Search

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract (1% to 2% of GI malignant tumors). They are most commonly located in the stomach (50 to 60%) and rarely in the small intestine (20-25% of all cases). The hallmark of most GISTs is their positivity for KIT (CD117) and DOG-1. Intussusception occurs rarely in adults with an incidence of approximately 2-3 per 1L per year. It represents 5% of all intussusceptions and is the cause of 1% of all intestinal obstructions. Ileocolic intussusception in adults is a unique variant in which most cases have a malignant lead point. In our case, we report an elderly patient presenting with intestinal obstruction, and imaging showed ileocecal intussusception with a solid nodular growth arising from the ileum. On exploration, the tumor was intraluminal arising from the ileum with ileocecal intussusception. Adhering to oncological principles, a right hemicolectomy was performed. The final pathologic diagnosis indicated the GIST of the ileum. Immunohistochemistry (IHC) showed CD117 negative and DOG-1 positive. Bowel obstruction due to intussusception in adults is rare. GIST in the ileum causing intussusception is unusual with a poorer prognosis than other GISTs. Intussusception in adults obstructing with small intestinal GIST which is CD117 negative makes it interesting and even rare. The diagnosis of intussusception and GISTs causing obstruction in adults is delicate, and timely surgical treatment can be vital. Given a high risk of malignancy, primary surgical resection using oncologic principles presents the best option in this scenario.

Introduction: Breast carcinoma is one of the most prevalent types of carcinoma and the leading cause of death among all carcinomas. Recently, vitamin D deficiency has been reported as a risk factor for breast carcinoma. Vitamin D, as an anticarcinoma agent, prevents cellular differentiation, stimulates cell death, reduces angiogenesis, tumour progression, and metastasis. Aim: To investigate the relationship between vitamin D deficiency and the risk of breast carcinoma. Materials and Methods: An observational study was conducted at the Armed Forces Medical College, Pune, Maharashtra, India, between November 2018 and October 2020. A total of 57 cases diagnosed with breast carcinoma and 57 healthy controls were analysed. Physical and reproductive health parameters were compared, along with vitamin D status using student’s t-test and Mann-Whitney U test. Logistic regression was used to assess the risk of breast carcinoma. Results: Out of 114 women, 57 were cases and 57 were controls with a mean age of 52 vs 48 years. The mean value of serum vitamin D levels was significantly lower (19.45 vs 27.91 ng/mL, p

IntroductionNon-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity.MethodsWe used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival.ResultsWe identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55–58) versus 72 months (95% CI 71–73) (hazard ratio (HR) 1.14, 95% CI 1.12–1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62–69) versus NHW 69 months (95% CI 97–71) (HR 1.02, 95% CI 0.98–1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p

Background and Aims: There are limited contemporary population-based data on Helicobacter pylori epidemiology and outcomes in the United States. Our primary aim was to create a validated cohort of veterans with H pylori testing or treatment using Veterans Health Administration data. Methods: Using Veterans Health Administration structured and unstructured data, we developed and validated 4 algorithms for H pylori infection (3 algorithms) and treatment status (1 algorithm). During the development phase, we iteratively modified each algorithm based on a manual review of random sets of electronic health records (reference standard). The a priori validation goal was to achieve a one-sided 95% confidence lower bound (LB) for positive predictive value (PPV) and/or negative predictive value (NPV) >90%. We applied the Bonferroni correction when both PPV and NPV were relevant. Results: For H pylori infection, we achieved 99.0% PPV (LB = 94.6%) and 100% NPV (LB = 96.4%) for discriminating H pylori positive vs negative status using structured (ie, laboratory tests) and 95% PPV (LB = 90.3%) and 97.9% NPV (LB = 93.9%) using unstructured (ie, histopathology reports) data. Diagnostic codes achieved 98% PPV (LB = 93.0%) for H pylori diagnosis. The treatment algorithm was composed of multiple antimicrobial combinations and overall achieved ≥98% PPV (LB = 93.0%) for H pylori treatment, except for amoxicillin/levofloxacin (PPV

Background and Aims: Gastrointestinal cancer incidence varies by race and ethnicity. In the United States (US), there are screening guidelines for esophageal cancer (EC) and colorectal cancer (CRC), but not gastric cancer (GC). We compared GC, CRC, and EC incidence among the most populous racial and ethnic groups to inform US interception strategies. Methods: We used SEER∗Stat to compare GC, CRC, and EC incidence rates across non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 8 largest Asian American populations using the Surveillance, Epidemiology, and End Results 9 registries (2010–2014). Results: Noncardia GC incidence was highest among Korean (18.7 cases per 100,000) and lowest among NHW (1.4 cases per 100,000) Americans. CRC incidence was highest among non-Hispanic Black, Southeast Asian, and Japanese (35.9, 34.2, and 33.8 per 100,000, respectively) Americans and lowest among South Asian Americans (18.9 per 100,000). EC incidence was greatest in NHW (4.7 per 100,000) and lowest in Filipino (1.2 per 100,000) Americans. The incidence of noncardia GC slightly exceeded colon cancer in Korean American men (25.5 vs 22.4 per 100,000). GC surpassed EC incidence in all non-White racial and ethnic groups. Conclusion: The burden of GC, CRC, and EC differs based on race and ethnicity. Non-White racial and ethnic groups experience a disproportionate burden of GC for which systematic programs for cancer interception, similar to CRC and EC, are needed.

Abstract Background Most asthma diagnoses and patient care take place in primary care settings. Electronic medical records (EMRs) offer an opportunity to utilize technology to improve asthma diagnosis and care. The purpose of this study was to create and validate separate case definitions for suspected and confirmed asthma in primary care EMRs, to enable surveillance, benchmarking, and quality improvement in primary care settings. The objective of this study was to develop a case definition for suspected and confirmed asthma for use in a primary care sentinel surveillance system. Methods A single chart abstractor conducted a manual audit of 776 randomly selected patient charts from an academic primary care practice EMR in Kingston, Ontario. Following the single chart abstractor classification, a consensus on chart classification as “not asthma”, “suspected asthma”, or “confirmed asthma” was achieved between the abstractor, a family physician, and a respirologist using Canadian Thoracic Society (CTS) criteria. Case definition algorithms based on billing codes, clinical data elements and medications were applied to the site’s Canadian Primary Care Sentinel Surveillance Network (CPCSSN) data for the same charts and compared to abstractor classifications to determine each algorithm’s measurement properties. Results The prevalence of suspected and confirmed asthma were 7.3% (n = 54) and 2.4% (n = 18), respectively. None of the proposed case definitions could differentiate between suspected and confirmed asthma. One algorithm consisting of billing, clinical, and medication elements had the highest Youden’s Index for either suspected or confirmed asthma. The algorithm had a sensitivity of 81%, a specificity of 96%, positive predictive value of 71%, negative predictive value of 98%, and a Youden’s Index of 0.77 for combined suspected or confirmed asthma cases. Conclusion An EMR case definition for suspected or confirmed adult asthma has been validated for use in CPCSSN. Implementation of this case definition will enable the development of a surveillance electronic tool (eTool) for adult asthma that can foster quality improvement.

Abstract Background Computerized clinical decision support systems (CDSSs) can improve care by bridging knowledge to practice gaps. However, the real-world uptake of such systems in health care settings has been suboptimal. We sought to: (1) use the Theoretical Domains Framework (TDF) to identify determinants (barriers/enablers) of uptake of the Electronic Asthma Management System (eAMS) CDSS; (2) match identified TDF belief statements to elements in the Guideline Implementation with Decision Support (GUIDES) Checklist; and (3) explore the relationship between the TDF and GUIDES frameworks and the usefulness of this sequential approach for identifying opportunities to improve CDSS uptake. Methods In Phase 1, we conducted semistructured interviews with primary care physicians in Toronto, Canada regarding the uptake of the eAMS CDSS. Using content analysis, two coders independently analyzed interview transcripts guided by the TDF to generate themes representing barriers and enablers to CDSS uptake. In Phase 2, the same reviewers independently mapped each belief statement to a GUIDES domain and factor. We calculated the proportion of TDF belief statements that linked to each GUIDES domain and the proportion of TDF domains that linked to GUIDES factors (and vice-versa) and domains. Results We interviewed 10 participants before data saturation. In Phase 1, we identified 53 belief statements covering 12 TDF domains; 18 (34.0%) were barriers, and 35 (66.0%) were enablers. In Phase 2, 41 statements (77.4%) linked to at least one GUIDES factor, while 12 (22.6%) did not link to any specific factor. The GUIDES Context Domain was linked to the largest number of belief statements (19/53; 35.8%). Each TDF domain linked to one or more GUIDES factor, with 6 TDF domains linking to more than 1 factor and 8 TDF domains linking to more than 1 GUIDES domain. Conclusions The TDF provides unique insights into barriers and enablers to CDSS uptake, which can then be mapped to GUIDES domains and factors to identify required changes to CDSS context, content, and system. This can be followed by conventional mapping of TDF domains to behaviour change techniques to optimize CDSS implementation. This novel step-wise approach combines two established frameworks to optimize CDSS interventions, and requires prospective validation.

Introduction/Objectives: Colonoscopy completion rates after an abnormal fecal immunochemical test (FIT) are suboptimal, resulting in missed opportunities for early detection and prevention of colorectal cancer. Patient navigation and structured follow-up may improve colonoscopy completion, but implementation of these strategies is not widespread. Methods: We conducted a quality improvement study using a Plan-Do-Study-Act (PDSA) Model to increase colonoscopy completion after abnormal FIT in a large federally qualified health center serving a diverse and low-income population. Intervention components included patient navigation, and a checklist to promote completion of key steps required for abnormal FIT follow-up. Primary outcome was proportion of patients achieving colonoscopy completion within 6 months of abnormal FIT, assessed at baseline for 156 patients pre-intervention, and compared to 208 patients during the intervention period from April 2017 to December 2019. Drop offs at each step in the follow-up process were assessed. Results: Colonoscopy completion improved from 21% among 156 patients with abnormal FIT pre-intervention, to 38% among 208 patients with abnormal FIT during the intervention ( P

Osteoblastoma is a rare benign bone tumor commonly located at spine and long bones. However, rib involvement has been reported less frequently. In this report, we describe a young adult female presenting with osteoblastoma of third rib, with the purpose of reviewing clinical, radiological, and histopathological features of osteoblastoma and emphasizing surgical resection as the treatment of choice to lessen chances of recurrence and avoid its confusion with other benign bone tumors by providing adequate tissue for histopathological analysis. Osteoblastoma is an uncommon primary bone tumor accounting for only 1% of all bone tumors. Ribs are involved in less than 5% of patients. The disease has usually a good prognosis with a tendency for local destruction and recurrence. Surgical excision remains the treatment of choice to prevent recurrences and to provide a definite diagnosis differentiating it from osteoblastoma-like osteosarcoma and other benign tumors of the rib.

Abstract Background Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). Methods A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. Results There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1–3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. Conclusion We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

Abstract Background Viable knowledge translation (KT) strategies are increasingly sought to improve asthma diagnosis, particularly in primary care. Despite this understanding, practical KT tools to support primary care practitioners are not widely available. Electronic medical records (EMRs) offer an opportunity to optimize the diagnosis and surveillance of chronic diseases such as asthma, and support quality improvement initiatives that increase adherence to guideline-recommended care. This review aims to describe the current state of electronic KT electronic tools (eTools) and surveillance systems for asthma and identify opportunities to increase adherence to asthma diagnostic guidelines by implementing digital KT eTools. Methods Systematic literature searches were conducted on Ovid MEDLINE that included the search terms: asthma, asthma diagnosis, asthma surveillance, electronic health records, translational medical research, quality improvement, professional practice gaps, and primary health care published in the previous 10 years. In total, the searches returned 971 articles, 163 of which were considered relevant and read in full. An additional 28 articles were considered after reviewing the references from selected articles. 75 articles were included in this narrative review. Results Established KT eTools for asthma such as electronic questionnaires, computerized clinical decision support systems (CDSS), chronic disease surveillance networks, and asthma registries have been effective in improving the quality of asthma diagnosis and care. As well, chronic disease surveillance systems, severe asthma registries, and workplace asthma surveillance systems have demonstrated success in monitoring asthma outcomes. However, lack of use and/or documentation of objective measures of lung function, challenges in identifying asthma cases in EMRs, and limitations of data sources have created barriers in the development of KT eTools. Existing digital KT eTools that overcome these data quality limitations could provide an opportunity to improve adherence to best-practice guidelines for asthma diagnosis and management. Conclusion Future initiatives in the development of KT eTools for asthma care should focus on strategies that assist healthcare providers in accurately diagnosing and documenting cases of asthma. A digital asthma surveillance system could support adherence to best-practice guidelines of asthma diagnosis and surveillance by prompting use of objective methods of confirmation to confirm an asthma diagnosis within the EMR.

Abstract Respiratory self-care places considerable demands on patients with chronic airways disease (AD), as they must obtain, understand and apply information required to follow their complex treatment plans. If clinical and lifestyle information overwhelms patients’ HL capacities, it reduces their ability to self-manage. This review outlines important societal, individual, and healthcare system factors that influence disease management and outcomes among patients with asthma and chronic obstructive pulmonary disease (COPD)—the two most common ADs. For this review, we undertook a comprehensive literature search, conducted reference list searches from prior HL-related publications, and added insights from international researchers and scientists with an interest in HL. We identified methodological limitations in currently available HL measurement tools in respiratory care. We also summarized the issues contributing to low HL and system-level cultural incompetency that continue to be under-recognized in AD management and contribute to suboptimal patient outcomes. Given that impaired HL is not commonly recognized as an important factor in AD care, we propose a three-level patient-centered model (strategies) designed to integrate HL considerations, with the goal of enabling health systems to enhance service delivery to meet the needs of all AD patients.

Introduction Climate change from greenhouse gas (GHG) emissions represents one of the greatest public health threats of our time. Inhalers (and particularly metred-dose inhalers (MDIs)) used for asthma and chronic obstructive pulmonary disease (COPD), constitute an important source of GHGs. In this analysis, we aimed to estimate the carbon footprint impact of improving three distinct aspects of respiratory care that drive avoidable inhaler use in Canada.Methods We used published data to estimate the prevalence of misdiagnosed disease, existing inhaler use patterns, medication class distributions, inhaler type distributions and GHGs associated with inhaler actuations, to quantify annual GHG emissions in Canada: (1) attributable to asthma and COPD misdiagnosis; (2) attributable to overuse of rescue inhalers due to suboptimally controlled symptoms; and (3) avoidable by switching 25% of patients with existing asthma and COPD to an otherwise comparable therapeutic option with a lower GHG footprint.Results We identified the following avoidable annual GHG emissions: (1) ~49 100 GHG metric tons (MTs) due to misdiagnosed disease; (2) ~143 000 GHG MTs due to suboptimal symptom control; and (3) ~262 100 GHG MTs due to preferential prescription of strategies featuring MDIs over lower-GHG-emitting options (when 25% of patients are switched to lower GHG alternatives). Combined, the GHG emission reductions from bridging these gaps would be the equivalent to taking ~101 100 vehicles off the roads each year.Conclusions Our analysis shows that the carbon savings from addressing misdiagnosis and suboptimal disease control are comparable to those achievable by switching one in four patients to lower GHG-emitting therapeutic strategies. Behaviour change strategies required to achieve and sustain delivery of evidence-based real-world care are complex, but the added identified incentive of carbon footprint reduction may in itself prove to be a powerful motivator for change among providers and patients. This additional benefit can be leveraged in future behaviour change interventions.

Introduction: Retinopathy of prematurity (ROP) is a multifactorial disease and a preventable cause of blindness in childhood. Hyperoxia and hypoxia can cause retinal neovascularization resulting in retinal detachment and blindness if left untreated. Besides oxygen treatment, other reasons for ROP development are well known. We prospectively adopt various strategies to keep oxygen saturation (SpO2) within targets, between 91 and 95% for those on supplemental oxygen. By adapting this, we postulated that the incidence of severe ROP might be reduced. Methods: 2018–2019 provided pre-intervention and 2020 post-intervention data for the project. For all babies (≤32 weeks, ≤1,500 g with FiO2 >0.21), target SpO2 between 91 and 95% was measured as a percentage of time spent within and outside target SpO2 during 1–4 weeks of life. Results: 112 and 60 preterm neonates were screened for ROP during the pre- and post-intervention phase. Twenty neonates (18.3%) during pre-intervention and 16 (26.7%) in the post-intervention phase developed severe ROP requiring treatment. Despite a statistically significant increase of 10 percent points in time spent within target SpO2 (91–95%) in the post-intervention phase (p < 0.05), the incidence of severe ROP did not decline. Using a multivariate model, odds of ROP development decreased with gestational age (25%) while increasing with PDA requiring treatment (4.33 times) and glucose ≥10 mg/dL (4.15 times), considering one variable at a time, keeping others constant. Conclusion: Our QI project showed successful attainment of maximum time; the SpO2 remained within targets during supplemental oxygen; however, the incidence of severe ROP had not declined. Factors other than SpO2 might be responsible for a high incidence of ROP in our neonatal intensive care unit.

BackgroundThe use of mobile health (mHealth) in asthma and chronic obstructive pulmonary disease (COPD) is growing, and as the population ages, a greater number of older adults stand to benefit from mHealth-enhanced airway disease care. Though older adults are a heterogeneous population of health technology users, older age represents a potential barrier to health technology adoption, and there is currently a lack of knowledge on how older age influences mHealth use in asthma and COPD. ObjectiveIn this qualitative study, we sought to explore the experiences and perspectives of adults who were aged 65 years and older with asthma and COPD toward mHealth use. MethodsSemistructured individual interviews were conducted with adults who were aged 65 years and older with asthma or COPD and owned a smartphone. Applying phenomenological methodology, we analyzed interview transcripts in order to develop themes and propose an essential experience of mHealth use among older adults with airway disease. We then summarized our qualitative findings and proposed strategies to leverage our results in order to guide future research and implementation efforts targeting older adults’ use of airway mHealth. ResultsTwenty participants (mean age 79.8, SD 4.4 years) were interviewed. Participants described a central tension between (1) the perception that mHealth could help maintain independence throughout aging and (2) an apprehension toward the ways in which mHealth could negatively affect established health care experiences. Several elements of these 2 themes are absent from previous research focusing on younger adults with asthma and COPD. The individual elements of these 2 themes informed potential strategies to optimize future older adults’ use of asthma and COPD mHealth tools. ConclusionsFocusing on the perspectives and experiences of older adults with asthma and COPD in their use of mHealth identified novel understandings of health technology use in this important demographic in need of greater care. These lessons were translated into potential strategies that will need to be objectively evaluated in future airway mHealth research, development, and implementation efforts.

Abstract Background Successful guideline implementation depends both on factors extrinsic to guidelines and their intrinsic features. In the Guideline Implementability for Decision Excellence Model (GUIDE-M), “communicating” content (language and format) is one of three core determinants of intrinsic implementability, but is seldom addressed. Our aims were to develop a tool that could be used by guideline developers to optimize language and format during development; identify gaps in this type of guidance in existing resources; and evaluate the perceived need for and usefulness of such a tool among guideline developers. Methods Our mixed-methods design consisted of (1) content development (selection and organization of evidence-based constructs from the GUIDE-M into a prototype Guideline Language and Format Instrument (GLAFI), followed by face validation with guideline developers); (2) document analysis (duplicate) of seven existing guideline tools to measure coverage of GLAFI items and identify new items; and (3) an international survey of guideline developers (corresponding authors of recent Canadian Medical Association or Guidelines International Network database guidelines) to measure perceived importance of language and format, quality of existing resources, and usefulness of a language and format tool. Results GLAFI items were organized into 4 language and 4 format subdomains. In face validation with guideline developers (17 clinicians, 1 methodologist), all agreed that the tool would improve guideline implementability and 93% indicated a desire for regular use. In the existing guideline tool document analysis, only 14/44 (31.8%) GLAFI items were operationalized in at least one tool. We received survey responses from 148/674 (22.0%) contacted guideline authors representing 45 organizations (9 countries). Language was rated as “extremely important” or “important” in determining uptake by 94% of respondents, and format by 84%. Correspondingly, 72% and 70% indicated that their organization would likely use such a tool. Conclusions Optimal language and format are fundamental to guideline implementability but often overlooked. The GLAFI tool operationalizes evidence-based constructs, most of which are absent in existing guideline tools. Guideline developers perceive these concepts to be important and express a willingness to use such a tool. The GLAFI should be further tested and refined with guideline developers and its impact on end-users measured.

Introduction: Chemoradiotherapy (CRT) with concurrent cisplatin-based chemotherapy is the treatment of choice of locally advanced head and neck cancers (LAHNC), but the optimal regimen of cisplatin remains contentious. Though 3-weekly cisplatin is the recommended schedule, it is associated with severe adverse reactions. A lower dose weekly schedule is generally accepted to be more tolerable and is widely used in our country. Methodology: Our study retrospectively compares the 3-weekly and the weekly concurrent cisplatin schedules in patients of LAHNC treated with CRT. Patients were selected for either schedule based on the treating physician’s preference. The two schedules were compared for treatment-related toxicities, radiotherapy interruptions, cumulative cisplatin doses delivered and overall survival (OS) as well as disease-free survival (DFS) at 2 years. Results: In our study, 43 patients received the 3-weekly schedule while 40 received the weekly schedule. Age, gender, disease stage or site did not affect selection for either regimen, except cancers of the nasopharynx and salivary glands, who almost exclusively received the 3-weekly schedule (90.1%). Patients who received adjuvant CRT after radical surgery were more likely to receive the weekly schedule (66.7%) while patients treated with up-front CRT were more often given the 3-weekly schedule (57.6%). Overall, the 3-weekly arm was associated with more toxicities and treatment breaks, but was more successful in delivering an adequate cumulative dose of cisplatin and had a better OS and DFS at 2 years follow up compared to the weekly arm. It also appeared that treating physicians were more likely to withhold one or more of the weekly cycles to manage treatment toxicity which lead to inadequate cumulative dosing in a high (45%) percentage of patients. Conclusion: Our study reiterates that the 3-weekly cisplatin arm has a better outcome profile than the weekly cisplatin arm at the price of increased toxicity. Weekly schedules have lower toxicities but may not achieve outcomes equivalent to 3-weekly unless adequate cumulative doses are achieved. As our study is retrospective and non-randomized, selection bias may have affected our results.

Abstract Background Computerized clinical decision support systems (CDSSs) are a promising knowledge translation tool, but often fail to meaningfully influence the outcomes they target. Low CDSS provider uptake is a potential contributor to this problem but has not been systematically studied. The objective of this systematic review and meta-regression was to determine reported CDSS uptake and identify which CDSS features may influence uptake. Methods Medline, Embase, CINAHL, and the Cochrane Database of Controlled Trials were searched from January 2000 to August 2020. Randomized, non-randomized, and quasi-experimental trials reporting CDSS uptake in any patient population or setting were included. The main outcome extracted was CDSS uptake, reported as a raw proportion, and representing the number of times the CDSS was used or accessed over the total number of times it could have been interacted with. We also extracted context, content, system, and implementation features that might influence uptake, for each CDSS. Overall weighted uptake was calculated using random-effects meta-analysis and determinants of uptake were investigated using multivariable meta-regression. Results Among 7995 citations screened, 55 studies involving 373,608 patients and 3607 providers met full inclusion criteria. Meta-analysis revealed that overall CDSS uptake was 34.2% (95% CI 23.2 to 47.1%). Uptake was only reported in 12.4% of studies that otherwise met inclusion criteria. Multivariable meta-regression revealed the following factors significantly associated with uptake: (1) formally evaluating the availability and quality of the patient data needed to inform CDSS advice; and (2) identifying and addressing other barriers to the behaviour change targeted by the CDSS. Conclusions and relevance System uptake was seldom reported in CDSS trials. When reported, uptake was low. This represents a major and potentially modifiable barrier to overall CDSS effectiveness. We found that features relating to CDSS context and implementation strategy best predicted uptake. Future studies should measure the impact of addressing these features as part of the CDSS implementation strategy. Uptake reporting must also become standard in future studies reporting CDSS intervention effects. Registration Pre-registered on PROSPERO, CRD42018092337

Background and Aims: There is a lack of convenient, sensitive, noninvasive strategies for screening and surveillance for colorectal neoplasia. An assay combining the results of circulating epithelial cells (CECs) and somatic mutations of cell-free DNA adjusting for age/sex using a unique algorithm is evaluated in patients requiring colonoscopy. Methods: A prospective single-site 458-subject study (asymptomatic: 43% screening/43% surveillance, enriched with 65 symptomatic subjects undergoing colonoscopy) was conducted. The test analyzed CECs and somatic mutations. The probability of advanced neoplasia (advanced adenoma [AA] and CRCs) was determined by logistic regression methods adjusted for expected CRC incidence rate, prior history of AA, and patient age and sex on a training subset. A linear predictor was developed to generate a score scaled from 0 to 100. The test performance was evaluated on an independent set of subjects using prespecified algorithms and cut point. Results: Based on a predefined clinical threshold and predictive model derived from the training set (n = 232), analysis of an independent asymptomatic validation set (n = 194) yielded 89% (lower exact one-sided 95% confidence interval [CI]: 80%) specificity and 100% (95% CI: 37%)/78% (95% CI: 61%) sensitivity for detection of CRC/AA. In a secondary analysis, excluding surveillance subjects, the 97-subject screening cohort yielded 91% (95% CI: 79%) specificity and CRC/AA sensitivity at 100% (95% CI: 37%)/83% (95% CI: 56%, 87% for advanced neoplasia 95% CI: 64%). Significant associations (P < .0001) were detected between FirstSight scores and adenoma size, number, and ordinally increasing pathology classification. Conclusion: A multimodal blood test that included CECs and somatic mutations with adjustment for age and sex demonstrated high sensitivity for the diagnosis of advanced colorectal neoplasia. The resulting score captures prognostic information for CRC progression of index adenoma size and number and has the potential to enable stratification of patients for screening or postpolypectomy surveillance colonoscopy.

Abstract Background Chronic obstructive pulmonary disease (COPD) causes 3 million deaths each year, yet 38% of COPD patients continue to smoke. Despite proof of effectiveness and universal guideline recommendations, smoking cessation interventions are underused in practice. We sought to develop an infographic featuring personalized biomedical risk assessment through future lung function decline prediction (with vs without ongoing smoking) to both prompt and enhance clinician delivery of smoking cessation advice and pharmacotherapy, and augment patient motivation to quit. Methods We recruited patients with COPD and pulmonologists from a quaternary care center in Toronto, Canada. Infographic prototype content and design was based on best evidence. After face validation, the prototype was optimized through rapid-cycle design. Each cycle consisted of: (1) infographic testing in a moderated focus group and a clinician interview (recorded/transcribed) (with questionnaire completion); (2) review of transcripts for emergent/critical findings; and (3) infographic modifications to address findings (until no new critical findings emerged). We performed iterative transcript analysis after each cycle and a summative qualitative transcript analysis with quantitative (descriptive) questionnaire analysis. Results Stopping criteria were met after 4 cycles, involving 20 patients (58% male) and 4 pulmonologists (50% male). The following qualitative themes emerged: Tool content (infographic content preferences); Tool Design (infographic design preferences); Advantages of Infographic Messaging (benefits of an infographic over other approaches); Impact of Tool on Determinants of Smoking Cessation Advice Delivery (impact on barriers and enablers to delivery of smoking cessation advice in practice); and Barriers and Enablers to Quitting (impact on barriers and enablers to quitting). Patient Likert scale ratings of infographic content and format/usability were highly positive, with improvements in scores for 20/21 questions through the design process. Providers scored the infographic at 77.8% (“superior”) on the Suitability Assessment of Materials questionnaire. Conclusions We developed a user preference-based personalized biomedical risk assessment infographic to drive smoking cessation in patients with COPD. Our findings suggest that this tool could impact behavioural determinants of provider smoking-cessation advice delivery, while increasing patient quit motivation. Impacts of the tool on provider care, patient motivation to quit, and smoking cessation success should now be evaluated in real-world settings.

BackgroundAsthma is a chronic respiratory disease that poses a substantial burden on individuals and the health care system. Despite published national guidelines for the diagnosis and management of asthma, considerable care gaps exist. Suboptimal adherence to asthma diagnosis and management guidelines contributes to poor patient outcomes. The integration of electronic tools (eTools) into electronic medical records (EMRs) represents a knowledge translation opportunity to support best practices. ObjectiveThe purpose of this study was to determine how best to integrate evidence-based asthma eTools into primary care EMRs across Ontario and Canada to improve adherence to guidelines as well as measure and monitor performance. MethodsIn total, 2 focus groups comprising physicians and allied health professionals who were considered experts in primary care, asthma, and EMRs were convened. One focus group also included a patient participant. Focus groups used a semistructured discussion-based format to consider the optimal methods for integrating asthma eTools into EMRs. Discussions were held on the web via Microsoft Teams (Microsoft Corp). The first focus group discussed integrating asthma indicators into EMRs using eTools, and participants completed a questionnaire evaluating the clarity, relevance, and feasibility of collecting asthma performance indicator data at the point of care. The second focus group addressed how to incorporate eTools for asthma into a primary care setting and included a questionnaire evaluating the perceived utility of various eTools. Focus group discussions were recorded and analyzed using thematic qualitative analysis. The responses to focus group questionnaires were assessed using descriptive quantitative analysis. ResultsQualitative analysis of the 2 focus group discussions revealed 7 key themes: designing outcome-oriented tools, gaining stakeholder trust, facilitating open lines of communication, prioritizing the end user, striving for efficiency, ensuring adaptability, and developing within existing workflows. In addition, 24 asthma indicators were rated according to clarity, relevance, feasibility, and overall usefulness. In total, 5 asthma performance indicators were identified as the most relevant. These included smoking cessation support, monitoring using objective measures, the number of emergency department visits and hospitalizations, assessment of asthma control, and presence of an asthma action plan. The eTool questionnaire responses revealed that the Asthma Action Plan Wizard and Electronic Asthma Quality of Life Questionnaire were perceived to be the most useful in primary care. ConclusionsPrimary care physicians, allied health professionals, and patients consider that eTools for asthma care present a unique opportunity to improve adherence to best-practice guidelines in primary care and collect performance indicators. The strategies and themes identified in this study can be leveraged to overcome barriers associated with asthma eTool integration into primary care EMRs. The most beneficial indicators and eTools, along with the key themes identified, will guide future asthma eTool implementation.

For meiosis I, homologous chromosomes must be paired into bivalents. Maintenance of homolog conjunction in bivalents until anaphase I depends on crossovers in canonical meiosis. However, instead of crossovers, an alternative system achieves homolog conjunction during the achiasmate male meiosis of Drosophila melanogaster. The proteins SNM, UNO and MNM are likely constituents of a physical linkage that conjoins homologs in D. melanogaster spermatocytes. Here, we report that SNM binds tightly to the C-terminal region of UNO. This interaction is homologous to that of the cohesin subunits stromalin/Scc3/STAG and α-kleisin, as revealed by sequence similarities, structure modeling and cross-link mass spectrometry. Importantly, purified SU_C, the heterodimeric complex of SNM and the C-terminal region of UNO, displayed DNA-binding in vitro. DNA-binding was severely impaired by mutational elimination of positively charged residues from the C-terminal helix of UNO. Phenotypic analyses in flies fully confirmed the physiological relevance of this basic helix for chromosome-binding and homolog conjunction during male meiosis. Beyond DNA, SU_C also bound MNM, one of many isoforms expressed from the complex mod(mdg4) locus. This binding of MNM to SU_C was mediated by the MNM-specific C-terminal region, while the purified N-terminal part common to all Mod(mdg4) isoforms multimerized into hexamers in vitro. Similarly, the UNO N-terminal domain formed tetramers in vitro. Thus, we suggest that multimerization confers to SUM, the assemblies composed of SNM, UNO and MNM, the capacity to conjoin homologous chromosomes stably by the resultant multivalent DNA-binding. Moreover, to permit homolog separation during anaphase I, SUM is dissociated by separase, since UNO, the α-kleisin-related protein, includes a separase cleavage site. In support of this proposal, we demonstrate that UNO cleavage by tobacco etch virus protease is sufficient to release homolog conjunction in vivo after mutational exchange of the separase cleavage site with that of the bio-orthogonal protease.

Abstract Background The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia—an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients. Methods We propose a randomized controlled crossover trial in patients with moderate HPS (PaO2 < 80 mmHg) and orthodeoxia (supine to upright PaO2 decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70–85% of the predicted peak work rate until the “stopping time” is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects. P < 0.05 will be considered statistically significant. Discussion HPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes. Trial registration ClinicalTrials.gov Protocol Registration and Results System (PRS) NCT04004104 . Registered on 1 July 2019

Meiosis in males of higher dipterans is achiasmate. In their spermatocytes, pairing of homologs into bivalent chromosomes does not include synaptonemal complex and crossover formation. While crossovers preserve homolog conjunction until anaphase I during canonical meiosis, an alternative system is used in dipteran males. Mutant screening in Drosophila melanogaster has identified teflon (tef) as being required specifically for alternative homolog conjunction (AHC) of autosomal bivalents. The additional known AHC genes, snm, uno and mnm, are needed for the conjunction of autosomal homologs and of sex chromosomes. Here, we have analyzed the pattern of TEF protein expression. TEF is present in early spermatocytes but cannot be detected on bivalents at the onset of the first meiotic division, in contrast to SNM, UNO and MNM (SUM). TEF binds to polytene chromosomes in larval salivary glands, recruits MNM by direct interaction and thereby, indirectly, also SNM and UNO. However, chromosomal SUM association is not entirely dependent on TEF, and residual autosome conjunction occurs in tef null mutant spermatocytes. The higher tef requirement for autosomal conjunction is likely linked to the quantitative difference in the amount of SUM protein that provides conjunction of autosomes and sex chromosomes, respectively. During normal meiosis, SUM proteins are far more abundant on sex chromosomes compared to autosomes. Beyond promoting SUM recruitment, TEF has a stabilizing effect on SUM proteins. Increased SUM causes excess conjunction and consequential chromosome missegregation during meiosis I after co-overexpression. Similarly, expression of SUM without TEF, and even more potently with TEF, interferes with chromosome segregation during anaphase of mitotic divisions in somatic cells, suggesting that the known AHC proteins are sufficient for establishment of ectopic chromosome conjunction. Overall, our findings suggest that TEF promotes alternative homolog conjunction during male meiosis without being part of the final physical linkage between chromosomes.

Abstract Cancer is the second leading cause of death in the United States. Although screening facilitates prevention and early detection and is one of the most effective approaches to reducing cancer mortality, participation is low—particularly among underserved populations. In a large, preregistered field experiment (n = 7711), we tested whether deadlines—both with and without monetary incentives tied to them—increase colorectal cancer (CRC) screening. We found that all screening invitations with an imposed deadline increased completion, ranging from 2.5% to 7.3% relative to control (ps

Abstract Background The Baby-OSCAR trial is a multi-centre, randomised, placebo-controlled parallel group trial of early treatment of large patent ductus arteriosus (PDA) with ibuprofen in extremely preterm infants. This paper describes the statistical analysis plan for the short-term health outcomes of the Baby-OSCAR trial. Methods and design This is a randomised controlled trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies improves short and long-term health and economic outcomes. Infants born between 23+0 and 28+6 weeks of gestation, confirmed by echocardiography as having a large PDA (with a diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern), with parental informed consent, were randomly allocated to receive either ibuprofen or placebo within 72 h of birth. The primary outcome is a composite of death by 36 weeks’ postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age. Results Baseline demographic and clinical characteristics will be described by randomised group. The primary analysis will be on the modified intention to treat (ITT) population. Counts and percentages will be presented for binary and categorical variables, and mean and standard deviation or median and interquartile range will be presented for continuous variables. For binary outcomes, risk ratios and confidence intervals will be calculated using log binomial or Poisson regression with a robust variance estimator. Continuous outcomes will be analysed using linear regression models, or quantile regression models if skewed. Analyses will be adjusted for all minimisation factors where technically possible, and correlation between siblings from multiple births will be accounted for by nesting the clusters as a random effect. Both crude and adjusted effect estimates will be presented, with the primary inference based on the adjusted estimates. Ninety-five per cent confidence intervals will be used for all pre-specified outcome comparisons. Conclusion This paper describes the statistical analysis plan for short-term health outcomes of the trial, including the analysis principles, definitions of important outcomes, methods for primary analysis, pre-specified subgroup analysis, and secondary analysis. The plan was finalised prior to completion of short-term follow-up. Trial registration ISRCTN registry ISRCTN84264977 . Registered on 15 September 2010.

Abstract Background The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks’ gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. Methods This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0–28+ 6 weeks’ gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0–28+ 6 weeks’ gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks’ postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Discussion Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks’ postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. Trial registration ISRCTN84264977 . Date assigned: 15/09/2010.

Abstract Background Screening for suicidal ideation in high-risk groups such as U.S. veterans is crucial for early detection and suicide prevention. Currently, screening is based on clinical interviews or self-report measures. Both approaches rely on subjects to disclose their suicidal thoughts. Innovative approaches are necessary to develop objective and clinically applicable assessments. Speech has been investigated as an objective marker to understand various mental states including suicidal ideation. In this work, we developed a machine learning and natural language processing classifier based on speech markers to screen for suicidal ideation in US veterans. Methodology Veterans submitted 588 narrative audio recordings via a mobile app in a real-life setting. In addition, participants completed self-report psychiatric scales and questionnaires. Recordings were analyzed to extract voice characteristics including prosodic, phonation, and glottal. The audios were also transcribed to extract textual features for linguistic analysis. We evaluated the acoustic and linguistic features using both statistical significance and ensemble feature selection. We also examined the performance of different machine learning algorithms on multiple combinations of features to classify suicidal and non-suicidal audios. Results A combined set of 15 acoustic and linguistic features of speech were identified by the ensemble feature selection. Random Forest classifier, using the selected set of features, correctly identified suicidal ideation in veterans with 86% sensitivity, 70% specificity, and an area under the receiver operating characteristic curve (AUC) of 80%. Conclusions Speech analysis of audios collected from veterans in everyday life settings using smartphones offers a promising approach for suicidal ideation detection. A machine learning classifier may eventually help clinicians identify and monitor high-risk veterans.

Objective To examine rates of vaccine hesitancy and their correlates among Canadian adults between April 2020 and March 2021.Design Five sequential cross-sectional age, sex and province-weighted population-based samples who completed online surveys.Setting Canada.Participants A total of 15 019 Canadians aged 18 years and over were recruited through a recognised polling firm (Leger Opinion). Respondents were 51.5% female with a mean age of 48.1 (SD 17.2) years (range 18–95 years) and predominantly white (80.8%).Primary and secondary outcome measures Rates of vaccine hesitancy over the five surveys (time points) and their sociodemographic, clinical and psychological correlates.Results A total of 42.2% of respondents reported some degree of vaccine hesitancy, which was lowest during surveys 1 (April 2020) and 5 (March 2021) and highest during survey 3 (November 2020). Fully adjusted multivariate logistic regression analyses revealed that women, those aged 50 and younger, non-white, those with high school education or less, and those with annual household incomes below the poverty line in Canada were significantly more likely to report vaccine hesitancy, as were essential and healthcare workers, parents of children under the age of 18 and those who do not get regular influenza vaccines. Endorsing prevention behaviours as important for reducing virus transmission and high COVID-19 health concerns were associated with 77% and 54% reduction in vaccine hesitancy, respectively. Having high personal financial concerns was associated with 1.33 times increased odds of vaccine hesitancy.Conclusions Results highlight the importance of targeting vaccine efforts to specific groups by emphasising the outsized health benefits compared with risks of vaccination. Future research should monitor changes in vaccine intentions and behaviour to better understand underlying factors.

BackgroundElectrical biosensing technology (EBT) is an umbrella term for non-invasive technology utilizing the body’s fluctuating resistance to electrical current flow to estimate cardiac output. Monitoring cardiac output in neonates may allow for timely recognition of hemodynamic compromise and allow for prompt therapy, thereby mitigating adverse outcomes. For a new technology to be safely used in the clinical environment for therapeutic decisions, it must be proven to be accurate, precise and be able to track temporal changes. The aim of this systematic review was to identify and analyze studies that describe the accuracy, precision, and trending ability of EBT to non-invasively monitor Left ventricular cardiac output and/or stroke volume in neonates.MethodsA qualitative systematic review was performed. Studies were identified from PubMed NCBI, SCOPUS, and EBSCOHost up to November 2021, where EBT technologies were analyzed in neonates, in comparison to a reference technology. Outcome measures were bias, limits of agreement, percentage error for agreement studies and data from 4-quadrant and polar plots for trending studies. Effect direction plots were used to present results.ResultsFifteen neonatal studies were identified, 14 for agreement and 1 for trending analysis. Only thoracic electrical biosensing technology (TEBT), with transthoracic echocardiography (TTE) as the comparator, studies were available for analyzes. High heterogeneity existed between studies. An equal number of studies showed over- and underestimation of left ventricular output parameters. All studies showed small bias, wide limits of agreement, with most studies having a percentage error >30%. Sub-analyses for respiratory support mode, cardiac anomalies and type of technology showed similar results. The single trending study showed poor concordance, high angular bias, and poor angular concordance.DiscussionOverall, TEBT shows reasonable accuracy, poor precision, and non-interchangeability with TTE. However, high heterogeneity hampered proper analysis. TEBT should be used with caution in the neonatal population for monitoring and determining therapeutic interventions. The use of TEBT trend monitoring has not been sufficiently studied and requires further evaluation in future trials.

Summary: Adult stem cells and their transit-amplifying progeny alter their proliferation rates to maintain tissue homeostasis. To test how the division rates of stem cells and transit-amplifying progeny affect tissue growth and differentiation, we developed a computation strategy that estimates the average cell-cycle lengths (lifespans) of germline stem cells and their progeny from fixed-tissue demography in the Drosophila testis. Analysis of the wild-type data using this method indicated that during the germline transit-amplification, the cellular lifespans extend by nearly 1.3-fold after the first division and shrink by about 2-folds after the second division. Cell-autonomous perturbations of the stem cell lifespan accordingly altered the lifespans of successive transit-amplifying stages. Remarkably, almost 2-fold alterations in the lifespans of stem cells and their immediate daughters did not affect the subsequent differentiation. The results indicate that the early germline division rates can adjust the following division rates and the onset of differentiation.

Background: Studies have identified health literacy (HL) as an important determinant of asthma and chronic obstructive pulmonary disease (COPD) management. There are, however, limited data on patients' and health care professionals (HCPs') insights about the link between HL and management of asthma and COPD. Objective: The aim of this study was to elicit patients' and HCPs' perspectives with respect to factors affecting HL in the context of asthma and COPD management. Methods: A total of 16 semi-structured focus groups (10 in English and 6 in French) with patients with asthma or COPD (n = 93) and 45 interviews with HCPs, researchers, and policymakers were conducted between June 2015 and April 2017. Participants were asked to share their perspectives with respect to five predefined HL domains—accessing, understanding, evaluating, communicating, and using health-related information—in relation to disease self-management practices. Data were analyzed qualitatively, using a content analysis approach. Key Results: Most patients and HCPs reflected on factors hampering HL in relation to asthma and COPD management. Thoughts such as “not having enough time during medical consultations,” “not receiving consistent messages from different health care professionals,” and “language or cultural differences” were frequently mentioned by both patients and HCPs. Conclusions: We identified multiple factors affecting communication between patients and HCPs as it relates to the self-management of their disease. These included inconsistent messages from different providers, limited consultation time, use of technical language, failure to account for cultural differences, and reduced health literacy, especially as it related to written communication. Future interventions that aim to enhance HL skills in the context of asthma and COPD self-management should consider these issues. [HLRP: Health Literacy Research and Practice. 2021;5(3):e179–e193.] Plain Language Summary: The current study advances the health literacy (HL) knowledge base by adding patients' and health care professionals' valuable insights on factors that hamper or facilitate HL in relation to asthma and chronic obstructive pulmonary disease (COPD) management. An important insight from this study is that receiving conflicting information from different health care professional's hampers HL in patients with asthma and/or COPD.

Background Breathe is a mobile health (mHealth) application developed for the self-management of asthma in adults. There is evidence to suggest that mHealth interventions can be used for asthma control; however, their effects on the use of health services remain poorly understood. We sought to determine whether Breathe reduces health services use amongst asthma patients who used the app compared to controls who did not. Methods The impact of Breathe on health services use was estimated using a quasi-experimental approach. Two groups of subjects who had participated in a previous randomised clinical trial were included: an intervention group of asthma patients who used the app for 12 months, and a group of controls who did not use the app but received equivalent quality asthma care. A third, external control group of asthma patients were matched to the intervention participants. Generalised linear mixed models were used to determine relative changes in rates of asthma hospitalisations, emergency department (ED) visits, outpatient physician visits and completion of pulmonary function tests (PFTs) over time. Results A total of 677 individuals with asthma were included in the study: 132 in the intervention group, and 149 and 396 in the internal and external control groups, respectively. There were no statistically significant differences in the change of asthma hospitalisations, ED visits, physician office visits or completion of PFTs between the intervention group and either control group. Conclusions Use of the Breathe app is not associated with changes in health services use in adults with asthma.

Latino adults are more likely to be diagnosed with colorectal cancer (CRC) at later stages compared to white adults which may be explained by disparities in screening rates. The aim of this study was to examine factors associated with three CRC screening indicators [i.e., 1) any CRC screening ever (via, fecal occult blood test (FOBT), sigmoidoscopy, or colonoscopy); 2) FOBT in last year, 3) sigmoidoscopy/colonoscopy in last 10 years) among US Hispanics/Latinos. We analyzed population-based data collected in 2008–2011 from 2265 adults aged 50–75 from San Diego, Bronx, Miami and Chicago from the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Based on the Behavioral Model of Health Services Use, the following correlates of CRC screening were examined: predisposing (i.e., age, education, income, acculturation), enabling (i.e., recent physician visit, insurance, recent mammogram), and need (i.e., health-related quality of life and family/personal history of cancer) factors. Separate logistic regression models were analyzed for the three CRC screening indicators. Enabling factors associated with all CRC screening indicators included: health insurance, a recent physician visit, and a mammogram in the last year (women only). For women, being older, more acculturated (i.e., English language or foreign-born but in the US for 10 or more years), and having a personal history of cancer was associated with at least one CRC screening. Findings suggest that improving access and utilization of care among Hispanics/Latinos may be critical for earlier CRC diagnosis and survival. Keywords: Cancer, Early detection of cancer, Behavioral medicine, Epidemiology

Objective To conduct an anatomic site-specific case–control study of candidate colorectal cancer (CRC) risk factors.Design Case–control study of US veterans with >1 colonoscopy during 1999–2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.Results 21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).Conclusion Candidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

The success of large-scale COVID-19 vaccination campaigns is contingent upon people being willing to receive the vaccine. Our study explored COVID-19 vaccine hesitancy and its correlates in eight different countries around the globe. We analyzed convenience sample data collected between March 2020 and January 2021 as part of the iCARE cross-sectional study. Univariate and multivariate statistical analyses were conducted to explore the correlates of vaccine hesitancy. We included 32,028 participants from eight countries, and observed that 27% of the participants exhibited vaccine hesitancy, with increases over time. France reported the highest level of hesitancy (47.3%) and Brazil reported the lowest (9.6%). Women, younger individuals (≤29 years), people living in rural areas, and those with a lower perceived income were more likely to be hesitant. People who previously received an influenza vaccine were 70% less likely to report COVID-19 vaccine hesitancy. We observed that people reporting greater COVID-19 health concerns were less likely to be hesitant, whereas people with higher personal financial concerns were more likely to be hesitant. Our findings indicate that there is substantial vaccine hesitancy in several countries, with cross-national differences in the magnitude and direction of the trend. Vaccination communication initiatives should target hesitant individuals (women, younger adults, people with lower incomes and those living in rural areas), and should highlight the immediate health, social and economic benefits of vaccination across these settings. Country-level analyses are warranted to understand the complex psychological, socio-environmental, and cultural factors associated with vaccine hesitancy.

Assess whether receipt of tailored printouts generated by the Cancer Risk Intake System (CRIS) – a touch-screen computer program that collects data from patients and generates printouts for patients and physicians – results in more reported patient-provider discussions about colorectal cancer (CRC) risk and screening than receipt of non-tailored information.Cluster-randomized trial, randomized by physician, with data collected via CRIS prior to visit and 2-week follow-up telephone survey among 623 patients.Patients aged 25–75 with upcoming primary-care visits and eligible for, but currently non-adherent to CRC screening guidelines.Patient-reported discussions with providers about CRC risk and testing.Tailored recipients were more likely to report patient-physician discussions about personal and familial risk, stool testing, and colonoscopy (all p

Lung cancer is one of the most common cancers in the world affecting both men and woman. Common site of metastasis includes liver, adrenals, bone, and brain. Metastasis to the maxilla is very rare with only a few cases being reported so far. Here, we present a case of a 32-year-old male where metastatic lesion was discovered before primary tumor.

Tight junctions prevent paracellular flow and maintain cell polarity in an epithelium. These junctions are also required for maintaining the blood-testis barrier, which is essential for sperm differentiation. Septate junctions in insects are orthologous to the tight junctions. In Drosophila testis, major septate junction components co-localize at the interface of germline and somatic cells initially, and then condense between the two somatic cells in a cyst after germline meiosis. Their localization is extensively remodeled in subsequent stages. We find that characteristic septate junctions are formed between the somatic cyst cells at the elongated spermatid stage. Consistent with previous reports, knockdown of essential junctional components – Discs-large-1 and Neurexin-IV – during the early stages disrupted sperm differentiation beyond the spermatocyte stage. Knockdown of these proteins during the final stages of spermatid maturation caused premature release of spermatids inside the testes, resulting in partial loss of male fertility. These results indicate the importance of maintaining the integrity of the somatic enclosure during spermatid coiling and release in Drosophila testis. It also highlights the functional similarity with the tight junction proteins during mammalian spermatogenesis. This article has an associated First Person interview with the first author of the paper.

Transit amplification (TA) of progenitor cells maintains tissue homeostasis by balancing proliferation and differentiation. In Drosophila testis, the germline proliferation is tightly regulated by factors present in both the germline and the neighbouring somatic cyst cells (SCCs). Although the exact mechanism is unclear, the epidermal growth factor receptor (EGFR) activation in SCCs has been reported to control spermatogonial divisions within a cyst, through downstream activations of Rac1-dependent pathways. Here, we report that somatic activation of the mitogen-activated protein kinase (Rolled/ERK) downstream of EGFR is required to synchronize the mitotic divisions and regulate the transition to meiosis. The process operates independently of the Bag-of-marble activity in the germline. Also, the integrity of the somatic cyst enclosure is inessential for this purpose. Together, these results suggest that synchronization of germ-cell divisions through somatic activation of distinct ERK-downstream targets independently regulates TA and subsequent differentiation of neighbouring germline cells.

BACKGROUND: Evidence-based, guideline-recommended practices improve multiple outcomes in patients admitted with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), but are incompletely implemented in actual practice. Admission order sets with evidence-based diagnostic and therapeutic guidance have enabled quality improvement and guideline implementation in other conditions.

Introduction: Pathophysiology of pneumonia involves leakage of plasma proteins into the airways and accumulation of cytokines within the lung. Several in vitro and in vivo studies have demonstrated that this proteinaceous material and lung inflammation inhibit surfactant function. Aim: To evaluate whether exogenous surfactant therapy improves oxygenation and gas exchange in late preterm and term neonates with early onset pneumonia and respiratory failure. Materials and Methods: This prospective interventional cohort study was conducted at a tertiary care neonatal unit. Twenty four late preterm and term neonates with early onset pneumonia requiring mechanical ventilation for respiratory failure were included and received surfactant therapy. Oxygenation index, arterial/alveolar PO2 (a/A ratio), mean airway pressure and fraction of inspired oxygen were calculated from arterial blood gases obtained before and after surfactant therapy. Wilcoxon signed rank sum test was used for assessment of change in oxygenation variables 12 hours after surfactant therapy. Data regarding clinical outcomes and complications were collected and analysed. Results: Just over half (54.2%) of the study neonates were of term gestation. After surfactant therapy, the median Oxygenation Index (OI) decreased from 11.15 to 3.7 at one hour and the change was sustained and significant at 12 hours (p

BACKGROUND: Asthma is a common chronic condition. Work-related asthma (WRA) has a large socioeconomic impact and is increasing in prevalence but remains under-recognized. Although international guidelines recommend patient education, no widely available educational tool exists.

BACKGROUND: Implementation of current clinical practice guidelines in asthma and chronic obstructive pulmonary disease (COPD) is suboptimal. New implementation strategies should be developed and evaluated.