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Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy. [ABSTRACT FROM AUTHOR]

Medical journals, such as the Journal of Clinical Medicine, have played a significant role in disseminating new knowledge in various medical fields. They provide a platform for researchers to share their discoveries, methodologies, and results in a peer-reviewed manner. Medical journals also contribute to the continuous improvement of healthcare by providing updates on practice standards, clinical guidelines, and novel therapeutic approaches. They address ethical and social issues related to medical advances and offer historical documentation of the evolution of medical knowledge. However, medical journals face challenges in adapting to societal changes and incorporating new advancements in medicine, such as data science, digital technology, personalized medicine, and sustainable development. [Extracted from the article]

Both society and human beings are evolving at exponential speeds. Health and medicine are following the same path. Digital technology and data are turning our world upside down. Information is becoming ephemeral, shared, sometimes inaccurate, incorrect and fragmented, and knowledge is shifting, evolving and sometimes uncertain. However, medical journals are still a vital channel for the transmission, validation and discussion of medical knowledge. They are an essential pillar of the medical community, contributing to the continuous improvement of healthcare and scientific progress in the medical field. Medical journals are both drivers and vehicles for medical innovation. They must, however, evolve and adapt to changes in society, and reinvent themselves in the light of medical issues, those of healthcare professionals and patients, and even new medical trends and themes such as data, artificial intelligence, sustainable development, transhumanism and unique health. [ABSTRACT FROM AUTHOR]

The Journal of Clinical Medicine (J. Clin. Med.) wishes its readers a happy and successful new year. The journal aims to enrich readers' knowledge and inspire them in patient care. It is recognized as a reference journal in the medical field and has maintained a fluctuating impact factor between 3.9 and 5.6 over the past five years. The journal emphasizes its commitment to scientific rigor, transparency, and independence from industry players. Reader participation is encouraged through article submissions, feedback, and suggestions for future topics. The journal values its readers' contributions and aims to support their pursuit of knowledge and excellence. [Extracted from the article]

The article offers information on the wishes for the new year 2024 from the editorial committee of the journal Cahiers Santé/Médecine Thérapeutique (Cs/Mt) to its readers, emphasizing health, happiness, and success. Topics include the importance of reader participation in contributing original articles, literature reviews, case studies, and other relevant contributions to the journal.

Résumé: Le protoxyde d'azote est un gaz incolore, inodore, utilisé assez largement par les services d'urgences (intra- ou extrahospitaliers) dans le cadre de la traumatologie adulte ou enfant ainsi que dans les cabinets dentaires. Il entre notamment dans la composition du mélange équimolaire d'oxygène et de protoxyde d'azote (MEOPA), où les deux gaz entrent à parts égales. Son utilisation dans le cadre du traitement des douleurs chroniques, en particulier neuropathiques, semble prometteuse. Le principal inconvénient du protoxyde d'azote est son cortège d'effets indésirables à type de nausées et de vomissements, ainsi que son accumulation dans une atmosphère confinée, notamment dans le cadre d'une utilisation au bloc opératoire. Dans le cadre d'une utilisation chronique, une toxicité neurologique et hématologique a été rapportée, en rapport avec une carence fonctionnelle en vitamine B12 (cobalamine) [1, 2]. Le protoxyde d'azote oxyde en effet de façon irréversible l'atome de cobalt présent au sein de la vitamine B12 et inactive partiellement la méthionine synthétase, aboutissant à un syndrome neuroanémique comme décrit dans la maladie de Biermer. Dans ce contexte, cet article se propose de définir les modalités pratiques de l'utilisation du protoxyde d'azote au long cours au regard du statut en vitamine B12 de chaque individu. [ABSTRACT FROM AUTHOR]

Ces dernières années, la prise en charge de la maladie thromboembolique veineuse (MTEV), incluant les thromboses veineuses profondes (TVP) et les embolies pulmonaires (EP), tend à se modifier. Une possibilité de prise en charge ambulatoire, exclusive ou après un court séjour hospitalier (moins de 24 h), est ainsi proposée par certaines sociétés savantes, principalement les EP à faible risque (simplified pulmonary embolism severity index = 0) et certaines EP à risque intermédiaire, pour certains patients (sujet jeune, sans comorbidité, ayant compris la maladie et le traitement anticoagulant, et non socialement isolés). C'est dans ce contexte qu'un groupe de travail pluridisciplinaire, regroupant des médecins de diverses spécialités, exerçant à l'hôpital ou en ville et impliqués dans la MTEV, a été créé dans notre région (Alsace) avec pour objectif de travailler sur le parcours de soin de la MTEV, surtout sur la prise en charge ambulatoire, et de proposer des recommandations pour les médecins exerçant en ville. Ces dernières font apparaître que la prise en charge de la MTEV, outre qu'elle doit cibler un phénotype bien précis de patients, doit reposer, en cas de prise en charge ambulatoire et en ville, un parcours de soins organisé, structuré et coordonné (« optimisée » ou « optimale »). [ABSTRACT FROM AUTHOR]

This is a narrative review of telemonitoring (remote monitoring) projects and studies within the field of diabetes, with a focus on results of the more recent studies. Since the beginning of the 1990s, several telemedicine projects and studies focused on type 1 and type 2 diabetes. Over the last 5 years, numerous telemedicine projects based on connected objects and new information and communication technologies (ICT) (elements defining telemedicine 2.0) have emerged or are still under development. Two examples are the DIABETe and Telesage telemonitoring project which perfectly fits within the telemedicine 2.0 framework -- the first to include artificial intelligence (AI) with MyPrediTM and DiabeoTM. Mainly, these projects and studies show that telemonitoring diabetic result in: improvements in control of blood glucose (BG) level and significant reduction in HbA1c (e.g., for Telescot et TELESAGE studies); positive impact on co-morbidities (arterial hypertension, weight, dyslipidemia) (e.g., for Telescot and DIABETe studies); better patient's quality of life (e.g., for DIABETe study); positive impact on appropriation of the disease by patients and/or greater adherence to therapeutic and hygienedietary measures (e.g., The Utah Remote Monitoring Project); and at least, good receptiveness by patients and their empowerment. To date, the magnitude of its effects remains debatable, especially with the variation in patients' characteristics (e.g., background, ability for self-management, medical condition), samples selection and approach for the treatment of control groups. All of the recent studies have been classified as "Moderate" to "High". [ABSTRACT FROM AUTHOR]

The article describes how high blood pressure (HTA) has always been a topic of debate and news, including the arrival, each year, new recommendations made by various learned societies and by government agencies each country. It notes that the recommendations are based on the latest data of science, integrate the data from the evidence based medicine and constitute a valuable tool for the clinician.

Contexte : cette revue présente les projets de télésurveillance dans le domaine du diabète de type 1 et de type 2, avec une attention particulière portée aux projets et aux études de télémédecine 2.0. Résultats : depuis le début des années 1990, de nombreux projets et études de télémédecine axés sur le diabète de type 1 et de type 2 ont été développés. L'analyse de ces derniers montre que la télésurveillance du diabète se traduit par une amélioration du contrôle glycémique, une réduction significative de l'hémoglobine glyquée, une meilleure appropriation de la maladie par les patients, une plus grande adhésion des patients aux mesures thérapeutiques et hygiénodiététiques, un impact positif sur les comorbidités (hypertension artérielle, poids, dyslipidémie), une meilleure qualité de vie des patients, une bonne réceptivité des solutions développées et une responsabilisation des patients vis-à-vis de leur maladie et de la connaissance qu'ils en ont. La quantification de ces effets bénéfiques est cependant difficile, compliquant la démonstration de l'utilité de la télémédecine dans le diabète, au regard de la médecine factuelle. Au cours des cinq dernières années, divers projets de télémédecine basés sur les objets connectés et les nouvelles technologies de l'information et de la communication (éléments définissant la télémédecine 2.0) ont vu le jour. Les projet de télésurveillance DIABETe et Telesage s'inscrivent parfaitement dans le cadre de la télémédecine 2.0. Ils sont notamment les premiers à inclure une intelligence artificielle avec MyPrediTM et DiabeoTM. [ABSTRACT FROM AUTHOR]

Information about several papers discussed at a symposium held March 23, 2017 sponsored by the Leo Pharma1on thromboembolism in gynecology and obstetrics is presented. Topics include relation between thrombosis and breast cancer, autoimmune pathologies during pregnancy and protection of pregnant women from hemorrhage during delivery.

The article presents the author's views on Tocilizumab drug for the treatment of Horton's disease or temporal arteritis. It discusses current treatment regimes in France which are based on the corticotherapy. The recommendations of the European League Against Rheumatism (Eular) concerning temporal arteritis retain the dose of prednisone.

The article presents information on "Symposium on the thromboembolism disease in gynecology-obstetrics and senology" that was held on March 23, 2017, in Strasbourg, France. The theme of the conference was thromboembolism and cancer. It discusses thromboembolic risk in the absence prophylaxis during gynecological carcinological prophylactic treatment.

La télémédecine est susceptible d'aider à la prise en charge des patients souffrant de pathologies chroniques et d'éviter des urgences vitales et des hospitalisations. Dans ce cadre, nous avons expérimenté, auprès de patients présentant une insuffisance cardiaque (IC), une e-plateforme, E-care, dédiée à la détection automatisée et « intelligente » des situations à risque de décompensation cardiaque. E-care repose sur des capteurs médicaux communicants, transmettant en temps réel des informations physiologiques à un système intelligent (MyPredi), associé à une ontologie médicale, aboutissant in fine à la génération ou non d'alertes. Ces dernières sont liées à une dégradation de l'état de santé des patients en rapport avec une décompensation des pathologies chroniques (critère 1), en particulier de l'IC (critère 2). Une expérimentation a été menée pour valider ces alertes. La plateforme E-care a ainsi été déployée entre février 2014 et avril 2015 auprès de patients suivis en médecine interne. Les alertes émises durant cette période ont été colligées et analysées rétrospectivement en termes de sensibilité (SE), de spécificité (SPE) et de valeurs prédictives positive (VPP) et négative (VPN). Cent quatre-vingts patients ont été inclus et 1 500 mesures réalisées. Le profil des patients inclus était celui d'un sujet âgé et polypathologique, avec un indice de Charlson moyen de 4,1, IC dans plus de 60 % des cas. L'analyse des alertes montre : pour le critère 1, des valeurs de SE, de SPE, de VPP et de VPN, de respectivement de 100, 30, 89 et 100 % ; et pour le critère 2, des valeurs de SE, de SPE, de VPP et de VPN, de respectivement de 100, 72, 90 et 100 %. La plateforme E-care permet ainsi de détecter 100 % des décompensations cardiaques, les trois quarts des alertes étant en outre en rapport avec cette dernière. Seuls 10 % des alertes ne sont pas en rapport directe avec l'IC. Ces résultats mettent en évidence qu'en l'absence d'alerte, le patient n'a pas de problème, au prix de nombreuses fausses alertes. En pratique, le système de télémédecine E-care et son intelligence artificielle MyPredi permettent donc, de façon automatique et non intrusive, de générer des alertes en rapport avec la dégradation de l'état de santé du patient, et surtout une décompensation cardiaque. [ABSTRACT FROM AUTHOR]

Objective : The objective of this narrative review is to provide an update on the effectiveness of oral and nasal vitamin B12 (cobalamin). Method : Relevant articles were identified by PubMed and Scholar Google search from January 2010 and June 2018 and through hand search of relevant reference articles. Additional studies were obtained from references of identified studies, the Cochrane Library and the ISI Web of Knowledge. Data gleaned from international meetings were also used, as information gleaned from commercial sites on the web and data from CARE-B12 research group. Results : For oral vitamin B12, four randomized controlled trials, one systematic and four reviews, three prospective papers, and thirteen prospective studies fulfilled our inclusion criteria. The present review documents that oral vitamin B12 replacement at 1,000 μg daily was adequate to cure mainly clinical manifestations related to vitamin B12 deficiency, with safety profile. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume, reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. For nasal vitamin B12, only few preliminary studies were available. Conclusions : We conclude that oral vitamin B12 is an effective alternative to vitamin B12 IM injections. Oral vitamin B12 treatment avoids the discomfort, inconvenience and cost of monthly injections. [ABSTRACT FROM AUTHOR]

Background: Despite major advances in its prevention and treatment, febrile neutropenia remains a most concerning complication of cancer chemotherapy. Outside the oncology setting, however, only few data are currently available on febrile neutropenia related to non-chemotherapy drugs. We report here data on 76 patients with febrile neutropenia related to non-chemotherapy drugs, followed up in a referral center within a university hospital. Patients and methods: Data from 76 patients with idiosyncratic drug-induced febrile neutropenia were retrospectively reviewed. All cases were extracted from a cohort study on agranulocytosis conducted at the Strasbourg University Hospital (Strasbourg, France). Results: Mean patient age was 52.2 years old (range: 18-93) and gender ratio (F/M) 1.6, with several comorbidities present in 86.8% of patients. The most common causative drugs were: antibiotics (37.4%), antithyroid drugs (17.2%), neuroleptic and anti-epileptic agents (13.1%), non-steroidal anti-inflammatory agents and analgesics (8%), and platelet aggregation inhibitors (8%). Main clinical presentations upon hospitalization included isolated fever (30%), sore throat, acute tonsillitis and sinusitis (18.4%), documented pneumonia (18.4%), septicemia (14.5%), and septic shock (6.6%). Mean neutrophil count at nadir was 0.13 x 10(9)/L (range: 0-0.48). While in hospital, 22 patients (28.9%) worsened clinically and required intensive care unit placement. All patients were promptly treated with broad-spectrum antibiotics, and 45 (59.2%) with hematopoietic growth factors. Mean duration of hematological recovery (neutrophil count ≥1.5 x 10(9)/L) was 7.5 days (range: 2-21), which was reduced to 0.7 days (range: 2-16) (p = 0.089) with hematopoietic growth factors. Outcome was favorable in 89.5% of patients, whereas eight died. Conclusions: Like in oncology and myelosuppressive chemotherapy settings, idiosyncratic febrile neutropenia is typically serious, about 40% of patients exhibiting severe pneumonia, septicemia, and septic shock, with a mortality rate of 10%. Like in febrile, chemotherapy-related neutropenia, modern and timely management (immediate broad spectrum antibiotherapy, hematopoietic growth factors) may reduce infection-related mortality. All practitioners should be aware of this potential side-effect that may even occur in the event of "daily medication" exposure. [ABSTRACT FROM AUTHOR]

La bronchite aiguë est une infection des voies aériennes basses et peut s'accompagner d'une toux sèche ou grasse au bout de quatre ou cinq jours d'évolution. L'étiologie de la bronchite aiguë est majoritairement virale et cette pathologie a une tendance à l'autoguérison dans les deux à trois semaines. Il s'agit d'une pathologie fréquente en médecine générale et souvent sujette à de nombreuses prescriptions d'efficacité variable. L'efficacité antitussive de la codéine est très limitée et, depuis un changement d'autorisation de mise sur le marché (AMM) en 2015, cette molécule ne peut être prescrite qu'à partir de 12 ans. Les niveaux de preuve pour le dextrométhorphane, la pholcodine et les antihistaminiques de première génération sont très limités chez les adultes et les enfants. Aucune étude prouvant l'efficacité antitussive de l'éthylmorphine, de la noscapine, de la pentoxyvérine ou de l'oxéladine n'a pu être identifiée. Le traitement de la bronchite est surtout symptomatique et se base sur des conseils simples tels qu'une hydratation suffisante per os et une humification de l'air ambiante. En cas de toux sèche invalidante, la prescription d'un antitussif peut se justifier en respectant les différentes contre-indications. La clopérastine et la lévodropropizine, qui disposent des meilleures preuves d'efficacité, ne sont pas commercialisées en France. [ABSTRACT FROM AUTHOR]

The significance of diet for disease prevention has long been recognised. Dietary recommendations have therefore been integrated in health promotion messages. Gastrointestinal functioning is essential for the digestion of nutrients. Oxidative stress has been observed in patients with constipation, as well as in those with colorectal cancer, cardiovascular disease and other chronic illnesses associated with constipation. The coexistence of colorectal neoplasia and coronary artery disease has been incriminated for exposure to common risk factors associated with increased oxidative stress. It was recently demonstrated that bowel movement frequency is inversely associated with cardiovascular mortality. The aim of the present study was to review the relevant literature in light of these findings. It was concluded that suboptimal functioning of the large bowel may contribute to oxidative stress and, therefore, to increased mortality. Bowel movement frequency may represent a simple quantifiable indicator of adequate colonic function and it is dependent on diet, exercise and other lifestyle factors, but also on individual characteristics, including colonic microbiota. Future health promotion actions may improve the prevention of a number of diseases by advocating lifestyle personalisation for assuring optimal intestinal functioning. [ABSTRACT FROM AUTHOR]

Les biguanides, auxquels appartient la metformine, peuvent être associés à des déficits et à des carences en vitamine B12 (cobalamine) - voire les générer - chez les patients diabétiques. Sur le plan épidémiologique, plusieurs travaux rapportent un lien entre une prise de metformine au long cours et une baisse de la vitamine B12 sérique, avec une fréquence de 5 à 20%. Cette corrélation pourrait procéder d'un syndrome de maldigestion des cobalamines alimentaires. D'un point de vue clinique, les carences en vitamine B12 se manifestent avant tout par une asthénie et des manifestations neurologiques, à type de polyneuropathie, observées chez la moitié des patients. Une carence en vitamine B12 liée à la prise de metformine peut être traitée par un apport oral de cyanocobalamine, sans arrêt du biguanide. [ABSTRACT FROM AUTHOR]

Les examens de la coagulation pertinents en pratique clinique sont, principalement, le temps de Quick (TQ), qui explore la voie extrinsèque et le temps de céphaline activée (TCA), pour la voie intrinsèque, ainsi que le fibrinogène et les D-dimères. La signification diagnostique de ces tests varie selon qu'un seul ou plusieurs sont altérés. Un allongement isolé du TCA suggère un déficit en facteurs VIII, IX, XI ou XII, ou une maladie de Willebrand. Si un allongement du TQ s'y associe, c'est un déficit des facteurs II, V, VII ou X qu'il faut évoquer. D'autres étiologies sont à envisager selon qu'il existe ou non des anomalies du fibrinogène et des D-dimères, et au vu de la clinique, notamment le syndrome hémorragique, et des antécédents. [ABSTRACT FROM AUTHOR]

La pathogenèse du diabète comprend plusieurs mécanismes moléculaires impliquant des voies de signalisation variées aboutissant in fine à une hyperglycémie. Celle-ci est due à un déficit de sécrétion de l’insuline par les cellules pancréatiques d’origine auto-immune (diabète de type 1) ou à une insulinorésistance décompensée (diabète de type 2). L’insulinorésistance est une condition qui se manifeste le plus souvent chez le sujet obèse dont le tissu adipeux blanc, notamment viscéral, sécrète un certain nombre de cytokines, les adipokines. Ces cytokines inflammatoires sont à l’origine d’un état inflammatoire nommé « métaflammation » qui concoure avec les cellules inflammatoires (macrophages et lymphocytes), le stress du réticulum endoplasmique et l’hypoxie à l’insulinorésistance, voire au syndrome métabolique et à terme au diabète. [ABSTRACT FROM AUTHOR]

: PurposeElderly patients with nonchemotherapy drug-induced agranulocytosis present commonly with severe infections, and have a mortality of at least 20%. We studied whether granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor that shortens the duration of neutropenia, is useful in these patients.: Subjects and methodsWe studied 54 patients ≥65 years of age who had drug-induced agranulocytosis, some of whom had been treated with G-CSF. We determined the times until hematologic recovery (defined as a neutrophil count >1.5 × 109/L), tolerance of G-CSF, and clinical outcomes.: ResultsOf the 54 patients, 20 received G-CSF. Two patients who had not been treated with G-CSF died of uncontrolled septic shock and extensive pneumonia. The mean (± SD) time until hematologic recovery was significantly less in patients treated with G-CSF (6.6 ± 3.9 days vs. 8.8 ± 4.9 days, P <0.04). Compliance with G-CSF therapy was good; only mild flu-like symptoms and transient bone pain were reported in 12 patients.: ConclusionOur findings suggest that G-CSF therapy may be beneficial in the management of drug-induced agranulocytosis in elderly patients. [Copyright &y& Elsevier]

Anemia is an important healthcare concern among the elderly. In these patients, the anemia is often mild, with a hemoglobin level >10 g/dL. It is usually well tolerated, but might be responsible for several proteiform and/or atypical presenting complaints. In the elderly, anemia is usually of multifactorial origin, including chronic inflammation, chronic kidney disease, nutrient deficiencies and iron deficiency (approximately two-thirds of all cases). The remaining cases are unexplained (unknown etiology). In the elderly, the classic diagnosis of anemia, which is based on the mean corpuscular volume associated with a low hemoglobin level, might not be accurate. A predefined standardized diagnostic procedure should be followed. In the common case of frail elderly patients, all investigations should be carefully considered and invasive examinations undertaken where justified (risk-benefit balance). Nevertheless, most cases of anemia require further investigation and the underlying cause should be identified and treated whenever possible. Geriatr Gerontol Int 2013; 13: 519-527. [ABSTRACT FROM AUTHOR]

Background: Today learning ausculation is still based on empirical tutoring. Objective: The aim of this study is to analyze the contribution of a structured teaching method combined with new phono- and spectrogram signal-visualization tools for medical students. Methods: The study included 30 graduate medical students who analyzed 10 respiratory- and cardiac-disease sounds (ASAP (Analyse des Sons Auscultatoires et Pathologiques) data (ANR Technology 2006)), with and without the contribution of phono- and spectrograms. To evaluate the accuracy of student diagnoses, a questionnaire was handed out at D0 (acoustic data) and D28 (acoustic and visual data) after which results were compared. Results: At D0, 45% of student diagnoses were accurate, including 40% for the DCEM2 (graduate medical studies), and respectively 43% and 60% for the DCEM3 (graduate medical studies) and DCEM4 (graduate medical studies). With respect to respiratory and cardiac sounds, the diagnostic accuracy was respectively 51% and 40%. At D28, 80% of students reported correct diagnoses (p < 0.01 compared to D0), with 70% diagnostic accuracy for respiratory sounds (p = 0.058) and 89% for heart sounds (p < 0.009). Conclusion: The study conducted with graduate medical students objectifies improved diagnosis accuracy using diagnostic tools such as phono- and spectrograms and a structured teaching method. [ABSTRACT FROM AUTHOR]

Drug-induced agranulocytosis (neutrophil count <0·5 × 109/l) is a rare haematological complication with an incidence of no more than 10 cases per million inhabitants per year in Europe. Over the past few years there has been a steady decline in mortality rate, (currently at <5%), which can be partly explained by earlier recognition and the improved clinical management of associated intercurrent infections that may lead to severe sepsis if left untreated. The true impact of the use of haematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF), on the decreased mortality rate remains unknown. Yet, most studies show that these molecules, especially G-CSF, reduce the duration of agranulocytosis, antibiotic course and length of hospital stay. Their use is particularly recommended in patients with poor prognostic factors, such as a neutrophil count <0·1 × 109/l, age over 65 years, severe infection or multiple co-morbidities. In all cases, the drug responsible for causing the agranulocytosis must be discontinued and remain permanently contraindicated. The appropriate Medicines Regulatory Agency must also be notified of the adverse event. [ABSTRACT FROM AUTHOR]

Abstract: Auscultation of pulmonary sounds provides valuable clinical information but has been regarded as a tool of low diagnostic value due to the inherent subjectivity in the evaluation of these sounds. This paper describes an ambitious study of in the so-called ASAP project or “Analyse de Sons Auscultatoires et Pathologiques”. ASAP is a 3-year-long French collaborative project developed in the context of the News Technologies of Information and Communication. ASAP aims at making evolve the auscultation technics: by 1) the development objective tools for the analyse of auscultation sounds: electronic stethoscopes paired with computing device; 2) the creation of an auscultation sounds'' database in order to compare and identify the acoustical and visual signatures of the pathologies; and 3) the capitalisation of these new auscultation techniques around the creation of a teaching unit: “Ecole de l''Auscultation”. This auscultation''s school will be destined to the initial and continuous formation of the medical attendants. [Copyright &y& Elsevier]

Abstract: Anemia, defined as a hemoglobin level < 13g/dL in men and < 12g/dL in women, is an important healthcare concern among the elderly. Nutrient-deficiency anemia represents one third of all anemias in elderly patients. About two thirds of nutrient-deficiency anemia is associated with iron deficiency and most of those cases are the result of chronic blood loss from gastrointestinal lesions. The remaining cases of nutrient-deficiency anemia are usually associated with vitamin B12, most frequently related to food-cobalamin malabsorption, and/or folate deficiency and are easily treated (nutrient-deficiency replacement). [Copyright &y& Elsevier]

The objective of this review is to evaluate the usefulness of oral cobalamin (vitamin B12) treatment in elderly patients. PubMed was systematically searched for English and French articles published from January 1990 to January 2007. Prospective randomized studies (n = 3), a systematic review by the Cochrane group (n = 1) and prospective studies in a well defined population (n = 5) provide evidence that oral cobalamin therapy may adequately treat cobalamin deficiency in elderly patients. However, the current literature does not suggest a strategy in terms of the form (hydroxy- or cyanocobalamin), frequency and duration of the treatment. This review confirms the previously reported efficacy of oral cobaiamin treatment in elderly patients. Oral cobalamin treatment avoids the discomfort, inconvenience and cost of monthly injections. [ABSTRACT FROM AUTHOR]

Cobalamin (vitamin B12) deficiency is particularly common in the elderly (>65 years of age) but is often unrecognized because its clinical manifestations are subtle; however, they are also potentially serious, particularly froma neuropsychiatric and hematological perspective. In the elderly, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. Food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or its binding proteins. This syndrome is usually caused by atrophic gastritis, related or unrelated to Helicobacter pylori infection, and longterm ingestion of antacids and biguanides. Management of cobalamin deficiency with cobalamin injections is currently well documented but new routes of cobalamin administration (oral and nasal) are being studied, especially oral cobalamin therapy for food-cobalamin malabsorption. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work was to review the literature concerning cobalamin deficiency in elderly patients. Articles were identified through searches of PubMed–MEDLINE (January 1990 to June 2006), restricted to: English and French language, human subjects, elderly patients (>65 years), clinical trial, review and guidelines. Additional unpublished data from our cohort with cobalamin deficiency at the University Hospital of Strasbourg, France, were also considered. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. In elderly people, the main causes of cobalamin deficiency are pernicious anemia and food-cobalamin malabsorption. The recently identified food-cobalamin malabsorption syndrome is a disorder characterized by the inability to release cobalamin from food or from its binding proteins. This syndrome is usually the consequence of atrophic gastritis, related or not to Helicobacter pylori infection, and of the long-term ingestion of antacids and biguanides (in around 60% of the patients). Management of cobalamin deficiency has been well established with the use of cobalamin injections. However, new routes of cobalamin administration (oral and nasal) are currently being developed, especially the use of oral cobalamin therapy to treat food-cobalamin malabsorption. [Copyright &y& Elsevier]

The article discusses the effects of food-B12 malabsorption on the incidence of B12 deficiency. According to the author, food-B12 malabsorption, which is the inability to release B12 from food or its binding proteins, is noted to be the primary cause of B12 deficiency among elderly patients. Clinical manifestations of the disease are highly polymorphic and of varying severity ranging from milder conditions, including isolated anomalies of macrocytis and hypersegmentation of neutrophils, to severe disorders such as combines sclerosis of spinal cord and hemolytic anemia. Intramuscular injection of cyanocobalamin was administered to treat B12 deficiency.

The article presents a report on the new manifestations in Sars-CoV-2. It states that social distancing has been made necessary during covid-19. It mentions that informations related to covid-19 has been circulating on social networking sites making people aware of what to do and what not to do during coronavirus.

The article presents a report on Sars-Cov-2. Topics discussed here include the Sars-Cov-2 potion, severe clinical infection like hypoxemic lung disease, and the diseases that negatively impact food and nutritional homeostasis of the human body. It also states that Sars-Cov-2 mainly attacks patients in intensive care and resuscitation.

Abstract: In this paper, we review the literature on idiosyncratic drug-induced agranulocytosis, a rare but life-threatening potential adverse event of most drugs. Articles were identified through MEDLINE searches (1966–2005). Additional references were localized through a review of textbooks on hematology and internal medicine, and information gleaned from international meetings. Additional unpublished data from our cohort with drug-induced agranulocytosis at the University Hospital of Strasbourg, France, were also considered. Searches were done using the following key words: “agranulocytosis”, “drug-induced agranulocytosis”, and “idiosyncratic agranulocytosis” and were restricted to: English- and French-language, human subjects, clinical trial, review, and guidelines. All of the papers and abstracts were reviewed by at least two senior researchers who selected the data used in the study. What we found is that, over the last 20 years, the incidence of idiosyncratic drug-induced agranulocytosis has remained stable – 2.4–15.4 cases per million – despite the emergence of new causative drugs, mainly antibiotics, antiplatelet agents, and antithyroid drugs. To date, drug-induced agranulocytosis remains a serious adverse event due to the frequency of severe sepsis with severe deep infections (such as pneumonia), septicemia, and septic shock in about two-thirds of all patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders such as renal failure, and a neutrophil count below 0.1×109/L are poor prognostic factors. Nevertheless, with appropriate management using pre-established procedures, with intravenous broad-spectrum antibiotic therapy, and hematopoietic growth factors, the mortality rate is currently around 5%. Given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, health care professionals should be aware of this adverse event and its management. [Copyright &y& Elsevier]

An editorial is presented on strikes and demonstrations at public hospitals in France, and its impact on medical care services. Topics discussed include the introduction of activity-based pricing in public hospitals since 2004, except for those providing mental health services; the partial abolition of activity pricing, especially for the monitoring of chronic diseases and the functioning of emergency services at hospitals; and regulation of emergency medical services (EMS) at hospitals.

Abstract: Purpose: Approximately 15% of people aged more than 60 years old have a cobalamin (vitamin B12) deficiency, mainly in relation with food-cobalamin malabsorption (FCM). To date, no study has documented this disorder in the elderly. There is also little information on clinical consequences. Subjects and methods: We studied 92 elderly patients with well-established FCM who were extracted from an observational cohort study (1995-2004) of 172 consecutive elderly patients with documented cobalamin deficiency. Results: The median patient age was 76 ± 8 years; 60 patients were women. The most common clinical manifestations were neurologic or psychologic: mild sensory polyneuropathy (44.6%), confusion or impaired mental functioning (22.8%), and physical asthenia (20.7%). Hematologic abnormalities were reported in at least one third of the patients: anemia (21%), leukopenia (10.9%), thrombopenia (8.7%), and pancytopenia (6.5%). All patients had low serum vitamin B12 levels (<200 pg/mL), with a mean value (± standard deviation) of 131 ± 38 pg/mL and total serum homocysteine level of 22.1 ± 9.3 μmol/L. The mean hemoglobin level was 10.9 ± 2.5 g/dL and the mean erythrocyte cell volume 95.7 ± 12.7 fL. Correction of the serum vitamin B12 levels and hematologic abnormalities was achieved equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. Conclusions: This study suggests that in elderly patients, FCM may be associated with significant neurologic, psychologic, and hematologic abnormalities, which seem to respond equally well to either oral or parenteral vitamin B12 therapy. [Copyright &y& Elsevier]

Abstract: Background:: Standard treatment of cobalamin (vitamin B12) deficiency involvesregular (1000 ?g/mo) IM cyanocobalamin administration. It has been suggested that high-dose (>2000 ?g/d) oral cyanocobalamin may be effective in patients with pernicious anemia. Objective:: The aim of this study was to assess the efficacy and tolerability of oral crystalline cyanocobalamin 1000 ?g/d in patients with cobalamin deficiency related to established pernicious anemia. Methods:: This open-label, prospective study was conducted at StrasbourgUniversity Hospital, Strasbourg, France. Patients aged ?18 years with well-documented cobalamin deficiency related to pernicious anemia were enrolled. Patients received crystalline cyanocobalamin 1000 ?g QD PO (capsule) for at least 3 months. Serum cobalamin, folate, iron, and homocysteine concentrations were measured, and a complete blood count was obtained, before (month 0; baseline) and after treatment. Results:: Ten patients (7 women, 3 men; mean [SD] age, 72.1 [15.5] years) entered the study. After 3 months of treatment, serum cobalamin concentration increased in all 9 patients in whom it was measured (mean [SD] increase, 117.4 [30.8] pg/mL; P &#60; 0.001 vs baseline). Serum cobalamin concentrations were normalized (>200 pg/mL) in 6 patients. The serum cobalamin concentration was unavailable in 1 patient because of technical problems. Eight patients had increased hemoglobin concentrations (mean [SD] increase, 2.5 [2.4] g/dL; P &#60; 0.01 vs baseline). All 10 patients had decreased mean erythrocyte corpuscular volumes (mean [SD] decrease, 10.4 [6.2] fL; P &#60; 0.003 vs baseline). Four patients received concomitant blood transfusions or folate and iron supplementation. Three patients experienced clinical improvement in paresthesia, reflex abolition, or combined medullary sclerosis (each, 1 patient). Conclusion:: The results of this small study in patients with cobalamin deficiencyrelated to pernicious anemia suggest that oral crystalline cyanocobalamin 1000 ?g/d may be an effective treatment [Copyright &y& Elsevier]

VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspec-tive. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), perni-cious anemia (15%--20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobal-amin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an empha-sis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency. [ABSTRACT FROM AUTHOR]

: BackgroundAdults with chronic idiopathic thrombocytopenic purpura (ITP) in whom standard-dose corticosteroids and splenectomy have failed or who have contraindications to these therapies often require further treatment for life-threatening thrombocytopenia or bleeding. We studied whether danazol, an attenuated androgen, is useful in this setting.: MethodsTo assess both clinical outcome and tolerance issues, 57 patients who had refractory chronic ITP (n = 27) or who had contraindications to splenectomy or corticosteroids or who refused these therapeutic options (n = 30) were studied.: ResultsThirty-eight patients experienced a partial or complete response to therapy (67%), among whom 27 (46%) remained in remission at a median (± SD) of 119 ± 45 months. Treatment tolerance was acceptable, although severe adverse events were reported in 9 patients (16%).: ConclusionOur findings suggest that danazol therapy may be beneficial in the management of refractory chronic ITP or when there are contraindications to splenectomy or corticosteroids (or both). [Copyright &y& Elsevier]

Agranulocytosis is a life-threatening disorder in any age, but particularly so in elderly patients who are receiving, on average, a larger number of drugs than younger patients. Drug-induced agranulocytosis still remains a rare event, with an annual incidence rate of approximately 3-12 cases per million population. This disorder frequently occurs as an adverse reaction to drugs, particularly antibacterial's, antiplatelet agents, antithyroid drugs, antipsychotics or antiepileptic drugs, and NSAIDs. Although patients experiencing drug-induced agranulocytosis may initially be asymptomatic, the severity of the neutropenia usually translates into the onset of severe sepsis that requires intravenous broad-spectrum antibacterial therapy. In this setting, haematopoietic growth factors have been shown to shorten the duration of neutropenia. Thus, with appropriate management, the mortality rate of idiosyncratic drug-induced agranulocytosis is now 5-10%. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to compare the value of the Von Reyn and the Duke diagnostic criteria for infective endocarditis (IE) in internal medicine practice. Methods: We determined the sensitivity and negative predictive value of these two sets of diagnostic criteria in 38 patients with established infective endocarditis who were followed in two departments of general internal medicine. The patients essentially had subacute endocarditis of the aortic valve (79%) with several systemic manifestations (100%). Microbial documentation included mainly gram-positive cocci (60%). Results: With transthoracic echocardiography (TTE), the sensitivities of the Duke and the Von Reyn criteria were 65% and 35%, respectively, while with transesophageal echocardiography (TEE), these sensitivities were 75% and 35%, respectively. With TTE and TEE, the negative predictive values were 100% for the Duke diagnostic criteria versus only 71% for the Von Reyn criteria. Conclusions: This study confirms that the Duke diagnostic criteria are useful in practice for the management of patients with infective endocarditis followed in internal medicine. [Copyright &y& Elsevier]

Objective: To review the influence of age on the response of patients with idiopathic thrombocytopenic purpura (ITP) to corticosteroids, splenectomy and danazol. Methods: We retrospectively reviewed a cohort of 139 consecutively treated patients with ITP diagnosed between 1985 and 1994. In particular, we analysed the therapies used, their response rates, prognostic indicators of response and adverse effects. Furthermore, we compared the efficacy and tolerability of the various therapies between younger and older patients (<60 and ≥60 years old). Results: Corticosteroids were used as first-line treatment in 118 patients with an initial response rate of 83%. Age did not affect the outcome of corticosteroid therapy, but all the patients aged ≥60 years reported adverse effects. A splenectomy was performed in 55 patients with an initial response rate of 87%. Older patients had significantly poorer outcomes from splenectomy with higher postoperative morbidity. Finally, danazol was given in 33 patients with a favourable response in 72% of cases. Compared with younger patients, older patients had a significantly better outcome with danazol. Conclusions: Age may have significant effects on the response to and adverse effects of therapy in ITP, and this should be considered when choosing the treatment modality for the elderly. [ABSTRACT FROM AUTHOR]

Background: To date, only case reports or small studies have documented the syndrome of food-cobalamin malabsorption in specific populations of patients or situations. In this paper, we present the data from 80 unselected patients with cobalamin deficiency related to food-cobalamin malabsorption. Methods: We studied 80 patients with well-established food-cobalamin malabsorption who were extracted from an observational cohort study (1995–2000) of 127 consecutive patients with cobalamin deficiency and who were followed in a department of internal medicine. Results: The median age of patients was 66 years and the female to male ratio was 1.2. The mean hemoglobin level was 113±27 g/l (range 32–159 g/l) and the mean erythrocyte cell volume was 95.4±12.3 fl (range 55–140 fl). Mean serum vitamin B12 and homocysteine levels were 153±74 pg/ml (range 35–200 pg/ml) and 20.6±15.7 μmol/l (range 8–97 μmol/l), respectively. The main clinical findings noted were peripheral neuropathy (46.2%), stroke (12.5%), confusion or dementia (10%), asthenia (18.7%), leg edema (11.2%), and digestive disorders (7.5%). The commonest associated conditions were atrophic gastritis (39%) with evidence of Helicobacter pylori infection (12.2%) and alcohol abuse (13.7%). Three patients had Sjo¨gren’s syndrome and one had systemic sclerosis. Ten percent of all patients were on long-term metformin (10%) and 7.5% on acid-suppressive drugs. Correction of the serum vitamin B12 levels and hematological abnormalities was achieved equally well in all patients treated with either intramuscular or oral crystalline cyanocobalamin. Conclusion: This study suggests that food-cobalamin malabsorption may be the leading cause of vitamin B12 deficiency in adults. As other studies have also reported, the condition is often associated with neuro-psychiatric findings and with several other conditions. Oral and parenteral cobalamin appear to be equally effective in correcting serum B12 levels and hematological abnormalities and, in many cases, they also relieve symptoms. [Copyright &y& Elsevier]

Recent advances in anticancer treatment have focused on the development of oral anticancer agents with the intention of improving the patients’ quality of life as well as providing therapeutic alternatives to intravenous chemotherapy. Until agents such as oxaliplatin and irinotecan became available, the treatment of colorectal cancer, one the most common cancers diagnosed in industralized countries, was mainly based on 5-fluorouracil modulation. The overwhelming majority of these new drugs are pyrimidine analogues intended to replace intravenous treatment or to make the therapy more acceptable to the patients. In this article, the use of oral chemotherapy, alone or in combination with radiotherapy, in colorectal cancer is reviewed and updated. The rationale for using oral compounds is discussed and newer agents, such as oral camptothecin analogues and antiangiogenic agents, are presented with the results of their clinical and preclinical developments. [Copyright &y& Elsevier]

Background: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. Methods: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Be´nichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). Results: Mean patient age was 63 (range 17–95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0–0.46)×109/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5×109/l), antibiotic therapy, and hospitalization was 8.5 (range 2–21) days, 9.2 (range 2–21) days, and 10.5 (range 3–23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2–16) days, 7.1 (range 2–16) days, and 9.1 (range 3–23) days, respectively (all P<0.05). Conclusions: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality. [Copyright &y& Elsevier]

Background: Breast-implant-associated anaplastic large cell lymphoma is a rare malignancy linked to texturized breast implants. Although many researchers focus on its etiopathogenesis, this topic is affected by a lack of evidence. Materials and Methods: A literature review about BIA-ALCL was made. Results and conclusions: Although the incidence is reported between 1:355–1:30,000, there is great attention to BIA-ALCL. The incidence is uncertain due to many reasons. It may well be lower, due to inclusion in multiple databases as pointed out by the FDA and undiagnosed cases. The role of chronic inflammation, bacterial contamination, and mechanical forces was discussed. Clarification is needed to understand the mechanisms underlying the progression of alterations and mutations for BIA-ALCL; new molecular analysis and pathogenetic models should be investigated. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods: A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan–Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is (p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure. [ABSTRACT FROM AUTHOR]

Objective: intravitreal therapy for macular edema (ME) is a common clinical approach to treating most retinal vascular diseases; however, it generates high costs and requires multiple follow-up visits. Combining intravitreal anti–vascular endothelial growth factor (VEGF) or steroid therapy with subthreshold diode micropulse laser (SDM) application could potentially reduce the burden of numerous intravitreal injections. This review sought to explore whether this combination treatment is effective in the course of ME secondary to retinal vascular disease, and in particular, determine whether it is comparable or superior to intravitreal therapy alone. Materials and methods: the following terms and Boolean operators were used to search the PubMed literature database: subthreshold micropulse laser, subthreshold diode micropulse OR micropulse laser treatment AND anti-VEGF, anti-VEGF treatment, intravitreal steroids, OR combined therapy.This analysis included all studies discussing the combination of SDM and intravitreal anti-VEGF or steroid treatment. Results: the search revealed nine studies that met the inclusion criteria, including five comparing combined treatment and anti-VEGF treatment alone, four covering diabetic ME, and one covering ME secondary to branch retinal vein occlusion. All of these five studies suggested that combination therapy results in fewer intravitreal injections than anti-VEGF monotherapy with non-inferior functional and morphological outcomes. The remaining four studies report functional and morphological improvements after combined treatment; however, SDM alone was never superior to intravitreal-alone or combined treatment. There were substantial differences in treatment protocols and inclusion criteria between the studies. Conclusions: the available material was too scarce to provide a reliable assessment of the effects of combined therapy and its relation to intravitreal monotherapy in the treatment of ME secondary to retinal vascular disease. One assumption of note is that it is possible that SDM plus anti-VEGF might require fewer intravitreal injections than anti-VEGF monotherapy with equally good functional and morphological results. However, further randomized research is required to confirm this thesis. [ABSTRACT FROM AUTHOR]