bluuebunny/crossref_metadata_2025_split huggingface dataset:
PERsistent Sitagliptin treatment & Outcomes (PERS&O 2.0) study, long-term results: a real-world observation on DPP4-inhibitor effectiveness
Authors: Bossi Antonio Carlo , De Mori Valentina , Galeone Carlotta , Bertola Davide Pietro , Gaiti Margherita , Balini Annalisa , Berzi Denise , Forloni Franco , Meregalli Giancarla , Turati Federica 
Published: September 2020

IntroductionSitagliptin is a dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes (T2D). Limited real-world data on its effectiveness and safety are available from an Italian population.Research design and methodsWe evaluated long-term clinical data from the single-arm PERsistent Sitagliptin Treatment & Outcomes (PERS&O) study, which collected information on 440 patients with TD2 (275 men, 165 women; mean age 64.1 years; disease median duration: 12 years) treated with sitagliptin ‘add-on’. For each patient, we estimated the 10-year cardiovascular (CV) risk using the UK Prospective Diabetes Study (UKPDS) Risk Engine (RE). Drug survival was evaluated using Kaplan-Meier survival curves; repeated measures mixed effects models were used to evaluate the evolution of glycated hemoglobin (HbA1c) and CV risk during sitagliptin treatment.ResultsAt baseline, most patients were overweight or obese (median body mass index (BMI) (kg/m2) 30.2); median HbA1c was 8.4%; median fasting plasma glucose: 172 mg/dL; median UKPDS RE score: 24.8%, being higher in men (median 30.2%) than in women (median 17.0%) as expected. Median follow-up from starting sitagliptin treatment was 5.6 years. From Kaplan-Meier curves, the estimated median drug survival was 32.8 months when considering discontinuation for any cause and 58.4 months when considering discontinuation for loss of efficacy. A significant improvement in HbA1c was evident during treatment with sitagliptin (p<0.01): the reduction was rapid (median HbA1c after 4–6 months: 7.5%) and continued at longer follow-up. When comparing patients treated with sitagliptin versus those stopping sitagliptin and switching to another antihyperglycemic drug, we detected a significant difference in the evolution of HbA1c in favor of patients who continued sitagliptin treatment. The UKPDS RE score at 10 years and the BMI significantly improved during treatment with sitagliptin (p<0.001). Adverse events were relatively uncommon.ConclusionPatients with T2D treated with sitagliptin achieved an improvement in metabolic control and a reduction in CV risk and did not experience relevant adverse events.
Differences between frequent emergency department users in a secondary rural hospital and a tertiary suburban hospital in central Japan: a prevalence study
Authors: Kaneko Makoto , Inoue Machiko , Okubo Masashi , Furgal Allison K Cullen , Crabtree Benjamin F , Fetters Michael D 
Published: September 2020

ObjectivesAlthough frequent emergency department (ED) use is a global issue, little research has been conducted in a country like Japan where universal health insurance is available. The study aims to (1) document the proportion of ED visits that are by frequent users and (2) describe the differences in characteristics of frequent ED users and other ED users including expenditures between a secondary and a tertiary hospital.DesignA prevalence study for a period of 1 year.SettingA secondary hospital and a tertiary hospital in central Japan.ParticipantsAll patients who presented to the EDs.Primary outcome measuresWe defined frequent ED user as a patient who visited the ED≥5 times/year. The main outcome measures were the proportion of frequent ED users among all ED users and the proportion of healthcare expenditures by the frequent ED users among all ED expenditures.ResultsOf 25 231 ED visits over 1 year, 134 frequent ED users accounted for 1043 visits—0.66% of all ED users, comprised 4.1% of all ED visits, and accounted for 1.9% of total healthcare expenditures. Median ED visits per one frequent ED user was 7.9. At the patient level, after adjusting for age, gender and receiving public assistance, older age (OR 1.01, 95% CI: 1.00 to 1.02) and receiving public assistance (OR 7.19, 95% CI 2.87 to 18.07) had an association with frequent ED visits. At the visit-level analysis, evaluation by internal medicine (OR 1.27, 95% CI 1.02 to 1.57), psychiatry (OR 124.69, 95% CI 85.89 to 181.01) and obstetrics/gynaecology (OR 2.77, 95% CI 2.09 to 3.67) were associated with frequent ED visits.ConclusionThe proportion of frequent ED users, of total visits, and of expenditures attributable to them—while still in the low end of the distribution of published ranges—are lower in this study from Japan than in reports from many other countries.
Risk of significant traumatic brain injury in adults with minor head injury taking direct oral anticoagulants: a cohort study and updated meta-analysis
Authors: Fuller Gordon , Sabir Lisa , Evans Rachel , Bradbury Daniel , Kuczawski Maxine , Mason Suzanne M 
Published: September 2020

BackgroundPatients taking direct oral anticoagulants (DOACs) commonly undergo CT head imaging after minor head injury, regardless of symptoms or signs. However, the risk of intracranial haemorrhage (ICH) in such patients is unclear, and further research has been recommended by the UK National Institute for Health and Care Excellence head injury guideline group.MethodsAn observational cohort study was performed in the UK South Yorkshire major trauma centre between 26 June and 3 September 2018. Adult patients taking DOACs with minor head injury were prospectively identified, with case ascertainment supplemented by screening of radiology and ED information technology systems. Clinical and outcome data were subsequently collated from patient records. The primary endpoint was adverse outcome within 30 days, comprising: neurosurgery, ICH or death due to head injury. A previously published meta-analysis was updated with the current results and the findings of other recent studies.Results148 patients with minor head injury were included (GCS 15, n=107, 72%; GCS 14, n=41, 28%). Patients were elderly (median 82 years) and most frequently injured from ground level falls (n=142, 96%). Overall risk of adverse outcome was 3.4% (5/148, 95% CI 1.4% to 8.0%). Five patients had ICH, of whom one died within 30 days. One patient was treated with prothrombin complex concentrate but no patient received critical care management or underwent neurosurgical intervention. Updated random effects meta-analysis, including the current results and two further recent studies, showed a weighted overall risk of adverse outcome of 3.2% (n=29/787, 95% CI 2.0% to 4.4%).ConclusionsThe risk of adverse outcome following mild head injury in patients taking DOACs appears low. These findings would support shared patient-clinician decision making, rather than routine imaging, following minor head injury while taking DOACs.
Nurse practitioner administered point-of-care ultrasound compared with X-ray for children with clinically non-angulated distal forearm fractures in the ED: a diagnostic study
Authors: Snelling Peter J , Jones Philip , Keijzers Gerben , Bade David , Herd David W , Ware Robert S 
Published: September 2020

BackgroundPaediatric distal forearm fractures are a common ED presentation. They can be diagnosed with point-of-care ultrasound (POCUS) as an alternative to X-rays. Given that ED nurse practitioners (NPs) are relied on for the diagnosis of paediatric fractures, it is important to describe the diagnostic accuracy of NP-conducted POCUS versus X-ray.MethodsThis prospective diagnostic study was conducted in a tertiary paediatric hospital in Queensland, Australia, between February 2018 and April 2019. Participants were children aged 4–16 years with a clinically non-angulated, suspected distal forearm fracture. Diagnosis from 6-view NP-administered POCUS of the distal radius and ulna was compared against the reference standard of 2-view X-ray. Each patient received both imaging modalities. Overall forearm diagnosis was classified as ‘no’, ‘buckle’ or ‘other’ fracture for both modalities. The primary outcome was diagnostic accuracy for ‘any’ fracture (‘buckle’ and ‘other’ fractures combined). Secondary outcomes included diagnostic accuracy for ‘other’ fractures versus ‘buckle’ and ‘no’ fractures combined, and pain, imaging duration and preference for modality.ResultsOf 204 recruited patients, 129 had X-ray-diagnosed forearm fractures. The sensitivity and specificity for NP-administered POCUS were 94.6% (95% CI 89.2% to 97.3%) and 85.3% (95% CI 75.6% to 91.6%), respectively. ‘Other’ fractures (mostly cortical breach fractures), when compared with ‘buckle’/ ‘no’ fractures, had sensitivity 81.0% (95% CI 69.1% to 89.1%) and specificity 95.9% (95% CI 91.3% to 98.1%). Pain and imaging duration were clinically similar between modalities. There was a preference for POCUS by patients, parents and NPs.ConclusionsNP-administered POCUS had clinically acceptable diagnostic accuracy for paediatric patients presenting with non-angulated distal forearm injuries. This included good sensitivity for diagnosis of ‘any’ fracture and good specificity for diagnosis of cortical breach fractures alone. Given the preference for POCUS, and the lack of difference in pain and duration between modalities, future research should consider functional outcomes comparing POCUS with X-ray in this population in a randomised controlled trial.
National trends in chest pain visits in US emergency departments (2006–2016)
Authors: Aalam Ahmad A , Alsabban Awad , Pines Jesse M 
Published: September 2020

BackgroundChest pain is a common complaint in EDs. In this study, we describe demographic, care and cost trends in US ED visits for chest pain over 11 years.MethodsThis is a retrospective descriptive study of trends in utilisation and care of ED chest pain visits from 2006 to 2016) using data from the Healthcare Cost and Utilization Project database, a national sample of US ED visits and hospitalisations.ResultsFrom 2006 to 2016, there were 42.48 million chest pain visits. Visits per 100 000 persons increased from 1140.4 in 2006 to 1611.7 in 2016 (p<0.001). The chest pain inpatient admission rate declined from 19% in 2006 to 3.9% in 2016 (p<0.001); associated inpatient hospitalisation costs declined from $10.4 billion (2006–2008) to $6.2 billion (2012–2014).ConclusionFrom 2006 to 2016, ED visits in the USA for chest pain increased with a significant decline in admission rates and inpatient hospitalisation costs.
Bi-allelic SHOC1 loss-of-function mutations cause meiotic arrest and non-obstructive azoospermia
Authors: Yao Chencheng , Yang Chao , Zhao Liangyu , Li Peng , Tian Ruhui , Chen Huixing , Guo Ying , Huang Yuhua , Zhi Erlei , Zhai Jing , Sun Hongfang , Zhang Jianxiong , Hong Yan , Zhang Li , Ji Zhiyong , Zhang Feng , Zhou Zhi , Li Zheng 
Published: September 2020

BackgroundThe genetic causes of human idiopathic non-obstructive azoospermia (NOA) with meiotic arrest remain unclear.MethodsTwo Chinese families with infertility participated in the study. In family 1, two brothers were affected by idiopathic NOA. In family 2, the proband was diagnosed with idiopathic NOA, and his elder sister suffered from infertility. Whole-exome sequencing (WES) was conducted in the two patients in family 1, the proband in family 2 and 362 additional sporadic patients with idiopathic NOA. Sanger sequencing was used to verify the WES results. Periodic acid–Schiff (PAS), immunohistochemistry (IHC) and meiotic chromosomal spread analyses were carried out to evaluate the stage of spermatogenesis arrested in the affected cases.ResultsWe identified compound heterozygous loss of function (LoF) variants of SHOC1 (c.C1582T:p.R528X and c.231_232del:p.L78Sfs*9, respectively) in both affected cases with NOA from family 1. In family 2, homozygous LoF variant in SHOC1 (c.1194delA:p.L400Cfs*7) was identified in the siblings with infertility. PAS, IHC and meiotic chromosomal spread analyses demonstrated that the spermatogenesis was arrested at zygotene stage in the three patients with NOA. Consistent with the autosomal recessive mode of inheritance, all of these SHOC1 variants were inherited from heterozygous parental carriers. Intriguingly, WES of 362 sporadic NOA cases revealed one additional NOA case with a bi-allelic SHOC1 LoF variant (c.1464delT:p.D489Tfs*13).ConclusionTo the best of our knowledge, this is the first report identifying SHOC1 as the causative gene for human NOA. Furthermore, our study showed an autosomal recessive mode of inheritance in the NOA caused by SHOC1 deficiency.
Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome
Authors: Peeters Silke , Decramer Arne , Cain Stuart Alan , Houpt Peter , Verstreken Frederik , Noyez Jan , Hermans Christophe , Jacobs Werner , Lammens Martin , Fransen Erik , Kumar Ajay Anand , Vandeweyer Geert , Loeys Bart , Van Hul Wim , Baldock Clair , Boudin Eveline , Mortier Geert 
Published: September 2020

BackgroundAlthough carpal tunnel syndrome (CTS) is the most common form of peripheral entrapment neuropathy, its pathogenesis remains largely unknown. An estimated heritability index of 0.46 and an increased familial occurrence indicate that genetic factors must play a role in the pathogenesis.Methods and resultsWe report on a family in which CTS occurred in subsequent generations at an unusually young age. Additional clinical features included brachydactyly and short Achilles tendons resulting in toe walking in childhood. Using exome sequencing, we identified a heterozygous variant (c.5009T>G; p.Phe1670Cys) in the fibrillin-2 (FBN2) gene that co‐segregated with the phenotype in the family. Functional assays showed that the missense variant impaired integrin-mediated cell adhesion and migration. Moreover, we observed an increased transforming growth factor-β signalling and fibrosis in the carpal tissues of affected individuals. A variant burden test in a large cohort of patients with CTS revealed a significantly increased frequency of rare (6.7% vs 2.5%–3.4%, p<0.001) and high-impact (6.9% vs 2.7%, p<0.001) FBN2 variants in patient alleles compared with controls.ConclusionThe identification of a novel FBN2 variant (p.Phe1670Cys) in a unique family with early onset CTS, together with the observed increased frequency of rare and high-impact FBN2 variants in patients with sporadic CTS, strongly suggest a role of FBN2 in the pathogenesis of CTS.
Exposure to tobacco imagery in popular films and the risk of ever smoking among children in southern India
Authors: Kulkarni Muralidhar M , Kamath Veena Ganesh , Kamath Asha , Lewis Sarah , Bogdanovica Ilze , Bains Manpreet , Cranwell Jo , Fogarty Andrew , Arora Monika , Nazar Gaurang P , Ballal Kirthinath , Bhagwath Rohith , Britton John 
Published: September 2020

BackgroundExposure to smoking in films is a recognised cause of smoking uptake among children. In India, in an attempt to protect children, films containing smoking are required to include tobacco control messaging including audiovisual disclaimers, on-screen health warnings when tobacco imagery is displayed and antitobacco ‘health spots’ before and during the film. We report a study of the association between ever smoking and exposure to tobacco imagery in locally popular films among children in Udupi district of Karnataka state in southern India.MethodsA cross-sectional questionnaire survey of all students in grades 6–8 in schools in the Udupi district ascertained smoking status and potential confounders of smoking uptake, and whether children had seen any of 27 locally popular films we had coded and found to contain imagery of actual or implied tobacco use. Ever-smoking status was defined as any reported smoking of cigarettes, beedis or other tobacco products currently or at any time in the past. Independent effects on ever-smoking status were estimated using multiple logistic regression.ResultsOf 46 706 students enrolled in grades 6–8 in 914 participating schools, 39 282 (84.1%) provided questionnaire responses sufficiently complete for analysis. Ever smoking was reported by 914 (2.3%) participants and in a mutually adjusted model was significantly related to age, male sex, living in a home where smoking is allowed, having parents or siblings who smoke, low paternal education, low levels of family wealth, low self-esteem, rebelliousness and poor school performance. After allowing for these effects, the odds of ever smoking were not increased among students who had seen any of the listed films containing tobacco imagery when included in the analysis as a binary exposure (OR 0.9, 95% CI 0.4 to 2.0), and decreased in relation to level of exposure graded into tertiles of tobacco intervals seen.ConclusionsIn this cross-sectional study, children in southern India who had seen films containing tobacco imagery are no more likely to smoke than those who had not, indicating that the tobacco control messaging mandated by Indian law may be attenuating the effect of tobacco imagery in films on smoking uptake.
Higher blood glucose impairs cardiac autonomic modulation in fasting and after carbohydrate overload in adults
Authors: Oliveira Caroline Maria , Ghezzi Ana Carolina , Cambri Lucieli Teresa 
Published: September 2020

This study aimed to assess whether the blood glucose levels influence cardiac autonomic modulation under fasting and after carbohydrate overload conditions. Participants (n = 108) were separated into lower blood glucose and higher blood glucose groups, based on the median (90.5 mg·dL−1) of fasting glucose assessed. The SD2, SDNN, LF indices, and LF/HF increased, and HF decreased after dextrose overload compared with fasting (p < 0.05). Body mass (78.9 vs 69.7 kg), abdominal circumference (90.2 vs 82.2 cm), systolic (113 vs 108 mm Hg) and diastolic (72 vs 67 mm Hg) blood pressure were higher (p < 0.05) in the higher blood glucose group. Heart rate variability (HRV) indices (SD1: 21.0 vs 26.5; SD2: 76.8: vs 86.1; RMSSD: 28.7 vs 37.5; SDNN: 56.1 vs 62.5 ms; pNN50: 10.6 vs 18.9%, HF: 328.4 vs 506.0; LF: 982.8 vs 1259.0 ms2), and the area under the curve of these indices after dextrose overload were lower in the higher blood glucose group (p < 0.05). Additionally, glycemia after dextrose overload was correlated with HRV indices (ρ = –0.216 to −0.273, p < 0.05). Individuals with higher blood glucose, even in the normality range, showed impairment in the cardiac autonomic modulation both at fasting and after carbohydrate overload. Novelty: Higher fasting blood glucose impairs cardiac autonomic modulation. Carbohydrate overload impairs cardiac autonomic modulation.
Condensation of a scalar field non-minimally coupled to gravity in a cosmological context
Authors: Ghalee Amir 
Published: September 2020

We present a new mechanism to condense a scalar field coupled to the Gauss–Bonnet term. We propose a scenario in which the condensed state will emerge from the background energy density in the late-Universe. During the radiation and dust-dominated eras, the energy density of the scalar field, [Formula: see text], decreases at a slower rate than the background density. Eventually, [Formula: see text] dominates over the energy density of dust and the scalar field could be condensed. In the condensed phase, we have the de Sitter phase for the universe with [Formula: see text]. Moreover, we study the cosmological perturbations of the model and explore predictions of the model.
Temporal Trend of Age at Diagnosis in Hypertrophic Cardiomyopathy
Authors: Canepa Marco , Fumagalli Carlo , Tini Giacomo , Vincent-Tompkins Justin , Day Sharlene M. , Ashley Euan A. , Mazzarotto Francesco , Ware James S. , Michels Michelle , Jacoby Daniel , Ho Carolyn Y. , Olivotto Iacopo ,   The SHaRe Investigators
Published: September 2020

Background:
Over the last 50 years, the epidemiology of hypertrophic cardiomyopathy (HCM) has changed because of increased awareness and availability of advanced diagnostic tools. We aim to describe the temporal trends in age, sex, and clinical characteristics at HCM diagnosis over >4 decades.

Methods:
We retrospectively analyzed records from the ongoing multinational Sarcomeric Human Cardiomyopathy Registry. Overall, 7286 patients with HCM diagnosed at an age ≥18 years between 1961 and 2019 were included in the analysis and divided into 3 eras of diagnosis (<2000, 2000–2010, >2010).

Results:

Age at diagnosis increased markedly over time (40±14 versus 47±15 versus 51±16 years,
P
<0.001), both in US and non-US sites, with a stable male-to-female ratio of about 3:2. Frequency of familial HCM declined over time (38.8% versus 34.3% versus 32.7%,
P
<0.001), as well as heart failure symptoms at presentation (New York Heart Association III/IV: 18.1% versus 15.8% versus 12.6%,
P
<0.001). Left ventricular hypertrophy became less marked over time (maximum wall thickness: 20±6 versus 18±5 versus 17±5 mm,
P
<0.001), while prevalence of obstructive HCM was greater in recent cohorts (peak gradient >30 mm Hg: 31.9% versus 39.3% versus 39.0%,
P
=0.001). Consistent with decreasing phenotypic severity, yield of pathogenic/likely pathogenic variants at genetic testing decreased over time (57.7% versus 45.6% versus 38.4%,
P
<0.001).

Conclusions:
Evolving HCM populations include progressively greater representation of older patients with sporadic disease, mild phenotypes, and genotype-negative status. Such trend suggests a prominent role of imaging over genetic testing in promoting HCM diagnoses and urges efforts to understand genotype-negative disease eluding the classic monogenic paradigm.
Elevated Cellular Oxidative Stress in Circulating Immune Cells in Otherwise Healthy Young People Who Use Electronic Cigarettes in a Cross‐Sectional Single‐Center Study: Implications for Future Cardiovascular Risk
Authors: Kelesidis Theodoros , Tran Elizabeth , Arastoo Sara , Lakhani Karishma , Heymans Rachel , Gornbein Jeffrey , Middlekauff Holly R. 
Published: September 2020

Background
Tobacco cigarettes (TCs) increase oxidative stress and inflammation, both instigators of atherosclerotic cardiac disease. It is unknown if electronic cigarettes (ECs) also increase immune cell oxidative stress. We hypothesized an ordered, “dose‐response” relationship, with tobacco‐product type as “dose” (lowest in nonsmokers, intermediate in EC vapers, and highest in TC smokers), and the “response” being cellular oxidative stress (COS) in immune cell subtypes, in otherwise, healthy young people.

Methods and Results

Using flow cytometry and fluorescent probes, COS was determined in immune cell subtypes in 33 otherwise healthy young people: nonsmokers (n=12), EC vapers (n=12), and TC smokers (n=9). Study groups had similar baseline characteristics, including age, sex, race, and education level. A dose‐response increase in proinflammatory monocytes and lymphocytes, and their COS content among the 3 study groups was found: lowest in nonsmokers, intermediate in EC vapers, and highest in TC smokers. These findings were most striking in CD14
dim
CD16
+
and CD14
++
CD16
+
proinflammatory monocytes and were reproduced with 2 independent fluorescent probes of COS.

Conclusions
These findings portend the development of premature cardiovascular disease in otherwise healthy young people who chronically vape ECs. On the other hand, that the COS is lower in EC vapers compared with TC smokers warrants additional investigation to determine if switching to ECs may form part of a harm‐reduction strategy.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03823885.