The circulation of substandard medicines in the developing world is a serious clinical and public health concern. Problems include under or over concentration of ingredients, contamination, poor ...quality ingredients, poor stability and inadequate packaging. There are multiple causes. Drugs manufactured for export are not regulated to the same standard as those for domestic use, while regulatory agencies in the less-developed world are poorly equipped to assess and address the problem. A number of recent initiatives have been established to address the problem, most notably the WHO pre-qualification programme. However, much more action is required. Donors should encourage their partners to include more explicit quality requirements in their tender mechanisms, while purchasers should insist that producers and distributors supply drugs that comply with international quality standards. Governments in rich countries should not tolerate the export of substandard pharmaceutical products to poor countries, while developing country governments should improve their ability to detect substandard medicines.
We report a case of a 79-years old man who sustained a Fragility Fracture of the Pelvis (FFP) classified type IVb according to Rommens and Hofmann. After a delayed diagnosis with persistence of pain ...and loss of mobility, a bilateral sacroplasty was performed. Although pain relief was achieved, a fracture progression (FP) occurred with bilateral neurologic compression of L5 and S1 nerve roots with pain recurrence. A percutaneous ilio-lumbar reduction was attempted with cemented augmentation and bilateral ilio-sacral screwing. Reduction was not achieved and screws finally pulled-out. The patient died one year after institutionalization with a significant loss of mobility and autonomy.
Misunderstanding in management of FFP according to Rommens and Hofmann recommendations can lead to bad results with fracture progression, implants failure, pain recurrence, loss of function, loss of autonomy and finally death of the patient.
L’unité de pharmacotechnie fabrique quotidiennement des poches de nutrition parentérale individualisées (NPI) et d’hydratation pour répondre aux besoins des services de pédiatrie (réanimation ...néonatale (RNN), soins intensifs (SI), pédiatrie médicale (PM) et oncologie pédiatrique (OP)). Une AMDEC réalisée sur ce circuit en 2018 avait mis en évidence 3 points critiques concernant l’étape de contrôle de l’ordonnance : l’incapacité du pharmacien à évaluer les besoins nutritionnels du patient, l’absence de formation des pharmaciens à la validation pharmaceutique et l’absence de validation pharmaceutique avant la production. Le contrôle des prescriptions a été renforcé et il est demandé de faire une intervention pharmaceutique (IP) sur les problèmes de conformité d’ordonnance, de modalités d’administration, de composition de poche (au regard du bilan biologique, des recommandations ESPGHAN pour la NPI et des protocoles de chimiothérapie pout l’hydratation). L’acceptation ou le refus est également tracé. L’objectif était d’analyser les IP sur l’année 2020.
Analyse rétrospective du recueil des IP au sein d’une unité de production de NPI sur 2020.
Sur l’année 2020, 607 IP ont été réalisées pour un total de 4152 prescriptions. Elles concernaient les modalités d’administration (41,2 %), la composition de la poche (32,6 %), l’identification du patient (14,2 %) et la conformité de l’ordonnance (12 %). Les IP les plus fréquentes concernaient : la voie d’accès non précisée (n=122), des surdosages (n=102) et sous dosage (n=63). Ces IP concernaient 15,4 % des prescriptions de RNN (343/2221) ; 16,3 % (119/728) pour les SI ; 10,8 % (105/970) pour l’OP et 16,5 % (40/242) pour la PM. Les problèmes d’identitovigilance ou en lien avec la prescription (p. ex. date de prescription, nom du prescripteur) représentaient 2,6 % des IP (9/343) en RNN et 56,8 % (150/264) des IP pour l’ensemble des autres services. Le taux global d’acceptation des IP était de 71,8 % (436/607). Une partie des IP (263/607) concernait un problème pouvant avoir un impact clinique pour le patient (identitovigilance, incompatibilité osmolarité/voie d’accès, inversion de solutés, sous ou surdosage, prescription non conforme au référentiel). Pour ces IP, le taux d’acceptation était de 36,1 %.
Cette étude montre que 14,6 % des prescriptions ont nécessité une IP dont 43,3 % concernaient une prescription pouvant être délétère pour le patient. L’outil de prescription informatique présent en RNN a permis de minimiser les problèmes d’identitovigilance ou en lien avec la conformité de l’ordonnance. La présence d’anomalie biochimique est responsable d’IP nécessaires, bien que souvent refusées au regard du terrain clinique après discussion avec le médecin. Les examens biochimiques sur sang total peuvent être responsables d’IP à faible valeur ajoutée compte tenu du caractère peu informatif de cet examen sur les dyskaliémies.
During cell division, chromosomes are distributed to daughter cells by the mitotic spindle. This system requires spatial cues to reproducibly self-organize. We report that such cues are provided by ...chromosome-mediated interaction gradients between the small guanosine triphosphatase (GTPase) Ran and importin-{szligbeta}. This produces activity gradients that determine the spatial distribution of microtubule nucleation and stabilization around chromosomes and that are essential for the self-organization of microtubules into a bipolar spindle.
Today, acetabular surgeons in training have to learn ilioinguinal and anterior intrapelvic approaches (AIP). The aim of this study was to describe the 5-years learning curve of a surgeon. Objective ...was to assess clinical and radiological results; and to assess factors which could influence this learning curve. Between November 2015 and May 2020, patients with an acetabular fracture operated by the surgeon during the 5-years learning curve with an anterior approach were included in this single-center retrospective study based on a prospective database. Epidemiological, operative, clinical, radiological and complications data's were collected. To assess learning-curve effect the series was divided into two groups: first 2.5-years and last 2-years. Subgroup analysis were performed according to the surgical approach, to the reduction quality and the prognostic factors. In total, 46 patients were included, 23 in period 1 and 23 in period 2. 16 patients (35%) had ilioinguinal approach and 30 patients (65%) had modified Stoppa-Cole approach. At mean follow-up of 24 months, 38 patients (83%) were reviewed. Anatomical reduction (< 1 mm) was achieved in 28 patients (60.9%) with a 9% rate of perioperative complications and 37% rate of post-operative complications. In conclusion, this study gives a realistic overview of the learning curve of anterior approaches in acetabular fractures surgery. Our results should encourage surgeons, while keeping in mind how much this surgery can be challenging, with high rate of complications and difficulty to obtain a systematic anatomical reduction.
Multidrug-resistant tuberculosis (MDR-TB) is caused by strains of Mycobacterium tuberculosis resistant to at least isoniazid and rifampin, the two most powerful first-line antituberculosis (anti-TB) ...drugs. Although drug resistance in TB is not a new phenomenon, several factors--including irrational antibiotic use, poor-quality anti-TB drugs, the collapse of public health infrastructures, the HIV epidemic, war, famine, and increasing inequality and poverty--have all contributed to the increasing incidence of TB. In recent years, outbreaks of MDR-TB in public institutions (hospitals, prisons, and homeless shelters) in the United States, Europe, and Latin America have caused many deaths and have raised concerns about epidemic transmission of drug-resistant strains of M. tuberculosis.
We present the first measurement of the timelike Compton scattering process, γp→p^{'}γ^{*}(γ^{*}→e^{+}e^{-}), obtained with the CLAS12 detector at Jefferson Lab. The photon beam polarization and the ...decay lepton angular asymmetries are reported in the range of timelike photon virtualities 2.25<Q^{'2}<9 GeV^{2}, squared momentum transferred 0.1<-t<0.8 GeV^{2}, and average total center-of-mass energy squared s=14.5 GeV^{2}. The photon beam polarization asymmetry, similar to the beam-spin asymmetry in deep virtual Compton scattering, is sensitive to the imaginary part of the Compton form factors and provides a way to test the universality of the generalized parton distributions. The angular asymmetry of the decay leptons accesses the real part of the Compton form factors and thus the D-term in the parametrization of the generalized parton distributions.
Recent evidence points at a role of protein interaction gradients around chromatin in mitotic spindle morphogenesis in large eukaryotic cells. Here, we explain how gradients can arise over distances ...of tens of microns around supramolecular structures from mixtures of soluble molecules. We discuss how coupled sets of such reaction diffusion processes generate the spatial information that determines the local dynamics of microtubules required to form a bipolar spindle. We argue that such reaction diffusion processes are involved in the self-organization of supramolecular structures in the cell.
To determine the quality, and especially the dissolution properties of rifampicin, of fixed-dose combination (FDC) formulations of anti-tuberculosis agents manufactured by major market holders in the ...anti-tuberculosis sector and supplied for use in national tuberculosis control programmes.
Dissolution studies were performed for four formulations supplied by four different manufacturers in four dissolution media (0.1N and 0.01N HCl, phosphate buffer PB and 20% vegetable oil in PB), at four different agitation rates using USP apparatus II. The formulations were subjected to 4-week accelerated stability studies (40 degrees C / 75% RH) and evaluated for physical, chemical and dissolution stability.
The formulations tested complied with pharmacopeial quality control (QC) tests. The extent of rifampicin release was independent of dissolution medium; however, a slight decrease in the dissolution rate was observed in two products. More than 75% of drug was released in 45 min at all agitation intensities except 30 rpm, and 20% oil in the medium reflected fed state. Formulations were stable in the packaging conditions recommended by the manufacturer for at least 4 weeks.
The formulations tested passed the QC tests and were found to be stable. A decrease in the rate, although not the extent, of dissolution necessitated multiple point dissolution in gastric and intestinal pH conditions to ensure consistency in in vivo bioavailability.
ObjectiveIn today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of ...medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline ‘Model Quality Assurance System (WHO MQAS) for procurement agencies’, and we investigated factors favouring or hindering the adequate implementation of the guideline.MethodsWe used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design.FindingsOur analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality.ConclusionsOur findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards.
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