bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resource implications of bortezomib therapy in a large UK cohort: An evaluation study
Authors: Djebbari Faouzi , Tatarczuch Maciej , Panitsas Fotios , Vallance Grant , Sultanova Manuela , Kothari Jaimal , Ramasamy Karthik , Peniket Andy 
Published: August 2019

Background Bortezomib is a cornerstone in the management of multiple myeloma. It remains an attractive treatment option because it is efficacious, reasonably well tolerated and easy to administer. However, data on resource implications in the UK for both patients and healthcare providers are limited. Methods We conducted a retrospective study of 127 patients to assess implications of bortezomib therapy on patients and healthcare resources. A patient-episode was defined as a patient attending the chemotherapy day treatment unit solely for bortezomib administration. Data were collected for the duration of therapy as follows: cost of drug calculated using the UK’s bortezomib indicative price as per British National Formulary, cost of drug administration in the chemotherapy day treatment unit calculated using the National Health Service’s schedule of service cost, time from check-in to drug administration, patient travel time and distance calculated using Google maps, and cost of travel. Results Median drug cost and administration cost per patient were £8336 (£2084–£108,368) and £4640 (£290–£15,080), respectively. Median time from check-in to administration was 63 min (range 5–433), median travel time was 90 min (range 8–270) and 80 min (range 8–280) during peak and off-peak periods, respectively. Median return travel distance was 33.4 miles (range 1.2–224) for travel cost per patient per trip was £8.35–£13.20. Conclusions Our real-world resource analysis demonstrated that delivering bortezomib therapy can be associated with significant cost and time implications for patients and healthcare providers. Our study method sets a basis for evaluating resource implications of other novel approaches to myeloma therapy.
“Mummy, my eyelids are heavy”: A case series of juvenile myasthenia gravis
Authors: Krishna Logeswari , Abdul Jalil Nor Fadzillah , Lott Pooi Wah , Singh Sujaya , Choo May May 
Published: August 2019

Purpose: To report three cases of juvenile myasthenia gravis aged between 18 and 24 months with ocular symptoms as their first presentation. Method: A case series. Results: We present a case series of juvenile myasthenia gravis in a tertiary centre in Malaysia. Two of the three cases consist of a pair of twins who presented with ptosis of bilateral eyes; the first twin presented 4 months later than the second twin. These two cases were positive for anti-acetylcholine receptor antibodies and had generalized myasthenia gravis, whereas the other case was negative for receptor antibodies and was purely ocular myasthenia gravis. Conclusion: Juvenile myasthenia gravis is relatively rare in toddlers. Early diagnosis and commencement of treatment is important to slow the progression of the disease and avoiding life-threatening events.
Brain Injury in Neonatal Hypoglycemia: A Hospital-Based Cohort Study
Authors: Gu Mei-Hong , Amanda Fanny , Yuan Tian-Ming 
Published: August 2019

Background: Neonatal hypoglycemia is more prevalent and can cause severe neurological sequelae. The objective of this study was to assess the patterns of neuroradiologic changes in neonatal hypoglycemia. Methods: A retrospective cohort study was conducted on 66 neonatal hypoglycemia patients, and the magnetic resonance imaging (MRI) and clinical records were reviewed. Results: Magnetic resonance imaging showed evidences of abnormality in 54.54% (36 of 66) of hypoglycemic infants. The most common abnormal findings were located on the parietal and occipital lobes of the brains. The number of days with hypoglycemia was significantly higher for abnormal MRI infants ( P < .001), and prolonged/recurrent hypoglycemia was remarkably distinguished for abnormal MRI infants ( P < .001). Patients with abnormal MRI findings did not have a lower blood glucose than infants without abnormal MRI findings ( P > .05), but the lowest blood glucose was significantly lower for the patients with seizures ( P < .01). Conclusions: The pattern of bilateral occipital cortical injury is the most common abnormality for neonatal hypoglycemia. The number of days with hypoglycemia, not the lower blood glucose, was significantly related to abnormal MRI infants.
Subclinical neurodegeneration in multiple sclerosis and neuromyelitis optica spectrum disorder revealed by optical coherence tomography
Authors: Pisa Marco , Ratti Francesco , Vabanesi Marco , Radaelli Marta , Guerrieri Simone , Moiola Lucia , Martinelli Vittorio , Comi Giancarlo , Leocani Letizia 
Published: August 2019

Background: Neuroretinal atrophy is associated with whole-brain atrophy and disease activity in multiple sclerosis (MS). Recent findings support that subclinical visual pathway involvement might also occur in neuromyelitis optica spectrum disorders (NMOSDs). Objective: The objective of this study is to assess retinal thinning in MS and NMOSD and its association with disease activity. Methods: In total, 27 NMOSD and 54 propensity-score-matched MS patients underwent optical coherence tomography, visual acuity, and visual-evoked potentials at 2.4 years apart, in addition to routine clinical and magnetic resonance imaging (MRI) assessment. We excluded eyes with acute optic neuritis. Results: In NMOSD, we detected peripapillary retinal nerve fiber layer (pRNFL) thinning in patients with disease activity during follow-up (−0.494 µm/year), but not in stable patients (−0.012 µm/year). Macular ganglion cell-inner plexiform layer (GCIPL) thinning occurred instead in all patients (−0.279 µm/year). Relapsing–remitting multiple sclerosis (RRMS) meeting NEDA-3 criteria had no pRNFL or GCIPL thinning during follow-up. Active-disease RRMS and progressive MS, both active and stable, displayed pRNFL (−0.724, −0.586, −0.556 µm/year, respectively) and GCIPL loss. Conclusion: In MS, neuroretinal atrophy was associated with disease activity but occurred in progressive MS even when achieving NEDA-3 criteria. In NMOSD, pRNFL thinning was associated with non-ocular relapses due to a spreading of inflammatory activity. GCIPL thinning was found in all patients, supporting a primary retinal pathology targeting AQP4-rich structures.
Examining the effects of activities of daily living on informal caregiver strain
Authors: Walsh Edel , Murphy Aileen 
Published: August 2019

Objectives This study examines the factors associated with caregiver strain experienced by informal caregivers of older people, using data from Ireland. Methods The analysis is based on a sample of 1394 informal caregivers obtained from Ireland’s Quarterly National Household Survey (2009). The Caregiver Strain Index is used to measure caregiver strain on a scale from 0 to 13. The analysis focuses on estimating the association between caregiving activities (measured using Activities of Daily Living) and caregiver strain, using multivariate regression analysis. Results Overall, 60% of informal caregivers report feeling strained. The results suggest that different types of caregiving assistance are associated with increasing caregiver strain, in line with Pearlin’s conceptual model of Stress Process theory and Process Utility theory of informal care. Female caregivers have significantly higher levels of strain. Moreover, caregiver strain amongst co-residential caregivers is 0.8 points higher compared to those who are non-resident. Conversely, caregivers over 65 years are less prone to strain than younger caregivers. The condition of the dependent is also a statistically significant factor: caring for someone with a physical condition, a mental condition or both a physical and mental condition, increases caregiver strain. Conclusions As Ireland and Europe’s populations are ‘greying’, sustainable systems and supports need to be designed to meet demand for care that limit strain for caregivers. In doing so, policymakers and their advisors need to better understand the impact of informal caring on caregivers.
Endovascular therapy for anterior circulation large vessel occlusion in telestroke
Authors: Moustafa Haidar , Barlinn Kristian , Prakapenia Alexandra , Winzer Simon , Gerber Johannes , Pallesen Lars-Peder , Siepmann Timo , Haedrich Kevin , Wojciechowski Claudia , Reichmann Heinz , Linn Jennifer , Puetz Volker , Barlinn Jessica 
Published: August 2019

Introduction Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT. Methods We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted. Results Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66–82) years, median (interquartile range), 46% men, NIHSS score 17 (13–20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6–8) vs. 8 (7–9); p < 0.0001) and shorter door-to-groin puncture times (71 (56–84) vs. 101 (79–133) min; p < 0.0001) than directly admitted patients. sICH (2.8% vs. 1.1%; p = 0.58), successful reperfusion (81% vs. 77%; p = 0.56), 90-day favourable outcome (25% vs. 29%; p = 0.65) and 90-day survival (73% vs. 67%; p = 0.39) rates were comparable among telestroke and direct admissions. Discussion Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.
Muslim transplant recipients’ family experiences following organ transplantation
Authors: Sheikhalipour Zahra , Zamanzadeh Vahid , Borimnejad Leili , Newton Sarah E , Valizadeh Leila 
Published: August 2019

Background Despite the importance of family and its relationship to positive transplant outcomes, little is known about family experiences following organ transplantation from the perspective of the transplant recipients. The literature is also devoid of information that describes the family experiences of Muslim transplant recipients. Aims The purpose of this study was to describe Muslim transplant recipients’ family experiences following organ transplantation. Methods A hermeneutical phenomenological approach was employed to determine the emergent themes present in the data. The sample was composed of 12 Muslim organ transplant recipients (heart, kidney and liver) living in Iran. Semi-structured interviews were conducted with each participant. Results The primary constitutive pattern that emerged from the interview data was ‘Altered Family Relationships’ and three themes: fear in relationships, abnormal relationships, and the family at the centre of organ transplant issues. Conclusions There are several important findings in this study, notably that Muslim transplant recipients describe their family experiences following organ transplantation as ‘altered’ and not as they were pre-transplant. More research is needed that focuses on the family experience post-transplant, and how Muslim transplant recipient families are impacted by the transplant experience.
Association between tumor necrosis factor-α and chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Yao Yang , Zhou Jing , Diao Xin , Wang Shengyu 
Published: August 2019

Background: Patients diagnosed with chronic obstructive pulmonary disease (COPD) have increased risks for a series of physical and mental illnesses. Tumor necrosis factor-α (TNF-α) has been reported to participate in the development of COPD and its complications. However, the values of blood TNF-α level used in the diagnosis of COPD remains controversial. In view of this, we performed a systematic review and meta-analysis to evaluate the correlation between TNF-α level and COPD. Methods: We searched PubMed, Web of Science, Embase and CNKI up to May 2018. The selection criteria were set according to the PICOS framework. A random-effects model was then applied to evaluate the overall effect sizes by calculating standard mean difference (SMD) and its 95% confidence intervals (CIs). Results: A total of 40 articles containing 4189 COPD patients and 1676 healthy controls were included in this meta-analysis. The results indicated a significant increase in TNF-α level in the COPD group compared with the control group (SMD: 1.24, 95% CI: 0.78–1.71, p < 0.00001). According to the subgroup analyses, we noted that TNF-α level was associated with predicted first second of forced expiration (FEV1) (%) and study region. However, no association between TNF-α level and COPD was found when the participants were nonsmokers, and the mean age was less than 60 years. Conclusions: Our results indicated that TNF-α level was increased in COPD patients when compared with healthy controls. Illness progression and a diagnosis of COPD might contribute to higher TNF-α levels. However, the underlying mechanism still remains unknown and needs further investigation. The reviews of this paper are available via the supplemental material section.
Prediction of Nocturnal Hypoglycemia From Continuous Glucose Monitoring Data in People With Type 1 Diabetes: A Proof-of-Concept Study
Authors: Jensen Morten H. , Dethlefsen Claus , Vestergaard Peter , Hejlesen Ole 
Published: August 2019

Background: Intensive insulin therapy has documented benefits but may also come at the expense of a higher risk of hypoglycemia. Hypoglycemia is associated with higher all-cause mortality and nocturnal hypoglycemia has been associated with the sudden dead-in-bed syndrome. This proof-of-concept study sought to investigate if nocturnal hypoglycemia can be predicted. Method: Continuous glucose monitoring, meal, insulin, and demographics data from 463 people with type 1 diabetes were obtained from a clinical trial. A total of 4721 nights without or with hypoglycemia (429) were available including data from three consecutive days before the night. Thirty-two features were calculated based on these data. Data were split into 20% participants for evaluation and 80% for training. The optimal feature subset was found from forward selection of the 80% participants with linear discriminant analysis as basis for the classifier. Results: The forward selection resulted in a feature subset of four features. The evaluation resulted in an area under the receiver operating characteristics curve (ROC-AUC) of 0.79 leading to a sensitivity and a specificity of, e.g., 75% and 70%. Conclusions: It was possible to predict nocturnal hypoglycemic episodes with a ROC-AUC of 0.79. A warning at bedtime about nocturnal hypoglycemia could be of great help for people with diabetes to enable preventive actions. Further development of the proposed algorithm is needed for implementation in everyday practice.
Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials
Authors: Hsu Yueh-Chwen , Chen Tsung-Chih , Lin Chien-Chin , Yuan Chang-Tsu , Hsu Chia-Lang , Hou Hsin-An , Kao Chein-Jun , Chuang Po-Han , Chen Yu-Ren , Chou Wen-Chien , Tien Hwei-Fang 
Published: August 2019

Abstract
Plant homeodomain finger gene 6 (PHF6) encodes a 365-amino-acid protein containing 2 plant homology domain fingers. Germline mutations of human PHF6 cause Börjeson-Forssman-Lehmann syndrome, a congenital neurodevelopmental disorder. Loss-of-function mutations of PHF6 are detected in patients with acute leukemia, mainly of T-cell lineage and in a small proportion of myeloid lineage. The functions of PHF6 in physiological hematopoiesis and leukemogenesis remain incompletely defined. To address this question, we generated a conditional Phf6 knockout mouse model and investigated the impact of Phf6 loss on the hematopoietic system. We found that Phf6 knockout mice at 8 weeks of age had reduced numbers of CD4+ and CD8+ T cells in the peripheral blood compared with the wild-type littermates. There were decreased granulocyte-monocytic progenitors but increased Lin–c-Kit+Sca-1+ cells in the marrow of young Phf6 knockout mice. Functional studies, including competitive repopulation unit and serial transplantation assays, revealed an enhanced reconstitution and self-renewal capacity in Phf6 knockout hematopoietic stem cells (HSCs). Aged Phf6 knockout mice had myelodysplasia-like presentations, including decreased platelet counts, megakaryocyte dysplasia, and enlarged spleen related to extramedullary hematopoiesis. Moreover, we found that Phf6 loss lowered the threshold of NOTCH1-induced leukemic transformation at least partially through increased leukemia-initiating cells. Transcriptome analysis on the restrictive rare HSC subpopulations revealed upregulated cell cycling and oncogenic functions, with alteration of key gene expression in those pathways. In summary, our studies show the in vivo crucial roles of Phf6 in physiological and malignant hematopoiesis.
Time-course of upper respiratory tract viral infection and COPD exacerbation
Authors: Stolz Daiana , Papakonstantinou Eleni , Grize Leticia , Schilter Daniel , Strobel Werner , Louis Renaud , Schindler Christian , Hirsch Hans H. , Tamm Michael 
Published: August 2019

Viral respiratory tract infections have been implicated as the predominant risk factor for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We aimed to evaluate, longitudinally, the association between upper respiratory tract infections (URTI) caused by viruses and AECOPD.Detection of 18 viruses was performed in naso- and orοpharyngeal swabs from 450 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stages 2–4) who were followed for a mean of 27 months. Swabs were taken during stable periods (n=1909), at URTI onset (n=391), 10 days after the URTI (n=356) and during an AECOPD (n=177) and tested using a multiplex nucleic acid amplification test.Evidence of at least one respiratory virus was significantly higher at URTI onset (52.7%), 10 days after the URTI (15.2%) and during an AECOPD (38.4%), compared with the stable period (5.3%, p<0.001). During stable visits, rhinovirus accounted for 54.2% of all viral infections, followed by coronavirus (20.5%). None of the viruses were identified in two consecutive stable visits. Patients with a viral infection at URTI onset did not have a higher incidence of exacerbation than patients without viral infection (p=0.993). Τhe incidence of any viral infection during an AECOPD was similar between URTI-related AECOPD and non-URTI-related AECOPD (p=0.359). Only 24% of the patients that had a URTI-related AECOPD had the same virus at URTI onset and during an AECOPD. Detection of parainfluenza 3 at URTI onset was associated with a higher risk of an AECOPD (p=0.003). Rhinovirus and coronavirus were the most frequently detected viruses during AECOPD visits, accounting for 35.7% and 25.9% of all viral infections, respectively.The prevalence of viral infection during the stable period of COPD was low. The risk of exacerbation following the onset of URTI symptoms depends on the particular virus associated with the event and was significant only for parainfluenza 3.
Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study
Authors: Fidler Lee M. , Balter Meyer , Fisher Jolene H. , To Teresa , Stanbrook Matthew B. , Gershon Andrea 
Published: August 2019

Sarcoidosis-related mortality appears to be rising in North America, with increasing rates in females and the elderly. We aimed to estimate trends in sarcoidosis incidence, prevalence and mortality in Ontario, Canada.We performed a cohort study using health administrative data from Ontario between 1996 and 2015. International Classification of Diseases and Ontario Health Insurance Plan codes were used for case detection. Three disease definitions were created: 1) sarcoidosis, two or more physician claims within 2 years; 2) chronic sarcoidosis, five or more physician claims within 3 years; and 3) sarcoidosis with histology, two or more physician claims with a tissue biopsy performed between claims.Overall, 18 550, 9199 and 3819 individuals with sarcoidosis, chronic sarcoidosis and sarcoidosis with histology, respectively, were identified. The prevalence of sarcoidosis was 143 per 100 000 in 2015, increasing by 116% (p<0.0001) from 1996. The increase in age-adjusted prevalence was higher in males than females (136%versus99%; p<0.0001). The incidence of sarcoidosis declined from 7.9 to 6.8 per 100 000 between 1996 and 2014 (15% decrease; p=0.0009). A 30.3% decrease in incidence was seen among females (p<0.0001) compared with a 5.5% increase in males (p=0.47). Age- and sex-adjusted mortality rates of patients with sarcoidosis rose from 1.15% to 1.47% between 1996 and 2015 (28% increase; p=0.02), with the overall trend being nonsignificant (p=0.39). Mortality rates in patients with chronic sarcoidosis increased significantly over the study period (p=0.0008).The prevalence of sarcoidosis is rising in Ontario, with an apparent shifting trend in disease burden from females to males. Mortality is increasing in patients with chronic sarcoidosis.
A systematic review of comorbidities and outcomes of adult patients with pleural infection
Authors: Cargill Tamsin N. , Hassan Maged , Corcoran John P. , Harriss Elinor , Asciak Rachelle , Mercer Rachel M. , McCracken David J. , Bedawi Eihab O. , Rahman Najib M. 
Published: August 2019

BackgroundPleural infection remains an important cause of mortality. This study aimed to investigate worldwide patterns of pre-existing comorbidities and clinical outcomes of patients with pleural infection.MethodsStudies reporting on adults with pleural infection between 2000 and 2017 were identified from a search of Embase and MEDLINE. Articles reporting exclusively on tuberculous, fungal or post-pneumonectomy infection were excluded. Two reviewers assessed 20 980 records for eligibility.Results211 studies met the inclusion criteria. 134 articles (227 898 patients, mean age 52.8 years) reported comorbidity and/or outcome data. The majority of studies were retrospective observational cohorts (n=104, 78%) and the most common region of reporting was East Asia (n=33, 24%) followed by North America (n=27, 20%). 85 articles (50 756 patients) reported comorbidity. The median (interquartile range (IQR)) percentage prevalence of any comorbidity was 72% (58–83%), with respiratory illness (20%, 16–32%) and cardiac illness (19%, 15–27%) most commonly reported. 125 papers (192 298 patients) reported outcome data. The median (IQR) length of stay was 19 days (13–27 days) and median in-hospital or 30-day mortality was 4% (IQR 1–11%). In regions with high-income economies (n=100, 74%) patients were older (mean 56.5versus42.5 years, p<0.0001), but there were no significant differences in prevalence of pre-existing comorbidity nor in length of hospital stay or mortality.ConclusionPatients with pleural infection have high levels of comorbidity and long hospital stays. Most reported data are from high-income economy settings. Data from lower-income regions is needed to better understand regional trends and enable optimal resource provision going forward.