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We investigated the high energy spin excitations in electron-doped La_{2-x}Ce_{x}CuO_{4}, a cuprate superconductor, by resonant inelastic x-ray scattering (RIXS) measurements. Efforts were paid to disentangle the paramagnon signal from non-spin-flip spectral weight mixing in the RIXS spectrum at Q_{â¥}=(0.6π,0) and (0.9π,0) along the (1 0) direction. Our results show that, for doping level x from 0.07 to 0.185, the variation of the paramagnon excitation energy is marginal. We discuss the implication of our results in connection with the evolution of the electron correlation strength in this system.
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Importance: Glucagon-like peptide 1 (GLP-1) receptor agonists were first approved for the treatment of type 2 diabetes in 2005. Demand for these drugs has increased rapidly in recent years, as indications have expanded, but they remain expensive. Objective: To analyze how manufacturers of brand-name GLP-1 receptor agonists have used the patent and regulatory systems to extend periods of market exclusivity. Evidence Review: The annual US Food and Drug Administration's (FDA) Approved Drug Products With Therapeutic Equivalence Evaluations was used to identify GLP-1 receptor agonists approved from 2005 to 2021 and to record patents and nonpatent statutory exclusivities listed for each product. Google Patents was used to extract additional data on patents, including whether each was obtained on the delivery device or another aspect of the product. The primary outcome was the duration of expected protection from generic competition, defined as the time elapsed from FDA approval until expiration of the last-to-expire patent or regulatory exclusivity. Findings: On the 10 GLP-1 receptor agonists included in the cohort, drug manufacturers listed with the FDA a median of 19.5 patents (IQR, 9.0-25.8) per product, including a median of 17 patents (IQR, 8.3-22.8) filed before FDA approval and 1.5 (IQR, 0-2.8) filed after FDA approval. Fifty-four percent of all patents listed on GLP-1 receptor agonists were on the delivery devices rather than active ingredients. Manufacturers augmented patent protection with a median of 2 regulatory exclusivities (IQR, 0-3) obtained at approval and 1 (IQR, 0.3-4.3) added after approval. The median total duration of expected protection after FDA approval, when accounting for both preapproval and postapproval patents and regulatory exclusivities, was 18.3 years (IQR, 16.0-19.4). No generic firm has successfully challenged patents on GLP-1 receptor agonists to gain FDA approval. Conclusions and Relevance: Patent and regulatory reform is needed to ensure timely generic entry of GLP-1 receptor agonists to the market.
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Diabetes Mellitus Tipo 2 , Aprovação de Drogas , Medicamentos Genéricos , Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipoglicemiantes , Patentes como Assunto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/economia , Aprovação de Drogas/legislação & jurisprudência , Medicamentos Genéricos/economia , Medicamentos Genéricos/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Preparações Farmacêuticas/economia , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Patentes como Assunto/legislação & jurisprudência , Estados Unidos , Equivalência Terapêutica , Comércio , Competição Econômica/economia , Competição Econômica/legislação & jurisprudência , Fatores de TempoRESUMO
OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.
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Cesárea/estatística & dados numéricos , Cuidado Pré-Natal , Adulto , China/epidemiologia , Estudos Transversais , Demografia , Feminino , Diretrizes para o Planejamento em Saúde , Hospitais , Humanos , Gravidez , Melhoria de Qualidade , Inquéritos e QuestionáriosAssuntos
Medicamentos Biossimilares , Indústria Farmacêutica , Medicamentos Genéricos , Competição Econômica , Patentes como Assunto , Humanos , Medicamentos Biossimilares/economia , Medicamentos Biossimilares/uso terapêutico , Custos de Medicamentos , Medicamentos Genéricos/economia , Medicamentos Genéricos/uso terapêutico , Indústria Farmacêutica/economia , Indústria Farmacêutica/legislação & jurisprudência , Patentes como Assunto/legislação & jurisprudência , Competição Econômica/economia , Competição Econômica/legislação & jurisprudênciaRESUMO
OBJECTIVE: To examine the longitudinal associations of fetal growth with adverse child growth outcomes and to assess whether maternal metabolic factors modify the associations. DESIGN: Prospective cohort study. SETTING: Born in Guangzhou Cohort Study, China. POPULATION: A total of 4818 mother-child pairs. METHODS: Fetal growth was assessed according to estimated fetal weight (EFW) from 22 weeks of gestation until birth and the measurement of the birthweight. Fetal growth Z-scores were computed from random effects in the multilevel linear spline models to represent fetal size in early pregnancy (22 weeks of gestation) and growth in mid-pregnancy (22-27 weeks of gestation), early third trimester (28-36 weeks of gestation) and late third trimester (≥37 weeks of gestation). MAIN OUTCOME MEASURES: Z-scores for childhood stunting, low weight, overweight or obesity, length/height for age (LAZ/HAZ), weight for age (WAZ) and body mass index for age (BMIZ) at the age of 3 years. Adjusted associations were examined using multiple Poisson or linear regression models. RESULTS: Increased Z-scores of fetal size in early pregnancy and growth in mid-pregnancy and early third trimester were associated with a higher risk of childhood overweight or obesity (risk ratios 1.25-1.45). Fetal growth in each period was negatively associated with stunting and low weight, with the strongest associations observed for fetal size in early pregnancy and growth in mid-pregnancy. The results for continuous outcomes (LAZ/HAZ, WAZ and BMIZ) were similar. The associations of fetal growth with overweight or obesity in childhood were stronger among mothers who were underweight and who were overweight or obese than among mothers of normal weight. CONCLUSIONS: Accelerated fetal growth before 37 weeks of gestation is associated with children who are overweight or obese, whereas the critical period for stunting and low weight occurs before 28 weeks of gestation. TWEETABLE ABSTRACT: Fetal growth during different periods is differentially associated with childhood stunting, underweight and overweight or obesity.
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Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Obesidade Infantil/epidemiologia , Adulto , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Obesidade Infantil/etiologia , Gravidez , Estudos ProspectivosRESUMO
Objective: To explore the efficacy and safety of intraoperative ultrasound-assisted neuroendoscopy for treating hypertensive intracerebral hemorrhage (HICH) via lateral fissure and insula approach. Methods: The clinical data of 66 patients with HICH in basal ganglia who underwent intraoperative ultrasound-assisted neuroendoscopy via lateral fissure and insula approach for hematoma evacuation were retrospectively analyzed, including operative data and follow-up results. All patients had no brain hernia before operation. The hematoma was located by the ultrasound and then the path into the hematoma cavity was determined. Meanwhile, the residual hematoma was also detected by using the ultrasound. The clearance rate of hematoma was observed by CT. Barthel index was used to evaluate the activity of daily living. Results: The amount of residual hematoma was less than 10% in 63 ases and 10%-20% in 3 cases. There were 11 cases of postoperative pneumonia, of whom 9 cases underwent percutaneous tracheotomy. Rebleeding occurred in 2 cases, but the amount was small, and there was no need for reoperation. Meanwhile, there was 1 case of secondary intracranial infection and 1 case of secondary hydrocephalus. No case of cerebral contusion was reported. Half a year after the operation, Barthel Index grading showed that there were 3 cases of grade I, 25 cases of grade â ¡, 34 cases of grade â ¢, 3 cases of grade â £ and 1 case of death, respectively. Conclusions: Intraoperative ultrasound-assisted neuroendoscopy via lateral fissure and insula approach can improve the efficacy and safety of treatment for HICH.
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Hemorragia Intracraniana Hipertensiva , Neuroendoscopia , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/cirurgia , Craniotomia , Hematoma , Humanos , Hemorragia Intracraniana Hipertensiva/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: This study aimed to compare the effects of cold plasma (CP), ultraviolet (UV-C) and aqueous ozone (AO) on Botrytis cinerea and explore their application in preserving blueberry. METHODS AND RESULTS: The effects of CP, UV-C or AO on B. cinerea were investigated. Results showed that three treatments effectively inhibited the growth of B. cinerea, increasing cell membrane penetrability and causing the leakage of cytoplasm and nucleic acid. Scanning electron microscopy showed that CP caused the mycelium fold and collapse depression; UV-C caused the mycelium shrivelled; mycelium treated with AO appeared to fold and break. In the in vivo test in blueberry, all treatments effectively inhibited the growth of micro-organisms, maintained qualities and enhanced antioxidant activities in blueberry during postharvest storage. CONCLUSION: Cold plasma, UV-C and AO effectively inhibited the growth of B. cinerea and significantly extended the shelf life of blueberry. Based on in vitro and in vivo tests, CP showed better effects to preserve blueberry compared with other treatments. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings revealed the effective mechanisms of CP, UV-C and AO to inhibit B. cinerea in vitro. CP exhibited better application potential to preserve fresh fruit than traditional sterilization methods such as UV-C and AO.
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Mirtilos Azuis (Planta) , Botrytis/efeitos dos fármacos , Botrytis/efeitos da radiação , Microbiologia de Alimentos , Conservação de Alimentos/métodos , Frutas/microbiologia , Raios Ultravioleta , Botrytis/crescimento & desenvolvimento , Botrytis/metabolismo , Qualidade dos Alimentos , Frutas/fisiologia , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Micélio/efeitos da radiação , Ozônio/farmacologia , Gases em Plasma/farmacologiaRESUMO
This study analyzes the use and timing of terminal disclaimers in all biologic patents involved in litigation from 2010 to 2023.
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Produtos Biológicos , Patentes como Assunto , Produtos Biológicos/uso terapêuticoRESUMO
This study evaluates the frequency of terminal disclaimers filed by drug patent holders to obviate obviousness-type double patenting rejections associated with drug patent thickets.
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This cross-sectional study identifies the prevalence of patents on risk evaluation and mitigation strategies and their association with delaying generic competition.
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Medicamentos Genéricos , Patentes como Assunto , Medicamentos sob Prescrição , Avaliação de Risco e Mitigação , Custos de Medicamentos , Indústria Farmacêutica , Medicamentos Genéricos/uso terapêutico , Competição Econômica , Avaliação de Risco e Mitigação/legislação & jurisprudência , Estados Unidos , Patentes como Assunto/legislação & jurisprudênciaRESUMO
This study analyzed the US Food and Drug Administrationlisted patents on glucagon-like peptide 1 (GLP-1) receptor agonists to determine their claim characteristics and the potential barriers they pose to generic entry.
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Diabetes Mellitus Tipo 2 , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Hipoglicemiantes , Legislação de Dispositivos Médicos , Patentes como Assunto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêuticoRESUMO
This Viewpoint looks at the lawsuits brought by pharmaceutical companies to challenge the Inflation Reduction Act of 2022, in particular claims under the First Amendment's protection of free speech.
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Direitos Civis , Fala , Direitos Civis/legislação & jurisprudência , Estados UnidosRESUMO
This Viewpoint discusses 3 bills introduced recently in Congress that focus on patent eligibility, fraud, and quality and that have major implications for clinical medicine and pharmaceutical development.
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Reforma dos Serviços de Saúde , Legislação de Medicamentos , Patentes como Assunto , Medicamentos sob Prescrição , Reforma dos Serviços de Saúde/legislação & jurisprudência , Estados Unidos , Patentes como Assunto/legislação & jurisprudênciaRESUMO
This Viewpoint discusses a current Supreme Court lawsuit, Amgen v Sanofi, involving Amgen's broad patents on PCSK9 that could effectively prevent other manufacturers from producing similar or even clinically superior antibodies, with important negative consequences for patients.
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Patentes como Assunto , Decisões da Suprema Corte , Estados Unidos , Patentes como Assunto/legislação & jurisprudênciaRESUMO
This study examines all patents associated with biologic litigation to understand how manufacturers use ancillary product patents to delay biosimilar market entry.
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Produtos Biológicos , Medicamentos Biossimilares , Patentes como Assunto , Produtos Biológicos/uso terapêutico , Aprovação de Drogas , Indústria Farmacêutica , Competição Econômica , Estados Unidos , Fatores de TempoRESUMO
This study assesses the frequency of continuation patents on brand-name drugs approved by the US Food and Drug Administration from 2000 to 2015.
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Custos de Medicamentos , Competição Econômica , Patentes como Assunto , Aprovação de Drogas/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos , Medicamentos Genéricos/uso terapêutico , Estados Unidos/epidemiologia , United States Food and Drug Administration , Patentes como Assunto/estatística & dados numéricosRESUMO
This study quantifies the revenue earned on all brand-name inhalers approved by the US Food and Drug Administration from 2000 to 2021 and compared earnings before and after expiration of primary patents on these products.
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Indústria Farmacêutica , Competição Econômica , Nebulizadores e Vaporizadores , Patentes como Assunto , Medicamentos Genéricos , Competição Econômica/economia , Nebulizadores e Vaporizadores/economia , Estados Unidos , Patentes como Assunto/legislação & jurisprudência , Indústria Farmacêutica/economia , Indústria Farmacêutica/legislação & jurisprudênciaRESUMO
This study examines the frequency of drug patent invalidations based on inequitable conduct.
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Patentes como Assunto , Preparações Farmacêuticas , Má Conduta Científica , United States Food and Drug Administration , Patentes como Assunto/ética , Patentes como Assunto/legislação & jurisprudência , Má Conduta Científica/ética , Má Conduta Científica/legislação & jurisprudência , Estados UnidosRESUMO
This study evaluates sales revenue earned in the first 5 years for newly marketed brand-name drugs with and without an initial orphan drug designation.