[Drug shortages : a fatality ?] / Médicaments indisponibles : une fatalité ?

In recent years, the number of drug shortages has risen alarmingly both in Belgium and internationally. Between 2010 and 2020, the number of reported shortages is almost 27 times higher, according to the French Agency for the Safety of Medicines and Health Products. A recent survey conducted by the European Association of Hospital Pharmacists showed that 95 % of hospital pharmacists consider drug shortages to be a major problem. The drug classes most affected include anti-infectives, analgesics and anaesthetics. The sudden and unpredictable occurrence of drug shortages has a negative impact on the daily lives of healthcare professionals and patients. Doctors are sometimes forced to prescribe alternative treatments that are considered less effective or even less well tolerated. These alternatives make it more difficult for patients to adhere to their treatment and generate an additional risk of medication errors. There are several possible solutions to minimize these shortages: relocating production sites to Europe, imposing penalties on offending companies, adopting a common European policy for managing shortages of medicines of major therapeutic interest,... As a corollary to these proposals, legal texts have been adopted to regulate and guarantee the supply of medicines in Belgium.

Depuis ces dernières années, le nombre de médicaments indisponibles a augmenté de manière inquiétante, tant en Belgique qu'au niveau international. Entre 2010 et 2020, le nombre de pénuries signalées sont près de 27 fois plus élevées, selon l'Agence Française de Sécurité du Médicament et des Produits de Santé. Une récente enquête réalisée par l'Association Européenne des Pharmaciens Hospitaliers a montré que 95 % des pharmaciens hospitaliers considèrent ces pénuries médicamenteuses comme un problème majeur. Parmi les classes médicamenteuses les plus touchées se retrouvent, notamment, les anti-infectieux, les analgésiques et les agents anesthésiques. De survenue soudaine et imprévisible, les ruptures entachent le quotidien tant des professionnels de la santé que des patients. Les médecins sont, parfois, contraints de prescrire des traitements alternatifs jugés moins efficaces, voire moins bien tolérés. Ces alternatives complexifient l'adhérence thérapeutique du patient en générant un risque supplémentaire d'erreur médicamenteuse. Pour pallier ces indisponibilités, certaines pistes de solutions peuvent être dégagées : relocaliser en Europe les sites de production, sanctionner les firmes fautives, adopter une politique européenne commune de gestion des pénuries de médicaments d'intérêt thérapeutique majeur,… En corollaire de ces propositions, des textes juridiques ont été édictés afin d'encadrer et de garantir l'approvisionnement en médicaments en Belgique.

Clinical consequences of diagnostic variability in the histopathological evaluation of early rectal cancer.

INTRODUCTION: In early rectal cancer, organ sparing treatment strategies such as local excision have gained popularity. The necessity of radical surgery is based on the histopathological evaluation of the local excision specimen. This study aimed to describe diagnostic variability between pathologists, and its impact on treatment allocation in patients with locally excised early rectal cancer. MATERIALS AND METHODS: Patients with locally excised pT1-2 rectal cancer were included in this prospective cohort study. Both quantitative measures and histopathological risk factors (i.e. poor differentiation, deep submucosal invasion, and lymphatic- or venous invasion) were evaluated. Interobserver variability was reported by both percentages and Fleiss' Kappa- (ĸ) or intra-class correlation coefficients. RESULTS: A total of 126 patients were included. Ninety-four percent of the original histopathological reports contained all required parameters. In 73 of the 126 (57.9%) patients, at least one discordant parameter was observed, which regarded histopathological risk factors for lymph node metastases in 36 patients (28.6%). Interobserver agreement among different variables varied between 74% and 95% or ĸ 0.530-0.962. The assessment of lymphovascular invasion showed discordances in 26% (ĸ = 0.530, 95% CI 0.375-0.684) of the cases. In fourteen (11%) patients, discordances led to a change in treatment strategy. CONCLUSION: This study demonstrated that there is substantial interobserver variability between pathologists, especially in the assessment of lymphovascular invasion. Pathologists play a key role in treatment allocation after local excision of early rectal cancer, therefore interobserver variability needs to be reduced to decrease the number of patients that are over- or undertreated.

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus's transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.

Vitamin D deficiency in children with cerebral palsy: A narrative review of epidemiology, contributing factors, clinical consequences and interventions.

Sufficient vitamin D levels are necessary, not only for mineralization, normal growth and development of bones, but also for the prevention of fatal chronic diseases like diabetes mellitus, metabolic syndrome and cancer. This is of particular importance in children with neuro- and musculoskeletal disorders, especially cerebral palsy (CP). CP is a heterogeneous group of childhood developmental disability disorders described by uncharacteristic posture, balance, and movement. Patients with CP are at an increased risk of vitamin D deficiency and as a result reduced bone mineral density, bone fragility, osteopenia, and rickets. The present review aims to combine and summarize available evidence, regarding the epidemiology, underlying contributing factors, clinical consequences, and treatment interventions of vitamin D deficiency in children with CP.

Effects and Causes of Detraining in Athletes Due to COVID-19: A Review.

Several aspects of systemic alterations caused by the SARS-CoV-2 virus and the resultant COVID-19 disease have been currently explored in the general population. However, very little is known about these particular aspects in sportsmen and sportswomen. We believe that the most important element to take into account is the neuromuscular aspect, due to the implications that this system entails in motion execution and coordination. In this context, deficient neuromuscular control when performing dynamic actions can be an important risk factor for injury. Therefore, data in this review refer mainly to problems derived in the short term from athletes who have suffered this pathology, taking into account that COVID-19 is a very new disease and the presented data are still not conclusive. The review addresses two key aspects: performance alteration and the return to regular professional physical activity. COVID-19 causes metabolic-respiratory, muscular, cardiac, and neurological alterations that are accompanied by a situation of stress. All of these have a clear influence on performance but at the same time in the strategy of returning to optimal conditions to train and compete again after infection. From the clinical evidence, the resumption of physical training and sports activity should be carried out progressively, both in terms of time and intensity.

Reflexiones acerca de algunos de los efectos de la pandemia en la clínica con niños y adolescentes / Reflections on some of the effects of the pandemic in the clinic with children and adolescents / Réflexions sur certains effets de la pandémie dans la clinique avec les enfants et les adolescents / Reflexões sobre alguns dos efeitos da pandemia na clínica com crianças e adolescentes

El presente artículo plantea reflexiones respecto de algunas consecuencias en la clínica con niños/as y adolescentes debidos al impacto de la pandemia por Covid19. Se señala la acción de la incertidumbre y lo imprevisible sobre la subjetividad de la población y se propone recordar los acontecimientos ligados a las medidas de protección (Aislamiento Social Preventivo y Obligatorio, de dos años de duración) y resignificarlos para aventurar una incipiente historización sobre algunos de los efectos que la pandemia produjo sobre la labor clínica con niños/as y adolescentes. A tal fin, se toma como eje conceptual rector el desarrollo freudiano sobre la retracción libidinal y sus consecuencias para el Yo, y los cambios en los recursos técnicos que debieron implementarse al incluirse las sesiones on-line. Se puntualizan las consecuencias perturbadoras de la pandemia respecto de los niños pequeños, con patologías graves y en los adolescentes tomando en cuenta la especificidad de sus características subjetivas AU

The following paper presents reflections on certain consequences on the clinic with children and teenagers due to the impact of the Covid-19 pandemic. The action of uncertainty and the unpredictable on the subjectivity of the population is pointedout and it is proposed to recall the events linked to protection measures (Mandatory Preventive Isolation, lasting two years) and resignify them to venture an incipient historicization about some of the effects that the pandemic produced on clinical work with children and adolescents.For this purpose, the Freudian development on libidinal withdrawal and its consequences for the Self, and the changes in the technical resources that had to be implemented when online sessions were installed, are taken as theguiding conceptual axis. The disturbing consequences of the pandemic are pointed out regarding young children, those with serious pathologies and in adolescents, taking into account the specificity of their subjective characteristics AU

Cet article propose des réflexions concernant certaines conséquences en clinique auprès des enfants et des adolescents dû à l'impact de la pandémie de Covid19. Les conséquences de l'incertitude et de l'imprévisible sur la subjectivité de la population sont dénotées et il est proposé de rappeler les événements liés aux mesures de protection (Isolement Préventif Obligatoire, d'une durée de deux ans) et de les resignifier pour s'aventurer à un début d'historisation de certains des effets que la pandémie a eu sur le travail clinique avec les enfants et les adolescents. Pour cela, le développement freudien sur le retrait libidinal et ses conséquences sur le Moi, et les évolutions des moyens techniques qu'il a fallu mettre en œuvre lors de l'implémentation des séances en ligne, sont pris comme axe conceptuel directeur.Les conséquences inquiétantes de la pandémie sont dénotées concernant les jeunes enfants, atteints de pathologies graves, et les adolescents, tout en prenant en compte la spécificité de leurs caractéristiques subjectives AU

Este artigo traz reflexões sobre algumas consequências na clínica com crianças e adolescentes devido ao impacto da pandemia de Covid19. Aponta-se a ação da incerteza e do imprevisível sobre a subjetividade da população e propõe-se relembrar os eventos vinculados às medidas de proteção (Isolamento Preventivo Obrigatório, com duração de dois anos) e ressignifica esses para arriscar uma incipiente historicização sobre alguns dos efeitos que a pandemia produziu no trabalho clínico com crianças e adolescentes. Para tanto, toma-se como eixo conceitual constitutivo o desenvolvimento freudiano sobre a retirada libidinal e suas consequências para o Ego, e as mudanças nos recursos técnicos que tiveram que ser implementados quando da inclusão das sessões online. As consequências perturbadoras da pandemia são apontadas em relação às crianças pequenas, aos portadores de patologias graves e aos adolescentes, tendo em conta a especificidade das suas características subjetivas AU

Socio-Behavioral Risk Indicators Linked to Untreated Early Childhood Caries and its Clinical Consequences in Preschool Children: A Cross-Sectional Study.

OBJECTIVES: This study aimed to determine the prevalence of and the socio-behavioral risk indicators associated with untreated dental caries (UDC) and its clinical consequences. STUDY DESIGN: A multi-stage cluster sampling approach was used to evaluate 168 preschool children in this cross-sectional study. The risk indicators associated with the presence of one or more decayed teeth (dt ≥ 1) and pulp-involved teeth (pt ≥ 1) were assessed using multiple logistic regression analysis. RESULTS: Overall, the prevalence of dt ≥ 1 and pt ≥ 1 was 82.1% and 27.9%, respectively. Children whose mothers had lower maternal education were 3.7 times more likely to have dt ≥ 1 than those whose mothers were graduates (adjusted odds ratio [AOR] = 3.74, 95% confidence interval [CI] 1.29-10.91). Children whose mothers had a history of maternal caries were 4.2 times more likely to have dt ≥ 1 (AOR = 4.23, 95% CI 1.56-11.44). Children whose mothers had lower maternal education were 5 times more likely to have pt ≥ 1 (AOR = 4.99, 95% CI 2.57-13.39). Underweight children were 7.2 times more likely to have pt ≥ 1 (AOR = 7.17, 95% CI 1.88-5.10). Children whose mothers had a history of maternal caries were 6.6 times more likely to have pt ≥ 1 (AOR = 6.62, 95% CI 7.17-18.88). CONCLUSIONS: Maternal education and caries were found to be significant risk indicators for UDC. The clinical consequences of UDC were related to child age, maternal education and caries, socioeconomic status and underweight.

Impact of alcohol on the progression of HCV-related liver disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: Despite a marked reduction in new cases of cirrhosis caused by HCV infection, over 500,000 new cirrhosis cases in this category were estimated globally in 2019. This contribution quantifies the relationship between alcohol use and the progression of liver disease in people with HCV infections. METHODS: The causal impact of different levels of alcohol use on cirrhosis has previously been established. The quantification of this relationship was undertaken based on a systematic search of the literature and a meta-analysis. We limited our search to longitudinal and case-control studies with biologically verified outcomes. Different sensitivity analyses were conducted to check on key assumptions and on the generalizability of the relationship. RESULTS: Alcohol use has a dose-dependent relationship with incident cirrhosis, which is linear on the log-linear level, and thus exponential on the level of odds ratios or other risk indicators. Each standard drink of 12 grams of pure alcohol per day increases the risk by about 11%. The results were stable regardless of the statistical model used, level of adjustment, quality of the study, or outcome (i.e., cirrhosis, decompensated cirrhosis, liver-related death). CONCLUSIONS: Alcohol use has a marked impact on the progression of HCV infections to cirrhosis and more severe liver outcomes. LAY SUMMARY: Alcohol consumption has a significant impact on the progression of liver disease in people with HCV infections. Each alcoholic drink per day is associated with an increase in the risk of cirrhosis of 11%.

Silent atrial fibrillation: epidemiology, diagnosis, and clinical impact.

Silent or subclinical asymptomatic atrial fibrillation (SAF) has currently gained wide interest in the epidemiologic, neurologic, and cardiovascular communities. It is well known that the electrophysiological and mechanical effects of symptomatic and silent atrial fibrillation (AF) are the same. It is probable that because "AF begets AF," progression from paroxysmal to persistent or permanent AF might be more rapid in patients with long-term unrecognized and untreated SAF, because no treatment is sought by or provided to such patients. Moreover, SAF is common and has significant clinical implications. The clinical consequences of SAF, which include emboli (silent or symptomatic), heart failure, and early mortality, are of paramount importance. Consequently, SAF should be considered in estimating the prevalence of the disease and its impact on morbidity, mortality, and quality of life. Several diagnostic methods of arrhythmia detection utilizing the surface electrocardiogram (ECG), subcutaneous ECG, or intracardiac devices have been utilized to seek meaningful arrhythmic markers of SAF. Whereas a wide range of clinical risk factors of SAF have been validated in the literature, there is an ongoing search for those arrhythmic risk factors that precisely identify and prognosticate outcome events in diverse populations at risk of SAF. Modern diagnostic modalities for the identification of SAF exist, but should be further explored, validated, and tailored to each patient needs. The scientific community should undertake the clinical challenge of identifying and treating SAF.

Hipominerazación de incisivos y molares: aspectos clínicos de la severidad / Molar and incisors hypomineralization: clinical aspects of the severity

La hipomineralización de incisivos y molares (HIM) es un trastorno de desarrollo de los primeros molares y de los incisivos permanentes. El esmalte afectado es frágil y fácilmente se puede desprender dejando expuesta la dentina, lo cual favorece la sensibilidad dentinaria y el desarrollo de lesiones cariosas. Los posibles factores etiológicos se asocian a alteraciones durante la gestación y a algunas enfermedades de la primera infancia. El tratamiento depende de la severidad del caso y puede incluir restauraciones de los dientes cariados, extracciones cuando estén indicadas, conservación y/o recuperación del espacio mediante aparatología ortodóncica. Los pacientes afectados por HIM exhiben signos y síntomas clínicos definidos, ello permite clasificarlos de acuerdo con la severidad y con las características de la hipomineralización. El objetivo de este trabajo es presentar las características clínicas asociadas con la hypomineralization incisivo-molar, de niños de 6 a 12 años de edad que asisten a la clínica de Estudios de Posgrado, la disciplina de Odontología Pediátrica de la Facultad de Odontología de Araraquara, UNESP, para ayudar al cirujano dentista en el diagnóstico y la toma de decisiones en el tratamiento

Molar-Incisor Hypomineralization (MIH) is an enamel development defect affecting one to four permanent first molars frequently associated with affected incisors. The enamel breakdown is common in the affected molars resulting in hypersensitivity and to dental caries development. The possible etiological factors are associated with systemic cause occurring in pregnancy, around the time of birth or in the first childhood. The treatment depends of the defect severity, and includes restorations and extractions of the teeth associated with orthodontic treatment in tooth severely affected. The aim of this study is present clinic characteristics relative to MIH in children aged 6 to 12 years treated and accompanied in Pediatric Dentistry Clinic of the Araraquara School of Dentistry, UNESP, to help dentistry in diagnosis and treatment plan

Repercusiones para la salud pública de la adherencia terapéutica deficiente / Impact of deficient adherence to therapy on the public health

El presenta trabajo pretende fundamentar la importancia del problema de la deficiente adherencia a los tratamientos médicos de larga duración y como esto se convierte en asunto difícil para la salud pública contemporánea. Se realiza un análisis de sus repercusiones en cuestiones que tienen que ver con la calidad de la atención, el uso racional de los recursos y servicios sanitarios, el cuadro de salud de la población y la calidad de vida del paciente. Se exponen las principales consecuencias clínicas o médicas, económicas y psicosociales que pueden aparecer debido a una baja adherencia al tratamiento médico indicado, sobre todo en enfermos crónicos. Se abordan algunos aspectos que el sistema de salud debe enfrentar en relación con la adherencia terapéutica para contribuir a mejorar la situación expuesta.

The present paper was aimed at substantiating the importance of the problem of a deficient adherence to long medical treatment and how this becomes a difficult issue in the contemporary public health. An analysis was made of the effects of this problem on some questions related to quality of care, rational use of health resources and services, the population's health picture and the quality of life of a patient. The main clinical, economic, and psychosocial consequences that might occur as a result of a low adherence to indicated medical treatment, mainly in chronically-ill patients, were explained. Some aspects that the healthcare system should cope with in relation to adherence to therapy in order to improve the above-mentioned situation were also addressed.