nils-herrmann/clean_scirepeval huggingface dataset:
Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist

The feasibility of exploiting genomic information for individualized treatment of polygenic diseases remains uncertain. A genetic variant in ADRA2A, which encodes the α2A-adrenergic receptor (α2AAR), was recently associated with type 2 diabetes. This variant causes receptor overexpression and impaired insulin secretion; thus, we hypothesized that blocking α2AAR pharmacologically could improve insulin secretion in patients with the risk genotype. A total of 50 type 2 diabetes patients were recruited on the basis of ADRA2A genotype for a randomized placebo-controlled intervention study with the α2AAR antagonist yohimbine. The patients received 0, 10, or 20 mg of yohimbine at three separate visits. The primary endpoint was insulin secretion at 30 min (Ins30) during an oral glucose tolerance test (OGTT). Patients with the risk variant had 25% lower Ins30 than those without risk genotype. After administration of 20 mg of yohimbine, Ins30 was enhanced by 29% in the risk group, making secretion similar to patients carrying the low-risk allele. The corrected insulin response and disposition index in individuals with the high-risk (but not low-risk) allele were improved by 59 ± 18% and 43 ± 14%, respectively. The beneficial effect of yohimbine was not a consequence of improved insulin sensitivity. In summary, the data show that the insulin secretion defect in patients carrying the ADRA2A risk genotype can be corrected by α2AAR antagonism. The findings show that knowledge of genetic risk variants can be used to guide therapeutic interventions that directly target the underlying pathophysiology and demonstrate the potential of individualized genotype-specific treatment of type 2 diabetes.
Locally delivered 0.5% clarithromycin, as an adjunct to nonsurgical treatment in chronic periodontitis with well-controlled type 2 diabetes: a randomized controlled clinical trial.

Several epidemiologic studies have identified a greater incidence of periodontitis in patients with type 2 diabetes. Recent developments suggest that local delivery of antimicrobials into periodontal pockets improve periodontal health. The present study was designed to investigate the adjunctive effects of subgingivally delivered clarithromycin (CLM) (0.5% concentration) as an adjunct to scaling and root planing for treating chronic periodontitis in patients with well-controlled type 2 diabetes.



Sixty-three patients were categorized into two treatment groups: Group 1, scaling and root planing (SRP) plus 0.5% CLM; Group 2, SRP plus placebo gel. Clinical parameters were recorded at baseline, 1, 2, and 3 months; which included gingival index (GI), sulcus bleeding index (SBI), plaque index (PI), probing depth (PD), and periodontal attachment level (PAL).



Both therapies resulted in significant improvements. Using a subject-based analysis, patients in Group 1 treated with SRP + CLM showed enhanced reductions in PI, GI, SBI, and PD, and gains in PAL (P < 0.001) over a period of 6 months as compared to Group 2.



Although both treatment strategies seemed to benefit the patients, the adjunctive use of 0.5% CLM as a controlled drug delivery system enhanced the clinical outcome.
Multicenter phase II study of antimicrobial prophylaxis in low-risk patients undergoing distal gastrectomy for gastric cancer

In Japan, antimicrobial prophylaxis (AMP) is typically administered for 3 to 4 days postoperatively for clean-contaminated operations such as distal gastrectomy. This far exceeds the recommended 2h or less laid out by the Centers for Disease Control (CDC) guidelines for the prevention of surgical-site infections (SSIs), after a clean-contaminated operation. Patients with gastric cancer, which was curable by distal gastrectomy with D2 lymphandectomy, were assigned to a multicenter phase II study. One gram of cefazolin within 3min of the first surgical incision and intraoperative supplements of g of cefazolin every h were administered. AMP was not administered after skin closure unless postoperative infection occurred. The occurrence of SSIs was monitored until postoperative day 30 as the primary endpoint of this study. In 56 patients, three SSIs (5.4%) and one remote site infection (1.8%) developed. No other postoperative infections were observed. Our data indicate that the CDC guidelines regarding AMP may also be sufficient for patients undergoing clean-contaminated operations in Japan.
Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial.

The generalized type of social phobia (social anxiety disorder) is a severe and often disabling form of social anxiety that affects approximately 5% of the general population. Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition, but neither has achieved widespread use.



To compare the efficacy of paroxetine, a selective serotonin reuptake inhibitor, with placebo in adults with generalized social phobia.



Twelve-week, multicenter, randomized, double-blind trial.



Thirteen centers across the United States and 1 in Canada.



Between April 13, 1995, and February 28, 1996, 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for generalized social phobia were randomized (and 183 returned for at least 1 efficacy assessment) to treatment.



After a 1-week, single-blind, placebo, run-in period, patients received a double-blind, 11-week course of either paroxetine or matching-image placebo. The initial daily dosage of paroxetine (or placebo) was 20 mg with increases of 10 mg/d weekly (flexible dosing to a maximum of 50 mg/d) permitted after the second week of treatment.



Number of responders based on the Clinical Global Impression Global Improvement Item ("much improved" or "very much improved"); mean change from baseline on the Liebowitz Social Anxiety Scale total score.



Fifty (55.0%) of 91 persons taking paroxetine and 22 (23.9%) of 92 persons taking placebo were much improved or very much improved at the end of treatment (odds ratio [OR], 3.88; 95% confidence interval [CI], 2.81-5.36). Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1% (the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up) in the paroxetine group compared with 17.4% (the mean baseline score of 83.5 declined 14.5 points at follow-up) in the placebo group, a difference of 21.7% (95% CI, 8.7%-34.7%) favoring paroxetine.



Paroxetine is an effective treatment for patients with generalized social phobia. Short-term (ie, 11-week) treatment results in substantial and clinically meaningful reductions in symptoms and disability. Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques.
Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.

To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy.



A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups.



Human gait analysis laboratory.



Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15).



Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method.



Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed.



Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P < 0.05). Kinematic data demonstrated that anterior tilt of the pelvis and hip flexion during a gait cycle was significantly ameliorated after rhythmic auditory stimulation (P < 0.05). Gait deviation index also showed modest improvement in cerebral palsy patients treated with rhythmic auditory stimulation (P < 0.05). However, neurodevelopmental treatment showed that internal and external rotations of hip joints were significantly improved, whereas rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P < 0.05).



Gait training with rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.
Effects of cognitive and motor tasks on the walking speed of individuals with chronic stroke

Walking speed is a measure of gait performance after a stroke and a predictor of community ambulatory competence. Although gait decrements during a cognitive or motor task after stroke are well-documented, the differential effects of motor and cognitive tasks on the comfortable and maximum walking speeds of individuals with chronic stroke have not been investigated. This study aimed to compare the effects of cognitive and motor tasks on the comfortable and maximum walking speeds of individuals with chronic stroke.This is a cross-sectional study. Thirty community-dwelling chronic stroke individuals were included. Time taken to complete the 10-meter Walk Test under various conditions, including walking alone, walking while completing a cognitive task, and walking while completing a motor task, was recorded, with each condition performed at comfortable as well as maximum walking speeds. Accuracy in performing the cognitive tasks was also assessed.The cognitive and motor tasks caused decrements in both comfortable and maximum walking speeds (P ≤ 0.001). The cognitive task had a greater influence than the motor task on maximum walking speed (P < 0.01).Individuals with chronic stroke tend to prioritize task accuracy and completion over maintaining walking speed. This phenomenon was more evident during the cognitive task than the motor task and was especially evident at maximum walking speed.
Factors associated with the development of self-harm amongst a socio-economically deprived cohort of adolescents in Santiago, Chile

Studies carried out in the West indicate that the incidence of self-harm (SH) is particularly high amongst adolescents, but few studies have investigated its incidence and aetiology in low-income countries. The purpose of this study was to investigate risk factors associated with new onset episodes of SH, amongst Chilean adolescents from low socio-economic backgrounds. Prospective cohort study nested within a cluster randomised controlled trial. A 6-month follow-up for 2,042 adolescents, median age 14 years, from socio-economically deprived areas of Santiago, Chile. The lifetime prevalence of SH was 23 %. The incidence rate of SH at 6 months was 14 % amongst those reporting no SH at baseline. In multivariable analyses, risk factors for incident SH include depressive symptoms, suicidal thoughts, poor problem-solving skills and cannabis misuse. The prevalence and incidence of SH in this socio-economically deprived sample differed highly according to gender. Poor problem-solving skills, suicidal thoughts, and cannabis misuse were associated with onset of SH.
Could Hyaluronic acid (HA) reduce Bacillus Calmette-Guérin (BCG) local side effects? Results of a pilot study

Bacillus Calmette-Guérin (BCG) is considered the most effective treatment to reduce recurrence and progression of non-muscle invasive bladder cancer (NMIBC) but can induce local side effects leading to treatment discontinuation or interruption. Aim of this exploratory study is to investigate if the sequential administration of Hyaluronic acid (HA) may reduce local side effects of BCG.



30 consecutive subjects undergoing BCG intravesical administration for high risk NMIBC were randomized to receive BCG only (Group A) or BCG and HA (Group B). A 1 to 10 Visual Analog Scale (VAS) for bladder pain, International Prostate Symptom Score (IPSS) and number of micturitions per day were evaluated in the two groups before and after six weekly BCG instillations. Patients were also evaluated at 3 and 6 months by means of cystostopy and urine cytology.



One out of 30 (3,3%) patients in group A dropped out from the protocol, for local side effects. Mean VAS for pain was significantly lower in group B after BCG treatment (4.2 vs. 5.8, p = 0.04). Post vs. pre treatment differences in VAS for pain, IPSS and number of daily micturitions were all significantly lower in group B. Three patients in group A and 4 in group B presented with recurrent pathology at 6 month follow up.



These preliminary data suggest a possible role of HA in reducing BCG local side effects and could be used to design larger randomized controlled trials, assessing safety and efficacy of sequential BCG and HA administration.
Supervised resistance training results in changes in postural control in patients with multiple sclerosis.

Postural disturbances are one of the first reported symptoms in patients with Multiple Sclerosis (MS). The purpose of this study was to investigate the effect of supervised resistance training on postural control in MS patients. Postural control was assessed using amount of sway variability [Root Mean Square (RMS)] and temporal structure of sway variability [Lyapunov Exponent (LyE)] from 15 MS patients. Posture was evaluated before and after completion of three months of resistance training. There were significant differences between MS patients pretraining and healthy controls for both LyE (p = .000) and RMS (p = .002), but no differences between groups after training. There was a significant decrease in RMS (p = .025) and a significant increase in LyE (p = .049) for MS patients pre- to posttraining. The findings suggested that postural control of MS patients could be affected by a supervised resistance training intervention.
Safety of zoledronic acid and incidence of osteonecrosis of the jaw (ONJ) during adjuvant therapy in a randomised phase III trial (AZURE: BIG 01–04) for women with stage II/III breast cancer

The AZURE trial is an ongoing phase III, academic, multi-centre, randomised trial designed to evaluate the role of zoledronic acid (ZOL) in the adjuvant therapy of women with stage II/III breast cancer. Here, we report the safety and tolerability profile of ZOL in this setting. Eligible patients received (neo)adjuvant chemotherapy and/or endocrine therapy and were randomised to receive neither additional treatment nor intravenous ZOL 4 mg. ZOL was administered after each chemotherapy cycle to exploit potential sequence-dependent synergy. ZOL was continued for 60 months post-randomisation (six doses in the first 6 months, eight doses in the following 24 months and five doses in the final 30 months). Serious (SAE) and non-serious adverse event (AE) data generated during the first 36 months on study were analysed for the safety population. 3,360 patients were recruited to the AZURE trial. The safety population comprised 3,340 patients (ZOL 1,665; control 1,675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. SAE were similar in both treatment arms. No significant safety differences were seen apart from the occurrence of osteonecrosis of the jaw (ONJ) in the ZOL group (11 confirmed cases; 0.7%; 95% confidence interval 0.3–1.1%). ZOL in the adjuvant setting is well tolerated, and can be safely administered in addition to adjuvant therapy including chemotherapy. The adverse events were consistent with the known safety profile of ZOL, with a low incidence of ONJ.
A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation.

It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use.



To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures.



Women (> or = 18 years of age) with IBS-C according to the Rome II criteria.



Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat.



2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p < 0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p < 0.05).



Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.
Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial

Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the effects of diet and physical activity on blood pressure and glucose concentrations.



We did a randomised, controlled trial in southwest England in adults aged 30-80 years in whom type 2 diabetes had been diagnosed 5-8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c)) concentration and blood pressure at 6 months. Analysis was done by intention to treat. 
Of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA(1c) percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA(1c) -0·28%, 95% CI -0·46 to -0·10; p=0·005) and diet plus activity group (-0·33%, -0·51 to -0·14; p<0·001). These differences persisted to 12 months, despite less use of diabetes drugs. Improvements were also seen in bodyweight and insulin resistance between the intervention and control groups. Blood pressure was similar in all groups.



An intensive diet intervention soon after diagnosis can improve glycaemic control. The addition of an activity intervention conferred no additional benefit.



Diabetes UK and the UK Department of Health.
Effect of famotidine on oesophageal sensitivity in gastro-oesophageal reflux disease.

Gastric acid suppression could improve heartburn by healing oesophagitis or by reduction of oesophageal sensitivity to acid. To independently assess changes in oesophageal sensitivity, it would be necessary to study patients with reflux disease but no oesophagitis. The aim of this study was to investigate the effect of acid suppression on oesophageal sensitivity and to assess the time course of any measured effect. Twenty seven patients were recruited, of whom 25 completed the study (14 men and 11 women, mean (SD) age 50 (15) years). All had classic symptoms of gastro-oesophageal reflux but normal results of upper gastrointestinal endoscopy and oesophageal mucosal histological tests. Each had abnormal 24 hour pH studies and a positive acid perfusion tests. Subjects were assigned double blind to placebo (n = 11) or famotidine 40 mg twice daily (n = 14) for four weeks. Acid perfusion tests were carried out at 0, 4, 5, and 8 weeks and time to heartburn recorded. Time to heartburn (mean (SEM)) was 124 (78) seconds in the famotidine and 187 (154) in the placebo group at week 0 (NS). Compared with baseline, significant increases in time to heartburn was found with famotidine at weeks 4 (383 (102), p < 0.01) and 5 (344 (92), p < 0.01) but not week 8 (336 (90) seconds). No significant effects were found with placebo (219 (41), 146 (23), and 144 (25) seconds for weeks 4, 5, and 8). Heartburn symptom score decreased significantly with famotidine (mean scores 3.6, 1.9, 2.1, and 2.6 at weeks 0, 4, 5, and 8 (p=0.001)) and showed a significant negative correlation with time to heartburn (r(s)=-0.60; p<0.0001). It is concluded that oesophageal sensitivity to acid is reduced by famotidine independent of and effect on oesophagitis; the effect wanes one to four weeks after the end of treatment and correlates with change in heartburn score.
The impact of frontline risk-adapted strategy on the overall survival of patients with newly diagnosed multiple myeloma: an analysis of the Singapore multiple myeloma study group.

Risk stratification is vital for prognostication and informing treatment decisions in multiple myeloma (MM). We study the prognostic values of the International Staging System (ISS) and underlying cytogenetics in the bortezomib era and assess the impacts of an upfront risk-adapted approach in the treatment of MM.



We compare the overall survival (OS) of 221 patients with MM diagnosed from 2006 to 2009 (era 2) where upfront bortezomib combination was approved for high-risk MM with the OS of 262 patients diagnosed from 2000 to 2005 (era 1) where bortezomib could only be administered at relapse. High-risk MM is defined by the presence of ISS III disease with renal impairment or adverse cytogenetics.



Baseline characteristics were comparable between the 2 eras. At median follow-up of 20 months, 0% and 26% of patients had received frontline bortezomib in eras 1 and 2, respectively. The median OS were 4.2 yrs and not reached for eras 1 and 2, respectively (P = 0.03). On multivariate analysis stratified by era, the most significant prognostic factor shifts from cytogenetics in era 1 to the quality of response in era 2.



Frontline use of bortezomib in a risk-adapted manner may avert early mortality and is better able to overcome adverse risks compared to its sequential use.