nils-herrmann/clean_scirepeval huggingface dataset:
Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial.

Additional benefits of the dual-hormone (insulin and glucagon) artificial pancreas compared with the single-hormone (insulin alone) artificial pancreas have not been assessed in young people in outpatient unrestricted conditions. We evaluated the efficacy of three systems for nocturnal glucose control in children and adolescents with type 1 diabetes.



We did a randomised, three-way, crossover trial in children aged 9-17 years with type 1 diabetes attending a diabetes camp in Canada. With use of sealed envelopes, children were randomly assigned in a 1:1:1:1:1:1 ratio with blocks of six to different sequences of the three interventions (single-hormone artificial pancreas, dual-hormone artificial pancreas, and conventional continuous subcutaneous insulin pump therapy). Each intervention was applied for 3 consecutive nights. Participants, study staff, and endpoint assessors were not masked. The primary outcome was the percentage of time spent with glucose concentrations lower than 4·0 mmol/L from 2300 h to 0700 h. Analysis was by intention to treat. A p value of less than 0·0167 was regarded as significant. 
Between June 30, 2014, and Aug 9, 2014, we enrolled 33 children of mean age 13·3 years (SD 2·3; range 9-17). The time spent at a glucose concentration lower than 4·0 mmol/L was median 0% (IQR 0·0-2·4) during nights with the dual-hormone artificial pancreas, 3·1% (0·0-6·9) during nights with the single-hormone artificial pancreas (p=0·032), and 3·4% (0-11·0) during nights with conventional pump therapy (p=0·0048 compared with dual-hormone artificial pancreas and p=0·32 compared with single-hormone artificial pancreas). 15 hypoglycaemic events (<3·1 mmol/L for 20 min measured by sensor then confirmed with capillary glucose <4·0 mmol/L) were noted during nights with conventional pump therapy compared with four events with the single-hormone system and no events with the dual-hormone system. None of the assessed outcomes varied with the order in which children and young adults were assigned interventions.



The dual-hormone artificial pancreas could improve nocturnal glucose control in children and adolescents with type 1 diabetes. Longer and larger outpatient studies are now needed.
Correlation of Selenium and Zinc Levels to Antiretroviral Treatment Outcomes in Thai HIV-infected Children without Severe HIV Symptoms

Deficiencies in antioxidants contribute to immune dysregulation and viral replication. To evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children.HIV-infected Thai children 1–12 years old, CD4 15–24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cutoffs were Se <0.1 μmol/l and Zn <9.9 μmol/l. Serum ferritin and C-reactive protein (CRP) were measured every 24 weeks. No micronutrient supplement was prescribed.In all, 141 children (38.3% male) with a median (interquartile range (IQR)) age of 7.3 (4.2–9.0) years were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6 log10copies/ml. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7–1.0) μmol/l and 5.9 (4.8–6.9) μmol/l, respectively. None had Se deficiency while all had Zn deficiency. Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/ml with 11% median CD4 gain. The mean change of Se was 0.06 μmol/l (P=0.003) and Zn was 0.42 μmol/l (P=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (P<0.01) and higher baseline Zn level (P=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both P<0.01). No association of CRP with the changes from baseline of CD4% or HIV-RNA was found.In HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between Se and ART treatment outcomes was found. Higher pre-ART Zn levels were associated with significant increases in CD4% at 48 weeks.
Improving Adherence to Cardiovascular Therapies: An Economic Evaluation of a Randomized Pragmatic Trial.

Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular medications (i.e., statins, angiotensin-converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]).



Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records.



Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls.



We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker's willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline.
Opinions about the new law on end-of-life issues in a sample of french patients receiving palliative care

In February 2nd 2016, the French government enacted the Claeys-Leonetti law that forbade euthanasia and established the right to deep and continuous sedation for end-of-life patients. Moreover, the law also obliges clinicians to abide by any advance directives regarding treatment and investigation, except in cases where they are "obviously inappropriate" in a given medical situation, or in cases of emergency, in order to allow medical staff to take time to assess the patient's situation. Artificial feeding and hydration are considered as treatment. The aim of this report is to investigate individuals receiving palliative care about their opinion about euthanasia, about advance directives, about the right to deep and continuous sedation, and the right to stopping artificial feeding and hydration.



The study was an opinion survey conducted among patients treated in two different palliative care institutions: a palliative care unit at the University Hospital (Timone, Marseille, France) and a non-profit association palliative care home ("La Maison", Gardanne, France). Face-to-face interviews were performed by two investigators. The survey included sociodemographics, clinical data, and opinions about euthanasia, deep and continuous sedation, stopping artificial feeding and hydration, and advance directives.



Forty patients were interviewed. The mean age was 59.8 years (standard deviation 12). Fifty three percent reported opposition to legalized euthanasia. Eighty three percent were in favour of the right to deep and continuous sedation in patients with refractory pain, 75% when it concerns a patient unable to express their wishes, and 68% when the patient decides to stop vital treatment. Fifty eight percent reported that artificial nutrition and hydration should be considered as care. Fifty eight percent of the patients interviewed would like to see doctors follow the express wishes contained in advance care directives and 53% that advance directives should be subject to a validity period.



This work demonstrates the feasibility of discussing sensitive issues such as euthanasia, continuous and deep sedation and cessation of care with patients receiving palliative care. These preliminary results point to the need to perform a larger study in order to find determinant factors in this specific situation and to incorporate them into thinking about end-of-life laws.
Preliminary evidence of cannabinoid effects on brain-derived neurotrophic factor (BDNF) levels in humans

Acute and chronic exposure to cannabinoids has been associated with cognitive deficits, a higher risk for schizophrenia and other drug abuse. However, the precise mechanism underlying such effects is not known. Preclinical studies suggest that cannabinoids modulate brain-derived neurotrophic factor (BDNF). Accordingly, we hypothesized that Δ9-tetrahydrocannabinol (Δ9-THC), the principal active component of cannabis, would alter BDNF levels in humans. Healthy control subjects (n = 14) and light users of cannabis (n = 9) received intravenous administration of (0.0286 mg/kg) Δ9-THC in a double-blind, fixed order, placebo-controlled, laboratory study. Serum sampled at baseline, after placebo administration, and after Δ9-THC administration was assayed for BDNF using ELISA. Δ9-THC increased serum BDNF levels in healthy controls but not light users of cannabis. Further, light users of cannabis had lower basal BDNF levels. Δ9-THC produced psychotomimetic effects, perceptual alterations, and “high” and spatial memory impairments. The effects of socially relevant doses of cannabinoids on BDNF suggest a possible mechanism underlying the consequences of exposure to cannabis. This may be of particular importance for the developing brain and also in disorders believed to involve altered neurodevelopment such as schizophrenia. Larger studies to investigate the effects of cannabinoids on BDNF and other neurotrophins are warranted.
Efficacy of ginger for prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving adriamycin–cyclophosphamide regimen: a randomized, double-blind, placebo-controlled, crossover study

The purpose of this study is to determine the efficacy of ginger for reducing chemotherapy-induced nausea and vomiting (CINV) in breast cancer patients receiving adriamycin and cyclophosphamide (AC) regimens. We enrolled breast cancer patients receiving AC who experienced moderate to severe nausea or vomiting during the first chemotherapy cycle. Subjects were randomized to receive a 500-mg ginger capsule or placebo twice a day for 5 days starting on the first day of the second AC cycle and were switched to the other treatment in the third cycle. All participants also received ondansetron and dexamethasone for CINV prophylaxis. Nausea severity was recorded once a day during the first 5 days of each cycle. The primary outcome was reduction in nausea score. Thirty-four subjects (68 cycles of AC) were enrolled. Mean (range) maximum nausea score in the first AC cycle was 58 (40–90). Thirty-three subjects (97 %) received the same AC doses in the second as in the third cycle. Mean (±standard error) maximum nausea scores in patients receiving ginger and placebo were 35.36 (±4.43) and 32.17 (±3.71), respectively. The difference in mean maximum nausea scores was 3 (95 % confidence interval, −3 to 9; P = 0.3). There were no significant differences between ginger and placebo in terms of vomiting incidence and severity, rescue medication use, chemotherapy compliance, and adverse events. Ginger (500 mg) twice daily was safe, but conferred no additional benefit in terms of reducing nausea severity in breast cancer patients receiving AC and ondansetron and dexamethasone for CINV prophylaxis.
Characterization and Prognostic Significance of Methylthioadenosine Phosphorylase Deficiency in Nasopharyngeal Carcinoma

Identification of cancer-associated genes by genomic profiling contributes to the elucidation of tumor development and progression. The methylthioadenosine phosphorylase (MTAP) gene, located at chromosome 9p21, plays a critical role in tumorigenicity and disease progression in a wide variety of cancers. However, the prognostic impact of MTAP in patients with nasopharyngeal carcinoma (NPC) remains obscured. Through data mining from published transcriptomic database, MTAP was first identified as a differentially downregulated gene in NPC. In this study, our aim was to evaluate the expression of MTAP in NPC and to clarify its prognostic significance.MTAP immunohistochemistry was retrospectively performed and analyzed in biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. The immunoexpression status was correlated with the clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Real-time quantitative polymerase chain reaction (PCR) was used to measure MTAP gene dosage. In some cases, we also performed methylation-specific PCR and pyrosequencing to assess the status of promoter methylation.MTAP deficiency was significantly associated with advanced tumor stages (P = 0.023) and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS. In the multivariate comparison, MTAP deficiency still remained prognostically independent to portend worse DSS (P = 0.021, hazard ratio = 1.870) and DMFS (P = 0.009, hazard ratio = 2.154), together with advanced AJCC stages III to IV. Homozygous deletion or promoter methylation of MTAP gene were identified to be significantly associated with MTAP protein deficiency (P < 0.001).MTAP deficiency was correlated with an aggressive phenotype and independently predictive of worse DSS and DMFS, suggesting its role in disease progression and as an independent prognostic biomarker of NPC, which potentially offers new strategy of targeted treatment for patients lacking MTAP expression.
Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.

This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.



A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale).



In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm.



Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life.
Olmesartan reduces inflammatory biomarkers in patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the OLIVUS trial

The OLmesartan on the progression of coronary atherosclerosis: evaluation by IntraVascular UltraSound (OLIVUS) trial demonstrated that an angiotensin II receptor blocker, olmesartan, reduces the rate of coronary atheroma progression as evaluated by intravascular ultrasound in patients with stable angina pectoris undergoing percutaneous coronary intervention. This substudy examined the impact of olmesartan on serum biomarkers and the relationship between biomarker changes and atheroma progression. Patients in the OLIVUS trial (n = 247) were randomly assigned to a control group or the olmesartan group. A subgroup of these patients (n = 135, 55 %) was analyzed at baseline and at 14 months. Patients’ characteristics and blood-pressure control were identical between the control group (n = 65) and the olmesartan group (n = 70), and also between the subpopulation and total population. The change in the level of high-sensitivity C-reactive protein (hs-CRP) (mg/l) and adiponectin (μg/ml) was significantly greater in the olmesartan group than in the control group (between-group differences: 0.5 and −0.7; 95 % confidence interval: 0.2–0.8 and −1.3 to −0.1; P = 0.001 and 0.02, respectively). Multiple regression analysis revealed that the nominal changes in total atheroma volume and percent atheroma volume were significantly associated with the nominal change in hs-CRP in the olmesartan group but not in the control group. Olmesartan reduced hs-CRP in patients with stable angina, and this correlated with the change in coronary atheroma.
Nuclear oxidative damage correlates with poor survival in colorectal cancer

Oxidative DNA damage results from DNA adducts such as 8-oxo-7, 8 dihydro-2′-deoxyguanosine (8-oxo-dG), which is a pro-mutagenic lesion. No known association between 8-oxo-dG, disease progression and survival exists in colorectal cancer (CRC). We examined levels of 8-oxo-dG in sporadic CRC to determine its relationship with pathological stage and outcome. A total of 143 CRC patients and 105 non-cancer patients were studied. Nuclear and cytoplasmic 8-oxo-dG was assessed using immunohistochemistry. Double immunofluorescence using 8-oxo-dG and manganese superoxide dismutase (MnSOD) antibodies localised cytoplasmic 8-oxo-dG. Apoptosis was detected using TUNEL. Nuclear staining levels were similar in tumour tissue and matched normal mucosa in both epithelial (P=0.22) and stromal (P=0.85) cells. Epithelial cytoplasmic staining was greater in tumour tissue (P<0.001). Double immunofluorescence localised cytoplasmic 8-oxo-dG to mitochondria. Epithelial and stromal nuclear 8-oxo-dG decreased with local disease spread, but highest levels were found in distant disease (P<0.01). Survival was related to epithelial nuclear and stromal staining in normal mucosa (P<0.001) and tumour (P<0.01) but was unrelated to cytoplasmic staining. Normal control cells in tissue from cancer patients with high levels of 8-oxo-dG failed to undergo cell death. 8-oxo-dG may be an important biomarker of disease risk, progression and survival for CRC patients.
Are shock index and adjusted shock index useful in predicting mortality and length of stay in community-acquired pneumonia?

Community Acquired Pneumonia (CAP) is a common infection which is associated with a significant mortality. Shock index, heart rate divided by blood pressure, has been shown to predict mortality in several conditions including sepsis, acute myocardial infarction and traumatic injuries. Very little is known about the prognostic value of shock index in community acquired pneumonia (CAP).



To examine the usefulness of shock index (SI) and adjusted shock index (corrected to temperature) (ASI) in predicting mortality and hospital length of stay in patients admitted to hospital with CAP.



A prospective study was conducted in three hospitals in Norfolk & Suffolk, UK. We compared risk of mortality and longer length of stay for low (=<1.0, i.e. heart rate =< systolic BP) and high (>1.0, i.e. heart rate > systolic BP) SI and ASI adjusting for age, sex and other parameters which have been shown to be associated with mortality in CAP.



A total of 190 patients were included (males=53%). The age range was 18-101 years (median=76 years). Patients with SI & ASI >1.0 had higher likelihood of dying within 6 weeks from admission. The adjusted odds ratio for 30 days mortality were 2.48 (1.04-5.92; p=0.04) for SI and 3.16 (1.12-8.95; p=0.03) for ASI. There was no evidence to suggest that they predict longer length of stay.



Both SI and ASI of >1.0 predict 6 weeks mortality but not longer length of stay in CAP.
Does cardioplegia type affect outcome and survival in patients with advanced left ventricular dysfunction? Results from the CABG Patch Trial.

There is controversy regarding which cardioplegic solution, temperature, and route of administration provides superior protection. The CABG Patch Trial enrolled a high-risk group of coronary artery disease patients with an ejection fraction of <36%. Thus, they constitute an ideal group to benefit most from optimal cardioplegic protection.



All patients randomized into the trial were compared with respect to the use of blood and crystalloid cardioplegia. In addition, a questionnaire was sent to surgeons requesting blood cardioplegic temperature and route. Patients receiving crystalloid cardioplegia versus those receiving blood cardioplegia were found to have significantly more operative deaths (2% versus 0.3%, P:=0.02), postoperative myocardial infarctions (10% versus 2%, P:<0.001), shock (13% versus 7%, P:=0. 013), and postoperative conduction defects (21.6% versus 12.4%, P:=0. 001). Despite this, early death (6% crystalloid versus 4% blood cardioplegia) and late death (24% crystalloid versus 21% blood cardioplegia) statistics were not significantly different. Patients receiving normothermic blood had less postoperative right ventricular dysfunction (10%) than did patients receiving cold blood (25%) or cold blood with warm reperfusion (30%) (P:=0.004). There was no significant difference in early or late death. Finally, patients who received combined antegrade and retrograde cardioplegia had significantly less inotrope use (71% versus 84%, P:=0.002), right ventricular dysfunction (23% versus 41%, P:=0.001), and postoperative balloon pump use (12% versus 19%, P:=0.02) than did those who received antegrade cardioplegia. There was no difference in survival.



Blood cardioplegia and combined antegrade and retrograde cardioplegia are superior to crystalloid and antegrade cardioplegia alone for postoperative morbidity. Despite this, there is no significant difference in early or late survival.