RESUMO
BACKGROUND: Financial conflicts of interest (FCOI) of medical professionals and associated organizations with pharmaceutical companies (pharma) might contribute to the use of low value oncological treatments. Value criteria for oncological drug approvals in the Netherlands have recently become more stringent leading to objections by cancer patient advocacy organizations (cPAOs). Considering the importance of cPAOs input in cancer patient care we analyzed whether pharma funding of cPAOs occurs in the Netherlands. METHODS: The cPAO websites and available annual reports were evaluated for disclosure of pharma funding for the years 2021 and 2022. Also, data from the Dutch Healthcare Transparency Registry (DHTR) were extracted. RESULTS: Twenty-one of 34 (61.8â¯%) cPAOs received pharma funding (with 20 registered in the DHTR), and for 13 (29.4â¯%) cPAOs no reporting of pharma funding could be found. Three of the cPAOs disclosed pharma funding directly on their main website. Online educational material was available from 22 cPAOs on their websites with pharma funding disclosed on the educational material in 5. The total registered amount of pharmaceutical funding was 667,232.00 in 2021 and 536,098.00 in 2022. The median (and interquartile ranges) DHTR registered amount of support per cPAO that received funding in the studied period was 23,799.50 (14,823.75-84,663.30). The most common funding category as defined in the DHTR was project sponsorship. CONCLUSIONS: Financial support by the pharmaceutical industry is common for Dutch cPAOs. Given the importance of cPAOs and their objective input in the societal debate on the availability of cancer drugs, the potential influence of pharma sponsoring should be critically evaluated.
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The quality of evidence leading to new oncological treatments suffers shortcomings, as has recently been addressed for drug approvals. In this 'Personal view', we evaluate the unintended effects of adopting stereotactic radiosurgery as the standard of care for patients with limited number of symptomatic brain metastases and favourable prognostic factors in international guidelines in view of the limitations in the evidence of efficacy and effectiveness, with special focus on countries with relatively limited resources.
RESUMO
The number of new oncological treatments is increasing rapidly, even though many offer limited benefit to patients. In these cases, the scientific research leading to approvals is marred by shortcomings. Nonetheless, many drugs of limited value are approved by regulatory agencies. One of the factors contributing thereto is financial conflict of interest (FCI) with the pharmaceutical industry (Pharma). This occurs at different levels, including researchers, opinion leaders and editors of medical journals. FCI contributes to patient exposure to treatments that offer limited or no benefit and to unjust spending of valuable resources while providing large revenues for Pharma. The important step of the 'NederlandsTijdschriftvoorGeneeskunde' (NTVG) to omit all pharmaceutical advertisement as well as advertisement for pharmaceutical industry sponsored medical education sends an important signal and is a first step to revalue the important relationship with the pharmaceutical industry.
Assuntos
Antineoplásicos , Conflito de Interesses , Humanos , Publicidade , Indústria Farmacêutica , Antineoplásicos/uso terapêutico , Preparações FarmacêuticasRESUMO
Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.
Assuntos
Aprovação de Drogas , Custos de Medicamentos , Oncologia/ética , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Viés , COVID-19/epidemiologia , Controle de Custos/ética , Controle de Custos/organização & administração , Controle de Custos/normas , Evolução Cultural , Aprovação de Drogas/economia , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/organização & administração , Custos de Medicamentos/ética , Custos de Medicamentos/legislação & jurisprudência , Humanos , Oncologia/economia , Oncologia/organização & administração , Oncologia/normas , Neoplasias/tratamento farmacológico , Neoplasias/economia , Neoplasias/mortalidade , Inovação Organizacional , PandemiasRESUMO
BACKGROUND: Enzalutamide is an orally administered drug that blocks signaling in the androgen receptor with clinical activity in both chemotherapy-naive and post-chemotherapy patients with castrate-resistant prostate cancer (CRPC). Enzalutamide is generally well-tolerated, but dose reductions are nonetheless needed in case of side effects. CASE: An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer was treated with a very low dose of 40 mg enzalutamide once daily. The trough levels of enzalutamide and the active metabolite N-desmethylenzalutamide were 4.5 mg/L and 3.0 mg/L, respectively. This exposure provided a long-term response without any significant side effects. CONCLUSION: Low doses of enzalutamide may be efficacious, while also reducing the risk of side effects. Furthermore, employing a lower dose would reduce healthcare costs and increase access to enzalutamide. Studies exploring the efficacy of lower enzalutamide doses are warranted.
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Benzamidas/administração & dosagem , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Andrógenos/administração & dosagem , Humanos , Masculino , Receptores Androgênicos/metabolismoRESUMO
BACKGROUND: Infant feeding practices are an important factor influencing malocclusion in deciduous dentition, which can have long-lasting negative outcomes on oral health-related quality of life. Hence, knowledge, attitudes and cultural practices of mothers are vital in prevention of this. OBJECTIVE: The present study was carried out to assess the mother's knowledge about feeding practices and its influence on primary dentition. MATERIALS AND METHODS: The current study was a cross-sectional study of 187 mothers of 3- to 5-year-old children identified with malocclusion, conducted in the pedodontics department of tertiary care teaching dental hospital in South India. RESULTS: Majority of the mothers were graduates (31.6%) or undergraduates or postgraduates (42.8%). The duration of breastfeeding was 0-3 months in 9.1%, 3-6 months in 23%, 6-12 months in 30.5%, and >12 months in 37.5%. Bottle-feeding was reported by 21.4%. Only 52.4% of the mothers were aware about caries, and 66.2% were aware of malocclusion. The prevalence of malocclusion was 63.6% in study population, and the prevalence of caries was 30.5%. The most common type of malocclusion was overjet seen in 20.9% of study subjects. The proportion of children with crowding, open bite, and crossbite was 17.1, 15, and 10.7%, respectively. There was a gradually increasing trend in malocclusion awareness with increasing educational status of the mother which was statistically not significant (p value = 0.119). The proportion of malocclusion was highest in children who received breastfeeding between 3 months and 6 months and was highest (69.8%) in children who received bottle-feeding for more than 12 months. None of the factors had shown a statistically significant association with malocclusion in study population. CONCLUSION: The prevalence of malocclusion is high in children, and mothers' awareness regarding malocclusion is poor. CLINICAL SIGNIFICANCE: There is a need to educate mothers about proper feeding practices to prevent dental malocclusion. HOW TO CITE THIS ARTICLE: Duraisamy V, Pragasam AX, Vasavaih SK, et al. Maternal Knowledge Regarding Feeding Practices and its Effect on Occlusion of Primary Dentition in Children: A Cross-sectional Study. Int J Clin Pediatr Dent 2020;13(1):31-34.
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Anemia Falciforme , Velocidade do Fluxo Sanguíneo/fisiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valva Tricúspide/fisiopatologia , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/mortalidade , Anemia Falciforme/fisiopatologia , Biomarcadores/sangue , Estudos de Coortes , Ecocardiografia , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ultrassonografia Doppler , Adulto JovemRESUMO
Oligodontia is one of the most common developmental abnormalities in humans. The present case report highlights the features of oligodontia in a 12-year-old male patient which was managed successfully with multidisciplinary approach. Familial oligodontia represents as an absence of varying numbers of secondary teeth seen as an isolated trait. The advance in the understanding of tooth development and genetic control of tooth morphology not only allows clinical research to broaden the knowledge of tooth agenesis but also provides optimum clinical care.
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Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSß(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.
Assuntos
Acetilcisteína/farmacologia , Anemia Falciforme/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Administração Oral , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Biomarcadores/sangue , Biomarcadores/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/farmacologia , Glutationa/análise , Glutationa/sangue , Hemólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Fosfatidilserinas/sangue , Fosfatidilserinas/metabolismo , Projetos Piloto , Adulto JovemRESUMO
Echocardiography is critical in the assessment of patients with hypoplastic left heart syndrome. Fundamental techniques and standardised approaches are useful when evaluating patients with hypoplastic left heart syndrome prenatally, after birth, and before the Norwood operation (Stage 1); after the Norwood operation, before and after the superior cavopulmonary anastomosis (Stage 2); before and after the Fontan operation (Stage 3); and for chronic surveillance after the Fontan operation. From foetal assessment to ongoing surveillance after the Fontan procedure, echocardiography remains the primary technique for cardiac monitoring in this growing population of children and adults.
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Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Ventrículos do Coração/embriologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/embriologia , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia Pré-Natal/métodosRESUMO
Erythrocytes are both an important source and target of reactive oxygen species in sickle cell disease. Levels of glutathione, a major antioxidant, have been shown to be decreased in sickle erythrocytes and the mechanism leading to this deficiency is not known yet. Detoxification of reactive oxygen species involves the oxidation of reduced glutathione (GSH) into glutathione-disulfide (GSSG) which is actively transported out of erythrocyte. We questioned whether under oxidative conditions, GSSG efflux is increased in sickle erythrocytes. Erythrocytes of 18 homozygous sickle cell patients and 9 race-matched healthy controls were treated with 2,3-dimethoxy-l,4-naphthoquinone, which induces intracellular reactive oxygen species generation, to stimulate GSSG production. Intra- and extracellular concentrations of GSH and GSSG were measured at baseline and during 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation. While comparable at baseline, intracellular and extracellular GSSG concentrations were significantly higher in sickle erythrocytes than in healthy erythrocyte after 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation (69.9 ± 3.7 µmol/l vs. 40.6 ± 6.9 µmol/l and 25.8 ± 2.7 µmol/l vs. 13.6 ± 1.7 µmol/l respectively, P<0.002). In contrast to control erythrocytes, where GSH concentrations remained unchanged (176 ± 8.4 µmol/l vs. 163 ± 13.6 µmol/l, NS), GSH in sickle erythrocytes decreased significantly (from 167 ± 8.8 µmol/l to 111 ± 11.8 µmol/l, P<0.01) after 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation. Adding multidrug resistance-associated protein-1 inhibitor (MK571) to erythrocytes blocked GSSG efflux in both sickle and normal erythrocytes. GSSG efflux, mediated by multidrug resistance-associated protein-1, is increased in sickle erythrocytes, resulting in net loss of intracellular glutathione and possibly higher susceptibility to oxidative stress.
Assuntos
Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Antioxidantes/metabolismo , Eritrócitos/metabolismo , Glutationa/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Adulto , Estudos de Casos e Controles , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Feminino , Dissulfeto de Glutationa/metabolismo , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Naftoquinonas/farmacologia , Propionatos/farmacologia , Quinolinas/farmacologia , Adulto JovemRESUMO
Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management.
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Anemia Falciforme/metabolismo , Estresse Oxidativo , Anemia Falciforme/fisiopatologia , Anemia Falciforme/terapia , Gerenciamento Clínico , Humanos , Espécies Reativas de OxigênioRESUMO
The painful crisis accounts for the majority of sickle cell disease (SCD) related hospital admissions. The prototypic long pentraxin 3 (PTX3), an acute phase protein, is elevated in patients with inflammatory and ischemic states. As the sickle cell painful crisis is associated with both inflammation and tissue ischemia, we questioned whether plasma PTX3 levels are increased during and associated with painful crisis severity. Furthermore, since PTX3 up-regulates endothelial expression of tissue factor we studied PTX levels in relation to markers of endothelial and coagulation activation. Plasma levels of PTX3, ultra-sensitive C-reactive protein (US-CRP), prothrombin fragment 1+2, thrombin-antithrombin (TAT) complexes, von Willebrand Factor antigen and soluble vascular adhesion molecule-1 were determined in 105 asymptomatic sickle cell patients, 33 patients during painful crisis and 30 race matched healthy controls. Plasma PTX3 levels were comparable between patients in asymptomatic state and healthy controls, but significantly higher during painful crisis (P<0.01). US-CRP levels were higher in asymptomatic patients compared to controls (P<0.0001) and increased further during painful crisis (P<0.0001). PTX3 levels at presentation with painful crisis correlated significantly with the duration of subsequent hospital admission (r(s) = 0.43; P = 0.013), whereas US-CRP levels did not. PTX3 levels did not correlate with markers of hypercoagulability. The increase of PTX3 levels during painful crisis and their relation to the duration of subsequent hospital stay suggest that PTX3 might serve both as a diagnostic and severity marker of the painful sickle cell crisis.
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Anemia Falciforme/sangue , Anemia Falciforme/complicações , Proteína C-Reativa/metabolismo , Dor/sangue , Dor/etiologia , Componente Amiloide P Sérico/metabolismo , Adulto , Anemia Falciforme/metabolismo , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Trombofilia/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto JovemRESUMO
The painful crisis is the hallmark of sickle-cell disease (SCD). Bone resorption, as part of physiological bone turnover, results in release into the circulation with subsequent urinary excretion of the collagen cross-links pyridinoline (PYD) and deoxypyridinoline (DPD). Urinary PYD and DPD concentrations could reflect the extent of bone infarction during painful sickle-cell crisis. Urinary concentrations of PYD and DPD, adjusted for urine creatinine, were measured in sickle-cell patients (38 clinically asymptomatics and 27 during painful crisis) and healthy controls (n 5 25) using high-performance liquid chromatography(HPLC). PYD and DPD concentrations were higher in asymptomatic HbSS/HbSb0-thalassemia patients compared to controls (P <0.05) with further increments during painful crisis in both HbSS/HbSb0-thalassemia and HbSC/HbSb1-thalassemia patients (P < 0.05). In the asymptomatic HbSS/HbSb0-thalassemia patients, there was a statistically significant positive correlation between DPD and hemolytic rate.Based on urinary PYD and DPD concentrations, bone degradation is increased in asymptomatic sickle-cell patients, with further increments during painful crisis. Urinary PYD and DPD concentrations are potentially diagnostic and prognostic tools in SCD.
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Aminoácidos/urina , Anemia Falciforme/complicações , Reabsorção Óssea/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Falciforme/diagnóstico , Anemia Falciforme/urina , Biomarcadores/urina , Reabsorção Óssea/etiologia , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Hemólise , Humanos , Pessoa de Meia-Idade , Dor , Adulto JovemRESUMO
Oxidative stress plays an important role in the pathophysiology of sickle cell disease (SCD). Plasma levels of advanced glycation end products (AGEs) are increased under oxidative conditions and are associated with disease severity in diabetes and inflammatory diseases. We investigated whether AGEs are increased in sickle cell patients and whether they are associated with SCD-related complications. Plasma levels of the AGEs pentosidine, N(ε) -(carboxymethyl)lysine (CML) and N(ε) -(carboxyethyl)lysine (CEL) were measured using single-column high performance liquid chromatography with fluorescence detection (pentosidine) and ultra performance liquid chromatography-tandem mass spectrometry (CML and CEL). Plasma levels of pentosidine and CML were increased in HbSS/HbSß°-thalassaemia (n=60) and HbSC/HbSß(+) -thalassaemia (n=42) patients during steady state as compared to healthy HbAA controls (n=30) without increments during painful crisis. CEL levels were comparable between all groups. Pentosidine and CML levels correlated significantly to haemolytic rate during the clinically asymptomatic state while pentosidine was significantly related to the number of haemolysis-related organ complications. The increased plasma AGE levels in sickle cell patients and their association with haemolysis and haemolysis-related complications suggest AGEs might be implicated in the pathophysiology of the haemolytic phenotype of SCD. Measurement of AGEs might be useful in predicting organ complications in SCD.
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Anemia Falciforme/sangue , Produtos Finais de Glicação Avançada/sangue , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Arginina/análogos & derivados , Arginina/sangue , Biomarcadores/sangue , Feminino , Hemólise/fisiologia , Humanos , Lisina/análogos & derivados , Lisina/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Adulto JovemRESUMO
Hypohidrotic ectodermal dysplasia (HED) is a rare group of disorders affecting the hair, teeth, nails and sweat glands to a variable degree. There is a wide range of clinical presentation of HED. Missing teeth or abnormal tooth form may be the first indicator of the disorder. We present a case report of 5 cases of HED with their intraoral findings and their treatment plan. We also consider the various etiological factors and their clinical diagnostic aids.