nils-herrmann/clean_scirepeval huggingface dataset:
Relationship of ADHD symptoms and global illness severity in adults treated with lisdexamfetamine dimesylate.

The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and global clinical assessment of functionality is complex. This post-hoc analysis explores this relationship and suggests implications for patient assessment in clinical practice. Adults with ADHD on a stable lisdexamfetamine dimesylate (LDX) dose for ≥ 6 months were enrolled in a double-blind, placebo-controlled, randomized withdrawal study. Participants entered a 3-week open-label phase continuing their prior LDX dose and were then randomized to placebo or the same LDX dose for a 6-week, double-blind, randomized withdrawal phase. ADHD symptom distribution was measured by the ADHD Rating Scale IV (ADHD-RS-IV) with Adult Prompts total score reflecting DSM-IV-TR ADHD symptom criteria and severity by Clinical Global Impressions-Severity (CGI-S) ratings at study entry and at end of study. Of 123 participants enrolled in the open-label phase, 116 were included in the randomized withdrawal phase (placebo, n = 60; LDX, n = 56). As reported in a prior publication, mean (standard deviation) ADHD-RS-IV total score change from baseline (week 3) to end of study (randomized-withdrawal phase) was 16.8 (11.80) for placebo and 1.6 (8.63) for LDX. At end of study, for placebo and LDX, 5.0% and 32.1% of participants, respectively, had a CGI-S = 1, 11.7% and 35.7% had a CGI-S = 2, 11.7% and 17.9% had a CGI-S = 3, 33.3% and 7.1% had a CGI-S = 4, 35.0% and 7.1% had a CGI-S = 5, and 3.3% and 0% had a CGI-S = 6; no participants had a CGI-S = 7 (P < 0.0001). The CGI-S ratings increased (worsened) as ADHD symptom scores worsened. Post-hoc regression analysis between ADHD-RS-IV scores and CGI-S demonstrated shared variance of 47% at week 3 and 69% for both placebo and LDX at end of study. Although ADHD symptom scores demonstrate a linear relationship with global illness severity, the variance suggests that other factors not captured by symptom scales are also important in assessing patient outcomes in clinical practice. (
Stroke mismatch volume with the use of ABC/2 is equivalent to planimetric stroke mismatch volume.

In the clinical setting, there is a need to perform mismatch measurements quickly and easily on the MR imaging scanner to determine the specific amount of treatable penumbra. The objective of this study was to quantify the agreement of the ABC/2 method with the established planimetric method.



Patients (n = 193) were selected from the NINDS Natural History Stroke Registry if they 1) were treated with standard intravenous rtPA, 2) had a pretreatment MR imaging with evaluable DWI and PWI, and 3) had an acute ischemic stroke lesion. A rater placed the linear diameters to measure the largest DWI and MTT lesion areas in 3 perpendicular axes-A, B, and C-and then used the ABC/2 formula to calculate lesion volumes. A separate rater measured the planimetric volumes. Multiple mismatch thresholds were used, including MTT volume - DWI volume ≥50 mL versus ≥60 mL and (MTT volume - DWI volume)/MTT volume ≥20% versus MTT/DWI = 1.8.



Compared with the planimetric method, the ABC/2 method had high sensitivity (0.91), specificity (0.90), accuracy (0.91), PPV (0.90), and NPV (0.91) to quantify mismatch by use of the ≥50 mL definition. The Spearman correlation coefficients were 0.846 and 0.876, respectively, for the DWI and MTT measurements. The inter-rater Bland-Altman plots demonstrated 95%, 95%, and 97% agreement for the DWI, MTT, and mismatch measurements.



The ABC/2 method is highly reliable and accurate for quantifying the specific amount of MR imaging-determined mismatch and therefore is a potential tool to quickly calculate a treatable mismatch pattern.
Arterial hypotension: prevalence of low blood pressure in the general population using ambulatory blood pressure monitoring

Chronic constitutional hypotension has been described in a proportion of the population, and has a symptom complex ascribed to it. The true prevalence of low blood pressure in the normal population has not been defined. This study was undertaken to determine the prevalence of low blood pressure states, as measured using ambulatory blood pressure monitoring, in a general population cohort, and to determine the association between low blood pressure and clinical and demographic variables. The population enrolled were a cohort of mainly urban dwelling Irish subjects, either employees or spouses of employees of a major national bank. Subjects had an ambulatory blood pressure monitor fitted between 09.00 and 12.00 and wore the monitor for 24 hours. The subjects also filled out a detailed lifestyle questionnaire, and kept an activity diary. Blood was drawn for serum electrolyte estimation. A total of 254 subjects were included, 49% of whom demonstrated hypotensive events. Hypotensive means and individual hypotensive values were more frequently found in women, and occurred in a group of individuals with a distinct body habitus, specifically thin subjects, with a lower creatinine suggesting a smaller muscle mass. Hypotensive events in these subjects were associated with a low risk cardiovascular profile, in that subjects who displayed these events had a lower blood pressure, a lower weight and were less likely to have a positive family history of hypertension or vascular disease. Hypotension is common in the general population and is associated with a distinct body habitus. It carries a generally benign cardiovascular risk factor profile.
Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l−1 onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl−1 (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels ⩽13 g dl−1 showed a lower treatment-induced reduction in Ki67 expression (P<0.04) and a higher Ki67 expression at postoperative evaluation (P<0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism.
Clinical research Heart failure / cardiomyopathy Characteristics , outcomes , and predictors of 1-year mortality in patients hospitalized for acute heart failure

Acute heart failure (AHF) is associated with poor prognosis and requires recurrent hospitalizations. However, studies on AHF characteristics, treatment, and prognostic factors are few. Our aim was to investigate the characteristics, treatment, and 1-year prognosis of AHF and identify prognostic factors in different clinical groups.  We conducted a prospective multicentre study with 620 patients hospitalized due to AHF; mean age 75.1 (10.4) years, 50% male. Half of the patients had new-onset heart failure. Acute congestion (63.5%) and pulmonary oedema (26.3%) were the most common clinical presentations. Left ventricular ejection fraction (LVEF) was reported in two-thirds of patients. Half of these had preserved systolic function (LVEF 45%). At discharge, 86% of patients had beta-blockers and 76% either ACE-inhibitors or angiotensin receptor blockers in use. The 12-month all-cause mortality was 27.4%. We identified several clinical and biochemical prognostic risk factors in univariate analysis. Independent predictors of 1-year mortality were older age, male gender, lower systolic blood pressure (SBP) on admission, C-reactive protein, and serum creatinine .120 mmol/L.  We present the characteristics and prognosis of an unselected population of AHF patients. One-year mortality is high, and independent clinical risk factors include age, male gender, lower SBP on admission, C-reactive protein, and renal dysfunction.
Acute mental stress impairs insulin sensitivity in IDDM patients

The effect of acute mental stress on insulin sensitivity was evaluated in ten IDDM patients, studied on two occasions (test day and control day) in random order and separated by a period of 1–3 weeks. Mental stress was evoked by a modified filmed version of Stroop's CWT for 20 min. On the control day, the patients were resting quietly during the corresponding period. Insulin sensitivity was estimated by an insulin (0.4 mU · kg−1 · min−1)-glucose (4.5 mg · kg−1 · min−1)-infusion test (IGIT) for 6.5 h. Mental stress evoked significant responses for adrenaline, cortisol and GH, their respective peak values being 0.27 ± 0.05 nmol/l, 426 ± 27 nmol/l and 7.6 ± 1.8 μg/l, as well as increases in systolic and diastolic blood pressure and pulse rate The steady-state blood glucose levels, i.e. the mean blood glucose levels 3–6.5 h after the start of the IGIT, were significantly higher after stress, compared with those on the control day, 10.6 ± 1.5 vs 8.7 ± 1.4 mmol/l, p = 0.01, demonstrating impairment of the insulin sensitivity by mental stress. It is concluded that acute mental stress induces a state of insulin resistance in IDDM patients, which can be demonstrated by an IGIT to appear 1 h after maximal stress and to last more than 5 h.
A single neurotoxic dose of MDMA decreases BDNF expression in the frontoparietal cortex but not in the hippocampus

The popular recreational abuse drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') produces acute and long-lasting deficits in several markers of the serotonergic (5-HT) system. BDNF (brain derived neurotrophic factor) is a prominent trophic factor of serotonergic fibers. The aim of this study was to characterize the damage of serotonergic fibers in the frontoparietal cortex and hippocampus in parallel with the expression of BDNF.
Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study

Surfactant protein D (SP-D), an innate immune molecule, plays an important protective role during airway inflammation. Deficiency of this molecule induces emphysematous changes in murine lungs, but its significance in human COPD remains unclear.



We collected bronchoalveolar lavage fluid from 20 subjects with varying degrees of COPD (8 former smokers and 12 current smokers) and 15 asymptomatic healthy control subjects (5 never smokers, 3 remote former smokers, and 7 current smokers). All subjects underwent a complete medical history and pulmonary function testing. SP-D was measured by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis was performed using nonparametric methods and multivariable linear regression for control of confounding. The effect of corticosteroid treatment on SP-D synthesis was studied in vitro using an established model of isolated type II alveolar epithelial cell culture.



Among former smokers, those with COPD had significantly lower SP-D levels than healthy subjects (median 502 and 1067 ng/mL, respectively, p = 0.01). In a multivariable linear regression model controlling for age, sex, race, and pack-years of tobacco, COPD was independently associated with lower SP-D levels (model coefficient -539, p = 0.04) and inhaled corticosteroid use was independently associated with higher SP-D levels (398, p = 0.046). To support the hypothesis that corticosteroids increase SP-D production we used type II alveolar epithelial cells isolated from adult rat lungs. These cells responded to dexamethasone treatment by a significant increase of SP-D mRNA (p = 0.041) and protein (p = 0.037) production after 4 days of culture.



Among former smokers, COPD is associated with lower levels of SP-D and inhaled corticosteroid use is associated with higher levels of SP-D in the lung. Dexamethasone induced SP-D mRNA and protein expression in isolated epithelial cells in vitro. Given the importance of this molecule as a modulator of innate immunity and inflammation in the lung, low levels may play a role in the pathogenesis and/or progression of COPD. Further, we speculate that inhaled steroids may induce SP-D expression and that this mechanism may contribute to their beneficial effects in COPD. Larger, prospective studies are warranted to further elucidate the role of surfactant protein D in modulating pulmonary inflammation and COPD pathogenesis.
The Effect of Inhaled Budesonide and Formoterol on Bronchial Remodeling and HRCT Features in Young Asthmatics

Asthma is a chronic disease that may cause remodeling of the airways. We aimed to observe the effects of the combined use of inhaled budesonide and formoterol on both the reversibility of remodeling and structural changes in the airways. Thirty-six male patients (age range, 20–31) with mild-to-moderate persistent asthma were given inhaled formoterol and budesonide treatment for three months. Bronchial diameter (BD) and bronchial wall thickness (BWT), as measured by high-resolution computerized tomography, and reticular basement membrane thickness (RBMT), assessed in bronchoscopic biopsy specimens, were compared with pretreatment findings. Twenty-two age-matched male controls were also enrolled. BDs of the patients were significantly smaller than in the controls, whereas BWT and RBMT were greater. After three months BWT and RBMT of the subsegmental airways significantly decreased and BD increased. There was a prominent eosinophilic and lymphocytic infiltration in the bronchial mucosa of the asthmatics, and the eosinophilic infiltration significantly improved with treatment. Both serum total IgE and eosinophil counts were related to eosinophilic infiltration in the biopsy samples (r = 0.494 and r = 0.463, respectively). FEV1 was positively correlated with the diameters of the segmental and subsegmental airways (r = 0.491 and r = 0.265, respectively) and negatively correlated with BWT of the subsegmental airways (r = −0.293) and with the RBMT of both the segmental and subsegmental airways (r = −0.597 and r = −0.590, respectively). We suggest that treatment with inhaled formoterol and budesonide may reverse increased RBMT and BWT as part of remodeling in patients with asthma.
A phase Ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer.

This phase Ib study aimed to establish the feasible everolimus dose given with standard-dose etoposide plus cisplatin (EP) for extensive-stage small-cell lung cancer (SCLC).



An adaptive Bayesian dose-escalation model and investigator opinion were used to identify feasible daily or weekly everolimus doses given with EP in adults with treatment-naive extensive-stage SCLC. A protocol amendment mandated prophylactic granulocyte colony-stimulating factor (G-CSF). Primary end point was cycle 1 dose-limiting toxicity (DLT) rate. Secondary end points included safety, relative EP dose intensity, pharmacokinetics, and tumor response.



Patients received everolimus 2.5 or 5 mg/day without G-CSF (n=10; cohort A), 20 or 30 mg/week without G-CSF (n=18; cohort B), or 2.5 or 5 mg/day with G-CSF (n=12; cohort C); all received EP. Cycle 1 DLT rates were 50.0%, 22.2%, and 16.7% in cohorts A, B, and C, respectively. Cycle 1 DLTs were neutropenia (cohorts A and B), febrile neutropenia (all cohorts), and thrombocytopenia (cohorts A and C). The most common grade 3/4 adverse events were hematologic. Best overall response was partial response (40.0%, 61.1%, and 58.3% in cohorts A, B, and C, respectively).



Everolimus 2.5 mg/day plus G-CSF was the only feasible dose given with standard-dose EP in untreated extensive-stage SCLC.
A COMPARISON OF OSTEOPATHIC SPINAL MANIPULATION WITH STANDARD CARE FOR PATIENTS WITH LOW BACK PAIN

A BSTRACT  The effect of osteopathic manual therapy (i.e., spinal manipulation) in patients with chronic and subchronic back pain is largely unknown, and its use in such patients is controversial. Nevertheless, manual therapy is a frequently used method of treatment in this group of patients.  We performed a randomized, controlled trial that involved patients who had had back pain for at least three weeks but less than six months. We screened 1193 patients; 178 were found to be eligible and were randomly assigned to treatment groups; 23 of these patients subsequently dropped out of the study. The patients were treated either with one or more standard medical therapies (72 patients) or with osteopathic manual therapy (83 patients). We used a variety of outcome measures, including scores on the Roland–Morris and Oswestry questionnaires, a visual-analogue pain scale, and measurements of range of motion and straight-leg raising, to assess the results of treatment over a 12-week period.  Patients in both groups improved during the 12 weeks. There was no statistically significant difference between the two groups in any of the primary outcome measures. The osteopathic-treatment group required significantly less medication (analgesics, antiinflammatory agents, and muscle relaxants) (P< 0.001) and used less physical therapy (0.2 percent vs. 2.6 percent, P<0.05). More than 90 percent of the patients in both groups were satisfied with their care.  Osteopathic manual care and standard medical care have similar clinical results in patients with subacute low back pain. However, the use of medication is greater with standard care. ( 1999;341:1426-31.
A randomized, double-blind study of valsartan versus metoprolol on arterial distensibility and endothelial function in essential hypertension.

Antihypertensive drugs may have differential, pressure-independent effects on hypertension-associated alterations of arterial function. We compared the effects of a 12-week therapy with the AT(1)-receptor antagonist valsartan (Val) versus the beta-blocker metoprolol (Met) on arterial stiffness and endothelial function in mildly hypertensive patients at rest and during generalized sympathetic stimulation.



Sixty-eight patients (37 male, 31 female, 46 +/- 6 years) were randomized to Val (80-160 mg/d) or Met (50-100 mg/d). Effects of therapy on endothelial function, brachial and carotid artery distensibility coefficients, pulse wave velocity, carotid intima-media thickness and elastic modulus were assessed at rest and during the cold pressor test.



Fifty-two patients were available for per protocol analysis. Blood pressure was comparably reduced in both treatment groups. Effects on endothelial function and large artery elastic wall properties did not differ significantly between the two antihypertensive treatment regimens. Trends did not differ significantly between groups for any parameter including carotid intima-media thickness and elastic modulus.



Short-term treatment with Val and Met had similar effects on large artery functional vessel wall properties in a population of mildly hypertensive patients.
Mucosa-associated lymphoid tissue lymphoma in patients with human immunodeficiency virus infection.

haemolytic anaemia and seven HS respectively, compared to the first-day-values). However, delayed EMA labelling did not affect the final results as neither HS false positives nor false negatives were observed on day 7, showing that, in contrast with other tests, analysis using the FC method for HS screening can be delayed for up to 7 d. In conclusion, this study showed that FC is an efficient tool for HS screening whatever the nature of the protein involved, including ankyrin-deficient HS. This method needs small quantities of blood (10 ll) and can be delayed for several days. More specialized methods, such as EC or SDSPAGE are only required in a few cases, especially in atypical cases or when the fluorescence reduction falls in the doubtful area.
Statins in Familial Hypercholesterolemia: Consequences for Coronary Artery Disease and All-Cause Mortality.

A statin-induced reduction of coronary artery disease (CAD) events and mortality has not been adequately quantified in patients with heterozygous familial hypercholesterolemia (FH).



This study estimated the relative risk reduction for CAD and mortality by statins in heterozygous FH patients.



The authors included all adult heterozygous FH patients, identified by the Dutch screening program for FH between 1994 and 2013, who were free of CAD at baseline. Hospital, pharmacy, and mortality records between 1995 and 2015 were linked to these patients. The primary outcome was the composite of myocardial infarction, coronary revascularization, and death from any cause. The effect of statins (time-varying) was determined using a Cox proportional hazard model, while correcting for the use of other lipid-lowering therapy, thrombocyte aggregation inhibitors, and antihypertensive and antidiabetic medication. The authors applied inverse-probability-for-treatment weighting (IPTW) to account for differences at baseline between statin users and never-users.



The authors obtained medical records of 2,447 patients, of whom 888 were excluded on the basis of age <18 years or previous CAD. Simvastatin 40 mg and atorvastatin 40 mg accounted for 23.1% and 22.8% of all prescriptions, respectively. Statin users (n = 1,041) experienced 89 CAD events and 17 deaths during 11,674 person-years of follow-up versus statin never-users (n = 518), who had 22 CAD events and 9 deaths during 4,892 person-years (combined rates 8.8 vs. 5.3 per 1,000 person-years, respectively; p < 0.001). After applying IPTW and adjusting for other medications, the hazard ratio of statin use for CAD and all-cause mortality was 0.56 (95% confidence interval: 0.33 to 0.96).



In patients with heterozygous FH, moderate- to high-intensity statin therapy lowered the risk for CAD and mortality by 44%. This is essential information in all cost-effectiveness studies of this disorder, such as when evaluating reimbursement of new lipid-lowering therapies.
Volumetric computed tomography screening for lung cancer: three rounds of the NELSON trial.

Several medical associations recommended lung cancer screening by low-dose computed tomography scanning for high-risk groups. Counselling of the candidates on the potential harms and benefits and their lung cancer risk is a prerequisite for screening. In the NELSON trial, screenings are considered positive for (part) solid lung nodules with a volume >500 mm3 and for (part) solid or nonsolid nodules with a volume-doubling time <400 days. For this study, the performance of the NELSON strategy in three screening rounds was evaluated and risk calculations were made for a follow-up period of 5.5 years. 458 (6%) of the 7582 participants screened had a positive screen result and 200 (2.6%) were diagnosed with lung cancer. The positive screenings had a predictive value of 40.6% and only 1.2% of all scan results were false-positive. In a period of 5.5 years, the risk of screen-detected lung cancer strongly depends on the result of the first scan: 1.0% after a negative baseline result, 5.7% after an indeterminate baseline and 48.3% after a positive baseline. The screening strategy yielded few positive and false-positive scans with a reasonable positive predictive value. The 5.5-year lung cancer risk calculations aid clinicians in counselling candidates for lung cancer screening with low-dose computed tomography.