nils-herrmann/clean_scirepeval huggingface dataset:
Radiographic progression of knee osteoarthritis is associated with MRI abnormalities in both the patellofemoral and tibiofemoral joint.

To investigate patterns of MRI abnormalities in the patellofemoral (PFJ) and tibiofemoral joint (TFJ) and their association with radiographic progression, using hypothesis free analyses.



205 patients from the GARP study with symptomatic OA at multiple sites (mean age 60 years, 80% woman, median BMI 26 kg/m(2)), underwent knee MRI at baseline. Cartilage damage, osteophytes, cysts, bone marrow lesions (BMLs) and effusion/synovitis were scored according to a validated scoring method. Baseline and 6-year TFJ and PFJ radiographs were scored (0-3) for JSN and osteophytes according to OARSI and Burnett atlases, respectively; progression was defined as ≥1 point increase. Baseline patterns of MRI abnormalities derived from principal component analysis (PCA) were associated with progression using adjusted generalized estimating equations (GEE).



PCA resulted in extraction of six components, explaining 69% of variance. In 29% and 29% of 133 patients with follow-up the TFJ progressed, whereas in 15% and 9% the PFJ progressed for osteophytes and JSN, respectively. Component 1 (cartilage damage of the PFJ and osteophytes of both joints) was statistically significant associated with TFJ JSN progression and PFJ osteophyte progression. Component 2 (all lateral PFJ abnormalities except osteophytes) was associated with JSN/osteophyte progression in the PFJ alone, whereas component 3 (all medial TFJ abnormalities except osteophytes) was associated with JSN and osteophyte progression in both PFJ and TFJ.



Baseline structural damage and bone turnover activity, as reflected by BMLs, seem to be involved in knee OA progression. Moreover, progression in PFJ and TFJ seems to be related.
Buprenorphine dosing regime for inpatient heroin withdrawal: a symptom-triggered dose titration study.

The study aimed to identify the range of buprenorphine doses required to comfortably alleviate symptoms in patients undergoing inpatient heroin withdrawal using a symptom-triggered titration dosing regime, and to identify the patient characteristics that impact upon the buprenorphine dose requirements. The study was conducted in two Australian inpatient withdrawal units, recruiting 63 dependent, injecting heroin users with no recent methadone treatment, dependence on other drugs, or other active medical or psychiatric conditions. In a single (patient) blinded case series, placebo or 2 mg sublingual buprenorphine tablets was administered four times a day according to severity of withdrawal (assessed with Subjective Opiate Withdrawal Scale). Up to 16 mg buprenorphine was available over the first 4 days of the admission, up to 8 mg on day 5, and placebo continued until day 6. Thirty-two subjects completed the dosing regime, with mean (+/-S.D.) daily doses of 3.8+/-2.8 on day 1, 5.8+/-3.2 on day 2, 4.8+/-3.3 on day 3, 2.3+/-2.6 on day 4, 0.8+/-1.3 on day 5, and a total dose of 17.4+/-9.7. Higher buprenorphine doses were required by those patients with more severe psychosocial dysfunction, women, those with more frequent heroin use, and those with more severe dependence on heroin at intake. A dosing regime using sublingual buprenorphine tablets for short inpatient heroin withdrawal is proposed.
Postal Workers’ Occupational and Leisure-time Sun Safety Behaviors (United States)

United States Postal Service letter carriers are exposed to long bouts of UVR and thus are vulnerable to skin cancer. While previous studies have shown that occupational sun protection is often deficient, few studies have examined outdoor workers’ behavior during leisure time.  Subjects (n = 2,660) self-reported widebrim hat and sunscreen use over the past five workdays and past two non-working days using Likert-type scales. Generalized linear mixed models and generalized estimating equations were used to compare hat and sunscreen rates and predictors during occupational and leisure time.  On average, carriers spent 3.9 h outside during workdays and 3.3 h during non-working days. Sunscreen and widebrim hat use during the workday is low and rates of use are significantly lower during non-working days.  Sun safety interventions for carriers should encourage sun protection at all times when outdoors.
Web-based screening and brief intervention for poly-drug use among teenagers: study protocol of a multicentre two-arm randomized controlled trial

Mid to late adolescence is characterised by a vulnerability to problematic substance use since the consumption of alcohol and illicit drugs is frequently initiated and increased in this life period. While the detrimental long- and short-term effects of problematic consumption patterns in adolescence pose a major public health concern, current prevention programs targeting alcohol- and other substance-using adolescents are scarce. The study described in this protocol will test the effectiveness of a web-based brief intervention aimed at reducing problematic alcohol use and promoting abstinence from illegal drugs in adolescents with risky substance use aged 16 to 18 years old in four EU-countries.



To determine the effectiveness of our web-BI, we apply a two-arm randomized controlled trial (RCT) study design, with baseline assessment at study entry and a three month follow-up assessment. Adolescents aged 16 to 18 years from Belgium, the Czech Republic, Germany, and Sweden will be randomly assigned to either the fully electronically delivered brief intervention group (N = 400) or an assessment only control group (N = 400) depending on their screening for risky substance use (using the CRAFFT). Recruitment, informed consent, randomization, intervention and follow-up will be implemented online. Primary outcomes are reductions in frequency and quantity of use of alcohol and drugs other than alcohol over a 30 day period, as well as consumption per typical occasion. Secondary outcomes concern changes in substance use related cognitions including the constructs of the Theory of Planned Behaviour, implementation intentions, and stages of change. Moreover the study addresses a number of moderator variables, including age of first use, general psychopathology and quality of parent-child relationship.



The trial is expected to contribute to the growing literature on theory- and web-based brief interventions for adolescents. We will explore the potential of using web-based technologies as means of delivering preventive interventions. In doing so we are among the first to target the relevant group of young poly-drug users in Europe.
Treatment with parathyroid peptides and estrogen replacement for severe postmenopausal vertebral osteoporosis: prediction of long-term responses in spine and femur

Fifteen women with severe vertebral osteoporosis were treated with daily parathyroid peptide (hPTH) plus hormone-replacement co-therapy (HRT) for 1 year. Eight other patients were randomized to HRT alone. Co-therapy with hPTH and HRT resulted in an impressive mean treatment response at the spine (dual-energy X-ray absorptiometry DXA) 15% above baseline; P < 0.015 compared with the HRT group) at 2 years, while at the proximal femur and radius there were smaller increases. hPTH co-therapy led to a significantly positive metabolic calcium balance at 1 year (by 2.13 mmol Ca/day, equivalent to a 5% annual increment in total body calcium; P = 0.015). The magnitude of the lumbar spine DXA response at 2 years depended statistically on the increase in bone formation rate, measured with 85Sr (r 2 adjusted 0.48; P < 0.005) and patients with a large spine DXA response had larger calcium balance improvements (P < 0.03). Plasma osteocalcin changes tracked closely with increases in bone formation rate (r 2 = 0.87). In seven patients treated throughout with HRT alone, and in eight hPTH-treated patients (three of whom switched to bisphosphonate therapy at year 4), DXA spine changes seen in years 3–5 were minimal, with no evidence of a statistically significant difference between groups. It is concluded that hPTH or comparable PTH receptor activators remain the most promising anabolic treatment for osteoporosis currently under clinical evaluation and a 6- or 12-month measurement of bone formation or a marker predicts the 2–5 year bone density outcome. Post-hPTH treatment, loss of bone appeared preventable with anti-resorptive therapy.
Psychological treatment of patients with psychogenic non-epileptic seizures: An outcome study

It is estimated that up to 25% of patients referred to specialised epilepsy centers suffer from psychogenic non-epileptic seizures (PNES). The prognosis is unfavourable and there are no generally accepted treatment protocols.



In this study, the effect of an uncontrolled, prospective inpatient treatment program for PNES patients is evaluated. The treatment is multidisciplinary and based on cognitive behavioural principles. Seizure control, general psychopathology, anxiety, depression, coping, dissociation and health related quality of life are evaluated. Twenty-two patients participated in the study of which 16 patients were followed 6 months after treatment.



After follow-up, 81% of patients had a seizure reduction of over 50%, and half of them became seizure-free. Measures of anxiety, depression and dissociation tended to normalize, coping was more adequate and health related quality of life was increased slightly. In the period between the end of treatment and follow-up the most positive effects are maintained and even strengthened. Patients who became seizure-free at follow-up improved more on the psychological outcome measures than patients with continuing seizures.



The outcome suggests effectiveness of the treatment. PNES patients may profit from a comprehensive, multidisciplinary treatment program following cognitive behavioural principles. Seizure cessation appears to be an important factor in the improvement of psychological functioning.
Brief alcohol intervention for college drinkers: how brief is?

Brief interventions for college student drinkers have been shown to be effective in reducing the amount of alcohol consumed as well as the number of alcohol-related problems. However, the duration of brief interventions varies substantially across studies.



In the present study 114 undergraduate students who drank alcohol heavily were randomly assigned to a 10-minute brief intervention, a 50-minute brief intervention, or assessment-only control. The content of the active interventions was based on the same concept, and both interventions incorporated motivational interviewing components. Participants were assessed at baseline and 4-week post intervention on quantity of alcohol use, alcohol-related problems, and protective behavioral strategies.



As hypothesized, there was a significant difference between participants in the 10-minute intervention and control condition regarding their alcohol consumption at 4-week follow up. However, there was no significant difference between the 50-minute intervention and the control condition on alcohol consumption. There were also no significant differences between active intervention conditions, and neither intervention showed advantages for reducing problems or increasing protective behaviors relative to the control condition.



Results suggest a very brief intervention can impact short-term alcohol use outcomes, with potentially no advantage of longer interventions for this population.
A randomised controlled trial of the efficacy of supported employment.

Although numerous randomised controlled trials indicated the superiority of supported employment (SE), we still have too little evidence that SE is more effective than traditional vocational rehabilitation programmes (TVR) in Western European countries with highly developed social security and welfare systems, sophisticated rehabilitation programmes and high thresholds to the open labour market. The aim of this study is to prove the efficacy of SE in Switzerland.


METHOD
  Following a 2-week intake assessment, 100 unemployed persons with stabilised severe mental illness (SMI) were randomly assigned to either the SE programme (n=46) or to the most viable locally available TVR (n=54). Follow-up lasted 24 months.


After the first year, the rate of competitive employment reached a mean level of 48.2% in the SE group and of 18.5% in the TVR group. 58.7% of the SE group were ever competitively employed as opposed to 25.9% of the TVR group. In the second year, SE group participants were competitively employed for 24.5 weeks as compared with 10.2 in the TVR group. The groups showed no significant differences in the non-vocational outcome criteria.


The SE programme in Switzerland also proved more effective than TVR and seems to be applicable to the socio-economic context of Western European countries.
Safety, tolerability, and pharmacokinetics of a single dose of pasireotide long-acting release in healthy volunteers: a single-center Phase I study.

This study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PKs) of different doses of a long-acting release (LAR) formulation of pasireotide in healthy subjects.



Single-center, open-label, randomized Phase I study.



Twelve healthy male subjects received a single s.c. dose of pasireotide 300 μg followed by a washout period of 7 days (or at least 5 days), before receiving an i.m. injection of pasireotide -LAR 40 mg (n=5) or 60 mg (n=7). Assessments included adverse events (AEs), PKs, and glucose, insulin, glucagon, and HbA1c levels.



Pasireotide LAR showed an extended-release profile over 1 month with two concentration peaks observed 1 and around 20 days after injection. The area under curve exposure of pasireotide LAR was dose proportional when the dose levels were compared, and the bioavailability of the LAR relative to the s.c. formulation was complete. Administration of pasireotide LAR resulted in an increase in fasting and postprandial glucose levels; however, an attenuation of the hyperglycemic effect was observed after 15 days. The most frequently reported AEs were mild-to-moderate diarrhea, abdominal pain, and flatulence. Only gastrointestinal AEs and injection site reactions were suspected to be drug related.



Pasireotide LAR was generally well tolerated with mostly mild AEs at doses up to 60 mg and showed a dose-proportional, extended-release profile in healthy subjects. Based on the favorable results of this study, further clinical development of pasireotide LAR is under way, which will give insight into the PKs, efficacy, and safety of pasireotide LAR in patient populations.
Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers.

Health claims link soy protein (SP) consumption, through plasma cholesterol reduction, to a decreased risk of heart disease. Soy isoflavones (ISOs), particularly in individuals who produce equol, might also contribute to lipid lowering and thus reduce SP requirements.



The objective was to examine the contributions of SP, ISOs, and equol to the hypocholesterolemic effects of soy foods.



Nonsoy consumers (33 men, 58 women) with a plasma total cholesterol (TChol) concentration >5.5 mmol/L participated in a double-blind, placebo-controlled, crossover intervention trial. The subjects consumed 3 diets for 6 wk each in random order, which consisted of foods providing a daily dose of 1) 24 g SP and 70-80 mg ISOs (diet S); 2) 12 g SP, 12 g dairy protein (DP), and 70-80 mg ISOs (diet SD); and 3) 24 g DP without ISOs (diet D). Fasting plasma TChol, LDL cholesterol, HDL cholesterol, and triglycerides (TGs) were measured after each diet.



TChol was 3% lower with the S diet (-0.17 +/- 0.06 mmol/L; P < 0.05) than with the D diet, and TGs were 4% lower with both the S (-0.14 +/- 0.05 mmol/L; P < 0.05) and SD (-0.12 +/- 0.05 mmol/L; P < 0.05) diets. There were no significant effects on LDL cholesterol, HDL cholesterol, or the TChol:HDL cholesterol ratio. On the basis of urinary ISOs, 30 subjects were equol producers. Lipids were not affected significantly by equol production.



Regular consumption of foods providing 24 g SP/d from ISOs had no significant effect on plasma LDL cholesterol in mildly hypercholesterolemic subjects, regardless of equol-producing status.
Effects of escitalopram on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, in Japanese patients.

The effects of escitalopram (10 mg/d) coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 13 Japanese psychiatric patients and compared with those of paroxetine (10 mg/d) coadministration.



The patients had received 6-24 mg/d of aripiprazole for at least 2 weeks. Patients were randomly allocated to one of 2 treatment sequences: paroxetine-escitalopram (n=6) or escitalopram-paroxetine (n=7). Each sequence consisted of two 2-week phases. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection.



Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during paroxetine coadministration were 1.7-fold (95% confidence intervals [CI], 1.3-2.1, p<0.001) and 1.5-fold (95% CI 1.2-1.9, p<0.01) higher than those values before the coadministration. These values were not influenced by escitalopram coadministration (1.3-fold, 95% CI 1.1-1.5 and 1.3-fold, 95% CI 1.0-1.5). Plasma dehydroaripiprazole concentrations remained constant during the study.



The present study suggests that low doses of escitalopram can be safely coadministered with aripiprazole, at least from a pharmacokinetic point of view.
A real world comparison of sulfonylurea and insulin vs. incretin-based treatments in patients not controlled on prior metformin monotherapy

Metformin is the first line drug for patients diagnosed with type-2 diabetes; however, the impact of different treatment escalation strategies after metformin failure has thus far not been investigated in a real world situation. The registry described herein goes some way to clarifying treatment outcomes in such patients.



DiaRegis is a multicentre registry including 3,810 patients with type-2 diabetes. For the present analysis we selected patients being treated with metformin monotherapy at baseline (n = 1,373), with the subsequent addition of incretin-based drugs (Met/Incr; n = 783), sulfonylureas (Met/SU; n = 255), or insulin (n = 220).



After two years 1,110 of the initial 1,373 patients had a complete follow-up (80.8%) and 726 of these were still on the initial treatment combination (65.4%). After treatment escalation, compared to Met/Incr (n = 421), Met/SU (n = 154) therapy resulted in a higher HbA1c reduction vs. baseline (-0.6 ± 1.4% vs. -0.5 ± 1.0%; p = 0.039). Insulin (n = 151) resulted in a stronger reduction in HbA1c (-0.9 ± 2.0% vs. -0.5 ± 1.0%; p = 0.003), and fasting plasma glucose (-24 ± 70 mg/dl vs. -19 ± 42 mg/dl; p = 0.001), but was associated with increased bodyweight (0.8 ± 9.0 kg vs. -1.5 ± 5.0 kg; p = 0.028). Hypoglycaemia rates (any with or without help and symptoms) were higher for patients receiving insulin (Odds Ratio [OR] 8.35; 95% Confidence Interval [CI] 4.84-14.4) and Met/SU (OR 2.70; 95% CI 1.48-4.92) versus Met/Incr. While there was little difference in event rates between Met/Incr and Met/SU, insulin was associated with higher rates of death, major cardiac and cerebrovascular events, and microvascular disease.



Taking the results of DiaRegis into consideration it can be concluded that incretin-based treatment strategies appear to have a favourable balance between glycemic control and treatment emergent adverse effects.
Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics.

This phase I trial examined the safety, pharmacokinetics, and pharmacodynamics of MLN8054, an oral, selective, small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received increasing doses of MLN8054 in 28-day cycles until dose-limiting toxicity (DLT) was seen in ≥2 of 3-6 patients in a cohort. For the 10-mg and 20-mg cohorts, treatment was administered once daily on days 1 to 5 and 8 to 12. Patients in later cohorts (25, 35, 45, 55, 60, 70, and 80 mg/day) were treated four times daily on days 1 to 14, with the largest dose at bedtime (QID-14D) to mitigate benzodiazepine-like effects possibly associated with peak plasma concentrations. Patients (n = 43) received a median of 1 cycle (range, 1-10). DLT of somnolence was first noted in the 20-mg cohort. Two DLTs of somnolence (n = 1) and transaminitis (n = 1) were seen at QID-14D 80 mg. Grade 2 oral mucositis (n = 1), predicted to be a mechanistic effect, was observed only at QID-14D 80 mg. MLN8054 exposure levels were roughly linear with dose; terminal half-life was 30 to 40 hours. Pharmacodynamic analyses of skin and tumor mitotic indices, mitotic cell chromosome alignment, and spindle bipolarity provided evidence of Aurora A inhibition. MLN8054 dosing for 10 to 14 days in 28-day cycles was feasible. Somnolence and transaminitis were DLTs. Pharmacodynamic analyses in mitotic cells of both skin and tumor provided proof of mechanism for Aurora A kinase inhibition. A more potent, selective, second-generation Aurora A kinase inhibitor, MLN8237, is in clinical development.
Animal-assisted activity and emotional status of patients with Alzheimer's disease in day care.

Preliminary studies suggest beneficial effects of animal-assisted activities (AAA) on behavioral and psychological symptoms of dementia (BPSD), but data are inconsistent. This study aimed to assess the effect of AAA with dogs on cognition, BPSD, emotional status and motor activity in severe Alzheimer's disease (AD).



Ten patients attending an Alzheimer Day Care Center (ADCC) participated in a repeated measures study, which included: two weeks' pre-intervention, three weeks' control activity with plush dogs (CA), and three weeks' AAA. Cognitive function (Severe Impairment Battery), mood (Cornell Scale for Depression in Dementia; CSDD), BPSD (Neuropsychiatric Inventory; NPI) and agitation (Cohen-Mansfield Agitation Inventory; CMAI) were assessed at baseline and after each period. Observed Emotion Rating Scale (OERS) for emotional status, Agitated Behavior Mapping Instrument (ABMI) and a checklist for motor activity were completed across the study periods, both during intervention sessions and after three hours.



Cognition and NPI were unchanged across the study. Declines in the CMAI and CSDD scores after AAA were not significant, while the NPI anxiety item score decreased in comparison with CA (CA 3.1±2.3, AAA 1.5±2.7, p = 0.04). OERS "sadness" decreased (p = 0.002), while "pleasure" (p = 0.016) and "general alertness" (p = 0.003) increased during AAA compared with CA sessions, and observed sadness remained lower after three hours (p = 0.002). Motor activity increased significantly during AAA.



In this sample of severe AD patients in ADCC, AAA was associated with a decrease in anxiety and sadness and an increase in positive emotions and motor activity in comparison with a control activity.