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INTRODUCTION: We know little about the evolution of perihaematomal oedema (PHO) >24 h after ICH onset. We aimed to determine the trajectory of PHO after ICH onset and its association with outcome. METHODS: We did a prospective cohort study using a pre-specified scanning protocol in adults with first-ever spontaneous ICH and measured absolute PHO volumes on CT head scans at ICH diagnosis and 3 ± 2, 7 ± 2, and 14 ± 2 days after ICH onset. We used the largest ICH if ICHs were multiple. The primary outcomes were (a) the trajectory of PHO after ICH onset and (b) the association between PHO (absolute volume at the time when most repeat CT head scans were obtained, and change in PHO volume at this time compared with the first CT head scan) and poor functional outcome (modified Rankin scale 3-6 at 90 days). We pre-specified multivariable logistic regression models of this association adjusting analyses for potential confounders: age, GCS, infratentorial ICH location, and intraventricular extension. RESULTS: In 106 participants of whom 49 (46%) were female, with a median ICH volume 7 mL (interquartile range [IQR] 2-22 mL), the trajectory of median PHO volume increased from 14 mL (IQR: 7-26 mL) at diagnosis to 18 mL (IQR: 8-40 mL) at 3 ± 2 days (n = 87), 20 mL (IQR: 8-48 mL) at 7 ± 2 days (n = 93) and 21 mL (IQR: 10-54 mL) at 14 ± 2 days (n = 78) (p = <0.001). PHO volume at each time point was collinear with ICH volume at diagnosis (ârâ >0.7), but the change in PHO volume between diagnosis and each time point was not. Given collinearity, we used total lesion (i.e., ICH + PHO) volume instead of PHO volume in a logistic regression model of its association at each time point with outcome. Increasing total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome (adjusted OR per mL 1.02, 95% CI: 1.00-1.03; p = 0.036), but the increase in PHO volume between diagnosis and day 7 ± 2 was not associated with poor functional outcome (adjusted OR per mL 1.03, 95% CI: 0.99-1.07; p = 0.132). CONCLUSION: PHO volume increases throughout the first 2 weeks after onset of mild to moderate ICH. Total lesion (ICH + PHO) volume at day 7 ± 2 was associated with poor functional outcome, but the change in PHO volume between diagnosis and day 7 ± 2 was not. Prospective cohort studies with larger sample sizes are needed to investigate these associations and their modifiers.
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OBJECTIVES: Nasal, paranasal sinus and mucosal disorders are common symptoms in autoimmune rheumatic diseases. Soft tissue changes and fluid accumulation in the osteomeatal complexes and paranasal sinuses manifest as opaqueness on radiological images which can be assessed using visual scoring and computational methods on CT scans, but their results do not always correlate. Using MRI, we investigate the applicability of different image analysis methods in SLE. METHODS: We assessed paranasal sinus opaqueness on MRI from 51 SLE patients, using three visual scoring systems and expert-delineated computational volumes, and examined their association with markers of disease activity, inflammation, endothelial dysfunction and common small vessel disease (SVD) indicators, adjusting for age and sex-at-birth. RESULTS: The average paranasal sinus volume occupation was 4.55 (6.47%) [median (interquartile range) = 0.67 (0.25-2.65) ml], mainly in the maxillary and ethmoid sinuses. It was highly correlated with Lund-Mackay (LM) scores modified at 50% opaqueness cut-off (Spearman's ρ: 0.71 maxillary and 0.618 ethmoids, P < 0.001 in all), and with more granular variations of the LM system. The modified LM scores were associated with SVD scores (0: B = 5.078, s.e. = 1.69, P = 0.0026; 2: B = -0.066, s.e. = 0.023, P = 0.0045) and disease activity (anti-dsDNA: B = 4.59, s.e. = 2.22, P = 0.045; SLEDAI 3-7: 2.86 < B < 4.30; 1.38 < s.e. < 1.63; 0.0083 ≤ P ≤ 0.0375). Computationally derived percent opaqueness yielded similar results. CONCLUSION: In patients with SLE, MRI computational assessment of sinuses opaqueness and LM scores modified at a 50% cut-off may be useful tools in understanding the relationships among paranasal sinus occupancy, disease activity and SVD markers.
Subject(s)
Autoimmune Diseases , Lupus Erythematosus, Systemic , Paranasal Sinuses , Sinusitis , Humans , Chronic Disease , Paranasal Sinuses/diagnostic imaging , Paranasal Sinuses/pathology , Magnetic Resonance Imaging , Autoimmune Diseases/pathology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnostic imaging , Lupus Erythematosus, Systemic/pathologyABSTRACT
Background: Natural language processing (NLP) has the potential to automate the reading of radiology reports, but there is a need to demonstrate that NLP methods are adaptable and reliable for use in real-world clinical applications. Methods: We tested the F1 score, precision, and recall to compare NLP tools on a cohort from a study on delirium using images and radiology reports from NHS Fife and a population-based cohort (Generation Scotland) that spans multiple National Health Service health boards. We compared four off-the-shelf rule-based and neural NLP tools (namely, EdIE-R, ALARM+, ESPRESSO, and Sem-EHR) and reported on their performance for three cerebrovascular phenotypes, namely, ischaemic stroke, small vessel disease (SVD), and atrophy. Clinical experts from the EdIE-R team defined phenotypes using labelling techniques developed in the development of EdIE-R, in conjunction with an expert researcher who read underlying images. Results: EdIE-R obtained the highest F1 score in both cohorts for ischaemic stroke, ≥93%, followed by ALARM+, ≥87%. The F1 score of ESPRESSO was ≥74%, whilst that of Sem-EHR is ≥66%, although ESPRESSO had the highest precision in both cohorts, 90% and 98%. For F1 scores for SVD, EdIE-R scored ≥98% and ALARM+ ≥90%. ESPRESSO scored lowest with ≥77% and Sem-EHR ≥81%. In NHS Fife, F1 scores for atrophy by EdIE-R and ALARM+ were 99%, dropping in Generation Scotland to 96% for EdIE-R and 91% for ALARM+. Sem-EHR performed lowest for atrophy at 89% in NHS Fife and 73% in Generation Scotland. When comparing NLP tool output with brain image reads using F1 scores, ALARM+ scored 80%, outperforming EdIE-R at 66% in ischaemic stroke. For SVD, EdIE-R performed best, scoring 84%, with Sem-EHR 82%. For atrophy, EdIE-R and both ALARM+ versions were comparable at 80%. Conclusions: The four NLP tools show varying F1 (and precision/recall) scores across all three phenotypes, although more apparent for ischaemic stroke. If NLP tools are to be used in clinical settings, this cannot be performed "out of the box." It is essential to understand the context of their development to assess whether they are suitable for the task at hand or whether further training, re-training, or modification is required to adapt tools to the target task.
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BACKGROUND: The paranasal sinus mucosal thickening, visible in magnetic resonance imaging (MRI), maybe a source of inflammation in microvessels, but its relationship with small vessel disease (SVD) is unclear. We reviewed the literature and analysed a sample of patients with sporadic SVD to identify any association between paranasal sinus opacification severity and SVD neuroimaging markers. METHODS: We systematically reviewed MEDLINE and EMBASE databases up to April 2020 for studies on paranasal sinus mucosal changes in patients with SVD, cerebrovascular disease (CVD), and age-related neurodegenerative diseases. We analysed clinical and MRI data from 100 participants in a prospective study, the Mild Stroke Study 3 (ISRCTN 12113543) at 1-3, 6 and 12 months following a minor stroke to test key outcomes from the literature review. We used multivariate linear regression to explore associations between modified Lund-Mackay (LM) scores and brain, white matter hyperintensities (WMH), enlarged perivascular spaces (PVS) volumes at each time point, adjusted for baseline age, sex, diabetes, hypercholesterolaemia, hypertension and smoking. RESULTS: The literature review, after screening 3652 publications, yielded 11 primary studies, for qualitative synthesis with contradictory results, as positive associations/higher risk from 5/7 CVD studies were contradicted by the two studies with largest samples, and data from dementia studies was equally split in their outcome. From the pilot sample of patients analysed (female N = 33, mean age 67.42 (9.70) years), total LM scores had a borderline negative association with PVS in the centrum semiovale at baseline and 6 months (B = -0.25, SE = 0.14, p = 0.06) but were not associated with average brain tissue, WMH or normal-appearing white matter volumes. CONCLUSION: The inconclusive results from the literature review and empirical study justify larger studies between PVS volume and paranasal sinuses opacification in patients with sporadic SVD.
Subject(s)
Cerebral Small Vessel Diseases , Cerebrovascular Disorders , Paranasal Sinuses , Stroke , Humans , Female , Aged , Male , Prospective Studies , Cerebral Small Vessel Diseases/pathology , Brain/pathology , Stroke/complications , Cerebrovascular Disorders/complications , Magnetic Resonance Imaging , Paranasal Sinuses/pathologyABSTRACT
Nutrition in pediatric populations who require life-saving extracorporeal membrane oxygenation (ECMO) remains a debate. We sought to identify if nutritional needs were met in a patient cohort. A retrospective chart review of patients (N = 64) requiring ECMO at Helen DeVos Children's Hospital between 2018 and 2022 was evaluated for demographics, daily nutritional data, laboratory values, ECMO complications, and outcome data, with primary outcome measures of percent protein and percent caloric intake. Secondary outcome measures included the intensive care unit length of stay, time on ECMO, mortality, and day 1 severity of illness scores (Pediatric Logistic Organ Dysfunction). The timeline partially overlapped with the COVID-19 pandemic. Data were collected for 467 ECMO days with a median age of 2.6 months; 57.8% of patients were male and 65.6% were with one pre-existing comorbidity. Venoarterial (VA) ECMO was utilized in 84.4% of patients; the ECMO indication was cardiac in 53.1% of patients. The 28-day mortality was 43.8%. The proportion of days in which the caloric goal was met was 0%; the proportion of days in which protein goals were met was 33.3%. Non-cardiac ECMO patients had a greater number of days where caloric goals were met (p-value = 0.04). Mortality at 28 days was not statistically significant (p-value = 0.28) for calories or protein administered. The patient cohort struggled to meet calorie and protein goals while on ECMO.
Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Child , Humans , Male , Infant , Female , Retrospective Studies , Pandemics , Treatment Outcome , Eating , ProteinsABSTRACT
BACKGROUND: Electronic patient portals are online applications that allow patients access to their own health information, a form of asynchronous virtual care. The long-term impact of portals on the use of traditional primary care services is unclear, but it is an important question at this juncture, when portals are being incorporated into many primary care practices. OBJECTIVE: We sought to investigate how an electronic patient portal affected the use of traditional, synchronous primary care services over a much longer time period than any existing studies and to assess the impact of portal messaging on clinicians' workload. METHODS: We conducted a propensity-score-matched, open-cohort, interrupted time-series evaluation of a primary care portal from its implementation in 2010. We extracted information from the electronic medical record regarding age, sex, education, income, family health team enrollment, diagnoses at index date, and number of medications prescribed in the previous year. We also extracted the annual number of encounters for up to 8 years before and after the index date and provider time spent on secure messaging through the portal. RESULTS: A total of 7247 eligible portal patients and 7647 eligible potential controls were identified, with 3696 patients matched one to one. We found that portal registration was associated with an increase in the number of certain traditional encounters over the time period surrounding portal registration. Following the index year, there was a significant jump in annual number of visits to physicians in the portal arm (0.42 more visits/year vs control, P<.001) but not for visits to nurse practitioners and physician assistants. The annual number of calls to the practice triage nurses also showed a greater increase in the portal arm compared to the control arm after the index year (an additional 0.10 calls, P=.006). The average provider time spent on portal-related work was 5.7 minutes per patient per year. CONCLUSIONS: We found that portal registration was associated with a subsequent increase in the number of some traditional encounters and an increase in clerical workload for providers. Portals have enormous potential to truly engage patients as partners in their own health care, but their impact on use of traditional health care services and clerical burden must also be considered when they are incorporated into primary care.
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The feasibility of gastrointestinal (GI) microbiome work in a pediatric intensive care unit (PICU) to determine the GI microbiota composition of infants as compared to control infants from the same hospital was investigated. In a single-site observational study at an urban quaternary care children's hospital in Western Michigan, subjects less than 6 months of age, admitted to the PICU with severe respiratory syncytial virus (RSV) bronchiolitis, were compared to similarly aged control subjects undergoing procedural sedation in the outpatient department. GI microbiome samples were collected at admission (n = 20) and 72 h (n = 19) or at time of sedation (n = 10). GI bacteria were analyzed by sequencing the V4 region of the 16S rRNA gene. Alpha and beta diversity were calculated. Mechanical ventilation was required for the majority (n = 14) of study patients, and antibiotics were given at baseline (n = 8) and 72 h (n = 9). Control subjects' bacterial communities contained more Porphyromonas, and Prevotella (p = 0.004) than those of PICU infants. The ratio of Prevotella to Bacteroides was greater in the control than the RSV infants (mean ± SD-1.27 ± 0.85 vs. 0.61 ± 0.75: p = 0.03). Bacterial communities of PICU infants were less diverse than those of controls with a loss of potentially protective populations.
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Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63-3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.
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Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.
Subject(s)
Lipidomics , Multiple Organ Failure/metabolism , Phospholipids/blood , Child , Critical Illness , Humans , Mass Spectrometry/methodsABSTRACT
We examined preadmission diet and zip code in infants with severe respiratory illness in the pediatric critical care unit. Patients aged 0 to 5 months admitted to the Helen DeVos Children's Hospital from January 2011 to May 2017 ( N = 187), as exclusively formula, exclusively breastfed or mixed diet were included. Formula-fed infants ( n = 88; 47%) clustered to zip codes with lower median incomes (<0.005), used public insurance as their payer type ( p < 0.005), and were prescribed more ranitidine ( p < 0.05) on admission.
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BACKGROUND:: Lack of compassion is claimed to result in poor and sometimes harmful nursing care. Developing strategies to encourage compassionate caring behaviours are important because there is evidence to suggest a connection between having a moral orientation such as compassion and resulting caring behaviour in practice. OBJECTIVE:: This study aimed to articulate a clearer understanding of compassionate caring via nurse educators' selection and use of published texts and film. METHODOLOGY:: This study employed discourse analysis. PARTICIPANTS AND RESEARCH CONTEXT:: A total of 41 nurse educators working in universities in the United Kingdom (n = 3), Ireland (n = 1) and Canada (n = 1) completed questionnaires on the narratives that shaped their understanding of care and compassion. FINDINGS:: The desire to understand others and how to care compassionately characterised educators' choices. Most narratives were examples of kindness and compassion. A total of 17 emphasised the importance of connecting with others as a central component of compassionate caring, 10 identified the burden of caring, 24 identified themes of abandonment and of failure to see the suffering person and 15 narratives showed a discourse of only showing compassion to those 'deserving' often understood as the suffering person doing enough to help themselves. DISCUSSION:: These findings are mostly consistent with work in moral philosophy emphasising the particular or context and perception or vision as well as the necessity of emotions. The narratives themselves are used by nurse educators to help explicate examples of caring and compassion (or its lack). CONCLUSION:: To feel cared about people need to feel 'visible' as though they matter. Nurses need to be alert to problems that may arise if their 'moral vision' is influenced by ideas of desert and how much the patient is doing to help himself or herself.
Subject(s)
Empathy , Faculty, Nursing/psychology , Personal Narratives as Topic , Canada , Humans , Ireland , Surveys and Questionnaires , United KingdomABSTRACT
GOAL: Magnetic resonance imaging (MRI) is the preferred modality for research on structural age-related brain changes. However, computed tomography (CT) is widely available and has practical and cost advantages over MRI for large-scale brain imaging research studies in acutely unwell patients. However, the relationships between MRI and CT measures of white matter hyperintensities (WMH) and atrophy are unclear. We examined the relationships between visual ratings of WMH, atrophy, and old infarcts in patients who had both CT and MRI scans. MATERIALS AND METHODS: Patients who had both CT and MRI scans in the International Stroke Trial-3 were studied. In both modalities, 2 raters independently completed standardized visual rating scales for WMH, and for central and superficial atrophy using a 5-point scale. In addition, 1 rater recorded old infarcts according to size and location. FINDINGS: Seventy patients with a mean age of 69 years were studied. There were moderate to substantial intrarater CT-MRI agreements for periventricular components of WMH scales (weighted Κappa = .55-.75). Agreements for basal ganglia ratings were lower (weighted Κappa = .18-.44), partly because of the misclassification of prominent perivascular spaces. Atrophy scales showed moderate to substantial CT-MRI agreements (weighted Κappa = .44-.70). MRI was more sensitive in the detection of smaller infarcts and cavitated lesions. CONCLUSIONS: Standardized visual rating scales of white matter lesions and atrophy mostly show substantial agreement between CT and MRI. Clinical CT scans have a strong potential for wider exploitation in research studies, particularly in acutely unwell populations.
Subject(s)
Brain/diagnostic imaging , Magnetic Resonance Imaging , Tomography, X-Ray Computed , White Matter/diagnostic imaging , Aged , Brain/pathology , Humans , Observer Variation , White Matter/pathologyABSTRACT
[This corrects the article DOI: 10.1016/j.intell.2014.05.006.].
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OBJECTIVE: Neuroimaging advances our understanding of delirium pathophysiology and its consequences. A previous systematic review identified 12 studies (total participants N = 764, delirium cases N = 194; years 1989-2007) and found associations with white matter hyperintensities (WMH) and cerebral atrophy. Our objectives were to perform an updated systematic review of neuroimaging studies in delirium published since January 2006 and summarise the available literature on predictors, correlates or outcomes. METHODS: Studies were identified by keyword and MeSH-based electronic searches of EMBASE, MEDLINE and PsycINFO combining terms for neuroimaging, brain structure and delirium. We included neuroimaging studies of delirium in adults using validated delirium assessment methods. RESULTS: Thirty-two studies (total N = 3187, delirium N = 1086) met the inclusion criteria. Imaging included magnetic resonance imaging (MRI; N = 9), computed tomography (N = 4), diffusion tensor imaging (N = 3), transcranial Doppler (N = 5), near infrared spectroscopy (N = 5), functional-MRI (N = 2), single photon emission computed tomography (N = 1), proton MRI spectroscopy (N = 1), arterial spin-labelling MRI (N = 1) and 2-13 fluoro-2-deoxyglucose positron emission tomography (N = 1). Despite heterogeneity in study design, delirium was associated with WMH, lower brain volume, atrophy, dysconnectivity, impaired cerebral autoregulation, reduced blood flow and cerebral oxygenation and glucose hypometabolism. There was evidence of long-term brain changes following intensive care unit delirium. CONCLUSIONS: Neuroimaging is now used more widely in delirium research due to advances in technology. However, imaging delirious patients presents challenges leading to methodological limitations and restricted generalisability. The findings that atrophy and WMH burden predict delirium replicates findings from the original review, while advanced techniques have identified other substrates and mechanisms that warrant further investigation.
Subject(s)
Brain , Delirium/diagnostic imaging , Delirium/physiopathology , Neuroimaging/methods , Atrophy/pathology , Brain/diagnostic imaging , Brain/metabolism , Brain/pathology , Diffusion Tensor Imaging , Glucose/metabolism , Humans , Magnetic Resonance Imaging , Oxygen/metabolism , Positron-Emission Tomography , Regional Blood Flow/physiology , Spectroscopy, Near-Infrared , Tomography, Emission-Computed, Single-Photon , White Matter/pathologyABSTRACT
BACKGROUND: The United Kingdom introduced the Six C's strategy to help address deficits in approaching nursing care in a compassionate and caring manner. OBJECTIVE: To identify the book, article, poem, film or play that most influenced nurse educators' understanding of care and compassion and to articulate a clearer understanding of compassionate caring. DESIGN: A qualitative study applying discourse analysis to respondents' questionnaires and their nominated narrative. SETTINGS AND PARTICIPANTS: 41 nurse educators working in 5 universities in the UK (n=3), Republic of Ireland and Canada participated. 39 items (10 books, 2 journal articles, 10 poems, 15 films and 2 plays) were nominated. FINDINGS: The desire to understand others and how to care compassionately characterised choices. Three main themes emerged. Abandonment of, and failure to see, the suffering person was evident in 25 narratives. Connecting with others was shown in 25 narratives as being able to truly seeing the other person. Comforting others was supported by 37 narratives with examples of kindness and compassion. CONCLUSION: Published narratives are valuable in developing compassionate responses. An annotated list is provided with suggestions for educational uses to help develop compassionate caring in student nurses. Compassionate, caring nurses recognise that patients need them to: "See who I am; Be present with me; Do not abandon me."
Subject(s)
Attitude of Health Personnel , Empathy , Literature , Philosophy, Nursing , Writing/standards , Canada , Humans , Ireland , Surveys and Questionnaires , United KingdomABSTRACT
INTRODUCTION: To examine treatment persistence and clinical outcomes associated with switching from a tumor necrosis factor inhibitor (TNFi) to a medication with a new mechanism of action (MOA) (abatacept, anakinra, rituximab, tocilizumab, or tofacitinib) versus cycling to another TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) among patients with rheumatoid arthritis. METHODS: This retrospective, longitudinal study included patients with rheumatoid arthritis in the JointMan® US clinical database who received a TNFi in April 2010 or later and either cycled to a TNFi or switched to a new MOA therapy by March 2015. Cox proportional hazards models were used for time to non-persistence (switching or discontinuing). An ordinary least squares regression model compared 1-year reduction from baseline for the Clinical Disease Activity Index (CDAI). RESULTS: There were 332 (54.2%) TNFi cyclers and 281 (45.8%) new MOA switchers. During a median follow-up of 29.9 months, treatment persistence was 36.7% overall. Compared with new MOA switchers, TNFi cyclers were 51% more likely to be non-persistent (adjusted hazard ratio, 1.511; 95% CI 1.196, 1.908), driven by a higher likelihood of switching again (adjusted hazard ratio, 2.016; 95% CI 1.428, 2.847). Clinical outcomes were evaluable for 239 (53.3%) TNFi cyclers and 209 (46.7%) new MOA switchers. One-year mean reduction in CDAI from baseline to end of follow-up was significantly higher for new MOA switchers than TNFi cyclers (-7.54 vs. -4.81; P = 0.037), but the difference was not statistically significant after adjustment for baseline CDAI (-6.39 vs. -5.83; P = 0.607). CONCLUSION: In this study, TNFi cycling was common in clinical practice, but switching to a new MOA DMARD was associated with significantly better treatment persistence and a trend toward greater CDAI reduction that was not significant after adjustment for baseline disease activity. FUNDING: Sanofi and Regeneron Pharmaceuticals.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Drug Substitution/statistics & numerical data , Medication Adherence , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Dose-Response Relationship, Drug , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome , United StatesABSTRACT
High, unabated glucocorticoid (GC) levels are thought to selectively damage certain tissue types. The hippocampus is thought to be particularly susceptible to such effects, and though findings from animal models and human patients provide some support for this hypothesis, evidence for associations between elevated GCs and lower hippocampal volumes in older age (when GC levels are at greater risk of dysregulation) is inconclusive. To address the possibility that the effects of GCs in non-pathological ageing may be too subtle for gross volumetry to reliably detect, we analyse associations between salivary cortisol (diurnal and reactive measures), hippocampal morphology and diffusion characteristics in 88 males, aged â¼73 years. However, our results provide only weak support for this hypothesis. Though nominally significant peaks in morphology were found in both hippocampi across all salivary cortisol measures (standardised ß magnitudes<0.518, puncorrected>0.0000003), associations were both positive and negative, and none survived false discovery rate correction. We found one single significant association (out of 12 comparisons) between a general measure of hippocampal diffusion and reactive cortisol slope (ß=0.290, p=0.008) which appeared to be driven predominantly by mean diffusivity but did not survive correction for multiple testing. The current data therefore do not clearly support the hypothesis that elevated cortisol levels are associated with subtle variations in hippocampal shape or microstructure in non-pathological older age.
Subject(s)
Hippocampus/diagnostic imaging , Hydrocortisone/analysis , Aged , Humans , Magnetic Resonance Imaging , Male , Organ Size/physiology , Saliva/chemistryABSTRACT
PURPOSE: Explore the use of a neighbourhood practice placement with nursing students to gain insight into how the experience influenced their learning and how the reconceptualization of community can be a model for students' professional development. BACKGROUND: The integration of community health nursing competencies in undergraduate nursing education is a critical element of student development. Neighbourhood placements have been found to support development of such competencies by exposing students to issues such as culture, social justice, partnership, and community development. DESIGN AND SAMPLE: A qualitative design was used with a sample of 48 Year 3 baccalaureate nursing students enrolled in a community health nursing practice course. METHODS: Students submitted reflective reviews where they responded to questions and subsequently participated in focus groups. Meaning making of narrative data took place using the descriptive qualitative analysis approach. FINDINGS: Students became more self-directed learners and developed team process skills. Some found it challenging to adapt to a role outside of the traditional acute care context. CONCLUSION: Nursing practice in a neighbourhood context requires students to be innovative and creative in problem-solving and relationship building. The placement also requires neighbourhood liaison persons who are adept at helping students bridge the theory-practice gap.
Subject(s)
Community Health Nursing/methods , Learning , Nursing Process , Students, Nursing/psychology , Education, Nursing, Baccalaureate , Female , Focus Groups , Humans , Ontario , Qualitative Research , Residence Characteristics , Young AdultABSTRACT
OBJECTIVE: The aims of this study were to compare distinct brain frontal lobe parcellation methods across 90 brain magnetic resonance imaging scans and examine their associations with cognition in older age. METHODS: Three parcellation methods (Manual, FreeSurfer, and Stereology) were applied to T1-weighted magnetic resonance imaging of 90 older men, aged â¼ 73 years. A measure of general fluid intelligence (gf) associated with dorsolateral frontal regions was also derived from a contemporaneous psychological test battery. RESULTS: Despite highly discordant raw volumes for the same nominal regions, Manual and FreeSurfer (but not Stereology) left dorsolateral measures were significantly correlated with gf (r > 0.22), whereas orbital and inferior lateral volumes were not, consistent with the hypothesized frontal localization of gf. CONCLUSIONS: Individual differences in specific frontal lobe brain volumes--variously measured--show consistent associations with cognitive ability in older age. Importantly, differences in parcellation protocol for some regions that may impact the outcome of brain-cognition analyses are discussed.
Subject(s)
Brain Mapping/methods , Brain/pathology , Cognition Disorders/pathology , Magnetic Resonance Imaging , Aged , Frontal Lobe/pathology , Humans , Male , Neuropsychological Tests/statistics & numerical data , Organ Size , Reproducibility of ResultsABSTRACT
Elevated glucocorticoid (GC) levels putatively damage specific brain regions, which in turn may accelerate cognitive ageing. However, many studies are cross-sectional or have relatively short follow-up periods, making it difficult to relate GCs directly to changes in cognitive ability with increasing age. Moreover, studies combining endocrine, MRI and cognitive variables are scarce, measurement methods vary considerably, and formal tests of the underlying causal hypothesis (cortisolâbrainâcognition) are absent. In this study, 90 men, aged 73 years, provided measures of fluid intelligence, processing speed and memory, diurnal and reactive salivary cortisol and two measures of white matter (WM) structure (WM hyperintensity volume from structural MRI and mean diffusivity averaged across 12 major tracts from diffusion tensor MRI), hippocampal volume, and also cognitive ability at age 11. We tested whether negative relationships between cognitive ageing differences (over more than 60 years) and salivary cortisol were significantly mediated by WM and hippocampal volume. Significant associations between reactive cortisol at 73 and cognitive ageing differences between 11 and 73 (r=-.28 to -.36, p<.05) were partially mediated by both WM structural measures, but not hippocampal volume. Cortisol-WM relationships were modest, as was the degree to which WM structure attenuated cortisol-cognition associations (<15%). These data support the hypothesis that GCs contribute to cognitive ageing differences from childhood to the early 70s, partly via brain WM structure.