nils-herrmann/clean_scirepeval huggingface dataset:
The relationship between need and capacity for multidisciplinary cardiovascular risk-reduction programs in Ontario.

Available evidence has demonstrated survival benefits associated with multidisciplinary cardiovascular risk-reduction (CR) (ie, cardiac rehabilitation) programs. The degree to which program capacity meets eligible service demands in Ontario is unknown. We sought to estimate the supply-need care-gap associated with CR programs across regions (Local Health Integration Networks [LHINs]) in Ontario.



We conducted a cross-sectional, population-based study during 2006. Administrative data provided estimates of the population eligible for multidisciplinary CR services due to (1) recent cardiovascular hospitalizations and (2) incident diabetes. An Ontario-wide survey of CR programs provided service supply estimates. The coverage rate and the absolute supply-need mismatch were use to quantify the care-gap by LHIN.



Based on cardiac hospitalizations alone, 53,270 patients in Ontario in 2006 (508.7 per 100,000) were eligible for CR services; 128,869 patients (1245 per 100,000) would have been eligible if newly diagnosed (incident cases) diabetic patients were included. Capacity for CR services was 18,087 patients, corresponding to 34% coverage of the eligible population (absolute unmet needs of 35,189 individuals) if capacity was entirely dedicated to recent hospitalizations and 14% coverage (absolute unmet needs of 110,782) if services were extended to include incident diabetes patients. Marked variation in disease burden, service capacity, and supply-need mismatch was observed across regions, in which supply was not correlated with need.



Despite proved benefits of multidisciplinary CR programs, unmet population needs remain high in Ontario and are unequally distributed across regions. The magnitude of unmet needs and the lack of correlation between supply and disease burden necessitate broader provincial strategies to plan, allocate, and subsidize CR programs.
Prophylaxis with povidone-iodine against induction of oral mucositis by radiochemotherapy

Oral mucositis is a frequent complication of radiochemotherapy. The origin of radiation-induced mucosal lesions is iatrogenic in nature, although further development of mucositis is essentially influenced by infection. It can be assumed that disinfection measures should decrease the severity of mucositis induced by radiochemotherapy. Therefore, in a prospective randomised study the efficacy of prophylactic oral rinsing with a disinfection agent was investigated. A randomised, prospective comparative trial was conducted with 40 patients undergoing radiochemotherapy of the head and neck region because of malignant disease. The treatment scheme consisted of irradiation to the tumour region and adjacent lymph nodes, with a total dose of 71.3 Gy, and simultaneous chemotherapy with carboplatin (60 mg/m2) on days 1–5 and 29–34. In all patients mucositis prophylaxis with nystatin, rutosides, panthenol and immunoglobulin was undertaken. In addition, 20 patients rinsed the oral cavity 4 times daily with povidone-iodine solution, while the group for comparison rinsed with sterile water. Clinical examination of the oral mucosa was performed weekly. Onset, grading and duration of mucositis were used as the main variables. Clinically manifest oral mucositis was observed in 14 patients in the iodine group (mean grading: 1.0) and in all 20 patients in the control group (mean grading: 3.0). The total duration (mean) of clinically observed mucositis was 2.75 weeks in treatment patients and 9.25 weeks in control patients. Median AUC (area under curve for grade vs duration) was 2.5 in the iodine rinsing patients and 15.75 in control patients. All differences found between the two groups were statistically significant. Increased iodine incorporation was not observed. A pathologic rise in thyroid hormone levels was not found in the iodine group. The results obtained indicate that incidence, severity and duration of radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing with povidone-iodine in addition to the standard prophylaxis scheme. It can be concluded that rinsing with povidone-iodine is an easy, cheap and safe prophylactic method and can be recommended as a supportive treatment during antineoplastic treatment of the head and neck region.
MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.

Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.
The effectiveness of choline citrate infusions monitored by lymphocyte transformation test (LTT) in multiple sclerosis. A new approach to the diagnosis and treatment of the disease.

The efficacy of intravenous choline citrate infusions was investigated in 34 patients with multiple sclerosis (MS) by clinical evaluation and by monitoring of lymphocyte proliferation in vitro against fragments of myelin basic protein (MOG-35-55, MBP15-31, PLP 39-15) over a period of 12 weeks. Patients have been diagnosed with MS at least one year before entering the study and suffered from mild relapsing/remitting course to long-term chronic progressive disease. Twenty one patients exhibited positive lymphocyte proliferation to myelin fragments prior to treatment and were therefore selected for further studies. Choline citrate was administered with a dosage of 1200mg/ 2x week for a period of 3 months. This treatment resulted in a significant decrease of lymphocyte proliferation to neural fragments (MOG- 35-55, MBP15-31) in lymphocyte transformation test (LTT). There was no significant SI change of PLP Peptide (PLP 39-15) LTT found after treatment with choline citrate. During the 3 mo observation period, patients remained stable and no side-effects of the treatment were observed. In addition, some patients reported long-lasting improvement (less paresthesia and increase of muscle strength in lower extremities) which was demonstrated up to 3 years later. In one spectacular case a commercial pilot was able to return to duty again after treatment. This pilot was allowed back in to his position as a commercial flying cockpit member and is on duty for more than 4 yrs now.
Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome

A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1–17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril. Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years. Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was −6.4 ml/min/1.73 m2 in the losartan group versus −9.1 ml/min/1.73 m2 in the enalapril group. The adverse event incidence was low and comparable in both treatment groups. In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.
Metabolic and orthostatic blood pressure responses to a low-sodium diet in elderly hypertensives

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65–79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 ± 36 vs 174 ± 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1–15 mm Hg, P < 0.05) and diastolic bp (dbp) by 1 mm hg (ci: −3 to 5 mm hg); there was no change in total ldl- and hdl-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. serum urate was significantly higher during the low compared to high sodium intake (304 ± 56 vs 277 ± 44  μ mols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.
Association between comorbidities and absence of chest pain in acute coronary syndrome with in-hospital outcome.

To evaluate the impact of comorbidities on the management and outcomes of acute coronary syndrome (ACS) patients without chest pain/discomfort (i.e. ACS without typical presentation).



Of the 11,458 ACS patients, enrolled by the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC;  The odds of atypical presentation increased proportionally with the number of comorbidities (odds ratio [OR]: 1, no-comorbid; OR: 1.64, 1 comorbidity; OR: 2.52, 2 comorbidities; OR: 4.57, ≥3 comorbidities).



Stratifying the study population by the presence/absence of comorbidities and typical presentation, we found a decreasing trend for use of medications and percutaneous intervention (OR: 1, typical presentation and no-comorbidities; OR: 0.70, typical presentation and comorbidities; OR: 0.23, atypical presentation and no-comorbidities; OR: 0.18, atypical presentation and comorbidities). On the opposite, compared with patients with typical presentation and no-comorbidities (OR: 1, referent), there was an increasing trend (p<0.001) in the risk of death (OR: 2.00, OR: 2.52 and OR: 4.83) in the above subgroups. However, after adjusting for comorbidities, medications and invasive procedures, atypical presentation was not a predictor of in-hospital death. Independent predictors of poor outcome were history of stroke (OR: 2.04), chronic kidney disease (OR: 1.57), diabetes mellitus (OR: 1.49) and underuse of invasive procedures.



In the ISACS-TC, atypical ACS presentation was often associated with comorbidities. Atypical presentation and comorbidities influenced underuse of in-hospital treatments. The latter and comorbidities are related with poor in-hospital outcome, but not atypical presentation, per se.
Population pharmacokinetic and pharmacodynamic analysis of tesamorelin in HIV-infected patients and healthy subjects

The objective of this analysis was to characterize the time course of selected pharmacodynamic (PD) markers of tesamorelin: growth hormone (GH) and insulin-like growth factor (IGF-1) concentrations in HIV-infected patients and healthy volunteers. A total of 41 subjects in Phase I trials receiving subcutaneous daily doses of 1 or 2 mg of tesamorelin during 14 consecutive days were included in this analysis. A previous pharmacokinetic (PK) model of tesamorelin was used as the input function for the PD model of GH. Tesamorelin was hypothesized to stimulate the secretion of GH in an “episodic” manner, i.e., for a finite duration of time. The resulting PK/PD model of GH was used to describe the time course of IGF-1. The effect of age, body weight, body mass index, sex, race, and health status on the model parameters was evaluated. The model was qualified using predictive checks and non-parametric bootstrap. Within the range of the values evaluated no covariates were significantly associated with GH or IGF-1 model parameters. Model evaluation procedures indicated accurate prediction of the selected pharmacodynamic markers. The time course of GH and IGF-1 concentrations following multiple doses of tesamorelin were well predicted by the sequential PK/PD model developed using Phase I data.
Quantitative evaluation of skeletal tumours with dynamic FDG PET: SUV in comparison to Patlak analysis

This study was carried out to evaluate bone lesions using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and to explore whether dynamic and quantitative PET data may help to differentiate benign lesions from malignant masses. Forty patients with primary bone lesions were studied. The final diagnosis was confirmed by histopathology. A 60-min dynamic FDG PET acquisition was undertaken in all subjects. From the dynamic PET images, indices such as the average and maximal standardised uptake values (SUVs), the tumour SUV-to-muscle SUV ratio (T/M) and the SUV at 60 min-to-SUV at 30 min ratio (averSUV60/30 min and maxSUV60/30 min) were produced. Patlak graphical analysis was used to obtain the influx constant (K i ), and the metabolic rate of FDG (MRFDG) was calculated. Based on the receiver operator characteristic curve, the sensitivity and specificity for each parameter in differentiating between malignant and benign lesions were evaluated. The histological results revealed 21 malignant tumours and 19 benign lesions in this group. The MRFDG and SUV indices in malignant lesions were significantly higher than those in benign lesions. However, each index showed a considerable overlap between benign and malignant lesions. Average SUV correlated positively with MRFDG (r=0.67). When a cut-off of 1.8 average SUV was used, the sensitivity and specificity for discrimination of malignancy from benign disease were 85% and 82.4%, respectively. MRFDG showed a similar sensitivity (82.4%) and a better specificity (92.9%). A combination consisting of a cut-off of average SUV (1.8) and averSUV60/30 min (1.1) resulted in an improvement of specificity to 93.3%, with a small reduction in sensitivity (81.3%) as compared with exclusive use of SUV. The results of this study indicate that a detectable difference in glucose metabolism exists between malignant and benign skeletal lesions. The static FDG uptake indices alone may not enable adequate differentiation between benign and malignant lesions. Quantitative dynamic imaging may provide more helpful information, but will not permit a definite diagnosis. The use of uptake indices may represent an alternative and interesting approach to the evaluation of bone lesions.
Simplifying psychotropic medication regimen into a single night dosage and reducing the dose for patients with chronic schizophrenia

Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia.
Comparison of Methods for Quantification of Global DNA Methylation in Human Cells and Tissues

DNA methylation is a key epigenetic modification which, in mammals, occurs mainly at CpG dinucleotides. Most of the CpG methylation in the genome is found in repetitive regions, rich in dormant transposons and endogenous retroviruses. Global DNA hypomethylation, which is a common feature of several conditions such as ageing and cancer, can cause the undesirable activation of dormant repeat elements and lead to altered expression of associated genes. DNA hypomethylation can cause genomic instability and may contribute to mutations and chromosomal recombinations. Various approaches for quantification of global DNA methylation are widely used. Several of these approaches measure a surrogate for total genomic methyl cytosine and there is uncertainty about the comparability of these methods. Here we have applied 3 different approaches (luminometric methylation assay, pyrosequencing of the methylation status of the Alu repeat element and of the LINE1 repeat element) for estimating global DNA methylation in the same human cell and tissue samples and have compared these estimates with the "gold standard" of methyl cytosine quantification by HPLC. Next to HPLC, the LINE1 approach shows the smallest variation between samples, followed by Alu. Pearson correlations and Bland-Altman analyses confirmed that global DNA methylation estimates obtained via the LINE1 approach corresponded best with HPLC-based measurements. Although, we did not find compelling evidence that the gold standard measurement by HPLC could be substituted with confidence by any of the surrogate assays for detecting global DNA methylation investigated here, the LINE1 assay seems likely to be an acceptable surrogate in many cases.
Enhancing rigour in the validation of patient reported outcome measures (PROMs): bridging linguistic and psychometric testing

A strong consensus exists for a systematic approach to linguistic validation of patient reported outcome measures (PROMs) and discrete methods for assessing their psychometric properties. Despite the need for robust evidence of the appropriateness of measures, transition from linguistic to psychometric validation is poorly documented or evidenced. This paper demonstrates the importance of linking linguistic and psychometric testing through a purposeful stage which bridges the gap between translation and large-scale validation.



Evidence is drawn from a study to develop a Welsh language version of the Beck Depression Inventory-II (BDI-II) and investigate its psychometric properties. The BDI-II was translated into Welsh then administered to Welsh-speaking university students (n = 115) and patients with depression (n = 37) concurrent with the English BDI-II, and alongside other established depression and quality of life measures. A Welsh version of the BDI-II was produced that, on administration, showed conceptual equivalence with the original measure; high internal consistency reliability (Cronbach's alpha = 0.90; 0.96); item homogeneity; adequate correlation with the English BDI-II (r = 0.96; 0.94) and additional measures; and a two-factor structure with one overriding dimension. Nevertheless, in the student sample, the Welsh version showed a significantly lower overall mean than the English (p = 0.002); and significant differences in six mean item scores. This prompted a review and refinement of the translated measure.



Exploring potential sources of bias in translated measures represents a critical step in the translation-validation process, which until now has been largely underutilised. This paper offers important findings that inform advanced methods of cross-cultural validation of PROMs.
Web-Based Collaborative Care for Type 2 Diabetes

To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes.



We conducted a trial of 83 adults with type 2 diabetes randomized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004. All patients had GHb > or =7.0%, had Web access from home, and could use a computer with English language-based programs. Intervention patients received 12 months of Web-based care management. The Web-based program included patient access to electronic medical records, secure e-mail with providers, feedback on blood glucose readings, an educational Web site, and an interactive online diary for entering information about exercise, diet, and medication. The primary outcome was change in GHb.



GHb levels declined by 0.7% (95% CI 0.2-1.3) on average among intervention patients compared with usual-care patients. Systolic blood pressure, diastolic blood pressure, total cholesterol levels, and use of in-person health care services did not differ between the two groups.



Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes.