nils-herrmann/clean_scirepeval huggingface dataset:
The relationship of disordered eating habits and attitudes to clinical outcomes in young adult females with type 1 diabetes.

To describe the clinical outcomes of adolescent and young adult female subjects with type 1 diabetes in relation to the disturbance of eating habits and attitudes over 8-12 years.



Patients were recruited from the registers of pediatric and young adult diabetes clinics (including nonattenders) and interviewed in the community. A total of 87 patients were assessed at baseline (aged 11-25 years), and 63 (72%) were reinterviewed after 8-12 years (aged 20-38 years). Eating habits and attitudes were assessed by a semistructured research diagnostic interview (Eating Disorder Examination).



Clinical eating disorders ascertained from the interview and/or case note review at baseline or follow-up were found in 13 subjects (14.9% [95% CI 8.2-24.2]), and an additional 7 subjects had evidence of binging or purging, bringing the total affected to 26%. Insulin misuse for weight control was reported by 31 (35.6% [25.7-46.6]) subjects. Overall outcome was poor; serious microvascular complications were common and mortality was high. There were significant relationships between disordered eating habits, insulin misuse, and microvascular complications.



Although the cross-sectional prevalence of clinical eating disorders in young women with diabetes is modest, the cumulative incidence of eating problems continues to increase after young adulthood, and this is strongly associated with poor physical health outcomes. The combination of an eating disorder and diabetes puts patients at high risk of mortality and morbidity. Better methods of detection and management are needed.
Antidepressants for cancer pain and other painful syndromes with deafferentation component: comparison of Amitriptyline and Trazodone

The Authors report a clinical multicentre experience with antidepressant agents (trazodone and amitriptyline) in the treatment of chronic cancer pain with deafferentation component. Fortyfive patients were admitted to the study: 27 with oncological peripheral nerve lesions, 6 with post herpetic neuralgias, 10 with not oncological nerve lesions, 2 with central nervous lesions. Almost all of them were already being treated with NSAID associated with weak or strong opioids. A random double blind study was performed: 23 patients were treated with trazodone, 22 with amitryptiline. In the assessment of results, pain intensity, hours of sleep, hours standing and lying, side effects, mood, anxiety, weakness were all taken into consideration. The therapeutic analgesic efficacy of the two drugs proved to be similar. Gli Autori riportano uno studio clinico multicentrico sull'uso di farmaci antidepressivi (amitriptilina e trazodone) nel trattamento del dolore cronico da cancro con componente da deafferentazione. Quarantacinque pazienti hanno partecipato allo studio, 27 con lesioni nervose periferiche oncologiche, 6 con nevralgia postherpetica, 10 con lesioni nervose non oncologiche e 2 con lesioni nervose centrali. Quasi tutti i pazienti erano già in trattamento con farmaci anti-infiammatori non steroidei associati a narcotici deboli o forti. È stato effettuato uno studio randomizzato in doppio cieco: 22 pazienti sono stati trattati con amitriptilina e 23 con trazodone. Nella valutazione dei risultati si è tenuto conto di: intensità del dolore, ore di sonno, ore passate in piedi o a letto, effetti collaterali, umore, ansietà, debolezza. L'efficacia terapeutica analgesica dei due farmaci si è dimostrata sovrapponibile.
Low contact force and force–time integral predict early recovery and dormant conduction revealed by adenosine after pulmonary vein isolation

After pulmonary vein isolation (PVI), dormant conduction (DC) is present in at least one vein in a substantial number of patients. The present study seeks to determine whether there is a relationship between poor contact forces (CF) and the presence of DC after PVI.



This prospective, operator-blinded, non-randomized dual-centre trial enrolled 34 consecutive patients with paroxysmal atrial fibrillation who were candidates for PVI. Radiofrequency (RF) energy was delivered by using an irrigated-tip force-sensing ablation catheter (Tacticath, St Jude Medical) at pre-defined target power. The operators were blinded to the CF data at all times. A total of 1476 RF applications were delivered in 743 pre-defined PV segments. For each application, the precise location of the catheter was registered and the following data were extracted from the Tacisys unit: application duration, minimum contact force, maximum contact force, average contact force (CF), and force-time integral (FTI). Sixty minutes after PVI, spontaneous early recovery (ER) of the left atrium (LA) to PV conduction was evaluated. In the absence of ER, the presence of a DC was evaluated by using intravenous adenosine (ATP). In the 34 patients recruited (23 males; mean age: 62 ± 9 years), all PVs were successfully isolated. At the end of the 60 min waiting period, 22 patients demonstrated at least one spontaneous ER or DC under ATP. The mean CF and FTI per PV segment differed significantly among the different veins but the sites of ER and DC were evenly distributed. However, both the minimum, the first and the mean CF and FTI per PV segment were significantly lower in the PV segments presenting either ER or DC as compared with those without ER or DC (mean CF: 4.9 ± 4.8 vs. 12.2 ± 1.65 g and mean FTI: 297 ± 291 vs. 860 ± 81 g s, P < 0.001 for both). Using multivariate analysis, both the mean CF and the FTI per lesion remained significantly associated with the risk of ER or DC. Moreover, a CF < 5 g per PV segment predicted ER+ and DC+ with a sensitivity of 71% and specificity of 82%. In contrast, ER and DC were very unlikely if RF application was performed with a mean CF > 10 g (negative predictive value: 98.7%).



Both a low CF and a low FTI are associated with the ER of the PVI and DC after PVI.
Efficacy and safety of tiotropium in COPD patients in primary care – the SPiRiva Usual CarE (SPRUCE) study

Clinical trials of tiotropium have principally recruited patients from secondary care with more severe chronic obstructive pulmonary disease (COPD), and typically had included limitation of concomitant medication. In primary care, which is the most common setting for COPD management, many patients may have milder disease, and also may take a broad range of concomitant medication.



This randomised, placebo-controlled, parallel-group, 12-week, 44-centre study investigated the efficacy (trough forced expiratory volume in 1 second [FEV1] response) and safety of additional treatment with once-daily tiotropium 18 mug via the HandiHaler in a primary care COPD population (tiotropium: N = 191, FEV1 = 1.25 L [47.91% predicted]; placebo: N = 183, FEV1 = 1.32 L [49.86% predicted]). Secondary endpoints included: trough forced vital capacity (FVC) response, weekly use of rescue short-acting beta-agonist, and exacerbation of COPD (complex of respiratory symptoms/events of >3 days in duration requiring a change in treatment). Treatment effects were determined using non-parametric analysis.



At Week 12, median improvement in trough FEV1 response with tiotropium versus placebo was 0.06 L (p = 0.0102). The improvement was consistent across baseline treatment and COPD severity. Median improvement in FVC at 2, 6 and 12 weeks was 0.12 L (p < 0.001). The percentage of patients with > or =1 exacerbation was reduced (tiotropium 9.5%; placebo 17.9%; p = 0.0147), independent of disease severity. Rescue medication usage was significantly reduced in the tiotropium group compared with placebo. Adverse event profile was consistent with previous studies.



Tiotropium provides additional benefits to usual primary care management in a representative COPD population.
Laparoscopy has a superior diagnostic yield than percutaneous image-guided biopsy for suspected intra-abdominal lymphoma

To date, no study has compared laparoscopy (LB) to percutaneous (PB) biopsy for the diagnosis of abdominal lymphoma. The objective of this study is to compare the success rate and safety profile of laparoscopic lymph node biopsy to the percutaneous approach in patients with intra-abdominal lymphadenopathy concerning for lymphoma. We performed a multi-institution, retrospective review of patients undergoing lymph node biopsy for suspected intra-abdominal lymphoma between 2005 and 2013. Our primary outcome was adequate tissue yield between the two techniques, both for histologic diagnosis and for ancillary studies such as flow cytometry. Secondary outcomes included 30-day morbidity, 30-day readmission rates, the need for additional lymph node biopsy procedures, and length of stay. All 34 of the LB patients had adequate specimen for histologic diagnosis compared to 92.3 % of patients with a PB (p = 0.18). Significantly more patients in the LB group had sufficient tissue for ancillary studies when needed than in the PB group, 95.5 and 68.2 %, respectively (p = 0.04). A second biopsy was pursued in 23.1 % of failed PB patients, 0 % with success on second attempt. When index of suspicion is high or when biopsy is performed for patient previously diagnosed with lymphoma and recurrence/transformation is suspected, LB safely and consistently provides adequate tissue for initial diagnosis and for ancillary studies. In contrast, image-guided PB may be more appropriate for patients for whom ancillary studies are unlikely to add to planned treatments or when there is a high risk of complications from either general anesthesia or patient comorbidities.
Effects of antihypertensive agents on circadian blood pressure in hypertensive patients with previous brain infarction

To evaluate the effects of antihypertensive agents on the circadian blood pressure (BP) of patients with previous brain infarction, the ambulatory BP was measured non-invasively for 24 h before and after administration of antihypertensive agents. One hundred milligrams of acebutolol twice daily (n = 15) is effective in lowering the BP during the daytime, but has little effect during the night and the morning. Twenty milligrams of slow-release nifedipine twice daily (n = 14) produced a consistent reduction in the BP over the entire 24-h period and effectively blunted the rise in BP in the morning. Captopril (12.5 mg) twice daily (n = 15) produced a mild reduction in BP with little change in the circadian pattern. The slow-release nifedipine group had the greatest decrease in mean systolic and diastolic BP. The heart rate significantly increased after administration of slow-release nifedipine and decreased after administration of acebutolol. To reduce stroke recurrence, we should consider the effects of antihypertensive agents on circadian BP in hypertensive patients with previous brain infarction.
Open clinical trial on the sigma ligand panamesine in patients with schizophrenia

The sigma (σ) receptor has been proposed as a target of neuroleptic drugs. Preclinical data suggest that panamesine (EMD 57445), a novel σ ligand, has antipsychotic effects and is free of side effects related to the extrapyramidal motoric system (EPMS). Here we report the results of an exploratory study aimed at determining the appropriate dose range and the safety of panamesine in patients with an acute episode of schizophrenia. The first trial with four patients revealed insufficient clinical efficacy of a protocol where the daily dosage was increased stepwise from 7.5 mg during week 1, up to 30 mg during weeks 3 and 4. In a second set of trials, 12 patients received 15 mg at the beginning, this being increased up to 60 mg/day within 3 days and then maintained at this level for 4 weeks. As assessed by a decrease in the Brief Psychiatric Rating Scale score by at least 50%, five patients were judged as responders, whereas six patients showed only a slight improvement, and one deteriorated. Moreover, intent-to-treat analysis showed significant improvement in psychometric variables. In all patients prolactin levels increased during treatment, probably due to an active metabolite with weak dopamine-2-receptor antagonistic effects. No major side effects occurred, and in particular, no EPMS symptoms were seen.
Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response

ABT-925, a selective dopamine D3 receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (N=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (P=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the DRD3 G allele than in those who carried the DRD3 SS genotype.
Phase I trial of an oral immunomodulator and interferon inducer in cancer patients.

Imiquimod [1-(2-methylpropyl)-1H-imidazo[4,5c]quinolin-4-amine] is a compound of low molecular weight that, when administered p.o., induces interferon-alpha in several animal species and inhibits tumor growth in mice. To determine maximum tolerated dose, toxicity, and biological response in humans, a phase I clinical trial was conducted with 14 eligible cancer patients who received 100-500 mg imiquimod p.o. either once or twice weekly. Imiquimod induced interferon-alpha in serum in 10 of 19 doses of 200-300 mg. Interferon serum levels peaked 8-24 h after treatment and reached a maximum of 23,000 IU/ml in one patient. Significant mean increases (P < 0.01) in serum beta 2-microglobulin (1.5-fold), serum neopterin (3.5-fold), and 2-5A synthetase activity in peripheral blood mononuclear cells (7.9-fold) indicated that 200-300 mg imiquimod had biological and immunological activity in all evaluable patients. Increases in serum interferon, beta 2-microglobulin, and neopterin correlated significantly with dose (P < 0.001). No patient developed measurable antibody to interferon-alpha. Dose-limiting side effects included fatigue, malaise, fever, headache, and lymphocytopenia; no hepatic or renal toxicity or other hematological changes exceeded the normal range. Patients tolerated weekly doses of up to 500 mg, with the longest treatment lasting 4 weeks at 200 mg weekly. Twice-weekly doses up to to 300 mg were tolerated, with the longest twice-weekly treatments being 200 mg for 9 weeks and 100 mg for 25 weeks. No clinical responses were observed. Imiquimod, as an oral inducer of interferon, may have therapeutic usefulness in human cancers, viral infections, and other diseases. However, before initiation of phase II trials, additional work will be required to establish a tolerated dose and schedule for continued administration.
Dichloroacetate enhances performance and reduces blood lactate during maximal cycle exercise in chronic obstructive pulmonary disease.

Impaired skeletal muscle function contributes to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). This is characterized by reduced mitochondrial adenosine triphosphate generation, and greater reliance on nonmitochondrial energy production. Dichloroacetate (DCA) infusion activates muscle pyruvate dehydrogenase complex (PDC) at rest, reducing inertia in mitochondrial energy delivery at the onset of exercise and diminishing anaerobic energy production.



This study aimed to determine whether DCA infusion enhanced mitochondrial energy delivery during symptom-limited maximal exercise, thereby reducing exercise-induced lactate and ammonia accumulation and, consequently, improving exercise performance in patients with COPD.



A randomized, double-blind crossover design was used. Eighteen subjects with COPD performed maximal cycle exercise after an intravenous infusion of DCA (50 mg/kg body mass) or saline (control). Exercise work output was determined, and blood lactate and ammonia concentrations were measured at rest, 1 and 2 minutes of exercise, peak exercise, and 2 minutes postexercise.



DCA infusion reduced peak blood lactate concentration by 20% (mean [SE]; difference, 0.48 [0.11] mmol/L, P < 0.001) and peak blood ammonia concentration by 15% (mean [SE]; difference, 14.2 [2.9] mumol/L, P < 0.001] compared with control. After DCA, peak exercise workload improved significantly by a mean (SE) of 8 (1) W (P < 0.001) and peak oxygen consumption by 1.2 (0.5) ml/kg/minute (P = 0.03) compared with control.



We have shown that a pharmacologic intervention known to activate muscle PDC can reduce blood lactate and ammonia accumulation during exercise and improve maximal exercise performance in subjects with COPD. Skeletal muscle PDC activation may be a target for pharmacologic intervention in the management of exercise intolerance in COPD.
Voxel-based analysis of gray matter and CSF space in idiopathic normal pressure hydrocephalus.

To investigate regional morphologic changes in idiopathic normal pressure hydrocephalus (INPH) based on diagnosis with INPH Guidelines using voxel-based morphometry.



Three-dimensional magnetic resonance imaging was performed in 34 INPH patients, who met probable INPH criteria, probable 34 Alzheimer disease patients, and 34 normal control subjects.



Statistical parametric mapping was used to conduct voxel-based morphometry analysis of the morphologic data and revealed enlarged ventricles and sylvian fissures and stenotic sulci of high convexity, especially in the precuneus in the INPH group, with decreased gray matter density in the insula, caudate and thalamus.



In INPH, morphologic change occurs in the frontoparietal high convexity with ventricular dilatations, dilated sylvian fissures and tight sulci in the medial parietal lobes.
Atlantoaxial Fixation for Basilar Invagination without Obvious Atlantoaxial Instability (Group B Basilar Invagination): Outcome Analysis of 63 Surgically Treated Cases.

We discuss the rationale of surgical treatment of group B basilar invagination by atlantoaxial facet joint stabilization and segmental arthrodesis.



From January 2010 to April 2016, 63 patients with group B basilar invagination were surgically treated. All patients had varying degree of myelopathy-related functional disability. Fifty-two patients had both Chiari malformation and syringomyelia. All patients were treated by atlantoaxial plate and screw fixation with the techniques described by us in 1994 and 2004. Foramen magnum decompression or syrinx manipulation was not carried out in any patient. Occipital bone and subaxial spinal elements were not included in the fixation construct.



Three patients died in the immediate postoperative phase. In the remaining patients, there was clinical improvement and no patient's neurologic function worsened after surgery. In 12 of 38 patients in whom postoperative magnetic resonance imaging was possible, at a follow-up of at least 3 months, there was reduction in the size of the syrinx.



The pathogenesis of basilar invagination in group B is related to atlantoaxial instability. The clinical outcome suggests that the surgical treatment in these cases should be directed toward atlantoaxial stabilization and aimed at segmental arthrodesis. Inclusion of the occipital bone in the fixation construct is not necessary. Foramen magnum decompression and procedures involving manipulation of Chiari malformation and syringomyelia are not necessary.
Pilot study of gemcitabine (10 mg/m2 per min) and cisplatin

Gemcitabine and cisplatin are routinely used in combination. In this combination, gemcitabine at conventional doses of 1000–1500 mg/m2 is delivered weekly as a 30-minute bolus. Laboratory data suggest that the synthesis of gemcitabine triphosphate is saturable, and that gemcitabine infused at a rate of 10 mg/m2 per min optimizes accumulation of the triphosphate. Early clinical experience suggests that gemcitabine delivered by a more prolonged infusion is more myelosuppressive. In this pilot study, we wished to assess if full-dose gemcitabine when given with cisplatin could be delivered by this more prolonged infusion.  In this study, all patients received cisplatin 75 mg/m2. All gemcitabine doses were delivered at 10 mg/m2 per min. For the initial cohort (level 1) the gemcitabine dose was 800 mg/m2 per min. Subsequent escalations were 1000 mg/m2 per min (level 2), and 1250 mg/m2 per min (levels 3 and 4). For the first three cohorts, patients received gemcitabine on days 1, 8, and 15 and cisplatin on day 15 on a 28-day cycle. Patients on level 4 received gemcitabine on days 1 and 8 and cisplatin on day 8 on a 21-day cycle. Dose omissions or delays (holds) were mandated for NCI CTC grade 3 or 4 granulocytopenia or grade 2–4 thrombocytopenia.  Entered onto this dose-finding study were 23 patients (12 male, 11 female) with advanced solid tumors. Seven patients were treatment-naive. Six patients were treated on level 1, five each on levels 2 and 3 and seven on level 4. Patients received one to seven cycles of treatment. Myelosuppression-related dose holds occurred at all levels. First-cycle dose holds occurred in three of six, four of five, three of five and two of seven patients on successive levels. First-cycle grade 3 or 4 granulocytopenia/thrombocytopenia occurred in three patients on level 1, one patient on level 2, two patients on level 3 and three patients on level 4. There were no partial or complete responses. Four patients were removed for toxicity (three myelosuppression, one nephrotoxicity), one at physician discretion, and 15 with disease progression. Three patients stopped therapy with stable disease after 5–6 months. On level 3, three of five patients remained on therapy for 4 months or more, compared to only one patient on each of the other three levels.  Weekly gemcitabine 1250 mg/m2, utilizing a 10 mg/m2 per min infusion rate, can be delivered with cisplatin 75 mg/m2 with tolerable toxicity. When used in combination with cisplatin, however, the benefit of this fixed dose rate infusion gemcitabine compared to standard bolus gemcitabine remains to be determined.
Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.