nils-herrmann/clean_scirepeval huggingface dataset:
Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of Systemic Cancer.

The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication.



To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time.



Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014.



Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed.



Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) µm at baseline to 316 (43) µm at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better.



The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present.
Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation.

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell-depleted haploidentical SCT. Eight patients were treated at 10(4) cells/kg/dose, and 8 patients received 10(5) cells/kg/dose. Patients receiving 10(5) cells/kg/dose showed significantly improved T-cell recovery at 3, 4, and 5 months after SCT compared with those receiving 10(4) cells/kg/dose (P < .05). Accelerated T-cell recovery occurred as a result of expansion of the effector memory (CD45RA(-)CCR-7(-)) population (P < .05), suggesting that protective T-cell responses are likely to be long lived. T-cell-receptor signal joint excision circles (TRECs) were not detected in reconstituting T cells in dose-level 2 patients, indicating they are likely to be derived from the infused allodepleted cells. Spectratyping of the T cells at 4 months demonstrated a polyclonal Vbeta repertoire. Using tetramer and enzyme-linked immunospot (ELISPOT) assays, we have observed cytomegalovirus (CMV)- and Epstein-Barr virus (EBV)-specific responses in 4 of 6 evaluable patients at dose level 2 as early as 2 to 4 months after transplantation, whereas such responses were not observed until 6 to 12 months in dose-level 1 patients. The incidence of significant acute (2 of 16) and chronic graft-versus-host disease (GVHD; 2 of 15) was low. These data demonstrate that allodepleted donor T cells can be safely used to improve T-cell recovery after haploidentical SCT and may broaden the applicability of this approach.
The effect of triple therapy on rapidly progressive type of Henoch-Schönlein nephritis

Twelve patients with Henoch-Schönlein purpura, aged 6–14 years (mean 10.3 years), presenting with rapidly progressive glomerulonephritis (RPGN) were investigated prospectively. Analysis of the initial clinical features revealed: oedema (8 patients), hypertension (7 patients), gross haematuria (11 patients), oliguria (5 patients) and a decreased glomerular filtration rate (GFR) (<40 ml/min per 1.73 m2, 8 patients). Renal biopsies were available in 9 patients and revealed focal necrotising and a fibroepithelial type of crescentic glomerulonephritis (with 60%–90% crescent formation). The remaining 3 patients fulfilled the clinical criteria of RPGN. Two patients who were in the acute stage required peritoneal dialysis for a period of 2 weeks. The treatment protocol in all patients consisted of intravenous pulse methylprednisolone (3 days), oral cyclophosphamide (2 months), oral dipyridamole (6 months) and oral prednisolone (3 months). At the end of triple therapy, GFR returned to normal in all but 1 patient. During a follow-up period of 9–39 months, 7 patients achieved complete remission, while 4 patients showed partial remission, 3 of whom had persistent proteinuria and haematuria and 1 microscopic haematuria only. One patient had persistent nephropathy with decreased GFR and macroscopic haematuria and nephrotic-range proteinuria. His renal biopsy, performed 30 months after the onset of the disease, showed chronic diffuse sclerosing glomerulonephritis and intratubular severe IgA deposition. Although our patient group was small, this type of intensive treatment appears to be effective; further studies are needed.
Coaching patients with early rheumatoid arthritis to healthy physical activity: a multicenter, randomized, controlled study.

To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis.



A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (> or =30 minutes, moderately intensive activity, most days of the week).



The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%; P > 0.05) and after (54% versus 44%; P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test; P = 0.000) (Grippit; P = 0.003), but not in any other variables assessed.



A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change.
The effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus

The need for colonoscopy is common among diabetics. In this study, we aimed to evaluate the effect of autonomous neuropathy on bowel preparation in type 2 diabetes mellitus (DM) patients. The study population consisted of 45 patients with DM and 48 non-diabetic, age- and sex-matched subjects. All colonoscopies were performed 5 h after the last dose of sodium phosphate. Colonoscopists rated the bowel preparation quality during the procedure using the Aronchick scale. All patients underwent a detailed cardiologic examination and 24-h Holter rhythm monitoring. Orthostatic hypotension and impairment in heart rate variability were accepted as indicators of autonomous neuropathy. Gender, age, blood pressure, and heart rates did not differ significantly between groups (p > 0.05). Autonomous neuropathy was detected in 14 (31.1%) patients in the DM group and in two (4.2%) in the control group (p < 0.05). Optimal bowel cleansing was achieved in 93.8% of controls and 73.3% of diabetics; bowel cleansing was suboptimal in 26.7% of diabetics and 6.2% of controls (p < 0.05). Optimal bowel cleansing was achieved in six of 14 (42.8%) diabetic patients with autonomous neuropathy; however, optimal bowel cleansing was achieved in 27 of 31 (87.1%) diabetic patients without autonomous neuropathy (p < 0.05). Although optimal bowel cleansing was more prevalent among control patients than in diabetic patients without autonomous neuropathy, the difference was not significant (87.1% vs 93.8%; p > 0.05). These data suggest that optimal bowel cleansing is poorer in diabetics with autonomous neuropathy than in those without autonomous neuropathy and controls.
Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.

Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking.



To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet.



Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study.



Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat).



Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global.



Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls.



In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function.
Development and validation of the Diabetes Numeracy Test (DNT)

Low literacy and numeracy skills are common. Adequate numeracy skills are crucial in the management of diabetes. Diabetes patients use numeracy skills to interpret glucose meters, administer medications, follow dietary guidelines and other tasks. Existing literacy scales may not be adequate to assess numeracy skills. This paper describes the development and psychometric properties of the Diabetes Numeracy Test (DNT), the first scale to specifically measure numeracy skills used in diabetes.



The items of the DNT were developed by an expert panel and refined using cognitive response interviews with potential respondents. The final version of the DNT (43 items) and other relevant measures were administered to a convenience sample of 398 patients with diabetes. Internal reliability was determined by the Kuder-Richardson coefficient (KR-20). An a priori hypothetical model was developed to determine construct validity. A shortened 15-item version, the DNT15, was created through split sample analysis.



The DNT had excellent internal reliability (KR-20 = 0.95). The DNT was significantly correlated (p < 0.05) with education, income, literacy and math skills, and diabetes knowledge, supporting excellent construct validity. The mean score on the DNT was 61% and took an average of 33 minutes to complete. The DNT15 also had good internal reliability (KR-20 = 0.90 and 0.89). In split sample analysis, correlations of the DNT-15 with the full DNT in both sub-samples was high (rho = 0.96 and 0.97, respectively).



The DNT is a reliable and valid measure of diabetes related numeracy skills. An equally adequate but more time-efficient version of the DNT, the DNT15, can be used for research and clinical purposes to evaluate diabetes related numeracy.
Dementelcoach: effect of telephone coaching on carers of community-dwelling people with dementia.

Dementelcoach is a new telephone intervention to support informal caregivers of community dwelling people with dementia. The effectiveness of this intervention was evaluated on burden and mental health problems of informal caregivers.



A pre-test/post-test comparison group design was used with three groups of informal caregivers.Two of the groups were experimental and received either (1) telephone coaching or (2) telephone coaching in combination with respite care (psychogeriatric day care); the third was a comparison group which received day care only. Telephone coaching was offered by trained coaches once every two to three weeks over a period of 20 weeks.



Informal caregivers who received telephone coaching in combination with respite care reported significantly less burden compared to caregivers who received telecoaching only, and they experienced significantly fewer mental health problems than those who received day care only.



Telecoaching according to the principles of Dementelcoach combined with respite care(psychogeriatric day care) is more effective in reducing burden and health complaints in informal caregivers of community-dwelling people with dementia than telecoaching or day care only.
Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients.

Darunavir is a potent protease inhibitor of HIV. To enhance its pharmacokinetic profile, darunavir must be co-administered with ritonavir. There is wide inter-patient variability in darunavir pharmacokinetics among HIV-infected individuals, however. Darunavir is a known substrate for influx transporters, such as the 1A2 and the 1B1 members of the solute carrier organic anion transporter family (SLCO1A2, SLCO1B1), as well as for efflux transporters such as the multi-drug resistance protein 1 (MRP1).



The aim of this study was to develop a semi-mechanistic population pharmacokinetic model for darunavir and ritonavir administered in HIV-infected adults. The desired model would incorporate patient characteristics and pharmacogenetic data contributing to variability in drug concentrations and also take into account the interaction between the two compounds.



A population pharmacokinetic analysis was performed with 705 plasma samples from 75 Caucasian individuals receiving darunavir/ritonavir (600/100 mg twice daily) for at least 4 weeks. At least one full pharmacokinetic profile was obtained for each participant, and darunavir and ritonavir concentrations in plasma were determined by high performance liquid chromatography. Genotyping for 148 polymorphisms in genes coding for transporters or metabolizing enzymes was conducted by two methods: MALDI-TOF mass spectrometry and real-time polymerase chain reaction-based allelic discrimination. A population pharmacokinetic model was developed for darunavir and for ritonavir. The effect of single nucleotide polymorphisms on the post hoc individual pharmacokinetic parameters was first explored using graphic methods and regression analysis. Those covariates related to changes in darunavir or ritonavir pharmacokinetic parameters were then further evaluated using non-linear mixed effects modeling (NONMEM version VII).



Darunavir and ritonavir pharmacokinetics were best described by a two- and one-compartment model, respectively, both with first-order absorption and elimination. The darunavir peripheral volume of distribution decreased as α1-acid glycoprotein concentrations increased. Darunavir clearance was 12 % lower in patients with SLCO3A1 rs8027174 GT/TT genotypes, while homozygosity for the rs4294800 A allele was associated with 2.5-fold higher central volume of distribution. Body weight influenced ritonavir clearance. Ritonavir inhibited darunavir clearance following a maximum-effect model.



A population pharmacokinetic model to simultaneously describe the pharmacokinetics of darunavir and ritonavir was developed in HIV-infected patients. The model provides better understanding of the interaction between darunavir and ritonavir and suggests an association between SLCO3A1 polymorphisms and darunavir pharmacokinetics. Bayesian estimates of individual darunavir parameters and ritonavir may be useful to predict darunavir exposure.
[HPV prophylactic vaccine coverage and factors impacting its practice among students and high school students in Marseilles' area].

To assess the coverage of HPV vaccine among young women from Marseilles' area and factors influencing the probability of this vaccination.



An anonymous survey was conducted among 2124 high school and university students from Marseilles' area, France from December 2011 to May 2012.



Mean age of participants was 20.4years (±SD: 3.3). Only 41.6% participants reported being vaccinated against HPV, of whom 768 (93.3) had completed the 3 injections scheme. Among non-vaccinated respondents, 33.6% acknowledged they would accept a catch-up vaccination. Factors influencing the probability of being vaccinated were young age (AOR: 0.728; 95% CI: 0.681-0.779; P<0.001), socioeconomic and/or education level of parents (AOR: 1.324; 95% CI: 1.006-1.742; P=0.045), information about vaccination (AOR: 24.279; 95% CI: 5.417-108.82; P<0.001) and having a general practitioner (GP) favourable to vaccination (AOR: 68.776; 95% CI: 34.511-137.061; P<0.001). Factors influencing the probability to accept a catch-up vaccination were age (AOR: 1.059; 95% CI: 1.001-1.120; P=0.046), socioeconomic and/or education level of parents (AOR: 1.637; 95% CI: 1.198-2.237; P=0.002) and having a GP favourable to vaccination (AOR: 4.381; 95% CI: 2.978-6.445; P<0.001). Only 35.5% of respondents were aware that screening remains necessary following HPV vaccination.



The coverage of HPV vaccine among young women from Marseilles' area is insufficient. Factors influencing the probability of being vaccinated against HPV are age, socioeconomic and/or education level of parents and information regarding vaccination. GP plays a major role in the acceptance of HPV vaccine.
Effect of low-threshold methadone maintenance therapy for people who inject drugs on HIV incidence in Vancouver, BC, Canada: an observational cohort study.

HIV infection in people who inject drugs (PWID) is an international public health concern. We aimed to assess the effect of methadone maintenance therapy on HIV incidence in PWID in Vancouver, BC, Canada, where methadone is widely available through family physicians' offices and dispensed by community pharmacies.



Data were derived from the Vancouver Injection Drug Users Study (VIDUS), a prospective cohort of PWID in Vancouver. Individuals were eligible to enrol in VIDUS if they had injected illicit drugs at least once in the previous month and lived in the Greater Vancouver region. Participants responded to an interviewer-administered questionnaire and provided blood samples at enrolment and follow-up visits every 6 months. We estimated time to HIV seroconversion with Kaplan-Meier methods and used Cox proportional hazards methods to assess associations between methadone use and time to seroconversion.



1639 HIV-negative individuals were recruited between May 1, 1996, and May 31, 2013. Of these individuals, 138 had HIV seroconversion during a median of 75·5 months (IQR 33·4-115·3) of follow-up. In multivariate Cox regression analyses, methadone maintenance therapy remained independently associated with a reduced hazard of HIV infection after adjustment for sociodemographic characteristics and drug use patterns (adjusted relative hazard 0·64, 95% CI 0·41-0·98).



Methadone maintenance therapy for PWID made available through primary care physicians and community pharmacies can help to achieve public health goals such as reducing the spread of HIV.