Endotyping in ARDS: one step forward in precision medicine.

BACKGROUND: The Berlin definition of acute respiratory distress syndrome (ARDS) includes only clinical characteristics. Understanding unique patient pathobiology may allow personalized treatment. We aimed to define and describe ARDS phenotypes/endotypes combining clinical and pathophysiologic parameters from a Canadian ARDS cohort. METHODS: A cohort of adult ARDS patients from multiple sites in Calgary, Canada, had plasma cytokine levels and clinical parameters measured in the first 24 h of ICU admission. We used a latent class model (LCM) to group the patients into several ARDS subgroups and identified the features differentiating those subgroups. We then discuss the subgroup effect on 30 day mortality. RESULTS: The LCM suggested three subgroups (n1 = 64, n2 = 86, and n3 = 30), and 23 out of 69 features made these subgroups distinct. The top five discriminating features were IL-8, IL-6, IL-10, TNF-a, and serum lactate. Mortality distinctively varied between subgroups. Individual clinical characteristics within the subgroup associated with mortality included mean PaO2/FiO2 ratio, pneumonia, platelet count, and bicarbonate negatively associated with mortality, while lactate, creatinine, shock, chronic kidney disease, vasopressor/ionotropic use, low GCS at admission, and sepsis were positively associated. IL-8 and Apache II were individual markers strongly associated with mortality (Area Under the Curve = 0.84). PERSPECTIVE: ARDS subgrouping using biomarkers and clinical characteristics is useful for categorizing a heterogeneous condition into several homogenous patient groups. This study found three ARDS subgroups using LCM; each subgroup has a different level of mortality. This model may also apply to developing further trial design, prognostication, and treatment selection.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Metabolomics in severe traumatic brain injury: a scoping review.

BACKGROUND: Diagnosis and prognostication of severe traumatic brain injury (sTBI) continue to be problematic despite years of research efforts. There are currently no clinically reliable biomarkers, though advances in protein biomarkers are being made. Utilizing Omics technology, particularly metabolomics, may provide new diagnostic biomarkers for sTBI. Several published studies have attempted to determine the specific metabolites and metabolic pathways involved; these studies will be reviewed. AIMS: This scoping review aims to summarize the current literature concerning metabolomics in sTBI, review the comprehensive data, and identify commonalities, if any, to define metabolites with potential clinical use. In addition, we will examine related metabolic pathways through pathway analysis. METHODS: Scoping review methodology was used to examine the current literature published in Embase, Scopus, PubMed, and Medline. An initial 1090 publications were identified and vetted with specific inclusion criteria. Of these, 20 publications were selected for further examination and summary. Metabolic data was classified using the Human Metabolome Database (HMDB) and arranged to determine the 'recurrent' metabolites and classes found in sTBI. To help understand potential mechanisms of injury, pathway analysis was performed using these metabolites and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. RESULTS: Several metabolites related to sTBI and their effects on biological pathways were identified in this review. Across the literature, proline, citrulline, lactate, alanine, valine, leucine, and serine all decreased in adults post sTBI, whereas both octanoic and decanoic acid increased. Hydroxy acids and organooxygen compounds generally increased following sTBI, while most carboxylic acids decreased. Pathway analysis showed significantly affected glycine and serine metabolism, glycolysis, branched-chain amino acid (BCAA) metabolism, and other amino acid metabolisms. Interestingly, no tricarboxylic acid cycle metabolites were affected. CONCLUSION: Aside from a select few metabolites, classification of a metabolic profile proved difficult due to significant ambiguity between study design, sample size, type of sample, metabolomic detection techniques, and other confounding variables found in sTBI literature. Given the trends found in some studies, further metabolomics investigation of sTBI may be useful to identify clinically relevant metabolites.

Deliberate practice of diagnostic clinical reasoning reveals low performance and improvement of diagnostic justification in pre-clerkship students.

PURPOSE: Diagnostic errors are a large burden on patient safety and improving clinical reasoning (CR) education could contribute to reducing these errors. To this end, calls have been made to implement CR training as early as the first year of medical school. However, much is still unknown about pre-clerkship students' reasoning processes. The current study aimed to observe how pre-clerkship students use clinical information during the diagnostic process. METHODS: In a prospective observational study, pre-clerkship medical students completed 10-11 self-directed online simulated CR diagnostic cases. CR skills assessed included: creation of the differential diagnosis (Ddx), diagnostic justification (DxJ), ordering investigations, and identifying the most probable diagnosis. Student performances were compared to expert-created scorecards and students received detailed individualized formative feedback for every case. RESULTS: 121 of 133 (91%) first- and second-year medical students consented to the research project. Students scored much lower for DxJ compared to scores obtained for creation of the Ddx, ordering tests, and identifying the correct diagnosis, (30-48% lower, p < 0.001). Specifically, students underutilized physical exam data (p < 0.001) and underutilized data that decreased the probability of incorrect diagnoses (p < 0.001). We observed that DxJ scores increased 40% after 10-11 practice cases (p < 0.001). CONCLUSIONS: We implemented deliberate practice with formative feedback for CR starting in the first year of medical school. Students underperformed in DxJ, particularly with analyzing the physical exam data and pertinent negative data. We observed significant improvement in DxJ performance with increased practice.

Using metabolomics to predict severe traumatic brain injury outcome (GOSE) at 3 and 12 months.

BACKGROUND: Prognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcomes. METHODS: We prospectively enrolled 59 adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn for metabolomic profiling on the 1st and 4th days following injury. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5-8) and unfavorable (GOSE 1-4), outcomes. RESULTS: Serum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4-0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids, and glutamate were associated with poor outcomes and mortality. DISCUSSION: Metabolomic profiles were strongly associated with the prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The metabolic phenotypes on day 4 post-injury were more predictive and significant for predicting the sTBI outcome compared to the day 1 sample. This may reflect the larger contribution of secondary brain injury (day 4) to sTBI outcome. Patients with unfavorable outcomes demonstrated more metabolite changes from day 1 to day 4 post-injury. These findings highlighted increased concentration of neurobiomarkers such as N-acetylaspartate (NAA) and tyrosine, decreased concentrations of ketone bodies, and decreased urea cycle metabolites on day 4 presenting potential metabolites to predict the outcome. The current findings strongly support the use of serum metabolomics, that are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI to be used for clinical practice.

Opioid-related emergency department visits and deaths after a harm-reduction intervention: a retrospective observational cohort time series analysis.

BACKGROUND: To date, there has been little research on the effect of safe consumption site and community-based naloxone programs on regional opioid-related emergency department visits and deaths. We sought to determine the impact of these interventions on regional opioid-related emergency department visit and death rates in the province of Alberta. METHODS: We used a retrospective observational design, via interrupted time series analysis, to assess municipal opioid-related emergency department visit volume and opioid-related deaths (defined by poisoning and opioid use disorder). We compared rates before and after program implementation in individual Alberta municipalities and province-wide after safe consumption site (March 2018 to October 2018) and community-based naloxone (January 2016) program implementation. RESULTS: A total of 24 107 emergency department visits and 2413 deaths were included in the study. After safe consumption site opening, we saw decreased opioid-related emergency department visits in Calgary (level change -22.7 [-20%] visits per month, 95% confidence interval [CI] -29.7 to -15.8) and Lethbridge (level change -8.8 [-50%] visits per month, 95% CI -11.7 to -5.9), and decreased deaths in Edmonton (level change -5.9 [-55%] deaths per month, 95% CI -8.9 to -2.9). We observed increased emergency department visits after community-based naloxone program implementation in urban Alberta (level change 38.9 [46%] visits, 95% CI 33.3 to 44.4). We also observed an increase in urban opioid-related deaths (level change 9.1 [40%] deaths, 95% CI 6.7 to 11.5). INTERPRETATION: The results of this study suggest differences exist between municipalities employing similar interventions. Our results also suggest contextual variation; for example, illicit drug supply toxicity may modify the ability of a community-based naloxone program to prevent opioid overdose without a thorough public health response.

Effects of music therapy on mood, pain, and satisfaction in the neurologic inpatient setting.

PURPOSE: Music therapy (MT) has been used in health care settings for a wide variety of treatment goals. Many inpatients with neurologic impairments struggle with low mood and pain for which MT may be a novel adjunct treatment. The aims of this study were to: (1) evaluate change in mood and pain following a single MT session; (2) explore the impact of an MT program on mood, pain and satisfaction from the perspective of the patient, family and staff. MATERIALS AND METHODS: A mixed-methods study was conducted. Forty participants completed pre/post MT surveys evaluating mood, pain and satisfaction. Individual semi-structured interviews and focus groups were conducted with 14 MT program participants (inpatients), 5 family members of participants and 16 staff. RESULTS: There was significant improvement in mood (p < 0.001) and decrease in pain (p < 0.05) from pre-to-post MT with 74% reporting being "very satisfied" with the session. "Benefits of MT" was the overarching theme of the qualitative data. Subthemes were emotional regulation, pain management, effects on self-concept, enjoyment, and social connectedness. CONCLUSIONS: Improvements in mood and pain were reported from pre-to-post MT session and in interviews. Further evaluation of MT effectiveness against standard of care rehabilitation and cost implications is required.Implications for RehabilitationMusic therapy (MT) is delivered by accredited music therapists (MTAs) in health care settings, including rehabilitation units, as an individual, group or co-treatment therapy.MT can be used for a range of health outcomes, including the treatment of mood and pain, in addition to improving inpatient satisfaction.Early evidence using pre/post MT surveys suggests an improvement in mood and pain following a single therapy session.Qualitative data suggest overall benefit of offering MT services in addition to standard neurorehabilitation therapy, including improvements to emotional regulation, pain management, self-concept, enjoyment, and social connectedness.

Effectiveness of intravenous prostaglandin to reduce digital amputations from frostbite: an observational study.

PURPOSE: We assessed the effectiveness and safety of a 5-day intravenous prostaglandin (iloprost) protocol at reducing digital amputation for patients with severe frostbite injuries at urban emergency departments. METHODS: This retrospective study examines consecutive patients who presented to Calgary emergency departments from April 2017 to April 2020 with Grade 2-4 frostbite injuries. Patients from February 2019 onward were managed using a 5-day iloprost infusion protocol, whereas patients prior to this time were managed with standard care (local best practice without iloprost as a therapeutic option). The primary effectiveness outcome was rate of affected digits amputated, stratified by frostbite severity. The secondary safety outcome was the incidence of serious adverse events associated with iloprost (allergic reactions or symptomatic hypotension requiring treatment or discontinuation of the infusion). RESULTS: 90 patients were included, 26 were treated with iloprost, compared to 64 patients who received usual care. Both the treatment and usual care groups experienced substantial rates of homelessness and substance use. No digital amputations were required for patients with Grade 2 injuries in either group, but significantly lower digital amputation rates were observed for patients with more severe frostbite injuries treated with iloprost versus usual care: Grade 3 (18% vs 44%, p < 0.001), Grade 4 (46% vs 95%, p < 0.001). No serious adverse events were associated with iloprost. CONCLUSION: In this unselected socially complex urban population, administration of iloprost for patients with frostbite was shown to be safe and was associated with lower digital amputation rates, particularly for those with more severe injuries.

RéSUMé: OBJECTIF: Nous avons évalué l'efficacité et la sécurité d'un protocole de 5 jours de prostaglandine intraveineuse (iloprost) pour réduire l'amputation digitale chez les patients souffrant d'engelures graves dans les services d'urgence urbains. MéTHODES: Cette étude rétrospective examine des patients consécutifs qui se sont présentés aux services d'urgence de Calgary d'avril 2017 à avril 2020 avec des engelures de niveau 2 à 4. À compter de février 2019, les patients ont été traités au moyen d'un protocole de perfusion d'iloprost de 5 jours, tandis que les patients avant cette période ont été pris en charge avec des soins standard (meilleures pratiques locales sans iloprost comme option thérapeutique). Le principal résultat d'efficacité était le taux de doigts affectés amputés, stratifié selon la gravité des gelures. Le critère secondaire de sécurité était l'incidence des événements indésirables graves associés à l'iloprost (réactions allergiques ou hypotension symptomatique nécessitant un traitement ou l'arrêt de la perfusion). RéSULTATS: 90 patients ont été inclus, 26 ont été traités avec de l'iloprost, contre 64 patients qui ont reçu les soins habituels. Les groupes de traitement et de soins habituels ont tous deux connu des taux importants de sans-abrisme et de consommation de substances. Aucune amputation digitale n'a été nécessaire pour les patients présentant des lésions de grade 2 dans l'un ou l'autre groupe, mais des taux d'amputation digitale significativement plus faibles ont été observés pour les patients présentant des lésions de gelures plus sévères traités par iloprost par rapport aux soins habituels : Grade 3 (18 % contre 44 %, p < 0,001), Grade 4 (46 % contre 95 %, p < 0,001). Aucun événement indésirable grave n'a été associé à l'iloprost. CONCLUSION: Dans cette population urbaine non sélectionnée et socialement complexe, l'administration d'iloprost pour les patients souffrant d'engelures s'est avérée sûre et a été associée à des taux d'amputation digitale plus faibles, en particulier pour ceux présentant des blessures plus graves.

Development and Pilot Testing of a Data-Rich Clinical Reasoning Training and Assessment Tool.

PROBLEM: Clinical reasoning is a core competency for physicians and also a common source of errors, driving high rates of misdiagnoses and patient harm. Efforts to provide training in and assessment of clinical reasoning skills have proven challenging because they are either labor- and resource-prohibitive or lack important data relevant to clinical reasoning. The authors report on the creation and use of online simulation cases to train and assess clinical reasoning skills among medical students. APPROACH: Using an online library of simulation cases, they collected data relevant to the creation of the differential diagnosis, analysis of the history and physical exam, diagnostic justification, ordering tests; interpreting tests, and ranking of the most probable diagnosis. These data were compared with an expert-created scorecard, and detailed quantitative and qualitative feedback were generated and provided to the learners and instructors. OUTCOMES: Following an initial pilot study to troubleshoot the software, the authors conducted a second pilot study in which 2 instructors developed and provided 6 cases to 75 second-year medical students. The students completed 376 cases (average 5.0 cases per student), generating more than 40,200 data points that the software analyzed to inform individual learner formative feedback relevant to clinical reasoning skills. The instructors reported that the workload was acceptable and sustainable. NEXT STEPS: The authors are actively expanding the library of clinical cases and providing more students and schools with formative feedback in clinical reasoning using our tool. Further, they have upgraded the software to identify and provide feedback on behaviors consistent with premature closure, anchoring, and confirmation biases. They are currently collecting and analyzing additional data using the same software to inform validation and psychometric outcomes for future publications.

Sedation strategy and ICU delirium: a multicentre, population-based propensity score-matched cohort study.

OBJECTIVES: We examined the relationship between dominant sedation strategy, risk of delirium and patient-centred outcomes in adults admitted to intensive care units (ICUs). DESIGN: Retrospective propensity-matched cohort study. SETTING: Mechanically ventilated adults (≥ 18 years) admitted to four Canadian hospital medical/surgical ICUs from 2014 to 2016 in Calgary, Alberta, Canada. PARTICIPANTS: 2837 mechanically ventilated adults (≥ 18 years) requiring admission to a medical/surgical ICU were evaluated for the relationship between sedation strategy and delirium. INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary exposure was dominant sedation strategy, defined as the sedative infusion, including midazolam, propofol or fentanyl, with the longest duration before the first delirium assessment. The primary outcome was 'ever delirium' identified using the Intensive Care Delirium Screening Checklist. Secondary outcomes included mortality, length of stay (LOS), ventilation duration and days with delirium. The cohort was analysed in two propensity score (patient characteristics and therapies received) matched cohorts (propofol vs fentanyl and propofol vs midazolam). RESULTS: 2837 patients (60.7% male; median age 57 years (IQR 43-68)) were considered for propensity matching. In propensity score-matched cohorts(propofol vs midazolam, n=712; propofol vs fentanyl, n=1732), the odds of delirium were significantly higher with midazolam (OR 1.46 (95% CI 1.06 to 2.00)) and fentanyl (OR 1.22 (95% CI 1.00 to 1.48)) compared with propofol dominant sedation strategies. Dominant sedation strategy with midazolam and fentanyl were associated with a longer duration of ventilation compared with propofol. Fentanyl was also associated with increased ICU mortality (OR 1.50, 95% CI 1.07 to 2.12)) ICU and hospital LOS compared with a propofol dominant sedation strategy. CONCLUSIONS: We identified a novel association between fentanyl dominant sedation strategies and an increased risk of delirium, a composite outcome of delirium or death, duration of mechanical ventilation, ICU LOS and hospital LOS. Midazolam dominant sedation strategies were associated with increased delirium risk and mechanical ventilation duration.

Understanding Home Hemodialysis Patient Attrition: A Cohort Study.

BACKGROUND: Home hemodialysis (HHD) offers a flexible, patient-centered modality for patients with kidney failure. Growth in HHD is achieved by increasing the number of patients starting HHD and reducing attrition with strategies to prevent the modifiable reasons for loss. OBJECTIVE: Our primary objective was to describe a Canadian HHD population in terms of technique failure and time to exit from HHD in order to understand reasons for exit. Our secondary objectives include the following: (1) determining reasons for training failure, (2) reasons for early exit from HHD, and (3) timing of program exit. DESIGN: A retrospective cohort study of incident adult HHD patients between January 1, 2013-June 30, 2020. SETTING: Alberta Kidney Care South, AKC-S HHD program. PARTICIPANTS: Patients who started training for HHD in AKC-S. METHODS: A retrospective, cohort study of incident adult HHD patients with primary outcome time on home hemodialysis, secondary outcomes include reason for train failure, time to and reasons for technique failure. Cox-proportional hazard model to determine associations between patient characteristics and technique failure. The cumulative probability of technique failure over time was reported using a competing risks model. RESULTS: A total of 167 patients entered HHD. Training failure occurred in 20 (12%), at 3.1 [2.0, 5.5] weeks; these patients were older (P < .001) and had 2 or more comorbidities (P < .001). Reasons for HHD exit after training included transplant (35; 21%), death (8; 4.8%), and technique failure (24; 14.4%). Overall, the median time to HHD exit, was 23 months [11, 41] and the median time of technique failure was 17 months [8.9, 36]. Reasons for technique failure included: psychosocial reasons (37%) at a median time 8.9 months [7.7, 13], safety (12.5%) at 19 months [19, 36], and medical (37.5%) at 26 months [11, 50]. LIMITATIONS: Small patient population with quality of data limited by the electronic-based medical record and non-standardized definitions of reasons for exit. CONCLUSIONS: Training failure is a particularly important source of patient loss. Reasons for exit differ according to duration on HHD. Early interventions aimed at reducing train failure and increasing psychosocial supports may help program growth.

CONTEXTE: Pour les patients atteints d'insuffisance rénale, l'hémodialyse à domicile (HDD) offre une modalité flexible et centrée sur le patient. Une meilleure adhésion à l'HHD s'obtient en augmentant le nombre de patients initiés à cette modalité et en réduisant l'attrition grâce à des stratégies visant la prévention des causes modifiables d'abandon. OBJECTIFS: Notre principal objectif était de décrire une population canadienne de patients suivant des traitements d'HDD en ce qui concerne l'échec de la modalité et de délai avant l'abandon de l'HDD, afin de comprendre les raisons qui mènent à cet abandon. En deuxième lieu, nous souhaitions: (1) déterminer les raisons de l'échec de la formation sur la modalité, (2) les raisons de l'abandon précoce de l'HDD et (3) le moment du retrait du programme. MÉTHODOLOGIE: Il s'agit d'une étude de cohorte rétrospective portant sur les patients adultes ayant adopté l'HDD comme modalité entre le 1er janvier 2013 et le 30 juin 2020. CADRE: Le programme d'HDD AKC-S (Alberta Kidney Care South). SUJETS: Les patients ayant commencé une formation sur l'HDD avec le programme AKC-S. MÉTHODOLOGIE: Une étude de cohorte rétrospective portant sur les patients adultes traités par HDD ayant pour principal critère d'évaluation la période pendant laquelle la modalité a été adoptée par les patients. La raison de l'échec de la formation, le délai avant l'abandon de la modalité et les raisons de l'abandon ont constitué les critères d'évaluations secondaires. Un modèle de risques proportionnels de Cox a été employé pour déterminer les associations entre les caractéristiques des patients et l'abandon de la modalité. La probabilité cumulative d'abandon de la modalité au fil du temps a été rapportée à l'aide d'un modèle des risques concurrents. RÉSULTATS: Les résultats portent sur les 167 patients qui étaient passés à l'HDD. L'échec de la formation a été observé chez 20 patients (12 %) après 3,1 [2,0, 5,5] semaines; ces patients étaient plus âgés (P < .001) et présentaient au moins deux maladies concomitantes (P < .001). La transplantation (n = 35; 21 %), le décès (n = 8; 4,8 %) et l'échec de la technique (n = 24; 14,4 %) ont constitué les principales raisons d'abandon de l'HDD après la formation. Dans l'ensemble, le délai médian avant l'abandon de l'HDD était de 23 mois [11, 41] et le délai médian avant l'échec de la technique était de 17 mois [8,9, 36]. Des raisons psychosociales (37 %) après un délai médian de 8,9 mois [7,7, 13], l'innocuité (12,5 %) après 19 mois [19, 36] et des raisons médicales (37,5 %) après 26 mois [11, 50] ont expliqué l'échec de la technique. LIMITES: L'étude porte sur un faible échantillon de patients dont la qualité des données était limitée par le dossier médical électronique. Des définitions non normalisées des raisons de l'abandon limitent également les résultats. CONCLUSION: L'échec de la formation est un facteur qui joue un rôle particulièrement important dans l'abandon de l'HDD par les patients. Les raisons de cet abandon varient en fonction de la durée d'utilisation de la modalité. Des interventions précoces visant à réduire l'échec de la formation et à augmenter le soutien psychosocial pourraient aider à accroître l'adhésion au programme.

Interactions between serum FSH, inhibin B and antral follicle count in the decline of serum AMH during the menstrual cycle in late reproductive age.

Objective: To investigate the hormonal interrelationships during the menstrual cycle in women of late reproductive age with suppressed serum AMH and antral follicle count (AFC). Methods: Serum hormones (AMH, FSH, LH, estradiol, progesterone, inhibin A, inhibin B), AFC (2-10 mm) and AMH/AFC ratio (an estimate of AMH/follicle) were assessed every 2-3 days across the menstrual cycle in 26 healthy ovulatory women aged 18-50 years. Results: An 11-fold fall in AMH/AFC was observed in women aged ≥45 years compared to those 18-45 years (P < .001). Although women ≥45 years exhibited normal menstrual cycle patterns of serum estradiol, progesterone, LH and inhibin A, FSH was elevated (P < .001) and inhibin B suppressed (P < .001) compared to the younger group. Overall FSH was inversely correlated (r = .55, P < .05) and AMH directly correlated (r = .88, P < .01) with AFC; however, these relationships were curvilinear and more pronounced when AFC was low. Inhibin B was directly linearly correlated (r = .70, P < .01) with AFC across both high and low AMH/follicle groups. Conclusions: It is hypothesized that the marked fall in AMH/follicle in late reproductive age is attributed to the change in the hormonal interplay between the pituitary and ovary. The fall in AFC leads to a decrease in inhibin B and a concomitant increase in FSH by a recognized feedback mechanism. It is postulated the elevated FSH suppresses AMH either directly or indirectly through oocyte-specific growth factors leading to a marked fall in AMH/follicle. We propose that pituitary-ovarian and intra-ovarian regulatory systems underpin the accelerated fall in AMH/follicle during the transition to menopause.

Quantifying the medical student learning curve for ECG rhythm strip interpretation using deliberate practice.

Objectives: Obtaining competency in medical skills such as interpretation of electrocardiograms (ECGs) requires repeated practice and feedback. Structured repeated practice and feedback for ECGs is likely not provided to most medical students, so skill development is dependent on opportunistic training during clinical rotations. Our aim was to describe: the amount of deliberate practice completed for learning ECG rhythm strip diagnoses in first year medical students, the learning curve for rhythm strip diagnosis, and student experiences with deliberate practice. Methods: First year medical students from two medical schools were provided with online rhythm strip practice cases. Diagnostic accuracy was measured throughout practice, and students were provided feedback for every case they completed. Total cases practiced and time spent practicing were correlated with their performance during practice and on an exam. Results: 314 of 384 (82%) students consented. The mean number of ECGs each student practiced was 59 (range 0-280), representing 18,466 total instances of deliberate practice. We generated mathematical models that accurately correlated both the number of cases practiced and time spent practicing, with diagnostic accuracy on an exam (p<0.001). For example, students would need to spend on average of 112 minutes and complete 34 practice cases to obtain 75% on an ECG rhythm strip exam. Student satisfaction was high using the online cases. Conclusions: We succeeded in delivering deliberate practice for ECG rhythm strip interpretation to a large cohort of students at 2 medical schools. We quantified a learning curve that estimates the number of cases and practice time required to achieve pre-determined levels of diagnostic accuracy. This data can help inform a competency-based approach to curriculum development.

Trajectories of pain severity in juvenile idiopathic arthritis: results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.

Age-related changes in luteal dynamics: preliminary associations with antral follicular dynamics and hormone production during the human menstrual cycle.

OBJECTIVE: The aim of the study was to test the hypothesis that the development of luteal phase dominant follicles (LPDFs) as women age is associated with abnormal luteal function. METHODS: Luteal and antral follicle diameter were quantified in ovulatory women of midreproductive age (MRA; 18-35 y; n = 9) and advanced reproductive age (ARA; 45-55 y; n = 16) every 1 to 3 days during one complete interovulatory interval. Blood was drawn at each visit and assayed for progesterone, estradiol, inhibin A, follicle-stimulating hormone, and luteinizing hormone. Luteal diameter and hormone profiles were compared within MRA and ARA women with versus without LPDFs. RESULTS: Luteal growth and regression profiles were similar in MRA women with typical versus no LPDFs (13.9, 14.8 mm; P > 0.1); however, luteal phase estradiol and progesterone were greater in MRA women with typical (91.1 ng/L, 8.81 µg/L) versus no (48.8 ng/L, 7.32 µg/L) LPDFs, respectively (LPDF effect, P < 0.1). In the ARA group, mean luteal diameter was lowest in women with atypical LPDFs (12.3 mm), greatest in those with typical LPDFs (16.0 mm), and moderate in those with no LPDFs (13.6 mm), (P < 0.1). Reduced luteal growth in ARA women with atypical versus typical and/or no LPDFs occurred simultaneously to greater luteal phase estradiol (199 vs 69.0, 78.4 ng/L) lower progesterone (7.38 vs 10.7, 13.8 ug/L), and lower inhibin A (36.3, 35.6, 51.2) (P < 0.1). CONCLUSIONS: The development of LPDFs as women age was associated with reduced luteal growth, greater estradiol, lower progesterone, and lower inhibin A. These findings provide preliminary evidence that variations in antral folliculogenesis contribute to luteal insufficiency during the menopausal transition.

Trajectories of Life Satisfaction and their Predictors among Korean Older Adults.

BACKGROUND: Among older adults, life satisfaction (LS) correlates with health, mortality, and successful ageing. As various potential threats to LS tend to increase with advancing years, patterns of age-related changes in LS among older adults remain inconsistent. This study aimed to identify LS trajectories in older adults and the characteristics of individuals who experience them. METHODS: Large-scale, nationally representative, longitudinal data collected from 2005 to 2013 were analyzed for this study. The outcome measure was a summary of multidimensional domains influencing LS: health, finance, housing, neighbor relationships, and family relationships. Latent class growth models and logistic regression models were used to identify trajectory groups and their predictors, respectively. RESULTS: Within 3517 individuals aged 65 or older, five trajectories were identified across eight follow-up years: "low-stable" (TG1; n = 282; 8%), "middle-stable" (TG2; n = 1146; 32.6%), "improving" (TG3; n = 75; 2.1%), "upper middle-stable" (TG4; n = 1653; 47%), and "high" (TG5; n = 361; 10.3%). High trajectory individuals more frequently had higher education, financial security, good physical health, and good mental health than those in the stable, but less satisfied, groups. Similarly, compared to the largest group (upper middle-stable trajectory), individuals in the low-stable or middle-stable trajectory group not only had poorer physical and mental health but were more likely to be living alone, financially stressed, and residing in urban locations. Individuals with improving trajectory were younger and in poorer mental health at baseline compared to the upper middle-stable trajectory group. CONCLUSION: Life satisfaction in the older follows distinct trajectories. For older adults, trajectories are stable over time and predictable, in part, from individual characteristics. Knowledge of these patterns is important for effective policy and program development.

The Effect of Extrinsic Material and Radiation Dose on Model-Based Iterative Reconstruction Chest Computed Tomography Reconstruction Time: A Phantom-Based Study.

OBJECTIVE: Compare effect of extrinsic materials and radiation dose levels on image processing times for model-based iterative reconstruction (MBIR) in computed tomography. METHODS: Chest computed tomography scans were performed on a phantom with three different levels of clothing and medical equipment at three tube current settings to reflect differing radiation doses. Reconstruction time for MBIR was recorded, and objective image quality was assessed via noise within the phantom mediastinum. Reconstruction time and noise were compared between scans, with noise also compared between MBIR and matching filtered back projection (FBP) images. RESULTS: Reconstruction times (minutes:seconds) ranged from 37:31 to 42:24. Times were generally faster with less extrinsic material and prolonged among high-dose scans when materials were present. On both the MBIR and FBP images, noise levels were improved with higher radiation doses, although for MBIR only minimally, and the relative effect of extrinsic materials at a given radiation dose was also minimal. In addition, noise was better with MBIR than FBP reconstruction for all conditions. CONCLUSIONS: Typical MBIR reconstruction times are faster with less extrinsic materials in the scan field of views, and removing extraneous blankets or medical devices could positively affect workflow over the course of the day. In addition, MBIR reconstruction times are also shorter when using lower dose protocols in situations requiring extensive materials.

Multidimensional construct of life satisfaction in older adults in Korea: a six-year follow-up study.

BACKGROUND: Aging raises wide-ranging issues within social, economic, welfare, and health care systems. Life satisfaction (LS) is regarded as an indicator of quality of life which, in turn, is associated with mortality and morbidity in older adults. The objective of this study was to identify the relevant predictors of life satisfaction and to investigate changes in a multidimensional construct of LS over time. METHODS: This analysis utilized data from the large-scale, nationally representative Korean Retirement and Income Study (KReIS), a longitudinal survey conducted biennially from 2005 to 2011. Outcome measures were degree of satisfaction with health, economic status, housing, neighbor relationships, and family relationships. GEE models were used to investigate changes in satisfaction within each of the five domains. RESULTS: Of a total 3531 individuals aged 65 or older, 2083 (59%) were women, and the mean age was 72 (s.d = ±6) years. The majority had a spouse (60.8%) and lived in a rural area (58%). Analysis showed that physical and mental health were consistently and significantly associated with satisfaction in each of the domains after adjusting for potential confounders. Living in a rural area and living with a spouse were related to satisfaction with economic, housing, family relationships, and neighbor relationships compared to living in urban areas and living without a spouse; the only outcome that did not show relationship to these predictors was health satisfaction. Female and rural residents reported greater economic satisfaction compared to male and urban residents. Living in an apartment was associated with 1.32 times greater odds of economic satisfaction compared to living in a detached house (95% CI: 1.14-1.53; p < 0.0001). Economic satisfaction was also 1.62 times more likely among individuals living with a spouse compared to single households (95% CI: 1.35-1.96; p < 0.0001). Financial stress index value was found to be a significant predictor of satisfaction with family relationships. CONCLUSIONS: Our study indicates that a single domain of LS or overall LS will miss many important aspects of LS as age-related LS is multi-faceted and complicated. While most studies focus on overall life satisfaction, considering life satisfaction as multidimensional is essential to gaining a complete picture.

A Clinical Randomized Trial Comparing the Cycloplegic Effect of Cyclopentolate Drops Applied to Closed Eyelids Versus Open Eyelids.

BACKGROUND AND PURPOSE: Adequate cycloplegia and dilation are required for refraction and fundus exam in children. Standard practice is to instill cycloplegic drops in the inferior cul-de-sac, and this is often traumatic for children. Our study assesses the use of cyclopentolate on closed lids as a method of instillation for ensuring complete cycloplegia. PATIENTS AND METHOD: Ninety children presenting for annual refraction were enrolled. Three were excluded as they did not finish the testing. One drop of Alcaine® and one drop of cyclopentolate HCL 1% were used in each eye. Cyclopentolate drops were placed on the inner canthus near the lid margin on the closed eye and directly onto the conjunctiva of the fellow eye. RESULTS: Overall, 145/174 eyes (83%) were fully cyclopleged with one drop. The methods of instillation were equally successful (seventy-two indirect vs. seventy-three direct). Age, eye color, spherical refractive error, astigmatic refractive error, and presence of amblyopia on the study visit played no role in the success of either method. Dark irises where the pupil margin was clinically indistinguishable had the largest number of failures (n = 17/44) in comparison to light irises (12/130), but had an equal amount of failures for both direct and indirect methods. CONCLUSION: Placing one drop of cyclopentolate HCL 1% on a closed eyelid had a success rate for complete cycloplegia that was equivalent to placing one drop directly on the cornea.

Interrelationships among reproductive hormones and antral follicle count in human menstrual cycles.

It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1-3 days across one interovulatory interval (IOI) from 26 healthy women aged 18-50 years. The antral follicle count (AFC) for follicles 2-5 mm, >6 mm and 2-10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.