Availability and cost of major and first-line antiepileptic drugs: a comprehensive evaluation in the capital of Madagascar

International audienceBackground: The prevalence of epilepsy is high in Madagascar (23.5/1000), as is the treatment gap (estimated at 92 %). The health system of the country is underfunded; some AEDs are used, and the national drug policy does not encourage price regulation or the administration of generic agents. We conducted a cross‑sectional study to assess the availability and cost of solid oral AED formulations in Antananarivo, capital of Madagascar. Data were gathered from all officially registered pharmacies (according to the drug agency list, updated in 2015) by means of telephone interviews lasting no more than 10 min and conducted by a native Malagasy speaker. With regard to other sources (hospitals, illicit sales) data were obtained at specific visits. The study received ethical approval from the Madagascar Ministry of Health.Findings: A total of 91 of 100 pharmacies (the nine not included were because of an inoperative phone number), two of three public hospitals, and two illegal outlets were investigated. Sodium valproate was available in 84.6 % of the pharmacies, while carbamazepine and phenobarbital were available in 68.1 % and 36.3 % of the pharmacies, respectively, but phenytoin was not available in any supply chain. There were more originator brands than generic for‑mulations, with a higher cost (range 20.3–81.1 %, median 40.7 %) compared to the equivalent generic. The public sys‑tem had only a very limited choice of AED, but offered the lowest costs. Illicit sources were more expensive by 54.3 % for carbamazepine and 62.5 % for phenobarbital. Concerning the annual cost of treatment, the average percentage of the gross national income per capita based on the purchasing power parity was 29.8 %/19.0 % (brand/generic) for sodium valproate, 16.4 %/7.3 % (brand/generic) for carbamazepine, 8.9 %/5.1 % (brand/generic) for phenobarbital.Conclusions: The main sources of AEDs were private pharmacies, but the stocks held were low. The financial burden was still important in the capital of Madagascar, mainly the consequence of a highly developed private sector at the expense of the public sector. Although sodium valproate remains the most expensive solution, it still remains the most available instead of phenobarbital. The most striking feature of this study concerns the cost of AEDs in the infor‑mal sector, mostly used because they are deemed to provide less costly drugs, the opposite was observed there. The assessment of the cost and availability of medicines was easily and quickly implemented. It provided a relevant focus of the situation in areas difficult to investigate, in terms of road network and geographical situation

Call to action for acute myocardial infarction in women: International multi-disciplinary practical roadmap

\ua9 2024 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.Cardiovascular diseases are the leading cause of death among women, and the incidence among younger women has shown the greatest increase over the last decades, in particular for acute myocardial infarction (AMI). Moreover, the prognosis of women post-AMI is poor when compared with men of similar ages. Since the 1990s, an abundant literature has highlighted the existing differences between sexes with regard to presentation, burden, and impact of traditional risk factors and of risk factors pertaining predominantly to women, the perception of risk by women and men, and the pathophysiological causations, their treatment, and prognosis. These data that have been accumulated over recent years highlight several targets for improvement. The objective of this collaborative work is to define the actions required to reverse the growing incidence of AMI in women and improve the patient pathway and care, as well as the prognosis. We aim to provide practical toolkits for different health professionals involved in the care of women, so that each step, from cardiovascular risk assessment to symptom recognition, to the AMI pathway and rehabilitation, thus facilitating that from prevention to intervention of AMI, can be optimized

E-Cadherin mediates UVR- and calcium-induced melanin transfer in human skin cells

yesSkin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca2+-dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca2+, while ultraviolet radiation (UVR) raises intra-MC Ca2+ via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis. However, how Ca2+ triggers melanin transfer remains unclear, and here we evaluated the role of E-Cadherin in UVR-mediated melanin transfer in human skin cells. MC and KC in human epidermis variably express filopodia-associated E-Cadherin, Cdc42, VASP and β-catenin, all of which were upregulated by UVR/UVA in human MC in vitro. Knockdown of E-cadherin revealed that this cadherin is essential for UVR-induced MC filopodia formation and melanin transfer. Moreover, Ca2+ induced a dose-dependent increase in filopodia formation and melanin transfer, as well as increased β-catenin, Cdc42, Myosin X, and E-Cadherin expression in these skin cells. Together these data suggest that filopodial proteins and E-Cadherin, which are upregulated by intracellular (UVR-stimulated) and extracellular Ca2+ availability, are required for filopodia formation and melanin transfer. This may open new avenues to explore how Ca2+ signalling influences human pigmentation

Refining the phenotype associated with biallelic DNAJC21 mutations

Accepted manuscriptInherited bone marrow failure syndromes (IBMFS) are caused by mutations in genes involved in genomic stability. Although they may be recognized by the association of typical clinical features, variable penetrance and expressivity are common, and clinical diagnosis is often challenging. DNAJC21, which is involved in ribosome biogenesis, was recently linked to bone marrow failure. However, the specific phenotype and natural history remain to be defined. We correlate molecular data, phenotype, and clinical history of 5 unreported affected children and all individuals reported in the literature. All patients present features consistent with IBMFS: bone marrow failure, growth retardation, failure to thrive, developmental delay, recurrent infections, and skin, teeth or hair abnormalities. Additional features present in some individuals include retinal abnormalities, pancreatic insufficiency, liver cirrhosis, skeletal abnormalities, congenital hip dysplasia, joint hypermobility, and cryptorchidism. We suggest that DNAJC21-related diseases constitute a distinct IBMFS, with features overlapping Shwachman-Diamond syndrome and Dyskeratosis congenita, and additional characteristics that are specific to DNAJC21 mutations. The full phenotypic spectrum, natural history, and optimal management will require more reports. Considering the aplastic anemia, the possible increased risk for leukemia, and the multisystemic features, we provide a checklist for clinical evaluation at diagnosis and regular follow-up.FCT—Fundação para a Ciência e a Tecnologia (SFRH/BD/84650/2010)info:eu-repo/semantics/publishedVersio

Women's perceptions of homebirths in two rural medical districts in Burkina Faso: a qualitative study

<p>Abstract</p> <p>Background</p> <p>In developing countries, most childbirth occurs at home and is not assisted by skilled attendants. The situation increases the risk of death for both mother and child and has severe maternal complications. The purpose of this study was to describe women's perceptions of homebirths in the medical districts of Ouargaye and Diapaga.</p> <p>Methods</p> <p>A qualitative approach was used to gather information. This information was collected by using focus group discussions and individual interviews with 30 women. All the interviews were tape recorded and managed by using QSR NVIVO 2.0, qualitative data management software.</p> <p>Results</p> <p>The findings show that homebirths are frequent because of prohibitive distance to health facilities, fast labour and easy labour, financial constraints, lack of decision making power to reach health facilities.</p> <p>Conclusion</p> <p>The study echoes the need for policy makers to make health facilities easily available to rural inhabitants to forestall maternal and child deaths in the two districts.</p

Comparison of Patient and Surgeon Expectations of Total Hip Arthroplasty

OBJECTIVES: Analysis of discrepancies between patient and surgeon expectations before total hip arthroplasty (THA) should enable a better understanding of motives of dissatisfaction about surgery, but this question has been seldom studied. Our objectives were to compare surgeons' and patients' expectations before THA, and to study factors which affected surgeon-patient agreement. METHODS: 132 adults (mean age 62.8+/-13.7 years, 52% men) on waiting list for THA in three tertiary care centres and their 16 surgeons were interviewed to assess their expectations using the Hospital for Special Surgery Total Hip Replacement Expectations Survey (range 0-100). Patients' and surgeons' answers were compared, for the total score and for the score of each item. Univariate analyses tested the effect of patients' characteristics on surgeons' and patients' expectations separately, and on surgeon-patient differences. RESULTS: Surgeon and patient expectations' mean scores were high (respectively 90.9+/-11.1 and 90.0+/-11.6 over 100). Surgeons' and patients' expectations showed no systematic difference, but there was little agreement on Bland and Altman graph and correlation coefficient was low. Patients had higher expectations than surgeons for sports. Patients rated their expectations according to trust in physician and mental quality of life, surgeons considered disability. More disabled patients and patients from a low-income professional category were often "more optimistic" than their surgeons. CONCLUSION: Surgeons and patients often do not agree on what to expect from THA. More disabled patients expect better outcomes than their surgeons

Knee Arthroplasty: Disabilities in Comparison to the General Population and to Hip Arthroplasty Using a French National Longitudinal Survey

International audienceBACKGROUND: Knee arthroplasty is increasing exponentially due to the aging of the population and to the broadening of indications. We aimed to compare physical disability and its evolution over two years in people with knee arthroplasty to that in the general population. A secondary objective was to compare the level of disabilities of people with knee to people with hip arthroplasty. METHODOLOGY/PRINCIPAL FINDINGS: 16,945 people representative of the French population were selected in 1999 from the French census and interviewed about their level of disability. This sample included 815 people with lower limb arthroplasty. In 2001, 608 of them were re-interviewed, among whom 134 had knee arthroplasty. Among the other participants re-interviewed, we identified 68 who had undergone knee arthroplasty and 145 hip arthroplasty within the last two years (recent arthroplasty). People with knee arthroplasty reported significantly greater difficulties than the general population with bending forward (odds ratio [OR] = 4.7; 95% confidence interval [CI]: 1.7, 12.6), walking more than 500 meters (OR = 6.0; 95% CI: 1.5, 24.7) and carrying 5 kg kilograms for 10 meters (OR = 4.6; 95% CI: 1.3, 16.4). However, the two years evolution in disability was similar to that in the general population for most activities. The level of mobility was similar between people with recent knee arthroplasty and those with recent hip arthroplasty. Nevertheless, people with recent knee arthroplasty reported a lower level of disability than the other group for washing and bending forward (OR = 0.3; 95% CI: 0.1, 0.6 and OR = 0.4; 95% CI: 0.1, 0.9, respectively). CONCLUSIONS/SIGNIFICANCE: People with knee arthroplasty reported a higher risk of disability than the general population for common activities of daily living but a similar evolution. There was no relevant difference between recent knee and hip arthroplasties for mobility

Evaluation of short‐term safety of ultrasound‐guided foetal fluid sampling in the dog (Canis lupus familiaris)

Background: In humans, analysis of amniotic fluid is widely used for diagnostic and prognostic purposes. Amniocentesis has scarcely been used in veterinary medicine to date, despite a tremendous potential for clinical and research applications in dogs. Our study aimed to establish a safe method for foetal fluid sampling in female dogs. Methods: Two transabdominal ultrasound-guided methods were assessed: the "free hand" and the needle-guided bracket sampling. In addition, through a subsequent routinely scheduled ovariohysterectomy, fluid was directly collected. Samples from 98 conceptuses were collected at day 46.7 +/- 7.5 of pregnancy. Results: The amount of fluid retrieved varied between 0.5 and 5.0 ml per collection. Macroscopic examination of the uterus and conceptuses identified 53% of the puncture sites. Neither fluid leakage nor foetal injury was detected, and six hematomas (5.8%) were visible. Ultrasound-guided foetal fluid collection was found to be potentially safe, and it can be performed by using either transabdominal method. Conclusion: Foetal fluid collection is possible with relative ease and low short-term risk, and may open paths for diagnostic, therapeutic and research purposes in dogs. The procedure can provide new insights into prenatal clinical medicine, including diagnostics of foetal deaths, early identification of heritable diseases and so on

Non-Antioxidant Properties of α-Tocopherol Reduce the Anticancer Activity of Several Protein Kinase Inhibitors In Vitro

The antioxidant properties of α-tocopherol have been proposed to play a beneficial chemopreventive role against cancer. However, emerging data also indicate that it may exert contrasting effects on the efficacy of chemotherapeutic treatments when given as dietary supplement, being in that case harmful for patients. This dual role of α-tocopherol and, in particular, its effects on the efficacy of anticancer drugs remains poorly documented. For this purpose, we studied here, using high throughput flow cytometry, the direct impact of α-tocopherol on apoptosis and cell cycle arrest induced by different cytotoxic agents on various models of cancer cell lines in vitro. Our results indicate that physiologically relevant concentrations of α-tocopherol strongly compromise the cytotoxic and cytostatic action of various protein kinase inhibitors (KI), while other classes of chemotherapeutic agents or apoptosis inducers are unaffected by this vitamin. Interestingly, these anti-chemotherapeutic effects of α-tocopherol appear to be unrelated to its antioxidant properties since a variety of other antioxidants were completely neutral toward KI-induced cell cycle arrest and cell death. In conclusion, our data suggest that dietary α-tocopherol could limit KI effects on tumour cells, and, by extent, that this could result in a reduction of the clinical efficacy of anti-cancer treatments based on KI molecules