bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Medication Misadventure Among People With Cognitive Impairment or Dementia: A Systematic Review and Meta-analysis
Authors: Zaidi Anum Saqib , Peterson Gregory M. , Bereznicki Luke R.E. , Curtain Colin M. , Salahudeen Mohammed 
Published: August 2020

Objective: To investigate mortality and hospitalization outcomes associated with medication misadventure (including medication errors [MEs], such as the use of potentially inappropriate medications [PIMs], and adverse drug events [ADEs]) among people with cognitive impairment or dementia. Data Sources: Ovid MEDLINE, Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched from inception to December 2019. Study Selection and Data Extraction: Relevant studies using any study design were included. Reviewers independently performed critical appraisal and extracted relevant data. Data Synthesis: The systematic review included 10 studies that reported the outcomes of mortality or hospitalization associated with medication misadventure, including PIMs (n=5), ADEs (n=2), a combination of MEs and ADEs (n=2), and drug interactions (n=1). Five studies examining the association between PIMs and mortality/hospitalization were included in the meta-analyses. Exposure to PIMs was not associated with either mortality (odds ratio [OR]=1.36; 95%CI=0.79-2.35) or hospitalization (OR=1.02; 95%CI=0.83-1.26). In contrast, single studies indicated that ADEs with cholinesterase inhibitors were associated with mortality and hospitalization. Relevance to Patient Care and Clinical Practice: Individuals with cognitive impairment or dementia are at increased risk of medication misadventure; based on relatively limited published data, this does not necessarily translate to increased mortality and hospitalization. Conclusions: Overall, medication misadventure was not associated with mortality or hospitalization in people with cognitive impairment or dementia, noting the limited number of studies, difficulty in controlling potential confounding variables, and that most studies focus on PIMs.
Small Cell Carcinoma of the Ovary: Clinicopathologic and Immunohistochemical Analysis of 7 New Cases of a Rare Malignancy
Authors: Gupta Parikshaa , Kapatia Gargi , Gupta Nalini , Dey Pranab , Rohilla Manish , Gupta Ankita , Rai Bhavana , Suri Vanita , Rajwanshi Arvind , Srinivasan Radhika 
Published: August 2020

Background Small cell carcinoma of ovary (SCCO) is extremely rare. Two types of SCCO are recognized, the pulmonary type (SCCOPT) and the hypercalcemic type (SCCOHT). Establishing an accurate diagnosis is challenging, owing to its rarity and paucity of data describing the distinctive histopathologic and immunohistochemical (IHC) features. Methods This was a retrospective study conducted over a period of 4 years. All cases reported as SCCO on histopathology were retrieved. All the available clinical, histopathological, and IHC features were studied in detail. Results A total of 7 cases of SCCO were diagnosed during the study period. There were 4 cases of SCCOPT and 3 cases of SCCOHT and with mean age of 57.25 and 22 years, respectively. All the cases presented as stage IV disease. Among the SCCOPT cases, 3 showed bilateral involvement with 1 showing concurrent uterine endometrioid adenocarcinoma. Microscopy revealed small hyperchromatic cells with brisk mitosis and multifocal necrosis. On IHC, these were consistently positive for chromogranin, CD56, and synaptophysin. All the SCCOHT cases showed unilateral involvement. Microscopically, in addition to small hyperchromatic cells, larger “rhabdoid” tumor cells were also seen. On IHC, chromogranin was negative, with positivity for vimentin and epithelial membrane antigen. The expression of SMARCA4/BRG1 was lost while SMARCB1/INI1 was retained in all cases. All of these patients developed recurrence and died due to disease progression despite treatment. Conclusions SCCO is an extremely infrequent ovarian malignancy with poor prognosis. Knowledge about its characteristic features is important for accurate tissue diagnosis and appropriate management.
Bullous pemphigoid in elderly woman affected by non-small cell lung cancer treated with pembrolizumab: A case report and review of literature
Authors: Cosimati Antonella , Rossi Luigi , Didona Dario , Forcella Chiara , Didona Biagio 
Published: August 2020

Introduction Immunotherapy has changed the management of patients with various types of malignancies (melanoma, renal, lung, and bladder cancers) but immune checkpoint inhibitors may be associated with several adverse events. Up to 20% of patients treated with immune checkpoint inhibitors may develop dermatological immune-related adverse events, mostly rashes and pruritus but rarely even bullous pemphigoid. Case report We report a case of an elderly patient with advanced non-small cell lung cancer in therapy with pembrolizumab, 200 mg/body every three weeks. After 26 cycles of therapy, the patient developed widespread itching and then after 28 cycles she developed strained blisters filled with serous fluids on predominantly erythematous skin with suspicious of bullous pemphigoid. Management and outcome: Skin biopsy confirms bullous pemphigoid, so we decided to permanently discontinue therapy with pembrolizumab and the patient is currently on therapy with doxycycline, nicotinamide, and clobetasol propionate with good regression of symptoms and cutaneous lesions. Discussion In the literature, the first case of bullous pemphigoid induced by pembrolizumab has been described in 2015. On Pubmed, from 2015 to date, we have found 19 cases of bullous pemphigoid during pembrolizumab therapy but only three of them are related to non-small cell lung cancer, adding our patient we reach a total of 20 cases. It could be interesting to investigate if there is a specific relationship between the appearance of itching and the development of bullous pemphigoid.
Efficacy and safety of intravitreal dexamethasone implant in treatment naïve eyes with diabetic macular edema: Real world experience
Authors: Ratra Dhanashree , Sharma Unnati , Dalan Daleena 
Published: August 2020

Purpose: To evaluate the efficacy and safety of intravitreal dexamethasone implant in treatment naïve eyes with diabetic macular edema (DME). Methods: A retrospective analysis of treatment naïve eyes with DME which received intravitreal dexamethasone implant between January 2016 and March 2018 was done. Demographic details of the patients, ocular examination findings at baseline and on follow up visits were noted. Morphological features of DME and central macular thickness were noted on optical coherence tomography at each visit. The details regarding additional treatment for macular edema on follow up were noted. Results: Sixty five eyes were included in the study. The mean age was 59.14 ± 9.59 years. The follow up ranged from 6 to 48 months. Psuedophakic eyes showed visual improvement whereas the phakic eyes showed stable vision. The central foveal thickness showed significant reduction ( p = 0.05) in all the eyes. The best corrected visual acuity at final follow up (+0.65 logMAR) was slightly less as compared to baseline (+0.62 logMAR). Retreatment was needed in 37% eyes and antiglaucoma medications in 8% eyes. Cataract progression was noted in 24 eyes (37%); 17 eyes (26.1%) underwent surgery. Notably, 27 eyes (41.5%) had some degree of macular ischemia at baseline. And five eyes (7.7%) showed progression of retinopathy leading to vitreous hemorrhage. Conclusion: Dexamethasone implant is helpful in reducing the macular thickness and stabilizing the vision in treatment naïve DME; requiring less number of treatment sessions. However, it does not prevent progression of diabetic retinopathy. The visual improvement may be affected by cataract and macular ischemia.
The safety of bovine tissue arterial repair in removal of infected prosthetic hemodialysis grafts
Authors: Sowa Patrick , Halandras Peggie , Blecha Matthew 
Published: August 2020

Background: More than 400,000 Americans require dialysis, and many receive it via a prosthetic arteriovenous graft. Infection of these grafts is rare, but associated with significant morbidity and mortality. The gold standard is total graft excision with arteriotomy closure. This was previously done with autologous vein, but bovine tissue offers a reasonable alternative. The objective of this article is to evaluate a community hospital experience with bovine tissue arterial repair after total graft excision of infected prosthetic arteriovenous graft. Methods: A retrospective review was performed of all cases of infected prosthetic arteriovenous graft removal with bovine tissue arterial repair was performed. Thirteen cases were identified. Presentation, location of graft, and causative organism were reviewed; outcomes including reoperation and mortality were recorded. Results: Of the 13 patients, 12 (92%) had positive cultures of the graft, bloodstream, or wound. Methicillin-resistant Staphylococcus aureus was the most commonly isolated organism (54%). There were two unplanned reoperations including hematoma drainage and wound debridement within the first year. Over the 1-year follow-up period, 1 patient died for a mortality of 8%. There were no re-infections during follow-up. Discussion: Prosthetic arteriovenous graft infection remains a difficult challenge and is associated with significant morbidity and mortality. It presents in a variety of ways, including within an old thrombosed graft. Over the last several years, the causative organism has increasingly become drug resistant. Treatment with total graft excision requires arteriotomy closure, and for this bovine tissue has been demonstrated to be a viable option.
Multiple sclerosis management during the COVID-19 pandemic
Authors: Moss Brandon P , Mahajan Kedar R , Bermel Robert A , Hellisz Kelsey , Hua Le H , Hudec Timothy , Husak Scott , McGinley Marisa P , Ontaneda Daniel , Wang Zhini , Weber Malory , Tagliani Paula , Cárdenas-Robledo Simón , Zabalza Ana , Arrambide Georgina , Carbonell-Mirabent Pere , Rodríguez-Barranco Marta , Sastre-Garriga Jaume , Tintore Mar , Montalban Xavier , Douglas Morgan , Ogbuokiri Esther , Aravidis Berna , Cohen Jeffrey A , Mowry Ellen M , Fitzgerald Kathryn C 
Published: August 2020

Background: People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. Objectives: To evaluate risk factors for COVID-19 susceptibility and describe the pandemic’s impact on healthcare delivery. Methods: Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d’Hebron-Centre d’Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. Results: There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. Conclusion: Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption.
Biomechanical Modeling of Connecting Intermetacarpal K-Wires in the Treatment of Metacarpal Shaft Fractures
Authors: Hutchison Richard L. , Boles Justina , Duan Yuanyuan 
Published: August 2020

Background Clinical series have been published using the configuration of 2 intercarpal Kirschner wires (K-wires) adjacent to the fracture being connected, but biomechanical analysis is lacking. The objective of this pilot biomechanical study was to model and compare the effects of externally connecting 2 intermetacarpal K-wires for the stabilization of transverse metacarpal shaft fractures. Our research hypothesis was that the connected constructs would be stiffer than the unconnected K-wires. Methods A 3-dimensional computer-based model of small finger transverse metacarpal fracture stabilization was designed with 3 transverse 1.1 mm K-wires being anchored to the adjacent metacarpal. Three arrangements were tested: all 3 K-wires in parallel, the middle K-wire angled toward the proximal wire, and the middle angled K-wire being rigidly fixed to the proximal K-wire. The proximal wire was proximal to the fracture. A finite element analysis was performed by applying a cantilever force of 100 N at the head of the metacarpal. The metacarpal was considered to be uniform in composition with parameters typical for human bone. Kirschner wire parameters for stainless steel were used. Force (N) versus displacement was measured. Results The configuration with the middle angled K-wire being rigidly fixed to the proximal K-wire showed greater stiffness (12 N/mm) than nonattached constructs. The connected construct was 2.3 times more stiff than the unattached parallel construct and 2.5 times more stiff than angling the middle K-wire without attachment. Conclusions In a computer model simulation, our results show that attaching 2 K-wires adjacent to the fracture provides more than twice the stiffness of unconnected K-wires.
Reduction of radiation exposure using low pulse rate fluoroscopy during neuroendovascular surgery
Authors: Shimizu Takeshi , Toyota Shingo , Nakagawa Kanji , Murakami Tomoaki , Kumagai Tetsuya , Mori Kanji , Taki Takuyu 
Published: August 2020

Introduction Endovascular surgery is minimally invasive, but the radiation exposure can be problematic. There is no report assessing whether radiation exposure can be reduced by using a low pulse rate during carotid artery stenting (CAS). The aim of this study was to evaluate whether reducing the pulse rate from 7.5 to 4 frames per second (f/s) can reduce the radiation exposure while maintaining safety during CAS procedure. Methods We retrospectively reviewed the radiation data and clinical features of all 100 patients who underwent CAS between 2014 and 2019. We changed the pulse rate from 7.5 to 4 f/s in 2017. The fluoroscopic time (FT), dose area product (DAP), and total air kerma (AK) were collected. Statistical analyses were performed between the pulse rate and clinical outcomes, including radiation exposure.
The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor mutation
Authors: Wu Shang-Gin , Yu Chong-Jen , Yang James Chih-Hsin , Shih Jin-Yuan 
Published: August 2020

Background and aims: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are effective against classical EGFR mutations in lung cancer. However, their effectiveness and the prognosis of lung cancer patients with complex EGFR mutations are not well delineated. Therefore, we aimed to investigate the treatment effectiveness of different EGFR TKIs in patients with complex EGFR mutations. Patients and methods: From 2005 to 2020, we collected lung adenocarcinoma tissue samples for EGFR mutation analysis using direct Sanger sequencing. Patients with EGFR mutations treated with EGFR TKIs as first-line treatment were enrolled. Clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed. Results: Among 2675 patients with EGFR mutations, 239 (8.9%) had complex EGFR mutations, of whom 125 received EGFR TKI treatment as first-line treatment. Multivariate analysis revealed that afatinib was a more favorable factor for PFS than gefitinib [hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.11–3.62] and erlotinib (HR, 2.61; 95% CI, 1.31–5.22), especially in patients with uncommon mutation patterns. Afatinib treatment as first-line treatment was also associated with longer OS compared with erlotinib (HR, 2.48; 95% CI, 1.20–5.12). Classical mutation pattern was associated with longer PFS ( p = 0.001) and OS ( p = 0.020). Secondary T790M was detected in 22 of 52 (42.3%) patients who had re-biopsied tissue samples after acquiring resistance to EGFR TKIs. There was no significant difference in secondary T790M formation after acquired resistance to the three EGFR TKIs ( p = 0.261). Furthermore, three (5.8%) patients had small-cell lung cancer transformation. Conclusion: Afatinib is an effective first-line treatment for patients with lung adenocarcinoma harboring complex EGFR mutations, especially those with uncommon mutation patterns.
Keloids: Current and emerging therapies
Authors: Ojeh Nkemcho , Bharatha Ambadasu , Gaur Uma , Forde Andrew LeRoy 
Published: August 2020

Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types. Lay Summary [Formula: see text] Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.
Genomics-assisted prediction of salt and alkali tolerances and functional marker development in apple rootstocks
Authors: Liu Jing , Shen Fei , Xiao Yao , Fang Hongcheng , Qiu Changpeng , Li Wei , Wu Ting , Xu Xuefeng , Wang Yi , Zhang Xinzhong , Han Zhenhai 
Published: August 2020

Abstract
Background
Saline, alkaline, and saline-alkaline stress severely affect plant growth and development. The tolerance of plants to these stressors has long been important breeding objectives, especially for woody perennials like apple. The aims of this study were to identify quantitative trait loci (QTLs) and to develop genomics-assisted prediction models for salt, alkali, and salt-alkali tolerance in apple rootstock.

Results
A total of 3258 hybrids derived from the apple rootstock cultivars ‘Baleng Crab’ (Malus robusta Rehd., tolerant) × ‘M9’ (M. pumila Mill., sensitive) were used to identify 17, 13, and two QTLs for injury indices of salt, alkali, and salt–alkali stress via bulked segregant analysis. The genotype effects of single nucleotide polymorphism (SNP) markers designed on candidate genes in each QTL interval were estimated. The genomic predicted value of an individual hybrid was calculated by adding the sum of all marker genotype effects to the mean phenotype value of the population. The prediction accuracy was 0.6569, 0.6695, and 0.5834 for injury indices of salt, alkali, and salt–alkali stress, respectively. SNP182G on MdRGLG3, which changes a leucine to an arginine at the vWFA-domain, conferred tolerance to salt, alkali, and salt-alkali stress. SNP761A on MdKCAB, affecting the Kv_beta domain that cooperated with the linked allelic variation SNP11, contributed to salt, alkali, and salt–alkali tolerance in apple rootstock.

Conclusions
The genomics-assisted prediction models can potentially be used in breeding saline, alkaline, and saline-alkaline tolerant apple rootstocks. The QTLs and the functional markers may provide insight for future studies into the genetic variation of plant abiotic stress tolerance.
Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol
Authors: Patterson Benjamin , Koch Anastasia , Gessner Sophia , Dinkele Ryan , Gqada Melitta , Bryden Wayne , Cobelens Frank , Little Francesca , Warner Digby F. , Wood Robin 
Published: August 2020

Abstract
Background
Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB. Notably, TB diagnosis is based on clinical symptoms and sputum laboratory findings. This is despite the fact that approximately half of all patients commencing TB treatment are sputum-negative, resulting in a high proportion of presumptive treatments. Here, we propose to use a sensitive air sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects, at the same time evaluating the potential to identify unrecognized transmitters of TB.

Methods
Our parallel-group design will identify viable Mtb in bioaerosols produced by individuals attending a TB clinic in South Africa. Sampling will be performed on eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive. Participants will be prospectively classified into three distinct groups based on National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling following a specific respiratory manoeuvre; and (2) indirect sampling during passive respiratory activity. Bioaerosol specimens will be analyzed for viable Mtb using DMN-trehalose staining and live-cell fluorescence microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the groups. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status and current isoniazid preventive therapy (IPT) use; we will also determine the impact of anti-TB chemotherapy on Mtb-containing bioaerosol production.

Discussion
Respiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring.

Trial registration
ClinicalTrials.gov: NCT04241809. Date of Registration: 27/1/2020.