Artificial intelligence to predict clinical disability in patients with multiple sclerosis using FLAIR MRI.

PURPOSE: The purpose of this study was to create an algorithm that combines multiple machine-learning techniques to predict the expanded disability status scale (EDSS) score of patients with multiple sclerosis at two years solely based on age, sex and fluid attenuated inversion recovery (FLAIR) MRI data. MATERIALS AND METHODS: Our algorithm combined several complementary predictors: a pure deep learning predictor based on a convolutional neural network (CNN) that learns from the images, as well as classical machine-learning predictors based on random forest regressors and manifold learning trained using the location of lesion load with respect to white matter tracts. The aggregation of the predictors was done through a weighted average taking into account prediction errors for different EDSS ranges. The training dataset consisted of 971 multiple sclerosis patients from the "Observatoire français de la sclérose en plaques" (OFSEP) cohort with initial FLAIR MRI and corresponding EDSS score at two years. A test dataset (475 subjects) was provided without an EDSS score. Ten percent of the training dataset was used for validation. RESULTS: Our algorithm predicted EDSS score in patients with multiple sclerosis and achieved a MSE=2.2 with the validation dataset and a MSE=3 (mean EDSS error=1.7) with the test dataset. CONCLUSION: Our method predicts two-year clinical disability in patients with multiple sclerosis with a mean EDSS score error of 1.7, using FLAIR sequence and basic patient demographics. This supports the use of our model to predict EDSS score progression. These promising results should be further validated on an external validation cohort.

Critical care capacity in Haiti: A nationwide cross-sectional survey.

OBJECTIVE: Critical illness affects health systems globally, but low- and middle-income countries (LMICs) bear a disproportionate burden. Due to a paucity of data, the capacity to care for critically ill patients in LMICs is largely unknown. Haiti has the lowest health indices in the Western Hemisphere. In this study, we report results of the first known nationwide survey of critical care capacity in Haiti. DESIGN: Nationwide, cross-sectional survey of Haitian hospitals in 2017-2018. SETTING: Haiti. SUBJECTS: All Haitian health facilities with at least six hospital beds. INTERVENTIONS: Electronic- and paper-based survey. RESULTS: Of 51 health facilities identified, 39 (76.5%) from all ten Haitian administrative departments completed the survey, reporting 124 reported ICU beds nationally. Of facilities without an ICU, 20 (83.3%) care for critically ill patients in the emergency department. There is capacity to ventilate 62 patients nationally within ICUs and six patients outside of the ICU. One-third of facilities with ICUs report formal critical care training for their physicians. Only five facilities met criteria for a Level 1 ICU as defined by the World Federation of Societies of Intensive and Critical Care Medicine. Self-identified barriers to providing more effective critical care services include lack of physical space for critically ill patients, lack of equipment, and few formally trained physicians and nurses. CONCLUSIONS: Despite a high demand for critical care services in Haiti, current capacity remains insufficient to meet need. A significant amount of critical care in Haiti is provided outside of the ICU, highlighting the important overlap between emergency and critical care medicine in LMICs. Many ICUs in Haiti lack basic components for critical care delivery. Streamlining critical care services through protocol development, education, and training may improve important clinical outcomes.

[Update in severe asthma physiopathology and treatments]. / Actualités physiopathologiques et thérapeutiques dans l'asthme sévère.

Asthma is an inflammatory airway disease which presentation is highly heterogeneous. Last two decades provided new clinical and basic data concerning asthma physiopathology that make global understanding much complex. Phenotypes based on clinical settings and paraclinical investigations from large cohorts confirm old paradigm (eosinophilic vs. non-eosinophilic asthma) but also introduce new concepts (obesity-related asthma, late onset asthma, etc.). Conversely, improvement of big data analytics allows to initiate new cohorts aiming at better understanding the pathophysiology underlying those phenotypes and unraveling new ones. However, clinical and therapeutic impacts of those big data need to be further detailed. In parallel, biotherapies and innovative techniques as bronchial thermoplasty become available for severe asthmatic patients who did not respond to specific treatment in the past. Development of a personalized medicine in severe asthma becomes an important challenge for tomorrow. This review will focus on new pathophysiological concepts arisen from large cohorts and new therapeutic strategies available and in progress for severe asthma.

Trends in work-related mental disorders by sector in France.

BACKGROUND: Notifications of work-related mental disorders (WRMDs) are increasing while little data are available on trends by industrial sector. AIMS: To assess WRMD notifications and trends from 2001 to 2011 by industrial sector using data collected by the French National Network for Occupational Disease Vigilance and Prevention (RNV3P) network. METHODS: We calculated standardized notification ratios (SNRs) per sector. To analyse trends over time, we used odds ratios, analysed by logistic regression, including time as a discrete variable or as a continuous variable. RESULTS: We found higher than expected WRMD notifications in manufacturing; paper and book (SNR = 2.16; 95% CI [1.88-2.48]), chemical and pharmaceutical (SNR = 1.79; 95% CI [1.58-2.03]), textile and clothing (SNR = 1.27; 95% CI [1.04-1.54]). In the trade sectors, retail (SNR = 1.60; 95% CI [1.52-1.68]), motor vehicle and cycle trade and repair (SNR = 1.19; 95% CI [1.05-1.34]). In the services sector personal (SNR = 2.09; 95% CI [1.83-2.38]), information technology (SNR = 1.54; 95% CI [1.36-1.74]), financial and insurance (SNR = 1.42; 95% CI [1.31-1.53]), post and telecommunication (SNR = 1.44; 95% CI [1.30-1.60]), human health and social work (SNR = 1.29; 95% CI [1.24-1.34]). We found an increase in notifications in agriculture, post-telecommunication services and the human health/social work sectors and a decrease in chemical/pharmaceutical, metal, and paper and book manufacturing sectors (P < 0.05). CONCLUSIONS: These results reveal trends in notifications for WRMDs by industrial sector. This highlights the importance of monitoring trends in WRMDs in specific worker subsets, using specialized networks such as the RNV3P.

Association of the Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) Score With Excess Hospital Mortality in Adults With Suspected Infection in Low- and Middle-Income Countries.

Importance: The quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score has not been well-evaluated in low- and middle-income countries (LMICs). Objective: To assess the association of qSOFA with excess hospital death among patients with suspected infection in LMICs and to compare qSOFA with the systemic inflammatory response syndrome (SIRS) criteria. Design, Settings, and Participants: Retrospective secondary analysis of 8 cohort studies and 1 randomized clinical trial from 2003 to 2017. This study included 6569 hospitalized adults with suspected infection in emergency departments, inpatient wards, and intensive care units of 17 hospitals in 10 LMICs across sub-Saharan Africa, Asia, and the Americas. Exposures: Low (0), moderate (1), or high (≥2) qSOFA score (range, 0 [best] to 3 [worst]) or SIRS criteria (range, 0 [best] to 4 [worst]) within 24 hours of presentation to study hospital. Main Outcomes and Measures: Predictive validity (measured as incremental hospital mortality beyond that predicted by baseline risk factors, as a marker of sepsis or analogous severe infectious course) of the qSOFA score (primary) and SIRS criteria (secondary). Results: The cohorts were diverse in enrollment criteria, demographics (median ages, 29-54 years; males range, 36%-76%), HIV prevalence (range, 2%-43%), cause of infection, and hospital mortality (range, 1%-39%). Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. Compared with a low or moderate score, a high qSOFA score was associated with increased risk of death overall (19% vs 6%; difference, 13% [95% CI, 11%-14%]; odds ratio, 3.6 [95% CI, 3.0-4.2]) and across cohorts (P < .05 for 8 of 9 cohorts). Compared with a low qSOFA score, a moderate qSOFA score was also associated with increased risk of death overall (8% vs 3%; difference, 5% [95% CI, 4%-6%]; odds ratio, 2.8 [95% CI, 2.0-3.9]), but not in every cohort (P < .05 in 2 of 7 cohorts). High, vs low or moderate, SIRS criteria were associated with a smaller increase in risk of death overall (13% vs 8%; difference, 5% [95% CI, 3%-6%]; odds ratio, 1.7 [95% CI, 1.4-2.0]) and across cohorts (P < .05 for 4 of 9 cohorts). qSOFA discrimination (area under the receiver operating characteristic curve [AUROC], 0.70 [95% CI, 0.68-0.72]) was superior to that of both the baseline model (AUROC, 0.56 [95% CI, 0.53-0.58; P < .001) and SIRS (AUROC, 0.59 [95% CI, 0.57-0.62]; P < .001). Conclusions and Relevance: When assessed among hospitalized adults with suspected infection in 9 LMIC cohorts, the qSOFA score identified infected patients at risk of death beyond that explained by baseline factors. However, the predictive validity varied among cohorts and settings, and further research is needed to better understand potential generalizability.

Food allergen-sensitized CCR9+ lymphocytes enhance airways allergic inflammation in mice.

BACKGROUND: The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors. OBJECTIVES: We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases. METHODS: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite. RESULTS: Compared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/Treg ratio, was abrogated in CCR9 knockout mice. Moreover, transfer of food-allergic CD4+ T cells from wild-type but not from CCR9-/- aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens. CONCLUSION: Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.

Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - EIP on AHA Twinning Reference Site (GARD research demonstration project).

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.

Perceived benefits of the hepatitis C peer educators: a qualitative investigation.

BACKGROUND: Although opioid-dependent patients are disproportionately impacted by hepatitis C (HCV), many do not receive treatment. In addition to HCV treatment-access barriers, substance-using patients may be reluctant to pursue treatment because of wariness of the medical system, lack of knowledge, or stigma related to HCV treatment. Implementation of a formal peer education program is one model of reducing provider- and patient-level barriers to HCV treatment, by enhancing mutual trust and reducing stigma. METHODS: We used thematic qualitative analysis to explore how 30 HCV patients and peer educators perceived a HCV peer program within an established methadone maintenance program in the USA. RESULTS: Participants unanimously described the program as beneficial. Participants described the peer educators' normalization and dispelling of myths and fears around HCV treatment, and their exemplification of HCV treatment success, and reductions in perceived stigma. Peer educators described personal benefits. CONCLUSIONS: These findings indicate that HCV peer educators can enhance HCV treatment initiation and engagement within opioid substitution programs.

Treatment outcomes after implementation of an adapted WHO protocol for severe sepsis and septic shock in Haiti.

PURPOSE: The World Health Organization (WHO) has developed a simplified algorithm specific to resource-limited settings for the treatment of severe sepsis emphasizing early fluids and antibiotics. However, this protocol's clinical effectiveness is unknown. We describe patient outcomes before and after implementation of an adapted WHO severe sepsis protocol at a community hospital in Haiti. MATERIALS AND METHODS: Using a before-and-after study design, we retrospectively enrolled 99 adult Emergency Department patients with severe sepsis from January through March 2012. After protocol implementation in January 2014, we compared outcomes to 67 patients with severe sepsis retrospectively enrolled from February to April 2014. We defined sepsis according to the WHO's Integrated Management of Adult Illness guidelines and severe sepsis as sepsis plus organ dysfunction. RESULTS: After protocol implementation, quantity of fluid administered increased and the physician's differential diagnoses more often included sepsis. Patients were more likely to have follow-up vital signs taken sooner, a radiograph performed, and a lactic acid tested. There were no improvements in mortality, time to fluids or antimicrobials. CONCLUSIONS: Use of a simplified sepsis protocol based primarily on physiologic parameters allows for substantial improvements in process measures in the care of severely septic patients in a resource-constrained setting.

Minimum standards on prevention, diagnosis and treatment of occupational and work-related skin diseases in Europe - position paper of the COST Action StanDerm (TD 1206).

BACKGROUND: Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. OBJECTIVE: To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). METHOD: Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. RESULTS: By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. CONCLUSION: The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of OSD and their socio-economic burden.

Occupational skin diseases: actual state analysis of patient management pathways in 28 European countries.

BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment and rehabilitation in different European countries. METHODS: A questionnaire-based survey of the current situation regarding OSD patient management pathways was carried out with experts on occupational dermatology and/or occupational medicine from 28 European countries contributing to the European Cooperation in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks (synonyms: insurance against work accidents and occupational injuries; statutory social accident insurance)]. Legal standards for the assessment of occupationally triggered diseases with a genetic background differ between different countries, however, in most European member states recognition as OSD is possible. In one-third of the countries UV light-induced tumours can be recognized as OSD under specific conditions. CONCLUSION: OSD definitions vary between European countries and are not directly comparable, which hampers comparisons between statistics collected in different countries. Awareness of this fact and further efforts for standardization are necessary.

Remote tele-mentored ultrasound for non-physician learners using FaceTime: A feasibility study in a low-income country.

PURPOSE: Ultrasound (US) is a burgeoning diagnostic tool and is often the only available imaging modality in low- and middle-income countries (LMICs). However, bedside providers often lack training to acquire or interpret US images. We conducted a study to determine if a remote tele-intensivist could mentor geographically removed LMIC providers to obtain quality and clinically useful US images. MATERIALS AND METHODS: Nine Haitian non-physician health care workers received a 20-minute training on basic US techniques. A volunteer was connected to an intensivist located in the USA via FaceTime. The intensivist remotely instructed the non-physicians to ultrasound five anatomic sites. The tele-intensivist evaluated the image quality and clinical utility of performing tele-ultrasound in a LMIC. RESULTS: The intensivist agreed (defined as "agree" or "strongly agree" on a five-point Likert scale) that 90% (57/63) of the FaceTime images were high quality. The intensivist felt comfortable making clinical decisions using FaceTime images 89% (56/63) of the time. CONCLUSIONS: Non-physicians can feasibly obtain high-quality and clinically relevant US images using video chat software in LMICs. Commercially available software can connect providers in institutions in LMICs to geographically removed intensivists at a relatively low cost and without the need for extensive training of local providers.

p53 binds the mdmx mRNA and controls its translation.

MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5' untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5'UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulating protein expression in the p53 pathway.

Sepsis in Haiti: Prevalence, treatment, and outcomes in a Port-au-Prince referral hospital.

PURPOSE: Developing countries carry the greatest burden of sepsis, yet few descriptive data exist from the Western Hemisphere. We conducted a retrospective cohort study to elucidate the presentation, treatment, and outcomes of sepsis at an urban referral hospital in Port-au-Prince, Haiti. MATERIALS AND METHODS: We studied all adult emergency department patient encounters from January through March 2012. We characterized presentation, management, and outcomes using univariable and multivariable analyses. RESULTS: Of 1078 adult patients, 224 (20.8%) had sepsis and 99 (9.2%) had severe sepsis. In-hospital mortality for severe sepsis was 24.2%. Encephalopathy was a predictor of intravenous fluid administration (adjusted odds ratio [OR], 5.63; 95% confidence interval [CI], 1.46-21.76; P=.01), and lower blood pressures predicted shorter time to fluid administration. Increasing temperature and lower blood pressures predicted antibiotic administration. Encephalopathy at presentation (adjusted OR, 6.92; 95% CI, 1.94-24.64; P=.003), oxygen administration (adjusted OR, 15.96; 95% CI, 3.05-83.59; P=.001), and stool microscopy (adjusted OR, 45.84; 95% CI, 1.43-1469.34; P=.03) predicted death in severe sepsis patients. CONCLUSIONS: This is the first descriptive study of sepsis in Haiti. Our findings contribute to the knowledge base of global sepsis and reveal similarities in independent predictors of mortality between high- and low-income countries.

Lesiones orales y coriorretinitis placoide posterior como forma de presentación de sífilis secundaria en un paciente inmunocompetente / Secondary syphilis presenting as oral lesions and posterior placoid chorioretinitis in an immunocompetent patient

No disponible

A review of occupational disease surveillance systems in Modernet countries.

BACKGROUND: To improve occupational health public policies and to facilitate coordinated research within the European Union to reduce the incidence of occupational diseases (ODs), it is important to know what OD surveillance systems exist and how they compare. Monitoring trends in occupational diseases and tracing new and emerging risks in a network (Modernet) participants are well placed to provide this information as most either contribute data to and/or are involved in the management of OD systems. AIMS: To identify and describe OD surveillance systems in Modernet countries with the longer-term objective of identifying a core template to be used on a large scale. METHODS: A questionnaire sent to Modernet participants, seeking structured information about the OD surveillance system(s) in their country. RESULTS: Overall 14 countries (70%) provided information for 33 OD systems, among them 11 compensation-based (CB) systems. Six countries provided information for non-CB systems reporting for any type of OD. The other systems reported either only ODs from a prescribed list, or specific diagnoses or diagnostic groups, with reports to most schemes being physician-based. Data collected varied but all systems collected diagnosis, age, gender, date reported and occupation (and/or industry) and most collected information on exposure. CONCLUSIONS: This review provides information beneficial to both policy makers and researchers by identifying data sources useable to measure OD trends in European countries and opening the way to future work, both on trend comparisons within Europe and on the definition of a core template to extend OD surveillance on a larger scale.

Occupational contact urticaria: lessons from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P).

BACKGROUND: Occupational contact urticaria (OCU) is an occupational contact dermatitis that can cause serious health consequences and disability at work. OBJECTIVES: To describe OCU and its temporal trends by the main causal agents and activity sectors in a nationwide scheme in France. METHODS: Using data from the French National Network for Occupational Disease Vigilance and Prevention (RNV3P), we described OCU reported during the period 2001-10 and analysed the temporal trends of OCU and OCU attributed to the most frequent agents over the study period. Trends analyses were supported by reporting odds ratios using a logistic regression model with reference to 2001, or with time as a continuous variable. RESULTS: During the study period, 251 cases of OCU were reported in RNV3P, half of which were due to natural rubber latex, in particular in the health and social work activity sector (HSW). The number of these cases declined significantly over the study period (19% per year), and particularly after 2006. Conversely, the other causes of OCU did not decrease. CONCLUSIONS: Using surveillance data from a French national network, this study has found that there was a significant decline in OCU due to natural rubber latex, particularly in the HSW, when powdered latex gloves were banned from French hospitals. Our results show the effectiveness of this preventive measure, and suggest that this practice should be extended to other sectors.