nils-herrmann/clean_scirepeval huggingface dataset:
Prehospital Stroke Identification: Factors Associated with Diagnostic Accuracy.

Stroke patients misdiagnosed by emergency medical services (EMS) providers have been shown to receive delayed in-hospital care. We aim at determining the diagnostic accuracy of Fire Department of New York (FDNY) EMS providers for stroke and identifying potential reasons for misdiagnosis.



Prehospital care reports of all patients transported by FDNY EMS to 3 hospitals from January 1, 2010, to December 31, 2011, were compared against the American Heart Association Get With The Guidelines (GWTG) database (reference standard) for the diagnosis of stroke. Age-adjusted logistic regression models were generated to explore prehospital patient characteristics which are associated with stroke misdiagnosis.



Of 72,984 patient transports during the study period, 750 had a GWTG diagnosis of stroke, 468 (62%) of which were identified correctly in the field and 282 (38%) were missed. An additional 268 patients were misdiagnosed as stroke when in fact they had an alternative diagnosis. Overall sensitivity was 62.4% (95% confidence interval [CI], 58.9-65.8) and specificity was 99.6% (95% CI, 99.6-99.7). No patients who presented with unilateral weakness, facial weakness, or speech problems were missed, whereas patients with atypical complaints like general malaise, dizziness, and headache were more likely to be missed. Seizures led the EMS providers to both overcall a stroke and miss the diagnosis.



FDNY EMS care providers missed more than a third of stroke cases. Seizures and other atypical presentations contribute significantly to stroke misdiagnosis in the field. Our findings highlight the need for better prehospital stroke identification methods.
Randomized trial of safinamide add-on to levodopa in Parkinson's disease with motor fluctuations

Levodopa is effective for the motor symptoms of Parkinson's disease (PD), but is associated with motor fluctuations and dyskinesia. Many patients require add-on therapy to improve motor fluctuations without exacerbating dyskinesia. The objective of this Phase III, multicenter, double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy and safety of safinamide, an α-aminoamide with dopaminergic and nondopaminergic mechanisms, as add-on to l-dopa in the treatment of patients with PD and motor fluctuations. Patients were randomized to oral safinamide 100 mg/day (n = 224), 50 mg/day (n = 223), or placebo (n = 222) for 24 weeks. The primary endpoint was total on time with no or nontroublesome dyskinesia (assessed using the Hauser patient diaries). Secondary endpoints included off time, Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor) scores, and Clinical Global Impression-Change (CGI-C). At week 24, mean ± SD increases in total on time with no or nontroublesome dyskinesia were 1.36 ± 2.625 hours for safinamide 100 mg/day, 1.37 ± 2.745 hours for safinamide 50 mg/day, and 0.97 ± 2.375 hours for placebo. Least squares means differences in both safinamide groups were significantly higher versus placebo. Improvements in off time, UPDRS Part III, and CGI-C were significantly greater in both safinamide groups versus placebo. There were no significant between-group differences for incidences of treatment-emergent adverse events (TEAEs) or TEAEs leading to discontinuation. The addition of safinamide 50 mg/day or 100 mg/day to l-dopa in patients with PD and motor fluctuations significantly increased total on time with no or nontroublesome dyskinesia, decreased off time, and improved parkinsonism, indicating that safinamide improves motor symptoms and parkinsonism without worsening dyskinesia.
Endurance Exercise as a Countermeasure for Aging

We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity.



Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18-30 years old) and older (59-76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry. Citrate synthase activity, mitochondrial DNA (mtDNA) abundance, and expression of nuclear-encoded transcription factors for mitochondrial biogenesis were measured. SIRT3, a mitochondrial sirtuin linked to lifespan-enhancing effects of caloric restriction, was measured by immunoblot.



Insulin-induced glucose disposal and suppression of endogenous glucose production were higher in the trained young and older subjects, but no age effect was noted. Age-related decline in mitochondrial oxidative capacity was absent in endurance-trained individuals. Although endurance-trained individuals exhibited higher expression of mitochondrial proteins, mtDNA, and mitochondrial transcription factors, there were persisting effects of age. SIRT3 expression was lower with age in sedentary but equally elevated regardless of age in endurance-trained individuals.



The results demonstrate that reduced insulin sensitivity is likely related to changes in adiposity and to physical inactivity rather than being an inevitable consequence of aging. The results also show that regular endurance exercise partly normalizes age-related mitochondrial dysfunction, although there are persisting effects of age on mtDNA abundance and expression of nuclear transcription factors and mitochondrial protein. Furthermore, exercise may promote longevity through pathways common to effects of caloric restriction.
Combined effects of MC4R and FTO common genetic variants on obesity in European general populations

Genome-wide association scans recently identified common polymorphisms, in intron 1 of FTO and 188 kb downstream MC4R, that modulate body mass index (BMI) and associate with increased risk of obesity. Although their individual contribution to obesity phenotype is modest, their combined effects and their interactions with environmental factors remained to be evaluated in large general populations from birth to adulthood. In the present study, we analyzed independent and combined effects of the FTO rs1421085 and MC4R rs17782313 risk alleles on BMI, fat mass, prevalence and incidence of obesity and subsequent type 2 diabetes (T2D) as well as their interactions with physical activity levels and gender in two European prospective population-based cohorts of 4,762 Finnish adolescents (NFBC 1986) and 3,167 French adults (D.E.S.I.R.). Compared to participants carrying neither FTO nor MC4R risk allele (20–24% of the populations), subjects with three or four risk alleles (7–10% of the populations) had a 3-fold increased susceptibility of developing obesity during childhood. In adults, their combined effects were more modest (~1.8-fold increased risk) and associated with a 1.27% increase in fat mass (P = 0.001). Prospectively, we demonstrated that each FTO and MC4R risk allele increased obesity and T2D incidences by 24% (P = 0.02) and 21% (P = 0.02), respectively. However, the effect on T2D disappeared after adjustment for BMI. The Z-BMI and ponderal index of newborns homozygous for the rs1421085 C allele were 0.1 units (P = 0.02) and 0.27 g/cm3 (P = 0.005) higher, respectively, than in those without FTO risk allele. The MC4R rs17782313 C allele was more associated with obesity and fat mass deposition in males than in females (P = 0.003 and P = 0.03, respectively) and low physical activity accentuated the effect of the FTO polymorphism on BMI increase and obesity prevalence (P = 0.008 and P = 0.01, respectively). In European general populations, the combined effects of common polymorphisms in FTO and MC4R are therefore additive, predictive of obesity and T2D, and may be influenced by interactions with physical activity levels and gender, respectively.
Acute effects of light emitting diodes therapy (LEDT) in muscle function during isometric exercise in patients with chronic obstructive pulmonary disease: preliminary results of a randomized controlled trial

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to early muscle fatigue. Light-emitting diodes therapy (LEDT) has been used to minimize muscle fatigue in athletes and healthy subjects. The aim of this study is to investigate the acute effects of LEDT on muscle fatigue and perception of effort in patients with COPD during isometric endurance test of the quadriceps femoris (QF). Ten patients (VEF1 50 ± 13 % of predicted) underwent a single LEDT and sham application, 48 h apart, in a randomized crossover design. The LEDT and sham were applied in three localized areas of the QF (rectus femoris, vastus lateralis, and vastus medialis). Before and after exposure to LEDT and sham, the patients performed an isometric endurance test (60 % of the maximum voluntary isometric contraction), until the limit of tolerance concomitant to surface electromyography recording (median frequency as mean outcome). The slope obtained from linear regression analysis of the median frequency (MF) over endurance time was also used as an endurance index. Endurance time increased significantly after exposure to LEDT (from 26 ± 2 to 53 ± 5 s) as compared to sham (from 23 ± 3 to 30 ± 4 s) (F = 64, P = 0.0001). A greater decline in MF was observed during isometric endurance test after sham, compared to LEDT (F = 14.6, P = 0.004). The slope of the MF over time was lower post-LEDT compared to post-sham (−0.7 ± 0.3 vs. −1.5 ± 0.8; P = 0.004). The dyspnea score corrected for endurance time was lower post-LEDT (P = 0.008) but similar for fatigue both post-LEDT and post-sham. A single application of LEDT minimizes muscle fatigue and increases isometric endurance time.
Effect of sprint interval exercise on postexercise metabolism and blood pressure in adolescents.

The current study examined the effect of sprint interval exercise on postexercise oxygen consumption, respiratory-exchange ratio (RER), substrate oxidation, and blood pressure in adolescents. Participants were 10 normal-weight healthy youth (7 female), age 15-18 years. After overnight fasts, each participant undertook 2 trials in a random balanced order: (a) two 30-s bouts of sprint interval exercise on a cycle ergometer and (b) rested in the laboratory for an equivalent period. Time-matched measurements of oxygen consumption, RER, and blood pressure were made 90 min into recovery, and substrate oxidation were calculated over the time period. Total postexercise oxygen uptake was significantly higher in the exercise than control trial over the 90 min (mean [SD]: control 20.0 [6.0] L, exercise 24.8 [9.8] L; p=.030). After exercise, RER was elevated above control but then fell rapidly and was lower than control 30-60 min postexercise, and fat oxidation was significantly higher in the exercise than control trial 45-60 min postexercise. However, total fat oxidation did not differ between trials (control 4.5 [2.5] g, exercise 5.4 [2.7] g; p=.247). Post hoc tests revealed that systolic blood pressure was significantly lower than in control at 90 min postexercise (control 104 [10] mm Hg, exercise 99  mm Hg; p<.05). These data indicate that acute sprint interval exercise leads to short-term increases in oxygen uptake and reduced blood pressure in youth. The authors suggest that health outcomes in response to sprint interval training be examined in children.
Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis).

Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant congenital hemolytic anemia with moderate splenomegaly and often compensated hemolysis. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated MCHC and MCV, and decreased osmotic fragility. The majority of symptomatic DHSt cases reported to date have been associated with gain-of-function mutations in the mechanosensitive cation channel gene, PIEZO1. A recent study has identified two families with DHSt associated with a single mutation in the KCNN4 gene encoding the Gardos channel (KCa3.1), the erythroid Ca(2+) -sensitive K(+) channel of intermediate conductance, also expressed in many other cell types. We present here, in the second report of DHSt associated with KCNN4 mutations, two previously undiagnosed DHSt families. Family NA exhibited the same de novo missense mutation as that recently described, suggesting a hot spot codon for DHSt mutations. Family WO carried a novel, inherited missense mutation in the ion transport domain of the channel. The patients' mild hemolytic anemia did not improve post-splenectomy, but splenectomy led to no serious thromboembolic events. We further characterized the expression of KCNN4 in the mutated patients and during erythroid differentiation of CD34+ cells and K562 cells. We also analyzed KCNN4 expression during mouse embryonic development.
Methodological Challenges in Determining Longitudinal Associations Between Anticholinergic Drug Use and Incident Cognitive Decline

To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies.



Longitudinal cohort study.



Outpatient clinics, Quebec, Canada.



Individuals aged 60 and older without dementia or depression (n = 102).



Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression.



The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1-25.8), ADS (OR = 5.7, 95% CI = 1.1-27.7), and ARS (OR = 6.5, 95% CI = 1.34-32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8-15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1-8.0). No associations were observed using the DSM-V criteria or RCI method.



The choice of different methods for defining drug exposure and cognitive decline will have a significant effect on the results of pharmacoepidemiological studies.
Randomized comparison of biolimus-eluting stents with biodegradable polymer versus everolimus-eluting stents with permanent polymer coatings assessed by optical coherence tomography

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6–8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63–3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21–12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43–2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6–8 months. In addition, PLIA—possible markers of delayed arterial healing—were observed with similar frequency in both groups.
Tobacco smoke exposure in pulmonary arterial and thromboembolic pulmonary hypertension.

Animal studies and data from a single-center study suggest that tobacco smoke exposure may be a risk factor for precapillary pulmonary hypertension (PH).



We aimed to survey tobacco smoke exposure in a large PH collective and to compare it with epidemiological data from healthy subjects.



This is an international, multicenter, case-control study including patients with pulmonary arterial and chronic thromboembolic PH. All patients were asked specific questions about tobacco smoke exposure. Healthy controls were retrieved from the Swiss Health Survey (n = 18,747).



Overall (n = 472), 49% of PH patients were smokers and there was a clear sex difference (women 37%, men 71%). Significantly more PH men were smokers compared with healthy controls, whereas less PH women were ever active smokers. However, 50% of the non-smoking PH women were exposed to secondhand smoke, leading to a significantly higher number of tobacco smoke-exposed individuals compared to healthy controls. PH smokers were significantly younger compared to those not exposed.



Active and environmental tobacco smoke exposure is common in PH. The higher prevalence of male PH smokers, the higher exposure to environmental tobacco smoke in PH women compared to healthy controls and the lower age at PH diagnosis in smokers may indicate a pathogenic role of tobacco smoke exposure in PH.
Efficacy of maternal tenofovir disoproxil fumarate in interrupting mother-to-infant transmission of hepatitis B virus.

The efficacy and safety of maternal tenofovir disoproxil fumarate (TDF) in reducing mother-to-infant hepatitis B virus (HBV) transmissions is not clearly understood. We conducted a prospective, multicenter trial and enrolled 118 hepatitis B surface antigen (HBsAg)- and hepatitis B e antigen-positive pregnant women with HBV DNA ≥7.5 log10 IU/mL. The mothers received no medication (control group, n = 56, HBV DNA 8.22 ± 0.39 log10 IU/mL) or TDF 300 mg daily (TDF group, n = 62, HBV DNA 8.18 ± 0.47 log10 IU/mL) from 30-32 weeks of gestation until 1 month postpartum. Primary outcome was infant HBsAg at 6 months old. At delivery, the TDF group had lower maternal HBV DNA levels (4.29 ± 0.93 versus 8.10 ± 0.56 log10 IU/mL, P < 0.0001). Of the 121/123 newborns, the TDF group had lower rates of HBV DNA positivity at birth (6.15% versus 31.48%, P = 0.0003) and HBsAg positivity at 6 months old (1.54% versus 10.71%, P = 0.0481). Multivariate analysis revealed that the TDF group had lower risk (odds ratio = 0.10, P = 0.0434) and amniocentesis was associated with higher risk (odds ratio 6.82, P = 0.0220) of infant HBsAg positivity. The TDF group had less incidence of maternal alanine aminotransferase (ALT) levels above two times the upper limit of normal for ≥3 months (3.23% versus 14.29%, P = 0.0455), a lesser extent of postpartum elevations of ALT (P = 0.007), and a lower rate of ALT over five times the upper limit of normal (1.64% versus 14.29%, P = 0.0135) at 2 months postpartum. Maternal creatinine and creatinine kinase levels, rates of congenital anomaly, premature birth, and growth parameters in infants were comparable in both groups. At 12 months, one TDF-group child newly developed HBsAg positivity, presumably due to postnatal infection and inefficient humoral responses to vaccines.



Treatment with TDF for highly viremic mothers decreased infant HBV DNA at birth and infant HBsAg positivity at 6 months and ameliorated maternal ALT elevations. (Hepatology 2015;62:375-386.
Epilepsy patients: health status and medical consumption

To study the health status and medical consumption of outpatients with active epilepsy in comparison with the general population.  Descriptive population study (multi-stage random sample).  Structured questionnaire.  Thirty-nine epilepsy patients compared with a general population of 12,975.  Epilepsy patients revealed poorer health, a higher mean complaint score (5.3 versus 3.7, P < 0.05), a higher score on the General Health Questionnaire (P < 0.05), a somewhat higher score on the biological problem list (BIOPRO) (1.8 versus 1.4, P > 0.05), less active sports engagement (16% versus 39%, P < 0.01), more fatigue (46 vs 29%, P < 0.05), dizziness (33 vs 10%, P < 0.01), nervousness (28 vs 18%, P > 0.05), sleep disturbance (23 vs 15%, P > 0.05) and excitability (33 vs 15%, P < 0.01) when compared with the general population. The BIOPRO showed problems in epilepsy patients on specific items related to self-confidence (P < 0.001). Epileptic patients do not show more absence due to illness, from work, school or at home (15 vs 18%, P > 0.05) and/or more problems at work or in the family when compared with the general population. Almost half of epilepsy patients had consulted a specialist in the past 2 months (46 vs 23% of the general population, P < 0.001). Epilepsy patients consulted the family physician slightly more often than other responders (3.0 versus 2.3, P > 0.05) and contacted the family physician’s assistant considerably more often (2.3 versus 0.7, P < 0.001). One-third of epilepsy patients consulted an alternative healer in the past 5 years versus 14% in the general population (P < 0.001).  The study shows an excess of psychosocial problems and medical consumption in epilepsy patients, but not more absence from work or problems at work or in the family. Further development of a quality of life instrument specific to epilepsy is advised.
Association between therapeutic alliance, care satisfaction, and pharmacological adherence in bipolar disorder.

We sought to understand the association of specific aspects of care satisfaction, such as patients' perceived relationship with their psychiatrist and access to their psychiatrist and staff, and therapeutic alliance with participants' likelihood to adhere to their medication regimens among patients with bipolar disorder.



We examined data from the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder, an effectiveness study investigating the course and treatment of bipolar disorder. We expected that participants (n = 3037) with positive perceptions of their relationship with their psychiatrist and quality of psychopharmacologic care, as assessed by the Helping Alliance Questionnaire and Care Satisfaction Questionnaire, would be associated with better medication adherence. We utilized logistic regression models controlling for already established factors associated with poor adherence.



Patients' perceptions of collaboration, empathy, and accessibility were significantly associated with adherence to treatment in individuals with bipolar disorder completing at least 1 assessment. Patients' perceptions of their psychiatrists' experience, as well as of their degree of discussing medication risks and benefits, were not associated with medication adherence.



Patients' perceived therapeutic alliance and treatment environment impact their adherence to pharmacotherapy recommendations. This study may enable psychopharmacologists' practices to be structured to maximize features associated with greater medication adherence.