bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-management interventions to reduce healthcare use and improve quality of life among patients with asthma: systematic review and network meta-analysis
Authors: Hodkinson Alexander , Bower Peter , Grigoroglou Christos , Zghebi Salwa S , Pinnock Hilary , Kontopantelis Evangelos , Panagioti Maria 
Published: August 2020

Abstract

Objective
To compare the different self-management models (multidisciplinary case management, regularly supported self-management, and minimally supported self-management) and self-monitoring models against usual care and education to determine which are most effective at reducing healthcare use and improving quality of life in asthma.

Design
Systematic review and network meta-analysis.

Data sources
Medline, the Cochrane Library, CINAHL, EconLit, Embase, Health Economics Evaluations Database, NHS Economic Evaluation Database, PsycINFO, and ClinicalTrials.gov from January 2000 to April 2019.

Review methods
Randomised controlled trials involving the different self-management models for asthma were included. The primary outcomes were healthcare use (hospital admission or emergency visit) and quality of life. Summary standardised mean differences (SMDs) and 95% credible intervals were estimated using bayesian network meta-analysis with random effects. Heterogeneity and publication bias were assessed.

Results
From 1178 citations, 105 trials comprising 27 767 participants were included. In terms of healthcare use, both multidisciplinary case management (SMD –0.18, 95% credible interval −0.32 to −0.05) and regularly supported self-management (–0.30, −0.46 to −0.15) were significantly better than usual care. For quality of life, only regularly supported self-management (SMD 0.54, 0.11 to 0.96) showed a statistically significant benefit compared with usual care. For trials including adolescents/children (age 5-18 years), only regularly supported self-management showed statistically significant benefits (healthcare use: SMD –0.21, −0.40 to −0.03; quality of life: 0.23, 0.03 to 0.48). Multidisciplinary case management (SMD –0.32, −0.50 to −0.16) and regularly supported self-management (–0.32, −0.53 to −0.11) were most effective at reducing healthcare use in patients with symptoms of severe asthma at baseline.

Conclusions
This network meta-analysis indicates that regularly supported self-management reduces the use of healthcare resources and improves quality of life across all levels of asthma severity. Future healthcare investments should provide support that offer reviews totalling at least two hours to establish self-management skills, reserving multidisciplinary case management for patients with complex disease.

Systematic review registration
PROSPERO number CRD42019121350.
Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model
Authors: Posma Rene A , Venema Leonie H , Huijink Tobias M , Westerkamp Andrie C , Wessels A Mireille A , De Vries Nynke J , Doesburg Frank , Roggeveld J , Ottens Petra J , Touw Daan J , Nijsten Maarten W , Leuvenink Henri G D 
Published: August 2020

IntroductionMetformin can accumulate and cause lactic acidosis in patients with renal insufficiency. Metformin is known to inhibit mitochondria, while renal secretion of the drug by proximal tubules indirectly requires energy. We investigated whether addition of metformin before or during ex vivo isolated normothermic machine perfusion (NMP) of porcine and rat kidneys affects its elimination.Research design and methodsFirst, Lewis rats were pretreated with metformin or saline the day before nephrectomy. Subsequently, NMP of the kidney was performed for 90 min. Metformin was added to the perfusion fluid in one of three different concentrations (none, 30 mg/L or 300 mg/L). Second, metformin was added in increasing doses to the perfusion fluid during 4 hours of NMP of porcine kidneys. Metformin concentration was determined in the perfusion fluid and urine by liquid chromatography-tandem mass spectrometry.ResultsMetformin clearance was approximately 4–5 times higher than creatinine clearance in both models, underscoring secretion of the drug. Metformin clearance at the end of NMP in rat kidneys perfused with 30 mg/L was lower than in metformin pretreated rats without the addition of metformin during perfusion (both p≤0.05), but kidneys perfused with 300 mg/L trended toward lower metformin clearance (p=0.06). Creatinine clearance was not different between treatment groups. During NMP of porcine kidneys, metformin clearance peaked at 90 min of NMP (18.2±13.7 mL/min/100 g). Thereafter, metformin clearance declined, while creatinine clearance remained stable. This observation can be explained by saturation of metformin transporters with a Michaelis-Menten constant (95% CI) of 23.0 (10.0 to 52.3) mg/L.ConclusionsMetformin was secreted during NMP of both rat and porcine kidneys. Excretion of metformin decreased under increasing concentrations of metformin, which might be explained by saturation of metformin transporters rather than a self-inhibitory effect. It remains unknown whether a self-inhibitory effect contributes to metformin accumulation in humans with longer exposure times.
Exercise training improves adipose tissue metabolism and vasculature regardless of baseline glucose tolerance and sex
Authors: Honkala Sanna Maria , Motiani Piryanka , Kivelä Riikka , Hemanthakumar Karthik Amudhala , Tolvanen Erik , Motiani Kumail Kumar , Eskelinen Jari-Joonas , Virtanen Kirsi A , Kemppainen Jukka , Heiskanen Marja Anneli , Löyttyniemi Eliisa , Nuutila Pirjo , Kalliokoski Kari K , Hannukainen Jarna Christina 
Published: August 2020

IntroductionWe investigated the effects of a supervised progressive sprint interval training (SIT) and moderate-intensity continuous training (MICT) on adipocyte morphology and adipose tissue metabolism and function; we also tested whether the responses were similar regardless of baseline glucose tolerance and sex.Research design and methods26 insulin-resistant (IR) and 28 healthy participants were randomized into 2-week-long SIT (4–6×30 s at maximum effort) and MICT (40–60 min at 60% of maximal aerobic capacity (VO2peak)). Insulin-stimulated glucose uptake and fasting-free fatty acid uptake in visceral adipose tissue (VAT), abdominal and femoral subcutaneous adipose tissues (SATs) were quantified with positron emission tomography. Abdominal SAT biopsies were collected to determine adipocyte morphology, gene expression markers of lipolysis, glucose and lipid metabolism and inflammation.ResultsTraining increased glucose uptake in VAT (p<0.001) and femoral SAT (p<0.001) and decreased fatty acid uptake in VAT (p=0.01) irrespective of baseline glucose tolerance and sex. In IR participants, training increased adipose tissue vasculature and decreased CD36 and ANGPTL4 gene expression in abdominal SAT. SIT was superior in increasing VO2peakand VAT glucose uptake in the IR group, whereas MICT reduced VAT fatty acid uptake more than SIT.ConclusionsShort-term training improves adipose tissue metabolism both in healthy and IR participants independently of the sex. Adipose tissue angiogenesis and gene expression was only significantly affected in IR participants.
Novel subgroups of type 2 diabetes and their association with microvascular outcomes in an Asian Indian population: a data-driven cluster analysis: the INSPIRED study
Authors: Anjana Ranjit Mohan , Baskar Viswanathan , Nair Anand Thakarakkattil Narayanan , Jebarani Saravanan , Siddiqui Moneeza Kalhan , Pradeepa Rajendra , Unnikrishnan Ranjit , Palmer Colin , Pearson Ewan , Mohan Viswanathan 
Published: August 2020

IntroductionType 2 diabetes is characterized by considerable heterogeneity in its etiopathogenesis and clinical presentation. We aimed to identify clusters of type 2 diabetes in Asian Indians and to look at the clinical implications and outcomes of this clustering.Research design and methodsFrom a network of 50 diabetes centers across nine states of India, we selected 19 084 individuals with type 2 diabetes (aged 10–97 years) with diabetes duration of less than 5 years at the time of first clinic visit and performed k-means clustering using the following variables: age at diagnosis, body mass index, waist circumference, glycated hemoglobin, serum triglycerides, serum high-density lipoprotein cholesterol and C peptide (fasting and stimulated). This was then validated in a national epidemiological data set of representative individuals from 15 states across India.ResultsWe identified four clusters of patients, differing in phenotypic characteristics as well as disease outcomes: cluster 1 (Severe Insulin Deficient Diabetes, SIDD), cluster 2 (Insulin Resistant Obese Diabetes, IROD), cluster 3 (Combined Insulin Resistant and Deficient Diabetes, CIRDD) and cluster 4 (Mild Age-Related Diabetes, MARD). While SIDD and MARD are similar to clusters reported in other populations, IROD and CIRDD are novel clusters. Cox proportional hazards showed that SIDD had the highest hazards for developing retinopathy, followed by CIRDD, while CIRDD had the highest hazards for kidney disease.ConclusionsCompared with previously reported clustering, we show two novel subgroups of type 2 diabetes in the Asian Indian population with important implications for prognosis and management. The coexistence of insulin deficiency and insulin resistance seems to be peculiar to the Asian Indian population and is associated with an increased risk of microvascular complications.
Lifestyle medicine for type 2 diabetes: practice-based evidence for long-term efficacy of a multicomponent lifestyle intervention (Reverse Diabetes2 Now)
Authors: Pot Gerda K , Battjes-Fries Marieke CE , Patijn Olga N , van der Zijl Nynke , Pijl Hanno , Voshol Peter 
Published: August 2020

IntroductionA wealth of evidence supports short-term efficacy of lifestyle interventions in type 2 diabetes (T2D). However, little is known about long-term effects of lifestyle interventions in real-life settings.MethodsThis observational, single-arm study evaluated long-term impact of ‘Voeding Leeft: Reverse-Diabetes2-Now’, a 6-month multicomponent lifestyle programme, on glycaemic control and glucose-lowering medication (GLmed) use, other T2D parameters and quality of life in 438 T2D participants at 6, 12, 18 and 24 months using paired sample t-tests, χ2and generalised linear models.ResultsAt 24 months, 234 participants provided information on GLmed and HbA1c (‘responders’). 67% of the responders used less GLmed, and 28% ceased all GLmed. Notably, 71% of insulin users at baseline (n=47 of 66 insulin users) were off insulin at 24 months. Mean HbA1c levels were similar at 24 months compared with baseline (55.6±12.8 vs. 56.3±10.5 mmol/mol, p=0.43), but more responders had HbA1c levels ≤53 mmol/mol at 24 months (53% vs 45% at baseline). Furthermore, triglyceride levels (−0.34±1.02 mmol/L, p=0.004), body weight (−7.0±6.8 kg, p<0.001), waist circumference (−7.9±8.2 cm, p<0.001), body mass index (−2.4±2.3 kg/m2, p<0.001) and total cholesterol/high-density lipoprotein (HDL) ratio (−0.22±1.24, p=0.044) were lower, while HDL (+0.17 ± 0.53 mmol/L, p<0.001) and low-density lipoprotein-cholesterol levels (+0.18 ± 1.06 mmol/L, p=0.040) were slightly higher. No differences were observed in fasting glucose or total cholesterol levels. Quality of life and self-reported health significantly improved.ConclusionThis study indicates robust, durable real-life benefits of this lifestyle group programme after up to 24 months of follow-up, particularly in terms of medication use, body weight and quality of life in T2D patients.
Cardiorespiratory fitness on a treadmill in an adult cystic fibrosis population
Authors: Torvanger Ole , Os Audun , Skjonsberg Ole Henning , Edvardsen Elisabeth 
Published: August 2020

Objectives(1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO2peak) and forced expiratory volume in 1 s (FEV1).MethodsA total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO2peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured.A low CRF was defined as a VO2peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV1and VO2peak were calculated using linear regression.ResultsThe VO2peak was 40.6±11.5 and 35.2±8.9 mL kg−1min−1, which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO2peak was moderately affected by age, for men (r=−0.36, p<0.001) and women (r=−0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO2peak and FEV1was r=0.64 (p<0.001). In participants with a low CRF, FEV1ranged from 20% to 112% of predicted.ConclusionsThe correlation between VO2peak and FEV1was moderate. The majority of the tests resulted in a VO2peak within normal limits. Interestingly, 44% of the tests with a low VO2peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients.
Statistical methods applied to the search of sterile neutrinos
Authors: Agostini Matteo , Neumair Birgit 
Published: August 2020

AbstractThe frequentist statistical methods applied to search for short-baseline neutrino oscillations induced by a sterile neutrino with mass at the eV scale are reviewed and compared. The comparison is performed under limit setting and signal discovery scenarios, considering both when an oscillation would enhance the neutrino interaction rate in the detector and when it would reduce it. The sensitivity of the experiments and the confidence regions extracted for specific data sets change considerably according to which test statistic is used and the assumptions on its probability distribution. A standardized analysis approach based on the most general kind of hypothesis test is proposed.
Visible-light photocatalytic activity of Fe@TiO2 core–shell composite synthesized by sol–gel method
Authors: Yeh Min Yen , Yang Tzu Yuan , Wu Tsung Chi , Lee Shiow Yueh , Chang Shun Hsyung 
Published: August 2020

Core–shell structure [Formula: see text] was synthesized by sol–gel method. The photocatalytic degradation of methylene blue over the [Formula: see text] reached 98% under UV light irradiation within 5 h. The band gap of the core–shell [Formula: see text] was found to have a redshift through a sintering treatment. The redshifted [Formula: see text] had a good performance of methylene-blue degradation (reaching 85%) under visible light irradiation for 5 h.
Simulation in design air spindle with orifice and distribution grooves
Authors: Thang Vu Toan , Duc Truong Minh , Dat Nguyen Trong , Trung Nguyen Thanh , Tung Vu Thanh 
Published: August 2020

This paper presents some results of simulation using ANSYS CFX software in design air spindle which has the structure in the form of orifice and grooves to ensure uniform pressure distribution and avoiding air hammer; it is also easy to manufacture and reduces costs. The results of simulation are good in investigating operation of air-spindle which is changed some parameters to find the optimal working mode for the air spindle with speed in the range of 5000–20,000 rpm.
Phase I Study of P-cadherin–targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors
Authors: Subbiah Vivek , Erwin William , Mawlawi Osama , McCoy Asa , Wages David , Wheeler Catherine , Gonzalez-Lepera Carlos , Liu Holly , Macapinlac Homer , Meric-Bernstam Funda , Hong David S. , Pant Shubham , Le Dao , Santos Elmer , Gonzalez Jose , Roszik Jason , Suzuki Takeaki , Subach Ruth Ann , Madden Timothy , Johansen Mary , Nomura Fumiko , Satoh Hirokazu , Matsuura Tadashi , Kajita Masamichi , Nakamura Eri , Funase Yuichi , Matsushima Satoshi , Ravizzini Gregory 
Published: August 2020

Abstract

Purpose:
90Y-FF-21101 is an Yttrium-90–conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors.

Patients and Methods:
The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5–25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months.

Results:
111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity.

Conclusions:
The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.
Tebentafusp, A TCR/Anti-CD3 Bispecific Fusion Protein Targeting gp100, Potently Activated Antitumor Immune Responses in Patients with Metastatic Melanoma
Authors: Middleton Mark R. , McAlpine Cheryl , Woodcock Victoria K. , Corrie Pippa , Infante Jeffrey R. , Steven Neil M. , Evans Thomas R. Jeffry , Anthoney Alan , Shoushtari Alexander N. , Hamid Omid , Gupta Avinash , Vardeu Antonella , Leach Emma , Naidoo Revashnee , Stanhope Sarah , Lewis Sion , Hurst Jacob , O’Kelly Ita , Sznol Mario 
Published: August 2020

Abstract

Purpose:
Tebentafusp is a first-in-class bispecific fusion protein designed to target gp100 (a melanoma-associated antigen) through a high affinity T-cell receptor (TCR) binding domain and an anti-CD3 T-cell engaging domain, which redirects T cells to kill gp100-expressing tumor cells. Here, we report a multicenter phase I/II trial of tebentafusp in metastatic melanoma (NCT01211262) focusing on the mechanism of action of tebentafusp.

Patients and Methods:
Eighty-four patients with advanced melanoma received tebentafusp. Treatment efficacy, treatment-related adverse events, and biomarker assessments were performed for blood-derived and tumor biopsy samples obtained at baseline and on-treatment.

Results:
Tebentafusp was generally well-tolerated and active in both patients with metastatic uveal melanoma and patients with metastatic cutaneous melanoma. A 1-year overall survival rate of 65% was achieved for both patient cohorts. On-treatment cytokine measurements were consistent with the induction of IFNγ pathway–related markers in the periphery and tumor. Notably, tebentafusp induced an increase in serum CXCL10 (a T-cell attractant) and a reduction in circulating CXCR3+ CD8+ T cells together with an increase in cytotoxic T cells in the tumor microenvironment. Furthermore, increased serum CXCL10 or the appearance of rash (likely due to cytotoxic T cells targeting gp100-expressing skin melanocytes) showed a positive association with patient survival.

Conclusions:
These data suggest that redirecting T cells using a gp100-targeting TCR/anti-CD3 bispecific fusion protein may provide benefit to patients with metastatic melanoma. Furthermore, the activity observed in these two molecularly disparate melanoma classes hints at the broad therapeutic potential of tebentafusp.
Mortality and Pre‐Hospitalization Use of Renin‐Angiotensin System Inhibitors in Patients with Hypertension and Coronavirus Disease 2019 (COVID‐19)
Authors: Chen Chen , Wang Feng , Chen Peng , Jiang Jiangang , Cui Guanglin , Zhou Ning , Moroni Francesco , Moslehi Javid J. , Ammirati Enrico , Wang Dao Wen 
Published: August 2020

Background
There has been significant controversy about the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of patients with hypertension and coronavirus disease 2019.

Methods and Results

We retrospectively assessed 2297 hospitalized patients with coronavirus disease 2019 at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1182 patients with known hypertension on pre‐hospitalization therapy. We compared the baseline characteristics and in‐hospital mortality between patients with hypertension taking RAS inhibitors (n=355) versus non‐RAS inhibitors (n=827). Of the 1182 patients with hypertension (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group versus 95/827 (11.5%) patients in the non‐RAS inhibitors group (
P
<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15–0.52,
P
<0.0001) at 45 days in the RAS inhibitors group compared with non‐RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (n=289) or angiotensin‐converting enzyme inhibitors (n=66) were separately compared with non‐RAS inhibitors group. The RAS inhibitors group compared with non‐RAS inhibitors group had lower levels of C‐reactive protein (median 13.5 versus 24.4 pg/mL;
P
=0.007) and interleukin‐6 (median 6.0 versus 8.5 pg/mL;
P
=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta‐analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29–0.65,
P
<0.0001).

Conclusions
In a large single center retrospective analysis, we observed a protective effect of pre‐hospitalization use of RAS inhibitors on mortality in patients with hypertension and coronavirus disease 2019, which might be associated with reduced inflammatory response.