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1.
Trials ; 22(1): 725, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674741

RESUMO

BACKGROUND: Mobile money-a service enabling users to receive, store, and send electronic money using mobile phones-has been widely adopted across low- and middle-income economies to pay for a variety of services, including healthcare. However, evidence on its effects on healthcare access and health outcomes are scarce and the possible implications of using mobile money for financing and payment of maternal healthcare services-which generally require large one-time out-of-pocket payments-have not yet been systematically assessed in low-resource settings. The aim of this study is to determine the impact on health outcomes, cost-effectiveness, feasibility, acceptability, and usefulness of mobile phone-based savings and payment service, the Mobile Maternal Health Wallet (MMHW), for skilled healthcare during pregnancy and delivery among women in Madagascar. METHODS: This is a hybrid effectiveness-implementation type-1 trial, determining the effectiveness of the intervention while evaluating the context of its implementation in Madagascar's Analamanga region, containing the capital, Antananarivo. Using a stratified cluster randomized design, 61 public-sector primary-care health facilities were randomized within 6 strata to either receive the intervention or not (29 intervention vs. 32 control facilities). The strata were defined by a health facility's antenatal care visit volume and its capacity to offer facility-based deliveries. The registered pre-specified primary outcomes are (i) delivery at a health facility, (ii) antenatal care visits, and (iii) total healthcare expenditure during pregnancy, delivery, and neonatal period. The registered pre-specified secondary outcomes include additional health outcomes, economic outcomes, and measurements of user experience and satisfaction. Our estimated enrolment number is 4600 women, who completed their pregnancy between July 1, 2020, and December 31, 2021. A series of nested mixed-methods studies will elucidate client and provider perceptions on feasibility, acceptability, and usefulness of the intervention to inform future implementation efforts. DISCUSSION: A cluster-randomized, hybrid effectiveness-implementation design allows for a robust approach to determine whether the MMHW is a feasible and beneficial intervention in a resource-restricted public healthcare environment. We expect the results of our study to guide future initiatives and health policy decisions related to maternal and neonatal health and universal healthcare coverage through technology in Madagascar and other countries in sub-Saharan Africa. TRIAL REGISTRATION: This trial was registered on March 12, 2021: Deutsches Register Klinischer Studien (German Clinical Trials Register), identifier: DRKS00014928 . For World Health Organization Trial Registration Data Set see Additional file 1.


Assuntos
Telefone Celular , Serviços de Saúde Materna , Feminino , Humanos , Recém-Nascido , Madagáscar , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Cuidado Pré-Natal
2.
Eur J Neurol ; 28(12): 3925-3937, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34411383

RESUMO

BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.


Assuntos
COVID-19 , Doenças Neurodegenerativas , Acidente Vascular Cerebral , Cefaleia , Humanos , SARS-CoV-2
4.
Front Neurosci ; 14: 576741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071747

RESUMO

Numerous studies on experimental ischemic stroke use the filament middle cerebral artery occlusion (fMCAo) model in C57BL/6 mice, but lesion sizes in this strain are highly variable. A known contributor is variation in the posterior communicating artery (PcomA) patency. We therefore aimed to provide a semiquantitative non-invasive in vivo method to routinely assess PcomA patency. We included 43 male C57BL/6 mice from four independent studies using a transient 45 min fMCAo model. Edema-corrected lesion sizes were measured by magnetic resonance (MR) imaging 24 h after reperfusion. Time-of-flight MR angiography was performed 7 days before and 24 h after fMCAo. Scores of PcomA size measured 24 h after, but not scores measured 7 days before fMCAo were negatively correlated with lesion size. Variability in PcomA patency explained 30% of the variance in our cohort (p < 0.0001, coefficient of determination r 2 = 0.3). In a simulation using parameters typical for experimental stroke research, the power to detect a true effect of d = 1 between two groups increased by 15% when an according covariate was included in the statistical model. We have demonstrated that in vivo measurement of PcomA size is feasible and can lead to increased accuracy in assessing the effect of treatments.

5.
Infection ; 48(4): 619-626, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32535877

RESUMO

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688).


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Sistema de Registros , Berlim/epidemiologia , Betacoronavirus , Bancos de Espécimes Biológicos , COVID-19 , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Humanos , Estudos Observacionais como Assunto , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Fatores de Tempo , Resultado do Tratamento , Organização Mundial da Saúde
8.
PLoS One ; 15(1): e0228017, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32004331

RESUMO

Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups: community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.


Assuntos
Telefone Celular , Acesso aos Serviços de Saúde , Serviços de Saúde Materna , Telemedicina , Adulto , Telefone Celular/economia , Telefone Celular/instrumentação , Feminino , Pessoal de Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Madagáscar , Motivação , Projetos Piloto , Gravidez , Gestantes , Pesquisa Qualitativa , Qualidade da Assistência à Saúde , Telemedicina/economia , Telemedicina/instrumentação
11.
Neurol Neuroimmunol Neuroinflamm ; 6(3): e558, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31044146

RESUMO

Objective: To investigate the relevance of dysfunctional T cells in immune-mediated myopathies. We analyzed T-cell exhaustion and senescence, in the context of programmed cell death protein 1 (PD1)-related immunity in skeletal muscle biopsies from patients with immune-mediated necrotizing myopathy (IMNM), sporadic inclusion body myositis (sIBM), and myositis induced by immune checkpoint inhibitors (irMyositis). Methods: Skeletal muscle biopsies from 12 patients with IMNM, 7 patients with sIBM, and 8 patients with irMyositis were analyzed by immunostaining and immunofluorescence as well as by quantitative PCR. Eight biopsies from nondisease participants served as controls. Results: CD3+CD8+ T cells in biopsies from IMNM, sIBM, and irMyositis were largely PD1-positive, while CD68+ macrophages were sparsely positive to the ligand of programmed cell death protein 1 (PD-L1). The sarcolemma of myofibers was PD-L2+ and was colocalized with major histocompatibility complex (MHC) class I. CD68+ macrophages were colocalized with PD-L2. Senescent T cells were strongly enriched in skeletal muscle of sIBM, revealing a distinct immunologic signature. Biopsies from patients with irMyositis showed mild signs of senescence and exhaustion. Conclusion: Persistent exposure to antigens in IMNMs and sIBM may lead to T-cell exhaustion, a process controlled by the PD1 receptor and its cognate ligands PD-L1/PD-L2. To our knowledge, these data are the first evidence of presence of dysfunctional T cells and relevance of the PD1 pathway in IMNM, sIBM, and irMyositis. These findings may guide the way to a novel understanding of the immune pathogenesis of immune-mediated myopathies.


Assuntos
Doenças Autoimunes/imunologia , Antígeno B7-H1 , Músculo Esquelético/patologia , Miosite/imunologia , Proteína 2 Ligante de Morte Celular Programada 1 , Receptor de Morte Celular Programada 1 , Linfócitos T , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite de Corpos de Inclusão/imunologia , Adulto Jovem
12.
Sci Adv ; 5(4): eaaw1567, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31001591

RESUMO

Designer receptors exclusively activated by designer drugs (DREADDs) derived from muscarinic receptors not only are a powerful tool to test causality in basic neuroscience but also are potentially amenable to clinical translation. A major obstacle, however, is that the widely used agonist clozapine N-oxide undergoes conversion to clozapine, which penetrates the blood-brain barrier but has an unfavorable side effect profile. Perlapine has been reported to activate DREADDs at nanomolar concentrations but is not approved for use in humans by the Food and Drug Administration or the European Medicines Agency, limiting its translational potential. Here, we report that the atypical antipsychotic drug olanzapine, widely available in various formulations, is a potent agonist of the human M4 muscarinic receptor-based DREADD, facilitating clinical translation of chemogenetics to treat central nervous system diseases.


Assuntos
Drogas Desenhadas/farmacologia , Olanzapina/química , Olanzapina/farmacologia , Receptor Muscarínico M4/agonistas , Receptor Muscarínico M4/genética , Inibidores de Captação de Serotonina/química , Inibidores de Captação de Serotonina/farmacologia , Simulação por Computador , Drogas Desenhadas/química , Ensaios de Triagem em Larga Escala , Humanos , Transdução de Sinais
14.
Eur J Cancer ; 106: 12-23, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30453170

RESUMO

AIM: To characterise clinical presentation, laboratory and histopathologic characteristics and assess the treatment and outcome of neuromuscular side-effects of checkpoint therapy. METHODS: The side-effect registry and the institutional database from ten skin cancer centres were queried for reports on myositis and neuromuscular side-effects induced by checkpoint inhibitors. In total, 38 patients treated with ipilimumab, tremelimumab, nivolumab and pembrolizumab for metastatic skin cancer were evaluated and characterised. RESULTS: Myositis was the most frequent neuromuscular adverse event. In 32% of cases, myositis was complicated by concomitant myocarditis. Furthermore, cases of isolated myocarditis, myasthenia gravis, polymyalgia rheumatica, radiculoneuropathy and asymptomatic creatine kinase elevation were reported. The onset of side-effects ranged from the first week of treatment to 115 weeks after the start of therapy. Most of the cases were severe (49% grade III-IV Common Terminology Criteria for Adverse Events), and there were two fatalities (5%) due to myositis and myositis with concomitant myocarditis. Only half of the cases (50%) completely resolved, whereas the rest was either ongoing or had sequelae. Steroids were given in 80% of the resolved cases and in 40% of the unresolved cases. CONCLUSION: Immune-mediated neuromuscular side-effects of checkpoint inhibitors greatly vary in presentation and differ from their idiopathic counterparts. These side-effects can be life threatening and may result in permanent sequelae. Occurrence of these side-effects must be taken into consideration for patient information, especially when considering adjuvant immunotherapy with anti-programmed cell-death protein 1 (PD-1) antibodies and monitoring, which should include regular surveillance of creatine kinase.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Miosite/induzido quimicamente , Doenças Neuromusculares/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Miosite/diagnóstico , Miosite/imunologia , Miosite/terapia , Metástase Neoplásica , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/imunologia , Doenças Neuromusculares/terapia , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Suíça , Fatores de Tempo , Adulto Jovem
15.
JMIR Mhealth Uhealth ; 7(3): e11420, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30457972

RESUMO

BACKGROUND: Mobile savings and payment systems have been widely adopted to store money and pay for a variety of services, including health care. However, the possible implications of these technologies on financing and payment for maternal health care services-which commonly require large 1-time out-of-pocket payments-have not yet been systematically assessed in low-resource settings. OBJECTIVE: The aim of this study was to determine the structural, contextual, and experiential characteristics of a mobile phone-based savings and payment platform, the Mobile Health Wallet (MHW), for skilled health care during pregnancy among women in Madagascar. METHODS: We used a 2-stage cluster random sampling scheme to select a representative sample of women utilizing either routine antenatal (ANC) or routine postnatal care (PNC) in public sector health facilities in 2 of 8 urban and peri-urban districts of Antananarivo, Madagascar (Atsimondrano and Renivohitra districts). In a quantitative structured survey among 412 randomly selected women attending ANC or PNC, we identified saving habits, mobile phone use, media consumptions, and perception of an MHW with both savings and payment functions. To confirm and explain the quantitative results, we used qualitative data from 6 semistructured focus group discussions (24 participants in total) in the same population. RESULTS: 59.3% (243/410, 95% CI 54.5-64.1) saved toward the expected costs of delivery and, out of those, 64.4% (159/247, 95% CI 58.6-70.2) used household cash savings for this purpose. A total of 80.3% (331/412, 95% CI 76.5-84.1) had access to a personal or family phone and 35.7% (147/412, 95% CI 31.1-40.3) previously used Mobile Money services. Access to skilled health care during pregnancy was primarily limited because of financial obstacles such as saving difficulties or unpredictability of costs. Another key barrier was the lack of information about health benefits or availability of services. The general concept of an MHW for saving toward and payment of pregnancy-related care, including the restriction of payments, was perceived as beneficial and practicable by the majority of participants. In the discussions, several themes pointed to opportunities for ensuring the success of an MHW through design features: (1) intuitive technical ease of use, (2) clear communication and information about benefits and restrictions, and (3) availability of personal customer support. CONCLUSIONS: Financial obstacles are a major cause of limited access to skilled maternal health care in Madagascar. An MHW for skilled health care during pregnancy was perceived as a useful and desirable tool to reduce financial barriers among women in urban Madagascar. The design of this tool and the communication strategy will likely be the key to success. Particularly important dimensions of design include technical user friendliness and accessible and personal customer service.


Assuntos
Financiamento da Assistência à Saúde , Serviços de Saúde Materna/economia , Telemedicina/instrumentação , Telemedicina/normas , Adolescente , Adulto , Telefone Celular/normas , Telefone Celular/tendências , Feminino , Grupos Focais , Acesso aos Serviços de Saúde/normas , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Madagáscar , Serviços de Saúde Materna/normas , Serviços de Saúde Materna/tendências , Pessoa de Meia-Idade , Gravidez , Pesquisa Qualitativa , Inquéritos e Questionários , Telemedicina/métodos
16.
Neurology ; 91(10): e985-e994, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30089619

RESUMO

OBJECTIVE: To report the clinicopathologic features and outcome of myositis in patients treated with immune checkpoint inhibitors (ICIs) (irMyositis). METHODS: We retrospectively analyzed patients diagnosed with irMyositis in tertiary centers in Paris, France, and Berlin, Germany, from January 2015 to July 2017. The main outcomes were clinical manifestations and muscle histology, which included major histocompatibility complex class I (MHC-I), C5b-9, CD3, CD4, CD8, CD20, CD68, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L) 1, and programmed cell death 1 ligand 2 (PD-L2). RESULTS: Ten patients with metastatic cancer were included; median age was 73 (range 56-87) years. Median follow-up duration was 48 (range 16-88) weeks. Six patients developed myositis during nivolumab therapy, 1 patient during pembrolizumab, 1 patient during durvalumab, and 2 patients during combined nivolumab and ipilimumab. Median delay between ICI initiation and myositis onset was 25 (range 5-87) days. Clinical manifestations were dominated by acute or subacute myalgia (8 patients) and limb-girdle (7), axial (7), and oculomotor (7) weakness. Four patients had evidence of myocarditis. In all patients, creatine kinase levels were elevated (median 2,668, range 1,059-16,620 U/L), while anti-acetylcholine receptor and myositis-associated antibodies were negative. Electrodiagnostic studies showed myopathic process without decrement in all patients. Muscle biopsy constantly showed multifocal necrotic myofibers, sarcolemmal MHC-I, and endomysial inflammation, consisting mainly of CD68+ cells expressing PD-L1 and CD8+ cells expressing PD-1. ICI treatment was withdrawn in all patients; 9 patients received immunosuppressive therapy, which consistently led to marked clinical improvement. CONCLUSIONS: irMyositis presents with remarkably homogeneous and unique clinicopathologic features, expanding the nosologic spectrum of inflammatory myopathies in patients with cancer. ICI withdrawal and treatment with corticosteroids improve outcome.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Citocinas/metabolismo , Miocardite/etiologia , Miosite/etiologia , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Creatina Quinase/metabolismo , Eletromiografia , Europa (Continente) , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Miocárdio/patologia , Miosite/diagnóstico por imagem , Receptores Proteína Tirosina Quinases/imunologia , Receptores Colinérgicos/imunologia , Estudos Retrospectivos , Adulto Jovem
17.
J Cereb Blood Flow Metab ; 38(1): 174-185, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29160120

RESUMO

Peroxisome proliferator-activated receptors are regulators of inflammatory signaling. This has fostered hope that PPAR agonists might have neuroprotective potential. We hypothesized that PPARδ activation by the novel orally administered lipophilic PPARδ agonist SAR145 may improve short- and long-term outcome after focal brain ischemia. We induced ischemia by transient filamentous middle cerebral artery occlusion (MCAo) in 227 C57BL/6 mice and administered SAR145 in varying doses and time windows post-injury. Outcome was assessed by three functional tests and histologically determining ischemic lesion sizes. In a second experiment, we tested SAR145 treatment in 40 PPARδ-knockout mice using the same procedures. Three independent groups treated with 10 mg/kg bodyweight SAR145 directly after filament removal showed a mean reduction in lesion sizes of 18 ± 10% compared to vehicle-treated groups. We did not observe a consistent improvement in the long-term functional outcome by SAR145-treatment. PPARδ-knockout mice showed a significantly higher mortality after MCAo. As expected, we did not find a reduction of lesion size by SAR145-treatment in PPARδ-knockout mice. In summary, we found no evidence of a long-term neuroprotective effect of post-injury SAR145 treatment in cerebral ischemia. However, PPARδ appears to play a pathophysiologic role in acute infarct development and overall mortality after brain ischemia.


Assuntos
Isquemia Encefálica/patologia , Fármacos Neuroprotetores/farmacologia , PPAR delta/agonistas , Administração Oral , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Distribuição Aleatória
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