dose escalation proceeded independently in patients with solid tumor and hematological malignancies (part B only). Pharmacokinetic studies were performed along with assessment of acetylated histones in peripheral blood mononuclear cells and tumor tissues.



No dose-limiting toxicities were observed in 8 patients enrolled in part A (75, 150, 300, 600, and 900 mg/m(2)/day). Among 12 hematological and 17 solid tumor patients enrolled in part B (300, 600, and 900 mg/m(2)/day), therapy was delayed > or = 1 week for grade 3/4 leukopenia and/or thrombocytopenia in 2 of 5 hematological patients at 600 mg/m(2)/day x 5 days for 3 weeks. The maximal-tolerated dose was 300 mg/m(2)/day x 5 days for 3 weeks for hematological patients. One solid patient on 900 mg/m(2)/day x 5 days for 3 weeks developed acute respiratory distress and grade 3 hypotension. The cohort was expanded to 6 patients, and no additional dose-limiting toxicities were observed. Mean terminal half-life ranged from 21 to 58 min, and there was dose-proportional increase in area under the curve. An accumulation of acetylated histones in peripheral blood mononuclear cells up to 4 h postinfusion was observed at higher dose levels. Posttherapy tumor biopsies showed an accumulation of acetylated histones by immunohistochemistry. Four (2 lymphoma and 2 bladder) patients had objective tumor regression with clinical improvement in tumor related symptoms.



Daily i.v. SAHA is well tolerated, inhibits the biological target in vivo, and has antitumor activity in solid and hematological tumors.
Influence of TCM therapy for supplementing Pi and nourishing Shen on dendritic cell function in patients with chronic hepatitis B treated by lamivudine.

To observe the influence of traditional Chinese medicine (TCM) therapy for supplementing Pi () and nourishing Shen (, SPNS) on dendritic cell function in patients with chronic hepatitis B (CHB) treated by lamivudine.



Sixty CHB patients with positive HBeAg were equally randomized by digital table into two groups: the observation group and the control group. Patients in the control group were treated with lamivudine only, while patients in the observation group were treated with lamivudine combined with SPNS fomula, for 12 weeks. The phenotype and function of dendritic cell, as well as its secretion factor interleukin 12 (IL-12) in all patients were determined after termination of therapy and the impacts on alanine transaminase (ALT) and HBVDNA were observed.



The phenotypes of dendritic cells such as CD1a, CD80, CD86, human leukocyte antigen (HLA-DR) and intercellular adhesion molecule-1, as well as the levels of stimulation index (SI) and IL-12 were higher in the observation group than those in the control group (P<0.05 or P<0.01). Meanwhile, signififi cant difference between the two groups was also shown in the normalizing rates of ALT and HBV-DNA (P<0.05).



TCM therapy for SPNS can signifificantly improve the function of dendritic cells in patients with CHB treated by lamivudine and enhance the early stage response of patients to the treatment.
Are factors related to dual-task performance in people with Parkinson's disease dependent on the type of dual task?

Impaired dual-task performance significantly impacts upon functional mobility in people with Parkinson's disease (PD). The aim of this study was to identify determinants of dual-task performance in people with PD in three different dual tasks to assess their possible task-dependency.



We recruited 121 home-dwelling patients with PD (mean age 65.93 years; mean disease duration 8.67 years) whom we subjected to regular walking (control condition) and to three dual-task conditions: walking combined with a backwards Digit Span task, an auditory Stroop task and a Mobile Phone task. We measured dual-task gait velocity using the GAITRite mat and dual-task reaction times and errors on the concurrent tasks as outcomes. Motor, cognitive and descriptive variables which correlated to dual-task performance (p < 0.20) were entered into a stepwise forward multiple linear regression model.



Single-task gait velocity and executive function, tested by the alternating intake test, was significantly associated with gait velocity during the Digit Span (R(2) = 0.65; p < 0.001), the Stroop (R(2) = 0.73; p < 0.001) and the Mobile Phone task (R(2) = 0.62; p < 0.001). In addition, disease severity proved correlated to gait velocity during the Stroop task. Age was a surplus determinant of gait velocity while using a mobile phone.



Single-task gait velocity and executive function as measured by a verbal fluency switching task were independent determinants of dual-task gait performance in people with PD. In contrast to expectation, these factors were the same across different tasks, supporting the robustness of the findings. Future study needs to determine whether these factors predict dual-task abnormalities prospectively.
Spread and distribution of 5-ASA colonic foam and 5-ASA enema in patients with ulcerative colitis

Rectal treatment with enemas, foams, and suppositories is the most efficient method of delivering an adequate quantity of locally active drugs to the distal colon. In a pilot study carried out by colonoscopy in four patients, it was observed that 4 g 5-ASA in 20 ml foam spread up or beyond the splenic flexure and more extensively than 2 g 5-ASA in 10 ml foam. Therefore we have undertaken a study in order to compare by scintigraphy the colonic distribution of 4 g 5-ASA foam versus 4 g 5-ASA in 100 ml liquid enemas in 10 patients with ulcerative colitis using a crossover randomized design. Both preparations were labeled with 100 MBq [99mTc] sulfur colloid before administration. Anterior scans were taken at intervals for 4 hr. Activity, expressed as a percentage of total radioactivity, was measured in the rectum, sigmoid, descending, transverse, and ascending colon. Six patients had the same extent of spread with the two formulations; in three patients with foam and in one patient with enema a greater spread was observed. the foam reached the upper limit of disease in all cases, while enema failed in two cases. The maximum spread with foam was observed within 30 min in nine of 10 patients compared with seven of 10 after enema. Compared to enema, foam distributes more uniformly and seems to persist longer in the descending and sigmoid colon. The 5-ASA colonic foam shows some more favorable characteristics than enema for the local treatment of left-sided ulcerative colitis.
Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration.

Experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. In clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. The authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration.



Elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n = 50 each). In a first group, patients received a propofol based intravenous regimen (propofol group). In a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (SEVO pre group). In a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (SEVO post group). In a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (SEVO all group). Postoperative concentrations of cardiac troponin I were followed during 48 h. Cardiac function was assessed perioperatively and during 24 h postoperatively.



Postoperative troponin I concentrations in the SEVO all group were lower than in the propofol group. Stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the SEVO all group. In the SEVO pre and SEVO post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. Duration of stay in the intensive care unit was lower in the SEVO all group than in the propofol group.



In patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.
Prevalence of anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with primary Sjögren's syndrome.

To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKA) in patients with primary Sjögren's syndrome.



149 patients with a diagnosis of primary Sjögren's syndrome according to the European/American consensus criteria were recruited from three French medical centres. The presence of anti-CCP was determined by enzyme linked immunosorbent assay and of AKA antibodies by indirect immunofluorescence. Radiographs of hands and feet were evaluated at the time of anti-CCP analysis.



Six patients with radiological erosions and nine patients with non-erosive arthritis fulfilling ACR criteria for rheumatoid arthritis were thought to have rheumatoid arthritis and secondary Sjögren's syndrome, while 134 were considered to have primary Sjögren's syndrome (mean (SD) disease duration, 11.1 (6.6) years). Of these, 80 tested positive for IgM rheumatoid factor (RF) (59%), 10 (7.5%) for anti-CCP, 7 (5.2%) for AKA, and 5 (3.7%) for both anti-CCP and AKA. There was no difference in clinical and biological features, including prevalence of RF, between anti-CCP positive and negative patients. The nine Sjögren patients with non-erosive arthritis, fulfilling ACR criteria for rheumatoid arthritis, were all CCP positive. Their response to disease modifying antirheumatic drugs could be different from classical rheumatoid patients.



Most patients with primary Sjögren's syndrome are negative for AKA and anti-CCP, but positive test results should not rule out this diagnosis. Anti-CCP positive patients, who may be prone to developing rheumatoid arthritis, require cautious clinical and radiographic follow up.
Residual air in the venous cannula increases cerebral embolization at the onset of cardiopulmonary bypass.

When the right atrium (RA) cannula is connected to the venous return line of the cardiopulmonary bypass (CPB) circuit, air is often introduced. Air in the venous cannula may increase cerebral air embolization at initiation of CPB despite the arterial line filter. We measured the volume of air present in the venous cannula after cannulation of the RA. Transcranial Doppler quantified emboli as high-intensity transient-signals (HITS) in both middle-cerebral arteries (MCA) at the beginning of CPB.



After RA cannulation, the air column in the venous line was measured and the total volume calculated using the known lumen diameter. CPB onset was defined as the instant when the CPB machine started moving the patient's blood from the RA into the venous reservoir. Starting from CPB onset, HITS were counted: (a) until completion of the first minute on CPB (1-min count) and (b) until aortic cross clamping (pre-clamping count).



We studied 135 patients during coronary artery bypass surgery operated on by 10 cardiac surgeons. HITS during onset of CPB were detected in 95% of patients. Median counts were 10 HITS (25th, 75th percentiles: 3, 26) at 1-min and 21 HITS (8, 51) during pre-clamping. A significant correlation was found between the volume of air in the venous cannula and the HITS counts (r=0.524, p<0.0001). Absence of retained air was associated with lower HITS counts [3 HITS (1, 11)] compared with any amount of air [13 HITS (4, 29), p=0.002)]. The volume of air in the venous cannula, the MCA mean blood flow velocity and the pre-clamping time were the only independent predictors of the pre-clamping HITS counts (p<0.001).



Air in the venous cannula can result in HITS in the MCA. Minimizing the volume of air introduced into the venous cannula after cannulation of the RA can decrease cerebral air embolization at the beginning of CPB.
Nicorandil Versus Nitroglycerin for Symptomatic Relief of Angina in Patients With Slow Coronary Flow Phenomenon: A Randomized Clinical Trial.

Patients with the coronary slow flow phenomenon frequently experience angina episodes. The present study aimed to compare the efficacy of nicorandil versus nitroglycerin for alleviation of angina symptoms in slow flow patients.



In a single-center, single-blind, parallel-design, comparator-controlled, randomized clinical trial (NCT02254252), 54 patients with slow flow and normal or near-normal coronary angiography who presented with frequent angina episodes were randomly assigned to 1-month treatment with nicorandil 10 mg, 2 times a day (n = 27) or sustained-release glyceryltrinitrate 6.4 mg 2 times a day (n =27). Frequency of angina episodes, pain intensity, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were assessed at baseline and after 1 month of treatment.



In all, 25 patients in the nicorandil arm and 24 patients in the nitroglycerin arm were analyzed. After 1 month, patients treated with nicorandil had fewer angina episodes (adjusted mean number of episodes per week, nicorandil versus nitroglycerin; 1.68 ± 0.15 vs 2.29 ± 0.15, P = .007, effect size = 14.6%). Patients also reported greater reductions in pain intensity with nicorandil versus nitroglycerin (adjusted mean of self-reported pain score; 3.03 ± 0.29 vs 3.89 ± 0.30, P = .046, effect size = 8.4%). A significantly higher proportion of patients in the nicorandil arm were categorized in CCS class I (76% vs 33.3%, P = .004) or class II (16.0% vs 45.8%, P = .032).



In slow flow patients, nicorandil provides better symptomatic relief of angina than nitroglycerin.