nils-herrmann/clean_scirepeval huggingface dataset:
Protein hydrolysate co-ingestion does not modulate 24 h glycemic control in long-standing type 2 diabetes patients

Evaluate the efficacy of protein hydrolysate co-ingestion as a dietary strategy to improve blood glucose homeostasis under free-living conditions in long-standing type 2 diabetes patients.A total of 13 type 2 diabetes patients were enrolled in a randomized, double-blind cross-over design and studied on two occasions for 40 h under strict dietary standardization but otherwise normal, free-living conditions. In one trial, subjects ingested a protein hydrolysate (0.4 g kg−1 bw casein hydrolysate, PRO) with every main meal. In the other trial, a placebo was ingested (PLA). Blood glucose concentrations were assessed by continuous glucose monitoring.Average 24 h glucose concentrations were similar between the PLA and the PRO trials (8.9±0.8 vs 9.2±0.7 mmol l−1, respectively). Hyperglycemia (glucose concentrations >10 mmol l−1) was experienced 34±9% of the time (8±2 h per 24 h) in the PLA trial. Protein hydrolysate co-ingestion with each main meal (PRO) did not reduce the prevalence of hyperglycemia (39±10%, 9±2 h per 24 h; P=0.2).Conclusion:Co-ingestion of a protein hydrolysate with each main meal does not improve glucose homeostasis over a 24 h period in long-standing type 2 diabetes patients.
Extent of Lumpectomy for Breast Cancer After Diagnosis by Stereotactic Core Versus Wire Localization Biopsy

Stereotactic core biopsy of mammographically defined breast abnormalities is an alternative to wire localization biopsy. The purpose of this study was to evaluate the extent of lumpectomy in patients diagnosed by stereotactic core versus wire localization biopsy.  A total of 67 consecutive patients diagnosed with invasive cancers or ductal carcinoma in situ (DCIS) were retrospectively reviewed. Thirty-four were diagnosed by core biopsy and the remaining 33 by wire localization biopsy.  Approximately 65% of patients subsequently had breast-conserving surgical therapy. Seventy-nine percent of patients undergoing wire localization biopsies had positive surgical margins. Achievement of negative surgical margins for lumpectomies performed after wire localization or stereotactic core biopsies was 100% and 89%, respectively, which was not significantly different. However, the total volume of breast tissue removed for breast conservation in patients undergoing lumpectomy after wire localization versus core biopsies was 183 cm3 and 104 cm3, respectively, which was significantly different (P = .003).  Diagnosis by stereotactic core biopsies resulted in less tissue removal to achieve margin-negative lumpectomies for breast conservation. Stereotactic core biopsy is the method of choice for biopsying nonpalpable, suspicious breast lesions.
Instrumentally Detected Changes in Motor Functioning in Patients with Low Levels of Antipsychotic Dopamine D2 Blockade

Extrapyramidal side-effects (EPSE) of antipsychotic medication are related to the occupancy of dopamine D2 receptors and there appears to be a threshold of D2 occupancy below which clinically EPSE are unlikely to occur. It is unclear whether there are motor changes produced by ‘subthreshold’ levels of D2 occupancy that are not detectable by clinical examination. This study was designed to investigate whether a number of electromechanical instrumental techniques could detect ‘subthreshold’ motor changes and whether these changes correlate with dopamine D2 occupancy as measured by [11C]-raclopride PET scan. Twenty medication naïve patients were studied before and during treatment with low dose haloperidol. Instrumental techniques detected an asymmetrical worsening in motor function with drug treatment despite the failure of the group to experience significant EPSE. These changes did not correlate with D2 occupancy and measurements of rigidity, tremor, and bradykinesia did not closely inter-correlate.
Understanding of diabetes prevention studies: questionnaire survey of professionals in diabetes care

Diabetes prevention studies have reported reductions of diabetes risk by up to 60%. Since the underlying metabolic changes are small, the clinical significance of this effect may be overestimated. The present survey explores the extent to which different formats of presenting study results may influence diabetes healthcare professionals’ perceptions of the importance of intervention effects on diabetes risk. Participants of three European diabetes conferences (160 nurse educators, 112 physicians, 27 other professionals) were presented with a questionnaire that included nine items, in which results from three diabetes prevention studies were presented in different ways. Participation rate was 96%. Effects were interpreted as important or very important by 92% (255/276) when results were presented as proportions of subjects with diabetes (14% intervention group, 29% control group), by 87% (248/285) when results were communicated as a risk reduction of 57%, by 39% (110/284) when the corresponding fasting plasma glucose values were presented (mean difference 0.3 mmol/l), and by 18% (52/283) when glycosylated haemoglobin values were used (6.0 vs 6.1%). Corresponding results of the three diabetes prevention studies were rated as being of identical importance by only 23, 13 and 16% of participants, respectively. Healthcare professionals rate the benefit of preventive interventions substantially higher when changes in diabetes risk are communicated rather than related glycaemic parameters. Transformation of continuous metabolic data into diagnostic categories may impair understanding of study effects.
Total and unbound darunavir pharmacokinetics in pregnant women infected with HIV-1: results of a study of darunavir/ritonavir 600/100 mg administered twice daily

Antiretroviral therapy during pregnancy is recommended to reduce the risk of mother-to-child transmission of HIV and for maternal care management. Physiological changes during pregnancy can affect pharmacokinetics, potentially altering pharmacological activity. We therefore evaluated the pharmacokinetics of twice-daily (bid) darunavir in HIV-1-infected pregnant women.



HIV-1-infected pregnant women receiving an antiretroviral regimen containing darunavir/ritonavir 600/100 mg bid were enrolled in this study. Total and unbound darunavir and total ritonavir plasma concentrations were obtained over 12 h during the second and third trimesters and postpartum. Total darunavir and ritonavir plasma concentrations were determined using a validated high-performance liquid chromatography tandem mass spectrometry assay and unbound darunavir was determined using (14) C-darunavir-fortified plasma. Pharmacokinetic parameters were derived using noncompartmental analysis.



Data were available for 14 women. The area under the plasma concentration-time curve from 0 to 12 h (AUC12h) for total darunavir was 17-24% lower during pregnancy than postpartum. The AUC12h for unbound darunavir was minimally reduced during pregnancy vs. postpartum. The minimum plasma concentration (Cmin) of total and unbound darunavir was on average 43-86% and 10-14% higher, respectively, during pregnancy vs. postpartum. The antiviral response (< 50 HIV-1 RNA copies/mL) was 33% at baseline and increased to 73-90% during treatment; the percentage CD4 count increased over time. One serious adverse event was reported (increased transaminase). All 12 infants born to women remaining in the study at delivery were HIV-1-negative; four of these infants were premature.



Total darunavir exposure decreased during pregnancy. No clinically relevant change in unbound (active) darunavir occurred during pregnancy, suggesting that no dose adjustment is required for darunavir/ritonavir 600/100 mg bid in pregnant women.
Incidence and Etiologies of Acquired Third Nerve Palsy Using a Population-Based Method.

Among cranial nerve palsies, a third nerve palsy is important because a subset is caused by life-threatening aneurysms. However, there is significant disagreement regarding its incidence and the reported etiologies.



To determine the incidence and etiologies of acquired third nerve palsy using a population-based method.



All newly diagnosed cases of acquired third nerve palsy from January 1, 1978, through December 31, 2014, in Olmsted County, Minnesota, were identified using the Rochester Epidemiology Project, a record-linkage system of medical records for all patient-physician encounters among Olmsted County residents. All medical records were reviewed to confirm a diagnosis of acquired third nerve palsy and determine the etiologies, presenting signs, and symptoms. Incidence rates were adjusted to the age and sex distribution of the 2010 US white population.



Incidence and etiologies of acquired third nerve palsies. The secondary outcome was incidence of pupil involvement in acquired third nerve palsies.



We identified 145 newly diagnosed cases of acquired third nerve palsy in Olmsted County, Minnesota, over the 37-year period. The age- and sex-adjusted annual incidence of acquired third nerve palsy was 4.0 per 100 000 (95% CI, 3.3-4.7 per 100 000). The annual incidence in patients older than 60 was greater than patients younger than 60 (12.5 vs 1.7 per 100 000; difference, 10.8 per 100 000; 95% CI, 4.7-16.9; P < .001). The most common causes of acquired third nerve palsy were presumed microvascular (42%), trauma (12%), compression from neoplasm (11%), postneurosurgery (10%), and compression from aneurysm (6%). Ten patients (17%) with microvascular third nerve palsies had pupil involvement, while pupil involvement was seen in 16 patients (64%) with compressive third nerve palsies.



This population-based cohort demonstrates a higher incidence of presumed microvascular third nerve palsies and a lower incidence of aneurysmal compression than previously reported in non-population-based studies. While compressive lesions had a higher likelihood of pupil involvement, pupil involvement did not exclude microvascular third nerve palsy and lack of pupil involvement did not rule out compressive third nerve palsy.
Cognitive behavioral therapy for chronic pain is effective, but for whom?

Moderator analyses are reported for posttreatment outcomes in a large, randomized, controlled effectiveness trial for chronic pain for hip and knee osteoarthritis (N = 256). Pain Coping Skills Training, a form of cognitive behavioral therapy, was compared to usual care. Treatment was delivered by nurse practitioners in patients' community doctors' offices. Consistent with meta-analyses of pain cognitive behavioral therapy efficacy, treatment effects in this trial were significant for several primary and secondary outcomes, but tended to be small. This study was designed to examine differential response to treatment for patient subgroups to guide clinical decision-making for treatment. Based on existing literature, demographic (age, sex, race/ethnicity, and education) and clinical variables (disease severity, body mass index, patient treatment expectations, depression, and patient pain coping style) were specified a priori as potential moderators. Trial outcome variables (N = 15) included pain, fatigue, self-efficacy, quality of life, catastrophizing, and use of pain medication.  yielded 5 significant moderators for outcomes at posttreatment: pain coping style, patient expectation for treatment response, radiographically assessed disease severity, age, and education. Thus, sex, race/ethnicity, body mass index, and depression at baseline were not associated with level of treatment response. In contrast, patients with interpersonal problems associated with pain coping did not benefit much from the treatment. Although most patients projected positive expectations for the treatment prior to randomization, only those with moderate to high expectations benefited. Patients with moderate to high osteoarthritis disease severity showed stronger treatment effects. Finally, the oldest and most educated patients showed strong treatment effects, while younger and less educated did not.
Interventional cardiovascular procedures in Belgium: effective dose and conversion factors.

Effective dose (E), representing the risk of late radiation-induced effects, can be estimated by the use of conversion factors (CF), converting direct measurable quantities such as dose-area-product into E. Eight Belgian hospitals participated in the study with a total number of 318 procedures. E-values, calculated with PCXMC, were compared for the different hospitals for diagnostic and therapeutic procedures separately. E-values varied significantly depending on the hospital where the procedure was performed (P < 0.001), on filtration insertion (P < 0.001), on whether a centre is a training centre or not, the dose conscious action of the cardiologists and the complexity of the procedure (P < 0.001). Hospital-specific CF were calculated. An average CF of 0.185 mSv Gycm(-2) was obtained with a satisfactory correlation (r = 0.966, P < 0.001). The differences in CF between hospitals were due to, a large extent, the availability of additional filtration in cinegraphy mode (P < 0.001) and not to the differences in irradiation geometries in the clinical protocol of the interventional procedures.
Radiofrequency ablation of breast cancer: first report of an emerging technology.

Radiofrequency (RF) energy applied to breast cancers will result in cancer cell death.



Prospective nonrandomized interventional trial.



A university hospital tertiary care center.



Five women with locally advanced invasive breast cancer, aged 38 to 66 years, who were undergoing surgical resection of their tumor. One patient underwent preoperative chemotherapy and radiation therapy, 3 patients received preoperative chemotherapy, and 1 had no preoperative therapy. All patients completed the study.



While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode was inserted into the tumor under sonographic guidance. Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. Only a portion of the tumor was treated to evaluate the zone of RF ablation and the margin between ablated and nonablated tissue. Immediately after RF ablation, the tumor was surgically resected (4 mastectomies, 1 lumpectomy). Pathologic analysis included hematoxylin-eosin staining and enzyme histochemical analysis of cell viability with nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) staining of snap-frozen tissue to assess immediate cell death.



Cancer cell death as visualized on hematoxylin-eosin-stained paraffin section and NADH-diaphorase cell viability stains.



There was evidence of cell death in all patients. Hematoxylin-eosin staining showed complete cell death in 2 patients. In 3 patients there was a heterogeneous pattern of necrotic and normal-appearing cells within the ablated tissue. The ablated zone extended around the RF electrode for a diameter of 0.8 to 1.8 cm. NADH-diaphorase cell viability stains of the ablated tissue showed complete cell death in 4 patients. The fifth patient had a single focus of viable cells (<1 mm) partially lining a cyst. There were no perioperative complications related to RF ablation.



Intraoperative RF ablation results in invasive breast cancer cell death. Based on this initial report of the use of RF ablation in breast cancer, this technique merits further investigation as a percutaneous minimally invasive modality for the local treatment of breast cancer.
Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty.

The objectives of this double-blind, placebo-controlled, randomized dose-ranging study were 1) to examine the safety and tolerability of tirofiban (MK-383), a new nonpeptide platelet IIb/IIIa receptor antagonist, on a background of intravenous heparin and aspirin therapy; 2) to study the pharmacodynamics and pharmacokinetics of tirofiban; and 3) to evaluate the incidence of adverse cardiac outcomes (urgent repeat revascularization, myocardial infarction and death) with tirofiban versus placebo in a high risk subset of patients undergoing coronary angioplasty.



Abrupt vessel closure complicates 4% to 8% of angioplasty procedures. Recent data have suggested that agents that antagonize the platelet glycoprotein IIb/IIIa receptor may reduce the incidence of adverse ischemic outcomes after coronary angioplasty.



Seventy-three patients received tirofiban in three sequential dose panels and 20 patients received placebo. Patients within each panel were randomized to receive either tirofiban or placebo in a 3:1 randomization design. Bolus doses of 5, 10 and 10 microg/kg and continuous infusion (16 to 24 h) doses of 0.05, 0.10 and 0.15 microg/kg per min were administered in panels I, II and III, respectively. Patients received concomitant heparin and aspirin for the angioplasty procedure. Data on patients receiving placebo (heparin and aspirin only) were pooled across panels for comparisons. The pharmacodynamic effect of tirofiban on ex vivo platelet aggregation to 5 micromol/liter adenosine diphosphate (ADP) and bleeding times were measured. Clinical outcomes were assessed in all patients, but the power to detect clinically meaningful differences (a one-third reduction in clinical events) between groups was limited (5%).



Tirofiban was associated with a dose-dependent inhibition of ex vivo ADP-mediated platelet aggregation that was sustained during intravenous infusion and resolved rapidly after drug cessation. Adverse bleeding events, largely related to vascular access site hemorrhage, were slightly increased at the highest dose. Adverse clinical outcomes were infrequent in all patients and were not different among the small number of patients within each group.



This study establishes a rational and generally well tolerated dosing regimen for administration of tirofiban as adjunctive therapy in high risk angioplasty patients. The impact of tirofiban on adverse clinical outcomes after angioplasty awaits definition by a larger clinical trial.
Clinical trials with human tumor necrosis factor: in vivo and in vitro effects on human mononuclear phagocyte function.

The purpose of this investigation was to understand the biological effects of recombinant human tumor necrosis factor used as therapy for cancer. We studied changes in mononuclear phagocyte function following exposure to this cytokine in vitro or in vivo. Tumor necrosis factor increased phorbol myristate acetate-induced hydrogen peroxide production 8- to 20-fold in peripheral blood monocytes and peritoneal macrophages in vitro in a dose-dependent manner. Similarly, tumor necrosis factor increased phorbol myristate acetate-induced peroxide production 2.3-fold in monocytes isolated from nine patients following an i.v. infusion of this cytokine (40 to 200 micrograms/m2). In addition, tumor necrosis factor induced a 2.3-fold increase in tissue factor-like activity in mononuclear phagocytes in vitro. In vivo, tumor necrosis factor induced a trend toward higher procoagulant activity in monocytes, although this change was not statistically significant. We also noted a trend toward increased activated partial thromboplastin times and the presence of fibrin D-dimer in patients treated with tumor necrosis factor, demonstrating activation of the coagulation and fibrinolytic systems. Thus, in vivo treatment of humans with i.v. recombinant human tumor necrosis factor induced functional changes in mononuclear phagocytes similar to those noted with in vitro treatment.
A scoping review of cost-effectiveness of screening and treatment for latent tubercolosis infection in migrants from high-incidence countries

In low-incidence countries, most tuberculosis (TB) cases occur among migrants and are caused by reactivation of latent tuberculosis infection (LTBI) acquired in the country of origin. Diagnosis and treatment of LTBI are rarely implemented to reduce the burden of TB in immigrants, partly because the cost-effectiveness profile of this intervention is uncertain. The objective of this research is to perform a review of the literature to assess the cost-effectiveness of LTBI diagnosis and treatment strategies in migrants.



Scoping review of economic evaluations on LTBI screening strategies for migrants was carried out in Medline.



Nine studies met the inclusion criteria. LTBI screening was cost-effective according to seven studies. Findings of four studies support interferon gamma release assay as the most cost-effective test for LTBI screening in migrants. Two studies found that LTBI screening is cost-effective only if carried out in immigrants who are contacts of active TB cases.



Our findings support the cost-effectiveness of LTBI diagnostic and treatment strategies in migrants especially if they are focused on young subjects from high incidence countries. These strategies could represent and adjunctive and synergistic tool to achieve the ambitious aim of TB elimination.
Circulating tumor cells as a longitudinal biomarker in patients with advanced chemorefractory, RAS-BRAF wild-type colorectal cancer receiving cetuximab or panitumumab.

A still relevant number of patients with RAS-BRAF wild-type colorectal cancer (CRC) do not respond to treatment with antiepidermal growth factor receptor (EGFR) monoclonal antibodies cetuximab and panitumumab, suggesting that additional biomarkers to guide patient selection are urgently needed. Circulating tumor cells (CTCs) may represent such a biomarker. In this prospective study, 38 patients with advanced RAS-BRAF-wild-type CRC received third-line therapy with cetuximab-irinotecan or panitumumab. Peripheral blood samples for CTC status determination were collected at baseline, during treatment at early (2-4 weeks) and at later (8-10 weeks) times. CTC enrichment was done with the AdnaTest ColonCancerSelect kit, whereas CTC detection was done with the AdnaTest ColonCancerDetect kit. CTC status positivity was defined according to the kit manufacturer's thresholds. Fifty percent of patients were defined as CTC positive at baseline and the overall RECIST response rate was 26%. CTC baseline status was not associated with treatment response, whereas early CTC status and CTC status changes during treatment were significantly associated with tumor response. Kaplan-Meier analysis showed a significantly shorter progression-free survival (median, 2.0 versus 4.0 months, p = 0.004) and overall survival (4.7 versus11.4, p = 0.039) in patients with early CTC + status compared with CTC - ones. In multivariable analysis including classical prognostic factors, the CTC status changes profile during treatment was an independent predictor of both progression-free survival (p < 0.001) and overall-survival (p = 0.001). CTC status assessed early during treatment with anti-EGFR monoclonal antibodies may predict treatment failure in advance compared to imaging-based tools.