nils-herrmann/clean_scirepeval huggingface dataset:
In obese individuals dexfenfluramine corrects molecular derangements reflecting insulin resistance

Circulating lymphocytes of obese individuals with and without type 2 diabetes have derangements of pyruvate dehydrogenase (PDH) that are described as reflecting a disorder underlying systemic insulin resistance, namely basal activity below normal and, in vitro, unresponsiveness to insulin at 33 pmol/l and activation at 330 pmol/l instead of activation and inhibition as in controls. To explore whether the above enzyme derangements are overcome in obese individuals on dexfenfluramine treatment, known to improve poor peripheral insulin sensitivity. Fifteen obese diabetic patients and 15 age-matched euglycaemic obese subjects with normal glucose tolerance were enrolled for a trial composed of two 21-day periods; in the first (D-21–D0), participants received a placebo, and in the second (D0–D21), dexfenfluramine (30 mg/day). At D-21, D0 and D21 participants were evaluated for weight, BMI, fasting glycaemia (FG), fasting insulinaemia (FI), fasting insulin resistance index (FIRI), area under the glycaemic (G-AUC) and insulinaemic (I-AUC) curves from an OGT test, and for PDH activity assayed in their circulating lymphocytes before (basal activity) and after incubation with 33 or 330 pmol/l insulin. At D2, basal PDH activity and clinical parameters were assayed. In both groups of participants at D0 all parameters tested were constant with respect to D-21; at D2, only basal PDH activity rose significantly; at D21, basal and insulin stimulated PDH activities were normalized and weight decreased significantly, as did FG, FI, FIRI and G-AUC in the diabetic, and FI, FIRI, G-AUC and I-AUC in the non-diabetic participants. In obese, non-diabetic and diabetic individuals on dexfenfluramine treatment, amelioration of clinical parameters and indexes of poor insulin sensitivity of blood glucose homeostasis are preceded by correction, in their circulating lymphocytes, of PDH derangements described as reflecting a disorder underlying insulin resistance.
Clinical performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project.

To test the sensitivity, specificity and accuracy of serum prostate-specific antigen isoform [-2]proPSA (p2PSA), %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer (PCa) undergoing prostate biopsy for suspected PCa. To evaluate the potential reduction in unnecessary biopsies and the characteristics of potentially missed cases of PCa that would result from using serum p2PSA, %p2PSA and PHI.



The analysis consisted of a nested case-control study from the PRO-PSA Multicentric European Study, the PROMEtheuS project. All patients had a first-degree relative (father, brother, son) with PCa. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis.



Of the 1026 patients included in the PROMEtheuS cohort, 158 (15.4%) had a first-degree relative with PCa. p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001), and free/total PSA (%fPSA) values significantly lower (P < 0.001) in the 71 patients with PCa (44.9%) than in patients without PCa. Univariable accuracy analysis showed %p2PSA (area under the receiver-operating characteristic curve [AUC]: 0.733) and PHI (AUC: 0.733) to be the most accurate predictors of PCa at biopsy, significantly outperforming total PSA ([tPSA] AUC: 0.549), free PSA ([fPSA] AUC: 0.489) and %fPSA (AUC: 0.600) (P ≤ 0.001). For %p2PSA a threshold of 1.66 was found to have the best balance between sensitivity and specificity (70.4 and 70.1%; 95% confidence interval [CI]: 58.4-80.7 and 59.4-79.5 respectively). A PHI threshold of 40 was found to have the best balance between sensitivity and specificity (64.8 and 71.3%, respectively; 95% CI 52.5-75.8 and 60.6-80.5). At 90% sensitivity, the thresholds for %p2PSA and PHI were 1.20 and 25.5, with a specificity of 37.9 and 25.5%, respectively. At a %p2PSA threshold of 1.20, a total of 39 (24.8%) biopsies could have been avoided, but two cancers with a Gleason score (GS) of 7 would have been missed. At a PHI threshold of 25.5 a total of 27 (17.2%) biopsies could have been avoided and two (3.8%) cancers with a GS of 7 would have been missed. In multivariable logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariable models including PSA and prostate volume by 8.7 and 10%, respectively (P ≤ 0.001). p2PSA, %p2PSA and PHI were directly correlated with Gleason score (ρ: 0.247, P = 0.038; ρ: 0.366, P = 0.002; ρ: 0.464, P < 0.001, respectively).



%p2PSA and PHI are more accurate than tPSA, fPSA and %fPSA in predicting PCa in men with a family history of PCa. Consideration of %p2PSA and PHI results in the avoidance of several unnecessary biopsies. p2PSA, %p2PSA and PHI correlate with cancer aggressiveness.
Protective effect of pre-infarction angina on microvascular obstruction after primary percutaneous coronary intervention is blunted in humans by cardiovascular risk factors.

Pre-infarction angina (PIA) has been shown to reduce the microvascular obstruction (MVO) rate in patients with ST-segment elevation myocardial infarction (STEMI). We sought to evaluate the potential modulator role of cardiovascular risk factors (CRFs) on this protective effect.



Two hundred patients with STEMI were enrolled. PIA was defined as typical chest pain within the 48 h preceding STEMI onset. Angiographic MVO was defined as TIMI flow grade <2 or TIMI flow 3 with myocardial blush grade <2; electrocardiographic (ECG) MVO was defined as ST-segment elevation resolution <70%. Common CRFs were collected. In the absence of hypertension, both angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas, in the presence of hypertension, they were similar in both study groups (P for interaction=0.01 and P=0.014, respectively). Among nonsmokers, angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within smokers, they were similar in both study groups (P for interaction=0.037 and P=0.037, respectively). In the absence of dyslipidemia, the angiographic and ECG MVO rates were lower in patients with PIA as compared with those without, whereas within dyslipidemic patients, they were similar in both study groups (P for interaction=0.012 and P=0.04, respectively).



The protective effect of PIA on MVO is blunted by CRFs.
Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes.

To examine whether and how improvement of glycemic control by long-term insulin therapy decreases endothelial activation as measured by serum levels of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule (VCAM-1) and whether the drug used to lower blood glucose in addition to insulin influences such a response.



Circulating adhesion molecules were measured before and after 3 and 12 months of therapy in 81 patients with type 2 diabetes and 41 subjects without diabetes. The patients were treated with bedtime administration of NPH insulin combined with either glibenclamide (n = 19), metformin (n = 17), glibenclamide and metformin (n = 17), or morning administration of NPH insulin (n = 23).



Before insulin therapy, serum sE-selectin level was 71% higher in the patients with type 2 diabetes (77 +/- 4 ng/ml) than in the normal subjects (45 +/- 3 ng/ml, P < 0.001), whereas levels of sVCAM-1 were comparable (420 +/- 25 vs. 400 +/- 11 ng/ml, respectively). Glycemic control in all patients improved as judged from a decrease in HbA1c from 9.7 +/- 0.2 to 7.6 +/- 0.1% (P < 0.001). sE-selectin decreased to 67 +/- 4 ng/ml by 3 months (P < 0.001 vs. 0 months) and then remained unchanged until 12 months (70 +/- 4 ng/ml P < 0.001 vs 0 months). sVCnM-1 levels at 12 months was similar to those at 0 months (416 +/- 25 ng/ml). The change in glycemic control, measured by HbA1c, but not in other parameters, was correlated with the change of sE-selectin (r = 0.41, P < 0.001) within the patients with type 2 diabetes. The decreases in sE-selectin were not different between the various treatment groups.



We conclude that improvement in glycemic control by administration of insulin alone or insulin combined with either glibenclamide, metformin, or both agents induces a sustained decrease in sE-selectin, the magnitude of which seems to be dependent on the degree of improvement in glycemia. These data suggest that sE-selectin might provide a marker of effects of treatment of chronic hyperglycemia on endothelial activation.
Can peak expiratory flow be measured accurately during a forced vital capacity manoeuvre?

Spirometry and peak flow measurements traditionally depend on different forced expiratory manoeuvres and have usually been performed on separate, dedicated equipment. As spirometry becomes more widely used in primary care settings, the authors wished to determine whether there was a systematic difference between peak expiratory flow (PEF) derived from a short sharp exhalation (PEF manoeuvre) and from a full forced vital capacity (FVC) manoeuvre, using the same turbine spirometer (Microloop, Micro Medical, Kent, UK). Eighty children (38 with current asthma) aged 7-16 yrs were asked to perform 2 blocks of PEF and FVC manoeuvres, the order being randomly assigned. PEF obtained from a peak flow manoeuvre (PEFPF) was significantly greater than that from a forced vital capacity manoeuvre (PEFVC) in both healthy (group mean difference 20 L x min(-1); p<0.001) and asthmatic children (group mean difference 9 L.min(-1); p<0.004). For clinical purposes, a mean difference of about 3% for children with asthma is of no practical significance, and peak expiratory flow data can usefully be obtained during spirometric recordings.
Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42-7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called 'Carter effect' could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared environmental component was estimated to be 0.01 (0.00-0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported.
Exercise and hand osteoarthritis symptomatology: a controlled crossover trial.

Randomized Clinical Trial.



Hand exercises have been recommended as treatment for hand osteoarthritis (OA) but research evidence is sparse.



To investigate effects of daily 16-week home-based hand exercise among persons with hand OA.



Forty-six older adults completed a crossover trial with washout between exercise and sham treatments. The AUSCAN physical function sub-scale served as the primary outcome measure. Other outcomes included pain and stiffness sub-scales, dexterity, and grip & pinch strengths.



Changes in AUSCAN sub-scales did not differ between exercise and sham treatments. No changes in dexterity were seen. Grip and pinch measures modestly improved after exercise but not sham.



It is possible that our exercise protocol may have been too ambitious for this age group. Future research will further the understanding of the role of hand exercise in hand OA symptomatology.
Orthotic aided training of the paretic upper limb in chronic stroke: results of a phase 1 trial.

This was a phase 1 investigation of an upper limb training program using the SaeboFlex dynamic orthosis to improve upper limb motor status. Thirteen individuals with chronic hemiparesis from stroke (age 26-71 years) participated. After being fitted with a SaeboFlex orthosis, each participant was engaged in 5 days of training (6 hours per day) that consisted of repetitive, task oriented activities with the SaeboFlex, exercises, and functional electrical stimulation. Individuals demonstrated improvements in movement at the shoulder and elbow. Wrist extension also improved, but wrist flexion and finger movement did not. Two more global measures of upper limb status improved. Muscle tone decreased. All participants remained pain free. This investigation demonstrates that a program using the orthosis was accompanied by many desirable changes and no untoward consequences.
Analysis of a care planning intervention for reducing depression in older people in residential care.

Approximately 40% of older people in residential care have significant symptoms of depression. A training and care-planning approach to reducing depression was implemented for 114 depressed residents living in 14 residential care homes in North Yorkshire, UK. Care staff were offered brief mental health training by community mental health teams for older people. They were then assigned to work individually with residents in implementing the care-planning intervention, which was aimed at alleviating depression and any health, social or emotional factors that might contribute to the resident's depression. Clinically significant improvements in depression scores were associated with implementation of the care-planning intervention as evidenced by changes in scores on the Geriatric Mental State Schedule-Depression Scale. There was evidence of an interaction between the power of the intervention and degree of dementia. These improvements were not accounted for by any changes in psychotropic medication. The training was highly valued by care staff and heads of homes, and they considered that the care-planning intervention represented an improvement in quality of care for all residents, irrespective of levels of dementia. Staff also reported improvements in morale and increased confidence in the caring role as a result of their participation. The limitations of this study are discussed. On the basis of a growing body of evidence, it is argued that there is an urgent need for a suitably powered randomised controlled trial and economic evaluation, to test the cost-effectiveness of personalised care planning interventions aimed at reducing depression in older people in residential care.
D-Ribose improves diastolic function and quality of life in congestive heart failure patients: a prospective feasibility study.

Patients with chronic coronary heart disease often suffer from congestive heart failure (CHF) despite multiple drug therapies. D-Ribose has been shown in animal models to improve cardiac energy metabolism and function following ischaemia. This was a prospective, double blind, randomized, crossover design study, to assess the effect of oral D-ribose supplementation on cardiac hemodynamics and quality of life in 15 patients with chronic coronary artery disease and CHF. The study consisted of two treatment periods of 3 weeks, during which either oral D-ribose or placebo was administered followed by a 1-week wash out period, and then administration of the other supplement. Assessment of myocardial functional parameters by echocardiography, quality of life using the SF-36 questionnaire and functional capacity using cycle ergometer testing was performed. The administration of D-ribose resulted in an enhancement of atrial contribution to left ventricular filling (40+/-11 vs. 45+/-9%, P=0.02), a smaller left atrial dimension (54+/-20 vs. 47+/-18 ml, P=0.02) and a shortened E wave deceleration (235+/-64 vs. 196+/-42, P=0.002) by echocardiography. Further, D-ribose also demonstrated a significant improvement of the patient's quality of life . In comparison, placebo did not result in any significant echocardiographic changes or in quality of life. This feasibility study in patients with coronary artery disease in CHF revealed the beneficial effects of D-ribose by improving diastolic functional parameters and enhancing quality of life.
Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.



To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.



Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.



The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.



Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians.
Enhanced Exercise Therapy in Parkinson’s disease: A comparative effectiveness trial

Exercise can improve motor function in people with Parkinson's disease but depression reduces the motivation to participate in regular exercise. The aim of this study was to develop a novel Enhanced Exercise Therapy program that uses manual-driven guided exercise and peer-facilitated psychoeducation for individuals with Parkinson's disease and depression.



24 week randomized controlled design.



Thirty individuals were randomized to Enhanced Exercise Therapy or self-guided therapy, and evaluated at baseline, 12-weeks and at 24-weeks. Enhanced Exercise Therapy included group exercise and group psychoeducation for 12 weeks. Between 13 and 24 weeks, individuals had access to the fitness facility but group sessions were not held. Self-guided therapy included written guidelines for a self-paced exercise program and psychoeducation. Primary outcome measures included the number of exercise sessions and International Physical Activity Questionnaire score. Secondary measures included resting heart rate, supine blood pressure, estimated VO2max and incidence of orthostatic hypotension.



Twenty four individuals completed the study (80% retention) and both groups attended similar number of exercise sessions. There were no significant changes in cardiovascular fitness measures but there was a significant increase in the amount of physical activity in the Enhanced Exercise Therapy group and a decrease in the self-guided therapy group during the post-intervention period.



Enhanced Exercise Therapy appears to promote engagement in an exercise program and more physical activity, even after group sessions were concluded in individuals with Parkinson's disease and depression.
Ketanserin, an Effective Third-Line Agent in Primary Hypertension

Thiazide diuretics and t/-adrenoceptor antagonists remain the cornerstone of therapy in the stepped care approach to the treatment of hypertension (Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure 1984). There is less consensus, however, as to the most appropriate third-line agent when this combination fails to control the blood pressure (McAreavey et al. 1984; Maclean et al. 1986; Ramsay et al. 1987). Thus, other agents need to be evaluated for this potential role. Ketanserin is a serotonin S2-receptor antagonist which also has weak a-adrenoceptor-blocking properties (Van Nueten et al. 1981). This combination of vasodilator properties makes ketanserin a potentially useful antihypertensive agent, whether used alone (Woittiez et al. 1986) or in conjunction with either thiazides or t/-blockers (Beretta-Piccoli et al. 1987). Ketanserin is also said to have a 'favourable' effect on serum lipoproteins. to reduce platelet activity, and to reduce the incidence of cardiovascular events in high risk patients (Hansson & Hedner 1987). Despite these properties, ketanserin has yet to find a role in the treatment of hypertension. The present study was designed to assess the value of ketanserin as a third-line agent in patients whose blood pressure was not adequately controlled by treatment with a fixed combination of ate nolo I and chlorthalidone.
'Does surgical management of the hand in children with unilateral spastic cerebral palsy affect muscle coordination and quality of reaching?'.

Judith C van Munster MD, Carel GB Maathuis MD PHD, Nienke Haga MD, Leo A Van Eykern, Mijna Hadders-Algra MD PHD 1 Center for Rehabilitation, University Medical Center Groningen (UMCG) Groningen, the Netherlands. 2 Rehabilitation Centre Revalidatie Friesland, Beetsterzwaag, the Netherlands. 3 Department of Paediatrics – Developmental Neurology, UMCG, Groningen, the Netherlands.