nils-herrmann/clean_scirepeval huggingface dataset:
Safety, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept, an activin receptor-like kinase-1 ligand trap, in patients with advanced cancer.

The angiogenesis inhibitor dalantercept (formerly ACE-041) is a soluble form of activin receptor-like kinase-1 (ALK1) that prevents activation of endogenous ALK1 by bone morphogenetic protein-9 (BMP9) and BMP10 and exhibits antitumor activity in preclinical models. This first-in-human study of dalantercept evaluated its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in adults with advanced solid tumors.



Patients in dose-escalating cohorts received dalantercept subcutaneously at one of seven dose levels (0.1-4.8 mg/kg) every 3 weeks until disease progression. Patients in an expansion cohort received dalantercept at 0.8 or 1.6 mg/kg every 3 weeks until disease progression.



In 37 patients receiving dalantercept, the most common treatment-related adverse events were peripheral edema, fatigue, and anemia. Edema and fluid retention were dose-limiting toxicities and responded to diuretic therapy. No clinically significant, treatment-related hypertension, proteinuria, gross hemorrhage, or gastrointestinal perforations were observed. One patient with refractory squamous cell cancer of the head and neck had a partial response, and 13 patients had stable disease according to RECISTv1.1, eight of whom had prolonged periods (≥12 weeks) of stable disease. Correlative pharmacodynamic markers included tumor metabolic activity and tumor blood flow, which decreased from baseline in 63% and 82% of evaluable patients, respectively, and telangiectasia in eight patients.



Dalantercept was well-tolerated at doses up to 1.6 mg/kg, with a safety profile distinct from inhibitors of the VEGF pathway. Dalantercept displayed promising antitumor activity in patients with advanced refractory cancer, and multiple phase II studies are underway.
[Being physically active modifies the detrimental effect of sedentary behavior on obesity and cardiometabolic markers in adults].

Sedentary behavior is a major risk factor for cardiovascular disease and mortality.



To investigate whether the associations between sedentary behavior and cardiometabolic markers differs across physical activity levels.



Cross sectional study of 314 participants aged 18 to 65 years. Body mass index (BMI) and waist circumference were measured, and body fat was derived from the sum of four skinfolds. Physical activity was measured objectively using accelerometers (Actigraph GT1M, USA®). A fasting blood sample was obtained to measure glucose, insulin, HOMA-IR, lipid profile and high sensitive C reactive protein (hsCRP). Those participants with an activity level > 600 MET.min-1.week-1 were classified as physically active.



Thirty four percent of participants were physically inactive and spent an average of 8.7 h.day-1 in sedentary pursuits. Physically inactive individuals had poorer cardiometabolic health than their physically active counterparts. Per one hour decrease in overall sedentary behavior, there was a significant improvement in glucose (-8.46 and -4.68 mg.dl-1), insulin (-2.12 and -1.77 pmol.l-1), HOMA-IR (-0.81 and -0.56) BMI (-0.93 and -0.62 kg.m-2) and waist circumference (-2.32 and -1.65 cm) in physically active and inactive participants, respectively.



Being physically active may modify the detrimental effects of sedentary behavior on cardiometabolic and obesity-related traits.
The effect of quadriceps femoris muscle strengthening exercises on spasticity in children with cerebral palsy.

The Bobath neurodevelopmental treatment approach advised against the use of resistive exercise, as proponents felt that increased effort would increase spasticity. The purpose of this study was to test the premise that the performance of exercises with maximum efforts will increase spasticity in people with cerebral palsy (CP). Spasticity, in the present study, was defined as a velocity-dependent hyperexcitability of the muscle stretch reflex.



Twenty-four subjects with the spastic diplegic form of CP (mean age=11.4 years, SD=3.0, range=7-17) and 12 subjects without known neurological impairments (mean age=11.6 years, SD=3.5, range=7-17) were assessed.



Knee muscle spasticity was assessed bilaterally using the pendulum test to elicit a stretch reflex immediately before and after 3 different forms of right quadriceps femoris muscle exercise (isometric, isotonic, and isokinetic) during a single bout of exercise training. Pendulum test outcome measures were: (1) first swing excursion, (2) number of lower leg oscillations, and (3) duration of the oscillations.



There were no changes in spasticity following exercise between the 2 groups of subjects.



These results do not support the premise that exercises with maximum efforts increase spasticity in people with CP.
Prevention of panic attacks and panic disorder in COPD.

This study examined whether cognitive behavioural therapy (CBT) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease (COPD). 41 patients with COPD, who had undergone pulmonary rehabilitation, were randomised to either a four-session CBT intervention condition (n = 21) or a routine care condition (n = 20). Assessments were at baseline, post-intervention, and at 6-, 12- and 18-month follow-ups. Primary outcomes were the rates of panic attacks, panic disorder and anxiety symptoms. Secondary outcomes were depressive symptoms, catastrophic cognitions about breathing difficulties, disease-specific quality of life and hospital admission rates. There were no significant differences between the groups on outcome measures at baseline. By the 18-month follow-up assessment, 12 (60%) routine care group participants had experienced at least one panic attack in the previous 6 months, with two (17%) of these being diagnosed with panic disorder, while no CBT group participants experienced any panic attacks during the follow-up phase. There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups. The study provides evidence that a brief, specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms.
Obtaining a male circumcision prevalence rate of 80% among adults in a short time

World Health Organization recommends a target for the male circumcision prevalence rate of 80%. This rate will have a substantial impact on the human immunodeficiency virus-acquired immunodeficiency syndrome epidemic in Eastern and Southern Africa. The objective of the study was to assess whether an innovative intervention can lead to an increased voluntary male medical circumcision (VMMC) uptake among adults in a short time. This prospective observational study of a demand generation intervention was conducted in the township of Orange Farm (South Africa) in August to November 2015. In this community male circumcision prevalence rate among adults was stable between 2010 and 2015 at 55% and 57%, despite regular VMMC campaigns at community level and the presence of a VMMC clinic that offered free VMMC. The intervention took place in a random sample of 981 households where 522 men aged 18 to 49 years accepted to participate in the study. Among the 226 uncircumcised men, 212 accepted to be enrolled in the intervention study. A personal male circumcision adviser trained in interpersonal communication skills was assigned to each uncircumcised participant. The male circumcision advisers were trained to explain the risks and benefits of VMMC, and to discuss 24 possible reasons given by men for not being circumcised. Participants were then followed for 9 weeks. Each participant had a maximum of 3 motivational interviews at home. Participants who decided to be circumcised received financial compensation for their time equivalent to 2.5 days of work at the minimum South African salary rate. Among the 212 uncircumcised men enrolled in the intervention, 69.8% (148/212; 95% confidence interval [CI]; 63.4%-75.7%) agreed to be circumcised, which defines the uptake of the intervention. The male circumcision prevalence rate of the sample increased from 56.7% (296/522) to 81.4% (425/522; 77.9%-84.6%), P < 0.001, corresponding to a relative increase of 43.6% (95% CI: 35.4%-53.7%). The reported reasons for accepting circumcision were motivational interviews with the male circumcision adviser (83.1%), and time compensation (39.4%).Increased uptake of VMMC uptake can be obtained in a short time among adult males but requires an intense intervention centered on uncircumcised men at an individual level and time compensation.
A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis.

To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib.  A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12.



A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg).



IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain.
Delayed shoulder exercises in reducing seroma frequency after modified radical mastectomy: A prospective randomized study

Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer. Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced, without increasing shoulder dysfunction, by delayed postoperative shoulder exercises.  In a prospective study 163 patients with breast cancer undergoing modified radical mastectomy were randomized to physiotherapy starting on postoperative day 1 or day 7. Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department. Seromas and other complications were registered by the surgeons. The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function.  There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 (38%) compared to the group that started physiotherapy postoperative day 7 (22%) (p<0.05). There was no significant difference between the groups in the late outcome of shoulder function.  The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.
Randomized controlled trial of laparoscopic versus open colectomy for advanced colorectal cancer

After confirming a favorable outcome of laparoscopic surgery for early colorectal cancer, we conducted a randomized controlled trial to compare short-term outcomes of laparoscopic and open colectomy for advanced colorectal cancer.  Fifty-nine patients with T2 or T3 colorectal cancer were randomized to undergo laparoscopic (n = 29) or open (n = 30) colectomy. Median follow-up was 20 months (range, 6–34 months).  Operative time was longer (p <0.0001) and blood loss (p = 0.0034) and postoperative analgesic requirement were less in the laparoscopic group than in the open group. An earlier return of bowel motility and earlier discharge from the hospital (p = 0.0164) were observed after laparoscopic surgery. Serum C-reactive protein levels on postoperative days 1 (p <0.0001) and 4 (p = 0.0039) were lower in the laparoscopic group than in the open group. Postoperative complications did not differ between the two groups.  Laparoscopic surgery for advanced colorectal cancer is feasible, with favorable short-term outcome.
Infliximab for Diabetic Macular Edema Refractory to Laser Photocoagulation

Because many patients with diabetic macular edema (DME) do not respond to focal/grid laser photocoagulation, the only currently approved treatment, alternatives are needed. Based on encouraging preliminary findings, we aimed to assess efficacy and safety of the anti-tumor necrosis factor (TNF) monoclonal antibody infliximab in this condition.



This was a single-center, double-blind, randomized, placebo-controlled, crossover study. Eleven patients with sight-threatening DME persisting after two sessions of laser photocoagulation received infliximab (5 mg/kg) intravenously at weeks 0, 2, 6, and 14, followed by placebo at weeks 16, 18, 22, and 30, or vice versa. Blinding was maintained to week 32, when the final assessments were performed. Best corrected visual acuity evaluated by a mixed-models approach for imbalanced crossover design using the percentage difference as the outcome variable was the primary study end point. Data were analyzed on an intention-to-treat basis.



Early Treatment of Diabetic Retinopathy Study (ETDRS) scores dropped from 31.6 +/- 5.1 (mean +/- SD) letters read at baseline to 28.8 +/- 11.6 letters read at week 16 in six placebo-treated eyes and improved to 35.4 +/- 11.2 letters read after infliximab. In contrast, visual acuity improved from 23.5 +/- 10.3 at baseline to 30.4 +/- 13.4 letters read at week 16 in eight infliximab-treated eyes and was sustained at completion of placebo treatment (31.4 +/- 12.1 letters read). The excess visual acuity in infliximab-treated eyes was greater by 24.3% compared with that in placebo-treated eyes (95% CI 4.8-43.7; P = 0.017). Infliximab treatment was well tolerated.



The positive results of this small phase III study suggest that larger and longer term trials should be conducted to assess the efficacy of systemic or intravitreal anti-TNF agent administration for primary treatment of DME.
Outcomes from a Therapeutic Community for Homeless Addicted Mothers and Their Children

A women's therapeutic community (TC) designed to prevent homelessness was evaluated using a quasi-experimental process. Propensity analysis selected comparable experimental (E) and comparison (C) participants. Significant improvements were found for the E group at the domain level, both in “psychological” dysfunction on symptoms (e.g., depression), and in “health,” including ratings of health and adherence to medication regimens. No significant difference was found at the domain level for “parenting” or “housing stabilization,” but specific outcomes did differ. For example, a greater number of children resided with the E group mothers who also assumed financial responsibility for more of their children.
The effect of challenge method on methacholine-induced changes in sensitivity and air trapping.

The methacholine challenge test performed with the tidal breathing method induces a greater fall in FEV(1) than the dosimeter method; however, the effect of the challenge method on methacholine-induced fall in FVC has not been investigated.



To determine the influence of the challenge method on methacholine-induced changes in FEV(1) and FVC.



Airway responsiveness to methacholine was determined by dosimeter method and tidal breathing method in 37 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method and the same nebulizer model was used for the two challenges. The response was expressed by the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and by the percent fall in FVC at the PC(20) value relative to FVC after saline inhalation.



The PC(20) values obtained with the tidal breathing method and the dosimeter method were similar, with geometric mean values of 3.15 (95%CI, 1.85-5.34 mg/mL) and 2.51 (1.37-4.61 mg/mL, P = 0.092), respectively. The percent fall in FVC at the PC(20) value obtained with the dosimeter was significantly greater than that obtained with the tidal breathing method, with mean values of 11.8 (95%CI, 10.0-13.5%) and 9.4 (95%CI, 8.1-10.8, P = 0.002), respectively.



Differences in methacholine PC(20) values obtained with the two challenge methods recommended in guidelines may be overcome by introducing some technical modifications in the dosimeter method. However, the technical factors that affect methacholine sensitivity and air trapping are at least partially different.
Vascular Plug-Assisted Retrograde Transvenous Obliteration for the Treatment of Gastric Varices and Hepatic Encephalopathy: A Prospective Multicenter Study.

To evaluate technical and clinical outcomes of vascular plug-assisted retrograde transvenous obliteration (PARTO) for the treatment of gastric varices (GVs) and hepatic encephalopathy (HE).



From March 2012 to June 2014, 73 consecutive patients (47 men, 26 women; mean age, 59 y; range, 28-79 y) who had undergone PARTO were evaluated in a prospective multicenter study. Among 57 patients with GVs, 28 had GVs in danger of rupture, 23 had experienced recent bleeding, and 6 had active variceal bleeding. The 16 patients with HE had been treated unsuccessfully with medical therapies.



Placement of the vascular plug and subsequent gelatin sponge embolization were technically successful in all 73 patients. There were no procedure-related complications. Follow-up CT obtained within 1 wk after PARTO showed complete thrombosis of GVs and portosystemic shunts in 72 of 73 patients (98.6%). Sixty patients who underwent follow-up longer than 3 mo showed complete obliteration of GVs and portosystemic shunts. There were no cases of variceal bleeding or HE at the end of follow-up (mean, 544 d). Improvement in Child-Pugh score was observed in 24 patients (40%) at 1-mo follow-up. Worsening of ascites and esophageal varices was observed in 14 (23.3%) and 16 (26.7%) patients at 3-mo follow-up.



The present results of PARTO indicate that it can be rapidly performed with high technical success and durable clinical efficacy for the treatment of GVs and HE in the presence of a portosystemic shunt. Therefore, PARTO might be considered a first-line treatment in appropriate patients.
French multicentre clinical evaluation of helical TomoTherapy® for anal cancer in a cohort of 64 consecutive patients

To assess feasibility and toxicity of Helical TomoTherapy for treating anal cancer patients.



From 2007 to 2011, 64 patients were consecutively treated with TomoTherapy in three centres for locally advanced squamous-cell anal carcinoma (T2 > 4 cm or N positive). Prescribed doses were 45 Gy to the pelvis including inguinal nodes and 59.4 Gy to the primary site and involved nodes with fractions of 1.8 Gy, five days a week. A positional Megavoltage Computed Tomography was performed before each treatment session. All acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 3.0. Survival analysis was performed using the Kaplan-Meier method.



Median follow-up was 22.9 months. Fifty-four women and 10 men were treated (median age: 62 years). Nineteen patients (29.7%) had T2, 16 patients (25.0%) T3, and 27 patients (42.2%) T4 tumours. Thirty-nine patients (60.9%) had nodal involvement. Median tumour size was 45 mm (range, 10-110 mm). Seven patients had a colostomy before treatment initiation. Fifty-seven patients received concomitant chemotherapy (5-FU/cisplatin or 5-FU/mitomycin-based therapy). Forty-seven patients (73.4 %) experienced a complete response, 13 a partial response or local recurrence, and 11 had salvage surgery; among these, six became complete responders, three experienced metastatic failure, and two local failure. At least four patients experienced metastatic recurrence (concomitant to a local failure for one patient). The two-year overall survival was 85.6% (95 %CI [71.1%-93.0%]), and the one-year disease-free survival, and colostomy-free survival were 68.7% (95 %CI [54.4%-79.4]), and 75.5% (95 %CI [60.7%-85.3%]) respectively. Overall survival, disease-free survival and colostomy free-survival were significantly better for women than men (p = 0.002, p = 0.004, and p = 0.002 respectively). Acute grade ≥3 toxicity included dermatologic (46.9% of patients), gastrointestinal (20.3%), and hematologic (17.2%) toxicity. Acute grade 4 hematologic toxicity occurred in one patient. No grade 5 event was observed.



TomoTherapy for locally advanced anal cancer is feasible. In our three centres of expertise, this technique appeared to produce few acute gastrointestinal toxicities. However, high rates of dermatologic toxicity were observed. The therapeutic efficacy was within the range of expectations and similar to previous studies in accordance with the high rates of locally advanced tumours and nodal involvement.
Transdermal rotigotine for the perioperative management of Parkinson’s disease

Continuous delivery of antiparkinsonian medication during a perioperative period is desirable to avoid ‘off’-symptom complications in surgical patients with concomitant Parkinson’s disease (PD). Fourteen PD patients undergoing surgery under general anesthesia were switched from oral dopaminergic medication to transdermally delivered 24-h rotigotine (median dose 12 mg/24 h) for the perioperative period. Rotigotine treatment was considered feasible by patients, their anesthesiologists and neurologists with good control of PD symptoms and easy switching and re-switching of PD medication.