Utilizing logistic regression to compare risk factors in disease modeling with imbalanced data: a case study in vitamin D and cancer incidence.

Imbalanced data, a common challenge encountered in statistical analyses of clinical trial datasets and disease modeling, refers to the scenario where one class significantly outnumbers the other in a binary classification problem. This imbalance can lead to biased model performance, favoring the majority class, and affecting the understanding of the relative importance of predictive variables. Despite its prevalence, the existing literature lacks comprehensive studies that elucidate methodologies to handle imbalanced data effectively. In this study, we discuss the binary logistic model and its limitations when dealing with imbalanced data, as model performance tends to be biased towards the majority class. We propose a novel approach to addressing imbalanced data and apply it to publicly available data from the VITAL trial, a large-scale clinical trial that examines the effects of vitamin D and Omega-3 fatty acid to investigate the relationship between vitamin D and cancer incidence in sub-populations based on race/ethnicity and demographic factors such as body mass index (BMI), age, and sex. Our results demonstrate a significant improvement in model performance after our undersampling method is applied to the data set with respect to cancer incidence prediction. Both epidemiological and laboratory studies have suggested that vitamin D may lower the occurrence and death rate of cancer, but inconsistent and conflicting findings have been reported due to the difficulty of conducting large-scale clinical trials. We also utilize logistic regression within each ethnic sub-population to determine the impact of demographic factors on cancer incidence, with a particular focus on the role of vitamin D. This study provides a framework for using classification models to understand relative variable importance when dealing with imbalanced data.

A Diagnostic Test Accuracy Study Investigating General Practitioner Clinical Impression and Brief Cognitive Assessments for Dementia in Primary Care, Compared to Specialized Assessment.

BACKGROUND: Many health systems are interested in increasing the number of uncomplicated and typical dementia diagnoses that are made in primary care, but the comparative accuracy of tests is unknown. OBJECTIVE: Calculate diagnostic accuracy of brief cognitive tests in primary care. METHODS: We did a diagnostic test accuracy study in general practice, in people over 70 years who had consulted their GP with cognitive symptoms but had no prior diagnosis of dementia. The reference standard was specialist assessment, adjudicated for difficult cases, according to ICD-10. We assessed 16 index tests at a research clinic, and additionally analyzed referring GPs clinical judgement. RESULTS: 240 participants had a median age of 80 years, of whom 126 were men and 132 had dementia. Sensitivity of individual tests at the recommended thresholds ranged from 56% for GP judgement (specificity 89%) to 100% for MoCA (specificity 16%). Specificity of individual tests ranged from 4% for Sniffin' sticks (sensitivity 100%) to 91% for Timed Up and Go (sensitivity 23%). The 95% centile of test duration in people with dementia ranged from 3 minutes for 6CIT and Time and Change, to 16 minutes for MoCA. Combining tests with GP judgement increased test specificity and decreased sensitivity: e.g., MoCA with GP Judgement had specificity 87% and sensitivity 55%. CONCLUSIONS: Using GP judgement to inform selection of tests was an efficient strategy. Using IQCODE in people who GPs judge as having dementia and 6CIT in people who GPs judge as having no dementia, would be a time-efficient and accurate diagnostic assessment.The original protocol for the study is available at https://bmcfampract.biomedcentral.com/articles/10.1186/s12875-016-0475-2.

Impact of Age and School Instruction Mode on Children's Occupations Early in the COVID-19 Pandemic: A Longitudinal Survey Study.

IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic disrupted participation in routines and daily activities. It is unclear how children reengaged in activities during the pandemic, particularly as a new school year began. Differences in school instruction mode (in person, hybrid, or remote) during the pandemic could further affect activity participation. OBJECTIVE: To examine changes in sedentary and nonsedentary activity participation in children and to determine whether school instruction mode was associated with participation. SETTING: Home-based survey of U.S. residents. PARTICIPANTS: Parents of 208 children (46.2% female) between ages 5 and 18 yr were surveyed at two waves: March through April 2020 and October 2020. OUTCOMES AND MEASURES: Frequency of sedentary (indoor play, electronic device usage) and nonsedentary (outdoor play, leisure and extracurriculars) activity participation was observed. Descriptive and inferential statistics of the changes from Wave 1 to Wave 2 and linear regression were used to determine statistically significant variables associated with activity participation. RESULTS: Nonsedentary activity participation increased and sedentary activity decreased from Wave 1 to Wave 2. Instruction mode was statistically associated with nonsedentary, but not sedentary, participation. Negative mood, local COVID-19 severity, and household income were also associated with nonsedentary and sedentary participation. CONCLUSIONS AND RELEVANCE: Children's participation in sedentary and nonsedentary activities normalized during the new school year; however, many factors likely contributed to these changes. What This Article Adds: Despite differences in school instruction mode and the influence of mental health early in the pandemic, children's nonsedentary activity participation increased. Occupational therapy practitioners can reinforce the importance of reengaging in activities and regular routines to promote health and well-being during challenging situations.

Long-Term Follow-up (14 to 25 Years) Following Closed Reduction and Early Movement for Simple Dislocation of the Elbow.

BACKGROUND: We have previously reported on the midterm outcomes after a nonoperative protocol to treat simple dislocations of the elbow that included a short period of splinting followed by early movement. We have now performed extended follow-up of the original patient group from the prior study to determine whether the excellent results that previously had been reported were maintained in the long term and also to determine the rate of and need for any late surgical intervention. METHODS: We attempted to contact all of the patients from the original study group. We requested that they complete the Oxford Elbow Score (OES) survey, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, and a validated patient satisfaction questionnaire. Patients also were requested to attend a face-to-face assessment to have a clinical examination that included neurovascular, range-of-motion, and ligamentous stability assessments. RESULTS: Seventy-one patients from the original patient group agreed to participate in the new study. The mean duration of follow-up was 19.3 years. At the time of the final follow-up, patients reported excellent functional outcome scores and a preserved functional range of movement in the injured elbow. The mean OES was 91.6 points, the mean DASH score was 5.22 points, and the mean satisfaction score was 90.9 points. None of the patients had undergone delayed or secondary surgery for instability during the interval period. CONCLUSIONS: This study demonstrated that the original excellent outcomes following treatment with a protocol of a short period of splinting and early movement remained excellent and were maintained into the very long term. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Acute Carpal Tunnel Syndrome: Early Nerve Decompression and Surgical Stabilization for Bony Wrist Trauma.

We undertook this study to investigate the outcomes of surgical treatment for acute carpal tunnel syndrome following our protocol for concurrent nerve decompression and skeletal stabilization for bony wrist trauma to be undertaken within 48 hours. Methods: We identified all patients treated at our trauma center following this protocol between January 1, 2014 and December 31, 2019. All patients were clinically reviewed at least 12 months after surgery and assessed using the Brief Michigan Hand Outcomes Questionnaire, the Boston Carpal Tunnel Questionnaire, and sensory assessment with Semmes-Weinstein monofilament testing. Results: The study group was made up of 35 patients. Thirty-three patients were treated within 36 hours. Patients treated with our unit protocol for early surgery comprising nerve decompression and bony stabilization within 36 hours report excellent outcomes at medium term follow-up. Conclusions: We propose that nerve decompression and bony surgical stabilization should be undertaken as soon as practically possible once the diagnosis is made. This is emergent treatment to protect and preserve nerve function. In our experience, the vast majority of patients were treated within 24 hours; however, where a short period of observation was required, excellent results were generally achieved when treatment was completed within 36 hours.

Impact of remote vital sign monitoring on health outcomes in acute respiratory infection and exacerbation of chronic respiratory conditions: systematic review and meta-analysis.

Background: Our aim was to investigate the effectiveness of virtual wards on health outcomes in patients with acute respiratory infection. Methods: We searched four electronic databases from January 2000 to March 2021 for randomised controlled trials (RCTs). We included studies in people with acute respiratory illness or an acute exacerbation of a chronic respiratory illness, where a patient or carer measured vital signs (oximetry, blood pressure, pulse) for initial diagnosis and/or asynchronous monitoring, in a person living in private housing or a care home. We performed random-effects meta-analysis for mortality. Results: We reviewed 5834 abstracts and 107 full texts. Nine RCTs were judged to be relevant for inclusion, in which sample sizes ranged from 37 to 389 (total n=1627) and mean ages ranged between 61 and 77 years. Five were judged to be at low risk of bias. Five RCTs had fewer hospital admissions in the intervention (monitoring) group, out of which two studies reported a significant difference. Two studies reported more admissions in the intervention group, with one reporting a significant difference. We were unable to perform a meta-analysis on healthcare utilisation and hospitalisation data due to lack of outcome definition in the primary studies and variable outcome measurements. We judged two studies to be at low risk of bias. The pooled summary risk ratio for mortality was 0.90 (95% CI 0.55-1.48). Conclusion: The limited literature for remote monitoring of vital signs in acute respiratory illness provides weak evidence that these interventions have a variable impact on hospitalisations and healthcare utilisation, and may reduce mortality.

Impact of COVID-19 on Cancer-Related Care in the United States: An Overview.

COVID-19 impacted several health services, including cancer-related care. Its implications were significant due to the lapse in hospital resources, compounded by the delays stemming from the economic effects on patients' jobs and medical coverage. Furthermore, reports suggesting an increased risk for morbidity and mortality from COVID-19 in patients with cancer and those on active cancer treatment caused additional fear and potential delays in seeking medical services. This review provides an overview of the pandemic's impact on cancer care in the United States and suggests measures for tackling similar situations in the future.

Effectiveness of exhaled nitric oxide for the prediction of non-invasive left atrial pressure in older people: a cross-sectional cohort study.

BACKGROUND: During left-sided heart failure (HF), left atrial and pulmonary venous pressure increase, which may lead to pulmonary congestion. Previous cohort studies, examining participants with symptomatic HF or rheumatic heart disease, suggest a relationship between increased left atrial pressure (LAP) and fractional exhaled nitric oxide (FeNO). AIM: To examine the strength of association between FeNO and echocardiographic assessment of LAP by the E/e' ratio, to determine if FeNO could be used to identify those with elevated LAP. DESIGN & SETTING: This cross-sectional cohort study examined a subset of the OxVALVE cohort aged ≥65 years. Data collection was undertaken in primary care practices in central England. METHOD: Each participant underwent a focused cardiovascular history and clinical examination. Standard transthoracic echocardiographic (TTE) assessment was performed on all participants, with the E/e' ratio calculated to obtain a validated surrogate of LAP. FeNO was measured in 227 participants. RESULTS: FeNO was higher in males compared with females and no different in participants with asthma, chronic obstructive pulmonary disease (COPD), or those using inhaled steroids. Participants with a high E/e' (>14) were older, with a higher proportion of females than males. There was no relationship between E/e' and FeNO, either when measured as a continuous variable or in the group with high E/e'. CONCLUSION: FeNO was not found to be an accurate predictor of elevated LAP in a primary care setting.

Functional analysis of arteriovenous fistulae in non-contrast magnetic resonance images.

BACKGROUND AND OBJECTIVE: Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis vascular access and their successful maturation is critical to reduce patient morbidity, mortality, cost, and improve quality of life. Peri-anastomotic venous segment stenosis is the primary cause of AVF maturation failure. The objective is to develop a software protocol for the functional analysis of arteriovenous fistula. METHOD: We have developed a standard protocol for the anatomical analysis of the AVF to better understand the mechanisms involved in AVF stenosis and to identify future imaging biomarkers for AVF success or failure using non-contrast magnetic resonance imaging (MRI). The 3D model of the AVF is created using a polar dynamic programming technique. Analysis has been performed on six Yorkshire cross domestic swine, but techniques can be applied into clinical settings. RESULTS: Differences in AVF angles and vein curvature are associated with significant variability of venous cross-sectional area. This suggests that the pattern of stenosis is likely to be dependent upon hemodynamic profiles which are largely determined by AVF anatomical features and could play an important role in AVF maturation. CONCLUSIONS: This protocol enables us to visualize and study the hemodynamic profiles indirectly allowing early stratification of patients into high and low risk groups for AVF maturation failure. High risk patients could then be targeted with an enhanced process of care or future maturation enhancing therapies resulting in a much-needed precision-medicine approach to dialysis vascular access.

Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes.

BACKGROUND: Patients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications. METHODS: 21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A 'hyperglycaemic clamp' of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days. Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure. RESULTS: Concentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential. Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis. CONCLUSIONS: Hyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes. TRIAL REGISTRATION: NCT number: NCT01984827.

The Perceptions and Experience of Surgical Trainees Related to Patient Safety Improvement and Incident Reporting: Structured Interviews With 612 Surgical Trainees.

Background We undertook a prospective qualitative study to ascertain the perceptions and experience of trainee doctors in the first two years of formal core surgical training related to patient safety improvement and incident reporting. We sought to explore the beliefs, knowledge and opinions of core surgical trainees related to patient safety improvement, their understanding of existing patient safety initiatives and their experience and attitudes to incident reporting. Methods We identified 1133 doctors in formal core surgical training posts in the United Kingdom at this time, and we contacted these doctors to invite them to participate in our study. We received responses from 687 (60.6%) core surgical trainees, and 612 trainees (54%) agreed to participate. The study participants underwent an interview using structured questions asked by trained assessors with an opportunity to explore any particular themes identified by the trainee in more detail. Qualitative data related to the knowledge, experience and perceptions of safety improvement and incident reporting were collected. Results Overall, 163 surgical trainees (26.6%) reported that they felt that they could impact patient safety positively. A total of 222 trainees (36.3%) had been involved in or witnessed an adverse patient safety event, while 509 trainees (83.2%) reported that they had witnessed a 'near-miss' event. Only 81 trainees (13.2%) had submitted a patient safety report at some point in their career. In addition, 536 trainees (87.6%) reported that they considered a patient safety or incident report to be 'negative' or 'seriously negative' and that they would be discouraged from making these because of the negative connotations associated with them. Of the 81 core surgical trainees who had submitted a patient safety report, only nine trainees (11.1%) reported that they had received a meaningful reply and update following their report. Several themes were identified during the interviews in response to open questions. These included a perception that patient safety improvement is the responsibility of senior surgeons and managers and that surgical trainees did not feel empowered to influence patient safety improvement. Trainees expressed the view that incident reporting reflected negatively on clinicians and the standard of care provided, and there were reports of culture based on blame and the fear of litigation or complaints. Surgical trainees did not feel that incident reporting was an effective tool for patient safety improvement, and those trainees who had made patient safety reports felt that these did not result in change and that they often received no feedback. Conclusions Core surgical trainees report that they are not well engaged in patient safety improvement and that their perceptions and experience of incident reporting are not positive. This represents a missed opportunity. We suggest that in order to recruit the surgical workforce to the improvement work and learning associated with patient safety, opportunities for focused education, training and culture change are needed from the early years of surgical training. In addition, improvements to the processes and systems that allow trainees to engage with safety improvement are needed in order to make these more user-friendly and accessible.

Clinical judgment of GPs for the diagnosis of dementia: a diagnostic test accuracy study.

BACKGROUND: GPs often report using clinical judgment to diagnose dementia. AIM: To investigate the accuracy of GPs' clinical judgment for the diagnosis of dementia. DESIGN & SETTING: Diagnostic test accuracy study, recruiting from 21 practices around Bristol, UK. METHOD: The clinical judgment of the treating GP (index test) was based on the information immediately available at their initial consultation with a person aged ≥70 years who had cognitive symptoms. The reference standard was an assessment by a specialist clinician, based on a standardised clinical examination and made according to the 10th revision of the International Classification of Diseases (ICD-10) criteria for dementia. RESULTS: A total of 240 people were recruited, with a median age of 80 years (interquartile range [IQR] 75-84 years), of whom 126 (53%) were men and 132 (55%) had dementia. The median duration of symptoms was 24 months (IQR 12-36 months) and the median Addenbrooke's Cognitive Examination III (ACE-III) score was 75 (IQR 65-87). GP clinical judgment had sensitivity 56% (95% confidence interval [CI] = 47% to 65%) and specificity 89% (95% CI = 81% to 94%). Positive likelihood ratio was higher in people aged 70-79 years (6.5, 95% CI = 2.9 to 15) compared with people aged ≥80 years (3.6, 95% CI = 1.7 to 7.6), and in women (10.4, 95% CI = 3.4 to 31.7) compared with men (3.2, 95% CI = 1.7 to 6.2), whereas the negative likelihood ratio was similar in all groups. CONCLUSION: A GP clinical judgment of dementia is specific, but confirmatory testing is needed to exclude dementia in symptomatic people whom GPs judge as not having dementia.

Pharmacological Predictors of Morbidity and Mortality in COVID-19.

The interaction of coronavirus disease (COVID-19) with the majority of common prescriptions is broadly unknown. The purpose of this study is to identify medications associated with altered disease outcomes in COVID-19. A retrospective cohort composed of all adult inpatient admissions to our center with COVID-19 was analyzed. Data concerning all antecedent prescriptions were collected and agents brought forward for analysis if prescribed to at least 20 patients in our cohort. Forty-two medications and 22 classes of medication were examined. Groups were propensity score matched and analyzed by logistic and linear regression. The majority of medications did not show a statistically significant relationship with altered disease outcomes. Lower mortality was associated with use of pregabalin (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01-0.92; P = .049) and inhalers of any type (HR, 0.33; 95%CI, 0.14-0.80; P = .015), specifically beclomethasone (HR, 0.10; 95%CI, 0.01-0.82; P = .032), tiotropium (HR, 0.07; 95%CI, 0.01-0.83; P = .035), and steroid-containing inhalers (HR, 0.35; 95%CI, 0.15-0.79; P = .013). Gliclazide (HR, 4.37; 95%CI, 1.26-15.18; P = .020) and proton pump inhibitor (HR, 1.72; 95%CI, 1.06-2.79; P = .028) use was associated with greater mortality. Diuretic (HR, 0.07; 95%CI, 0.01-0.37; P = .002) and statin (HR, 0.35; 95%CI, 0.17-0.73; P = .006) use was associated with lower rates of critical care admission. Our data lends confidence to observing usual practice in patients with COVID-19 by continuing antecedent prescriptions in the absence of an alternative acute contraindication. We highlight potential benefits in investigation of diuretics, inhalers, pregabalin, and statins as therapeutic agents for COVID-19 and support further assessment of the safety of gliclazide and proton pump inhibitors in the acute illness.

Clinical and Demographic Factors, Treatment Patterns, and Overall Survival Associated With Rare Triple-Negative Breast Carcinomas in the US.

Importance: Triple-negative breast cancers are known collectively to demonstrate a more aggressive clinical course and earlier recurrence than cancers of other histological subtypes. However, the literature on rare triple-negative breast cancers and the association of histological type with survival and risk of metastasis is sparse. Objective: To present the clinical and demographic characteristics, treatment patterns, and overall survival (OS) for histologically rare (<10% of breast cancers) triple-negative breast cancer types: medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast carcinoma. Design, Setting, and Participants: This cohort study was performed in the US using data reported by the National Cancer Database between 2010 and 2016. Confirmed cases of medullary carcinoma, adenoid cystic carcinoma, and metaplastic breast cancer were analyzed. Univariable analyses and multivariable Cox regression models were performed. Data analysis was performed from April to May 2020. Main Outcomes and Measures: The primary outcome was 5-year OS. Secondary outcomes included site of metastasis, effect of immunohistochemistry, management, and 2-year mortality. Results: A total of 8479 patients with breast cancer (mean [SD] age; 62.6 [14.3] years; 8435 women [99.48%]) were analyzed. Metaplastic carcinoma was the most commonly diagnosed histological type in this cohort, with 6867 patients (81%), followed by 1357 (16%) with adenoid cystic carcinoma and only 255 (3%) with medullary carcinoma. Medullary carcinoma presented earlier in life, at a median (interquartile range) age of 53 (45-62) years, compared with 62 (53-72) years for patients with adenoid cystic carcinoma and 63 (52-74) years for patients with metaplastic carcinoma. The proportion of tumors with triple-negative immunohistochemistry varied by histological type for medullary carcinoma (57 patients [22.4%]), adenoid cystic carcinoma (653 patients [48.1%]), and metaplastic carcinoma (3637 patients [53.0%]). Patients with adenoid cystic carcinoma were less likely to receive radiotherapy (711 patients [52.4%]) and chemotherapy (175 patients [12.9%]) compared with patients with medullary carcinoma (radiotherapy, 156 patients [61.2%]; chemotherapy, 190 patients [74.5%]) and metaplastic carcinoma (radiotherapy, 3416 patients [49.7%]; chemotherapy, 4709 patients [68.6%]). The 5-year OS rate was superior for patients with medullary (91.7%) and adenoid cystic carcinoma (88.4%) compared with patients with metaplastic carcinoma (63.1%). The 5-year mortality rate for adenoid cystic carcinoma was 8.33% vs 36.91% for metaplastic carcinoma. Conclusions and Relevance: Nationally, over the course of 7 years, medullary carcinoma was most common and metaplastic carcinoma had the worst 5-year OS among the rare histological breast cancer subtypes analyzed. Factors associated with a poor prognosis for metaplastic carcinoma included advanced stage, lung metastasis, older age, and not receiving chemotherapy or radiation therapy. Future research focusing on rare subtypes of breast cancer is desirable and could inform the optimal management of these relatively understudied carcinomas.

Inpatient Omission of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Is Associated With Morbidity and Mortality in Coronavirus Disease 2019.

PURPOSE: Due to the affinity of severe acute respiratory syndrome coronavirus 2 for the human angiotensin-converting enzyme 2 (ACE2) receptor, use of ACE inhibitors and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in patients with severe acute respiratory syndrome coronavirus 2 infection. To date, only a limited number of studies have directly evaluated the safety of inpatient prescription of ACE inhibitors/ARBs during acute coronavirus disease 2019 (COVID-19) illness. METHODS: A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACE inhibitors/ARBs on morbidity and mortality in patients admitted to the hospital with COVID-19. Relationships were explored by using linear and logistic regression. FINDINGS: A total of 612 adult patients met the inclusion criteria, of whom 151 (24.7%) patients were established on ACE inhibitors/ARBs. Despite correction for known confounders, discontinuation of ACE inhibitors/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in the hospital was significantly associated with increased mortality (OR, 9.59; 95% CI, 2.55-36.09; P < 0.001), maximum National Early Warning Score 2 (OR, 1.66; 95% CI, 1.27-2.17; P < 0.001), maximum oxygen requirements (OR, 3.00; 95% CI, 1.83-4.91; P < 0.001), and maximum C-reactive protein concentration (OR, 1.83; 95% CI, 1.06-3.17; P = 0.030). IMPLICATIONS: Our data show a strong association between missed ACE inhibitor/ARB doses with increased morbidity and mortality. The available evidence supports continuation of currently accepted practice surrounding ACE inhibitor/ARB therapy in acute illness, which is to limit drug omission to established acute contraindications, to actively monitor such decisions, and to restart therapy as soon as it is safe to do so. (Clin Ther. 2021;43:e97-e110) © 2021 Elsevier HS Journals, Inc.

Atomistic Simulation of Water Incorporation and Mobility in Bombyx mori Silk Fibroin.

Bombyx mori silk fibroin (SF) is a biopolymer that can be processed into materials with attractive properties (e.g., biocompatibility and degradability) for use in a multitude of technical and medical applications (including textiles, sutures, drug delivery devices, tissue scaffolds, etc.). Utilizing the information from experimental and computational SF studies, a simplified SF model has been produced (alanine-glycine [Ala-Gly] n crystal structure), enabling the application of both molecular dynamic and density functional theory techniques to offer a unique insight into SF-based materials. The secondary structure of the computational model has been evaluated using Ramachandran plots under different environments (e.g., different temperatures and ensembles). In addition, the mean square displacement of water incorporated into the SF model was investigated: the diffusion coefficients, activation energies, most and least favorable positions of water, and trajectory of water diffusion through the SF model are obtained. With further computational study and in combination with experimental data, the behavior/degradation of SF (and similar biomaterials) can be elucidated. Consequently, greater control of the aforementioned technologies may be achieved and positively affect their potential applications.

Why the SARS-CoV-2 antibody test results may be misleading: insights from a longitudinal analysis of COVID-19

To estimate the effectiveness of vaccines in development, a robust mechanism is required to understand immunity, risks of reinfection and measure the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and how this may change over time. This study is a longitudinal analysis of COVID-19 infection rates using PCR, membrane immunoassay and chemiluminescent microparticle immunoassay (CMIA) diagnostic tests. Our data confirm that antibody levels wane in the three months after symptom onset. Comparison of the three methods used suggests that quantitative CMIA testing may exaggerate numbers of COVID-19 negative individuals.

Practical and cost-effective model to build and sustain a cardio-oncology program.

BACKGROUND: Cardio-Oncology (CO) is a new subspecialty that thrives mostly in large academic quaternary centers. This study describes how to establish a successful cardio-oncology program, with limited resources, in order to effectively manage the unique care required by this patient population. METHODS: Clinical data was collected from 25 consecutive months. There were four foundational elements to establish a CO program: 1. Clinical program: integrating staff and resources from the Heart and Vascular, and Cancer Centers; 2. Education Program: establishing a platform to educate/advocate with respect to CO; 3. Engagement with professional societies: active engagement allowed for the successful establishment of the proposed CO program; and 4. Research program: establishing data collection modalities/cooperation with other institutions. RESULTS: 474 consecutive patients were treated by our CO program during the first 25 months of operation. Clinical data, information about cancer treatment, cardiovascular co morbidities, cardiac testing and impact of CO management are reported. CONCLUSIONS: A successful CO program can be established utilizing existing resources without the need for significant additional assets. Integration with professional societies, advocacy, education and research, provide a platform for learning and growth. This model improves access to care and can be reproduced in a variety of settings.

Left atrial stiffness in women with ischemia and no obstructive coronary artery disease: Novel insight from left atrial feature tracking.

BACKGROUND: Women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) are at risk of heart failure with preserved ejection fraction (HFpEF); however, the mechanism for HFpEF progression remains unclear. Studies in INOCA have largely focused on left ventricular function. The left atrium serves an important role in maintaining transmitral flow, and is impaired in HFpEF; however, it remains unclear if left atrial function is impaired in INOCA. HYPOTHESIS: Left atrial function is progressively worse in INOCA and HFpEF compared to controls. METHODS: We compared 39 reference control subjects to 64 women with INOCA and 22 subjects with HFpEF. Left atrial strain was assessed by feature tracking using magnetic resonance cine images. RESULTS: Peak left atrial strain was reduced in HFpEF compared to controls (22.9 ± 4.8% vs 25.9 ± 3.2%, P < .01), but similar in INOCA (24.8 ± 4.5%) compared to HFpEF and controls (P = .18). However, left ventricular end-diastolic pressure (LVEDP) was elevated in 33% of INOCA participants, suggesting that left atrial stiffness (LVEDP/LA strain) is elevated in a large portion of women with INOCA. CONCLUSIONS: Taken together, we interpret these data to support our working hypothesis that INOCA is a pre-HFpEF state, with left atrial stiffness preceding overt left atrial dysfunction; representing a putative therapeutic target to prevent HFpEF progression in this at-risk population.

Cost-Effectiveness Analysis of Recombinant Factor VIII Fc-Fusion Protein (rFVIIIFc) for the Treatment of Severe Hemophilia A in Italy Incorporating Real-World Dosing and Joint Health Data.

BACKGROUND: Patients with severe hemophilia A (SHA) in Italy are routinely treated with standard half-life recombinant factor VIII (rFVIII) products. rFVIII Fc-fusion protein (rFVIIIFc) is an extended half-life rFVIII product that enables less frequent administration than rFVIII, which may support improved adherence. Available data indicate low breakthrough bleed rates and potentially improved long-term joint health for patients treated with rFVIIIFc prophylaxis. OBJECTIVE: This study assessed the cost effectiveness of rFVIIIFc versus rFVIII from an Italian healthcare perspective. METHODS: A Semi-Markov model was constructed to assess the lifetime costs and benefits of rFVIII and rFVIIIFc prophylaxis. rFVIII product acquisition costs from a published Italian database were included for both prophylaxis and the resolution of breakthrough bleeding. Clinical outcomes within the model were determined based on published annualized bleeding rates and literature regarding the development of target joints (TJs) as the incidence of bleeds and TJs is associated with impaired health-related quality of life. Cost effectiveness was assessed using cost per quality-adjusted life-year (QALY) gained. RESULTS: Compared with rFVIII, rFVIIIFc was associated with a per-patient cost saving of approximately €1.3 million and QALY gains of 0.39 over a lifetime horizon. Sensitivity analyses considering alternative efficacy, dosing, and structural assumptions each showed that rFVIIIFc dominated rFVIII (i.e., provided more QALYs at a reduced cost). CONCLUSIONS: This cost-effectiveness analysis demonstrated that rFVIIIFc may offer a cost-effective treatment option for patients with SHA in Italy.