bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbidity of dementia and age-related macular degeneration calls for clinical awareness: a meta-analysis
Authors: Rong Shi Song , Lee Bo Yee , Kuk Andrew K , Yu Xin Ting , Li Suki S , Li Jian , Guo Yanjun , Yin Yilin , Osterbur David L , Yam Jason C S , Cheung Carol Y , Chen Li Jia , Wong Tien Y , Ng Danny Siu-Chun 
Published: April 2019

AimTo determine the association between dementia and age-related macular degeneration (AMD) using meta-analysis.MethodsWe searched in the MEDLINE, EMBASE, Web of Knowledge, PsycInfo and Cochrane database of systematic reviews for studies published from March 1959 to March 2018. We included cross-sectional, case–control and cohort studies that evaluated the association of dementia/Alzheimer's disease (AD) with AMD (as outcome) and the association of AMD with dementia/AD (as outcome). Studies that compared cognitive functions between AMD and controls were also included. The summary outcomes, namely odds ratio (OR), relative risk, mean differences and corresponding 95% CIs, were estimated using random effects models. We performed sensitivity analysis based on study quality and individual study effect to control for potential biases.ResultsAmong 2159 citation records, we identified 21 studies consisting of 7 876 499 study subjects for meta-analysis. Patients with dementia (padjusted≤0.017, OR≥1.24, I2≤9%) or AD (p=0.001, ORunadjusted=2.22, I2=50%) were at risk for AMD, particularly for late AMD (padjusted<0.001, OR=1.37, I2=0). AMD was also significantly associated with increased risk of AD/cognitive impairment (padjusted=0.037, OR=2.42, I2=38%). Moreover, patients with AMD had poorer cognitive functions when compared with controls, including Mini-Mental State Examination (p<0.001, I2≤79%) and Trail Making Test A (p<0.001, I2=0). Sensitivity analysis and Egger’s test indicated our results were less likely biased.ConclusionsA significant association between dementia/AD and AMD calls for greater clinical awareness. The cost-effectiveness of routine screening for the other condition in patients with primary diagnosis of dementia/AD or AMD requires further study.
Excess risk of lower extremity amputations in people with type 1 diabetes compared with the general population: amputations and type 1 diabetes
Authors: Ólafsdóttir Arndís Finna , Svensson Ann-Marie , Pivodic Aldina , Gudbjörnsdottir Soffia , Nyström Thomas , Wedel Hans , Rosengren Annika , Lind Marcus 
Published: April 2019

ObjectiveThis study investigates how the excess risk of lower extremity amputations (amputations) in people with type 1 diabetes mellitus (DM) differs from the general population by diabetes duration, glycemic control, and renal complications.Research design and methodsWe analyzed data from people with type 1 DM from the Swedish National Diabetes Register without prior amputation from January 1998 to December 2013. Each person (n=36 872) was randomly matched with five controls by sex, age, and county (n=184 360) from the population without diabetes. All were followed until first amputation, death or end of follow-up.ResultsThe overall adjusted HR for all amputation was 40.1 (95% CI 32.8 to 49.1) for type 1 DM versus controls. HR increased with longer diabetes duration. The incidence of amputation/1000 patient-years was 3.18 (95% CI 2.99 to 3.38) for type 1 DM and 0.07 (95% CI 0.05 to 0.08) for controls. The incidence decreased from 1998–2001 (3.09, 95% CI 2.56 to 3.62) to 2011–2013 (2.64, 95% CI 2.31 to 2.98). The HR for major amputations was lower than for minor amputations and decreased over the time period (p=0.0045). Worsening in glycemic control among patients with diabetes led to increased risk for amputation with an HR of 1.80 (95% CI 1.72 to 1.88) per 10 mmol/mol (1%) increase in hemoglobin A1c.ConclusionsAlthough the absolute risk of amputation is relatively low, the overall excess risk was 40 times that of controls. Excess risk was substantially lower for those with good glycemic control and without renal complications, but excess risk still existed and is greatest for minor amputations.
Co-prescription patterns of cardiovascular preventive treatments: a cross-sectional study in the Aragon worker’ health study (Spain)
Authors: Aguilar-Palacio Isabel , Malo Sara , Lallana MªJesús , Feja Cristina , González Juan , Moreno-Franco Belén , Rabanaque MªJosé 
Published: April 2019

ObjectivesTo identify cardiovascular disease (CVD) preventive treatments combinations, among them and with other drugs, and to determine their prevalence in a cohort of Spanish workers.DesignCross-sectional study.SettingAragon Workers’ Health Study (AWHS) cohort in Spain.Participants5577 workers belonging to AWHS cohort. From these subjects, we selected those that had, at least, three prescriptions of the same therapeutic subgroup in 2014 (n=4605).Primary and secondary outcome measuresDrug consumption was obtained from the Aragon Pharmaceutical Consumption Registry (Farmasalud). In order to know treatment utilisation, prevalence analyses were conducted. Frequent item set mining techniques were applied to identify drugs co-prescription patterns. All the results were stratified by sex and age.Results42.3% of men and 18.8% of women in the cohort received, at least, three prescriptions of a CVD preventive treatment in 2014. The most prescribed CVD treatment were antihypertensives (men: 28.2%, women 9.2%). The most frequent association observed among CVD preventive treatment was agents acting on the renin-angiotensin system and lipid-lowering drugs (5.1% of treated subjects). Co-prescription increased with age, especially after 50 years old, both in frequency and number of associations, and was higher in men. Regarding the association between CVD preventive treatments and other drugs, the most frequent pattern observed was lipid-lowering drugs and drugs used for acid related disorders (4.2% of treated subjects).ConclusionsThere is an important number of co-prescription patterns that involve CVD preventive treatments. These patterns increase with age and are more frequent in men. Mining techniques are a useful tool to identify pharmacological patterns that are not evident in the individual clinical practice, in order to improve drug prescription appropriateness.
Exploring the impacts of the 2012 Health and Social Care Act reforms to commissioning on clinical activity in the English NHS: a mixed methods study of cervical screening
Authors: Hammond Jonathan , Mason Thomas , Sutton Matt , Hall Alex , Mays Nicholas , Coleman Anna , Allen Pauline , Warwick-Giles Lynsey , Checkland Kath 
Published: April 2019

ObjectivesExplore the impact of changes to commissioning introduced in England by the Health and Social Care Act 2012 (HSCA) on cervical screening activity in areas identified empirically as particularly affected organisationally by the reforms.MethodsQualitative followed by quantitative methods. Qualitative: semi-structured interviews (with NHS commissioners, managers, clinicians, senior administrative staff from Clinical Commissioning Groups (CCGs), local authorities, service providers), observations of commissioning meetings in two metropolitan areas of England. Quantitative: triple-difference analysis of national administrative data. Variability in the expected effects of HSCA on commissioning was measured by comparing CCGs working with one local authority with CCGs working with multiple local authorities. To control for unmeasured confounders, differential changes over time in cervical screening rates (among women, 25–64 years) between CCGs more and less likely to have been affected by HSCA commissioning organisational change were compared with another outcome—unassisted birth rates—largely unaffected by HSCA changes.ResultsInterviewees identified that cervical screening commissioning and provision was more complex and ‘fragmented’, with responsibilities less certain, following the HSCA. Interviewees predicted this would reduce cervical screening rates in some areas more than others. Quantitative findings supported these predictions. Areas where CCGs dealt with multiple local authorities experienced a larger decline in cervical screening rates (1.4%) than those dealing with one local authority (1.0%). Over the same period, unassisted deliveries decreased by 1.6% and 2.0%, respectively, in the two groups.ConclusionsArrangements for commissioning and delivering cervical screening were disrupted and made more complex by the HSCA. Areas most affected saw a greater decline in screening rates than others. The fact that this was identified qualitatively and then confirmed quantitatively strengthens this finding. The study suggests large-scale health system reforms may have unintended consequences, and that complex commissioning arrangements may be problematic.
Visual impairment and objectively measured physical activity and sedentary behaviour in US adolescents and adults: a cross-sectional study
Authors: Smith Lee , Jackson Sarah E , Pardhan Shahina , López-Sánchez Guillermo Felipe , Hu Liang , Cao Chao , Vancampfort Davy , Koyanagi Ai , Stubbs Brendon , Firth Joseph , Yang Lin 
Published: April 2019

ObjectivesTo compare levels of physical activity and sedentary time in a representative sample of US adolescents and adults with and without visual impairment.DesignCross-sectional analyses were carried out using data from the National Health and Nutrition Examination Survey.ParticipantsThe study population consisted of 6001 participants (adolescents n=1766, adults n=4235). The present analysis aggregated data from 2003 to 2004 and 2005–2006.MeasuresObjective physical activity and sedentary behaviour assessment was conducted over 7 days. Distance visual acuity was measured for each eye in all participants 12 years and older. Participants’ vision was categorised as: normal vision, uncorrected refractive error, non-refractive visual impairment. We estimated the sex-specific linear associations between presenting vision and objectively measured physical activity and sedentary patterns using adjusted generalised linear models in adolescents and adults.Results and conclusionsAdolescents with uncorrected refractive error and non-refractive visual impairment did not accumulate higher levels of sedentary time or lower levels of moderate-to-vigorous physical activity (MVPA) compared with those with normal vision. We observed no association between vision status and accelerometer measured MVPA in adults aged 20–49 years. We observed more time spent sedentary among females 20–49 years old with non-refractive visual impairment compared with those presenting normal vision (mean difference 329.8 min/week, 95% CI: 12.5 to 647.0). Adults 50 years and older with non-refractive visual impairment appeared to accumulate less lifestyle physical activity, particularly in women (mean difference −82.8 min/week, 95% CI: −147.8 to −17.8). Adult women with non-refractive visual impairment have lower levels of lifestyle physical activity and higher levels of sedentary time than those with normal vision. Taken together, these findings highlight the need for interventions to promote physical activity and reduce sedentary time in adult populations with visual impairment, specifically adult women.
Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: qualitative study
Authors: Charman Sarah , Okwose Nduka , Maniatopoulos Gregory , Graziadio Sara , Metzler Tamara , Banks Helen , Vale Luke , MacGowan Guy A , Seferović Petar M , Fuat Ahmet , Deaton Christi , Mant Jonathan , Hobbs Richard F D , Jakovljevic Djordje G 
Published: April 2019

ObjectiveTo explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care.DesignQualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach.SettingNewcastle upon Tyne, UK.ParticipantsFourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists).ResultsFour themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices.ConclusionThe development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored.
Exploring standardisation, monitoring and training of medical devices in assisted vaginal birth studies: protocol for a systematic review
Authors: Hotton Emily J , Renwick Sophie , Barnard Katie , Lenguerrand Erik , Wade Julia , Draycott Tim , Crofts Joanna F , Blencowe Natalie S 
Published: April 2019

IntroductionAssisted vaginal birth (AVB) can markedly improve maternal and neonatal outcomes arising from complications in the second stage of labour. Historically, both forceps and ventouse devices have been used to assist birth; however, they are not without risk and are associated with complications, such as cephalohaematoma, retinal haemorrhage and perineal trauma. As new devices are developed to overcome the limitations of existing techniques, it is necessary to establish their efficacy and effectiveness within randomised controlled trials (RCTs). A major challenge of evaluating complex interventions (ie, invasive procedures/devices used to assist vaginal birth) is ensuring they are delivered as intended. It can be difficult to standardise intervention delivery and monitor fidelity, and account for the varying expertise of clinicians (accoucher expertise). This paper describes the protocol for a systematic review aiming to investigate the reporting of device standardisation, monitoring and training in trials evaluating complex interventions, using AVB as a case study.Methods and analysisRelevant keywords and subject headings will be used to conduct a comprehensive search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature and ClinicalTrials.gov, for RCTs and pilot/feasibility studies evaluating AVB. Abstracts will be screened and full-text articles of eligible studies reviewed for inclusion. Information relating to the following categories will be extracted: standardisation of device use (ie, descriptions of operative steps, including mandatory/flexible parameters), monitoring of intervention delivery (ie, intervention fidelity, confirming that an intervention is delivered as intended) and accoucher expertise (ie, entry criteria for participation, training programmes and previous experience with the device). Risk of bias of included studies will be assessed.Ethics and disseminationEthical approval is not required because primary data will not be collected. Findings will be disseminated by publishing in a peer-reviewed journal and presentations at relevant conferences.
Designing and evaluating provider results-based financing for tuberculosis care in Georgia: a realist evaluation protocol
Authors: Marchal Bruno , Giralt Ariadna Nebot , Sulaberidze Lela , Chikovani Ivdity , Abejirinde Ibukun-Oluwa Omolade 
Published: April 2019

IntroductionIn 2016, Georgian researchers and policymakers were developing a policy to improve the performance of the national tuberculosis (TB) control programme. The research programme ‘Designing and Evaluating Provider Results-Based Financing for Tuberculosis Care in Georgia: Understanding Costs, Mechanisms of Effect and Impact (Results4TB)’ was initiated to inform the policy formulation phase, document the policy implementation and assess the effectiveness, cost-effectiveness and the processes of change. To achieve this, the research team intends to combine an impact evaluation, a cost-effectiveness study and a realist evaluation (RE) within an overarching theory-informed design. This protocol is the RE component of the programme.MethodsA realist methodological approach will be adopted to guide the research design and evaluation. RE answers the question of ‘what works in which conditions for whom?’ and starts with the development of an initial programme theory (IPT). The IPT will feed into other phases of the realist research cycle (study design, data collection, data analysis and synthesis and theory refinement). Data will be collected in a multiple embedded case study design (five intervention and three control sites) through document reviews, in-depth interviews, non-participant observations and context mapping at facility and national levels. Additional data from other research components (cost-effectiveness and impact evaluation) will aid data triangulation.Ethics and disseminationThe Institutional Review Boards of the National Centre for Disease Control and Public Health in Georgia (ref. IRB # 2018–019) and the Institute of Tropical Medicine, Antwerp (ref. IRB #- 1240/18) have granted ethical approval to the study.Trial registration numberISRCTN14667607
Effect of nanosecond and femtosecond pulse laser on the formation of WS2 nanostructures and field emission characteristics
Authors: Koinkar Pankaj , Sasaki Kohei , Furube Akihiro , Murai Kei-Ichiro , Moriga Toshihiro , Shinde Manish , Rane Sunit , Bhopale Somnath , More Mahendra A. 
Published: April 2019

The pulse laser ablation is a simple and direct method used for the generation of nanostructures in liquid environment. In this paper, formation of tungsten sulfide [Formula: see text] nanostructures has been carried out using nanosecond (ns) and femtosecond (fs) laser ablation with ablation time 120 min. In addition, the field emission studies were performed of the prepared sample. The characterization techniques such as the transmission electron microscopy (TEM), X-ray diffraction (XRD) and UV-visible spectroscopy have been used to confirm the surface morphology as well as structural details. It is observed that the laser pulse regime plays a vital role on the size reduction of [Formula: see text] nanostructure. The X-ray spectra reveal the formation of [Formula: see text] nanoparticles for ns laser ablation, while [Formula: see text] nanosheets for fs laser ablation. The TEM images indicate that the transformation of [Formula: see text] microsheet into nanosheet of the size about 15–200 nm for the sample treated with ns laser and fs laser ablation. Also, the results clearly shows the improvement in the field emission characteristics for laser ablated [Formula: see text] nanosheets. The enhanced field emission characteristics is attributed to the formation and separation of few layer [Formula: see text] nanosheets. The [Formula: see text] nanostructures may have great potential for the applications in optoelectronic devices.
Genome–Epigenome–Senescence: Is TET1 a Caretaker of p53-Injured Lung Cancer Cells?
Authors: Kondo Yutaka 
Published: April 2019

Abstract
The study by Filipczak and colleagues identified the interplay between mutant p53 proteins and methylcytosine dioxygenase ten-eleven translocation 1 (TET1) in lung cancers. p53 transversion mutations were closely associated with high TET1 expression, which prevented genomic instability–associated cellular senescence. Depletion of TET1 was synergistic with classical antitumor drugs, such as cisplatin or doxorubicin, providing an attractive rationale for targeted therapies against TET1 combined with antitumor drugs in patients with p53-mutant lung cancer.
See related article by Filipczak et al., p. 1758
Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases
Authors: Morikawa Aki , de Stanchina Elisa , Pentsova Elena , Kemeny Margaret M. , Li Bob T. , Tang Kendrick , Patil Sujata , Fleisher Martin , Van Poznak Catherine , Norton Larry , Seidman Andrew D. 
Published: April 2019

Abstract

Purpose:
Lapatinib and capecitabine cross the blood–tumor barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high-dose tyrosine kinase inhibitor has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS). We derived a rational drug scheduling of intermittent high-dose lapatinib alternating with capecitabine based on our preclinical data and Norton–Simon mathematical modeling. We tested this intermittent, sequential drug schedule in patients with breast cancer with CNS metastasis.

Patients and Methods:
We conducted a phase I trial using an accelerated dose escalation design in patients with HER2-positive (HER2+) breast cancer with CNS metastasis. Lapatinib was given on day 1–3 and day 15–17 with capecitabine on day 8–14 and day 22–28 on an every 28-day cycle. Lapatinib dose was escalated, and capecitabine given as a flat dose at 1,500 mg BID. Toxicity and efficacy were evaluated.

Results:
Eleven patients were enrolled: brain only (4 patients, 36%), leptomeningeal (5 patients, 45%), and intramedullary spinal cord (2 patients, 18%). Grade 3 nausea and vomiting were dose-limiting toxicities. The MTD of lapatinib was 1,500 mg BID. Three patients remained on therapy for greater than 6 months.

Conclusions:
High-dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in patients with HER2+ breast cancer with CNS metastasis and warrants further investigation.
A First-in-Human Study and Biomarker Analysis of NKTR-214, a Novel IL2Rβγ-Biased Cytokine, in Patients with Advanced or Metastatic Solid Tumors
Authors: Bentebibel Salah-Eddine , Hurwitz Michael E. , Bernatchez Chantale , Haymaker Cara , Hudgens Courtney W. , Kluger Harriet M. , Tetzlaff Michael T. , Tagliaferri Mary A. , Zalevsky Jonathan , Hoch Ute , Fanton Christie , Aung Sandra , Hwu Patrick , Curti Brendan D. , Tannir Nizar M. , Sznol Mario , Diab Adi 
Published: April 2019

AbstractNKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist, designed to provide sustained signaling through heterodimeric IL2 receptor βγ to drive increased proliferation and activation of CD8+ T and natural killer cells without unwanted expansion of T regulatory cells (Treg) in the tumor microenvironment. In this first-in-human multicenter phase I study, NKTR-214 administered as an outpatient regimen was well tolerated and showed clinical activity including tumor shrinkage and durable disease stabilization in heavily pretreated patients. Immune activation and increased numbers of immune cells were observed in the periphery across all doses and cycles with no loss of NKTR-214 activity with repeated administration. On-treatment tumor biopsies demonstrated that NKTR-214 promoted immune cell increase with limited increase of Tregs. Transcriptional analysis of tumor biopsies showed that NKTR-214 engaged the IL2 receptor pathway and significantly increased genes associated with an effector phenotype. Based on safety and pharmacodynamic markers, the recommended phase II dose was determined to be 0.006 mg/kg every three weeks.Significance:We believe that IL2- and IL2 pathway–targeted agents such as NKTR-214 are key components to an optimal immunotherapy treatment algorithm. Based on its biological activity and tolerability, NKTR-214 is being studied with approved immuno-oncology agents including checkpoint inhibitors.See related commentary by Sullivan, p. 694.This article is highlighted in the In This Issue feature, p. 681