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1.
Medicine (Baltimore) ; 99(52): e23453, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350727

RESUMO

BACKGROUND: Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc, mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but cannot be cured; glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult BA can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA. METHODS: The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult BA from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures. RESULTS: This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult BA. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/CKQFM.


Assuntos
Acetatos/administração & dosagem , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Ciclopropanos/administração & dosagem , Fluticasona/administração & dosagem , Metanálise como Assunto , Quinolinas/administração & dosagem , Projetos de Pesquisa , Sulfetos/administração & dosagem , Revisões Sistemáticas como Assunto/métodos , Acetatos/efeitos adversos , Adulto , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Ciclopropanos/efeitos adversos , Combinação de Medicamentos , Fluticasona/efeitos adversos , Humanos , Quinolinas/efeitos adversos , Sulfetos/efeitos adversos , Resultado do Tratamento
2.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370973

RESUMO

We report two cases of anaplastic thyroid cancer (ATC) which had a very good response to a treatment with lenvatinib at 14 mg. A 73-year-old man with ATC stage IVB was operated on, undergoing a near-total thyroidectomy, and the pathological remnant tissue showed a quick and partial response to treatment with the drug. The patient had a single metastasis in the brain after 9 months, but then died due to bronchopneumonia after undergoing a neurosurgical intervention for the complete removal of the lesion. A 74-year-old woman with ATC stage IV was operated on, undergoing a near-total thyroidectomy after a neoadjuvant treatment with the drug, that was continued after surgical treatment. She had a partial remission of the local disease and of distant metastasis, which lasted for 14 months. She then died 4 months later due to cancer progression. Lenvatinib at 14 mg appears to be effective, fast and well tolerated.


Assuntos
Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Carcinoma Anaplásico da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Idoso , Quimioterapia Adjuvante/métodos , Relação Dose-Resposta a Droga , Humanos , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Carcinoma Anaplásico da Tireoide/diagnóstico , Carcinoma Anaplásico da Tireoide/patologia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
4.
Anticancer Res ; 40(9): 5271-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878816

RESUMO

BACKGROUND/AIM: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration. PATIENTS AND METHODS: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration. RESULTS: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration. CONCLUSION: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Hiperamonemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Veia Porta/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco
5.
Int J Nanomedicine ; 15: 5433-5443, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801698

RESUMO

Background: Human epidermal growth factor receptor2 (Her2) positive breast cancer represents 25% of breast cancer cases. Targeted therapy with Her2 monoclonal antibody, trastuzumab (TZ), represents the first-line treatment for this type of breast cancer. In addition, neratinib, an irreversible inhibitor of the HER-2 receptor tyrosine kinase, has recently been approved as adjuvant therapy to TZ. This study aims to formulate (TZ)-grafted dendrimers loaded with neratinib, allowing a dual treatment alongside reducing the associated resistance as well as targeted therapy. Methods: TZ was conjugated on the surface of dendrimer using hetero-cross linker, MAL-PEG-NHS, and the zeta potential, and in vitro release of neratinib from dendrimers was characterized. Formulated dendrimers were also fluorescently conjugated with fluorescein isothiocyanate to visualize and quantify their SKBR-3 cellular uptake. Results: The G4 PAMAM dendrimer showed successful encapsulation of neratinib and a sustained release profile. Comparative in vitro studies revealed that these TZ-targeted dendrimers loaded with neratinib were more selective and have higher antiproliferation activity against SKBR-3 cells compared to neratinib alone and neratinib loaded dendrimer. Conclusion: In the current study, neratinib loaded in plain and trastuzumab-grafted dendrimer were successfully prepared. Enhanced cellular uptake of trastuzumab conjugated dendrimers was shown, together with a higher cytotoxic effect than plain neratinib dendrimers. These findings suggest the potential of TZ-conjugated dendrimers as targeting carrier for cytotoxic drugs, including neratinib.


Assuntos
Dendrímeros/química , Nanocápsulas/administração & dosagem , Nylons/química , Quinolinas/química , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Dendrímeros/administração & dosagem , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Fluoresceína-5-Isotiocianato , Humanos , Terapia de Alvo Molecular/métodos , Nanocápsulas/química , Poliaminas/química , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/química , Trastuzumab/farmacocinética
6.
Am J Trop Med Hyg ; 103(2_Suppl): 28-36, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618242

RESUMO

From 2014 to 2016, a community-randomized controlled trial in Southern Province, Zambia, compared mass drug administration (MDA) and focal MDA (fMDA) with the standard of care. Acceptability of the intervention was assessed quantitatively using closed-ended and Likert scale-based questions posed during three household surveys conducted from April to May in 2014, 2015, and 2016 in 40 health catchments that implemented MDA and fMDA and 20 catchments that served as trial controls. In 2014 and 2015, 47 households per catchment were selected, targeting 1,880 households in MDA and fMDA trial arms; in 2016, 55 households per catchment were selected for a target of 2,200 households in MDA and fMDA trial arms. Concurrently, 27 focus group discussions and 23 in-depth interviews with 248 participants were conducted on reasons for testing and treatment refusal, reasons for nonadherence, and community perception of the MDA campaign. Results demonstrated that the MDA campaign was highly accepted with more than 99% of respondents stating that they would take treatment if positive for malaria. High acceptability at baseline could be associated with test-and-treat campaigns recently conducted in the study area. There was a large increase in the acceptability of prophylactic treatment if negative for malaria from the baseline to follow-up survey for adults and children, from 62% to 96% for each. This likely resulted from an intensive community-wide sensitization program that occurred before the first treatment round at each household during community health worker visits.


Assuntos
Artemisininas/administração & dosagem , Atitude Frente a Saúde , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Aceitação pelo Paciente de Cuidados de Saúde , Quinolinas/administração & dosagem , Adulto , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Feminino , Grupos Focais , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
7.
Am J Trop Med Hyg ; 103(2_Suppl): 54-65, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618245

RESUMO

Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.


Assuntos
Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Incidência , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Adulto Jovem , Zâmbia/epidemiologia
8.
Am J Trop Med Hyg ; 103(2_Suppl): 7-18, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618247

RESUMO

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Humanos , Incidência , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
10.
Am J Trop Med Hyg ; 103(2_Suppl): 46-53, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618249

RESUMO

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.


Assuntos
Antimaláricos/economia , Artemisininas/economia , Erradicação de Doenças/economia , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/economia , Quinolinas/economia , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Análise Custo-Benefício , Erradicação de Doenças/métodos , Custos de Medicamentos , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Custos de Cuidados de Saúde , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/economia , Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos/métodos , Plasmodium falciparum/efeitos dos fármacos , Anos de Vida Ajustados por Qualidade de Vida , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
11.
Am J Trop Med Hyg ; 103(2_Suppl): 74-81, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618250

RESUMO

As Zambia continues to reduce its malaria incidence and target elimination in Southern Province, there is a need to identify factors that can reintroduce parasites and sustain malaria transmission. To examine the relative contributions of types of human mobility on malaria prevalence, this analysis quantifies the proportion of the population having recently traveled during both peak and nonpeak transmission seasons over the course of 2 years and assesses the relationship between short-term travel and malaria infection status. Among all residents targeted by mass drug administration in the Lake Kariba region of Southern Province, 602,620 rapid diagnostic tests and recent travel histories were collected during four campaign rounds occurring between December 2014 and February 2016. Rates of short-term travel in the previous 2 weeks fluctuated seasonally from 0.3% to 1.2%. Travel was significantly associated with prevalent malaria infection both seasonally and overall (adjusted odds ratio [AOR]: 2.55; 95% CI: 2.28-2.85). The strength of association between travel and malaria infection varied by travelers' origin and destination, with those recently traveling to high-prevalence areas from low-prevalence areas experiencing the highest odds of malaria infection (AOR: 7.38). Long-lasting insecticidal net usage while traveling was associated with a relative reduction in infections (AOR: 0.74) compared with travelers not using a net. Although travel was directly associated with only a small fraction of infections, importation of malaria via human movement may play an increasingly important role in this elimination setting as transmission rates continue to decline.


Assuntos
Malária Falciparum/transmissão , Plasmodium falciparum , Viagem , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Prevalência , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco , Zâmbia/epidemiologia
12.
Am J Trop Med Hyg ; 103(2_Suppl): 19-27, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618251

RESUMO

Mass drug administration (MDA) is currently being considered as an intervention in low-transmission areas to complement existing malaria control and elimination efforts. The effectiveness of any MDA strategy is dependent on achieving high epidemiologic coverage and participant adherence rates. A community-randomized controlled trial was conducted from November 2014 to March 2016 to evaluate the impact of four rounds of MDA or focal MDA (fMDA)-where treatment was given to all eligible household members if anyone in the household had a positive malaria rapid diagnostic test-on malaria outcomes in Southern Province, Zambia (population approximately 300,000). This study examined epidemiologic coverage and program reach using capture-recapture and satellite enumeration methods to estimate the degree to which the trial reached targeted individuals. Overall, it was found that the percentage of households visited by campaign teams ranged from 62.9% (95% CI: 60.0-65.8) to a high of 77.4% (95% CI: 73.8-81.0) across four rounds of treatment. When the maximum number of visited households across all campaign rounds was used as the numerator, program reach for at least one visit would have been 86.4% (95% CI: 80.8-92.0) in MDA and 83.5% (95% CI: 78.0-89.1) in fMDA trial arms. As per the protocol, the trial provided dihydroartemisinin-piperaquine treatment to an average of 58.8% and 13.3% of the estimated population based on capture-recapture in MDA and fMDA, respectively, across the four rounds.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada , Características da Família , Humanos , Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
13.
Am J Trop Med Hyg ; 103(2_Suppl): 82-89, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618252

RESUMO

Malaria burden in Zambia has significantly declined over the last decade because of improved coverage of several key malaria interventions (e.g., vector control, case management, bed net distributions, and enhanced surveillance/responses). Campaign-based mass drug administration (MDA) and focal MDA (fMDA) were assessed in a trial in Southern Province, Zambia, to identify its utility in elimination efforts. As part of the study, a longitudinal cohort was visited and tested (by PCR targeting the 18s rRNA and a Plasmodium falciparum-specific rapid diagnostic test [RDT] from SD Bioline) every month for the trial duration (18 months). Overall, there was high concordance (> 97%) between the PCR and RDT results, using the PCR as the gold standard. The RDTs had high specificity and negative predictive values (98.5% and 98.6%, respectively) but low sensitivity (53.0%) and a low positive predictive value (53.8%). There was evidence for persistent antigenemia affecting the low specificity of the RDT, while false-negative RDTs were associated with a lower parasite density than true positive RDTs. Plasmodium falciparum was the dominant species identified, with 98.3% of all positive samples containing P. falciparum. Of these, 97.5% were mono-infections and 0.8% coinfections with one other species. Plasmodium malariae was found in 1.4% of all positive samples (50% mono-infections and 50% coinfections with P. falciparum), whereas Plasmodium ovale was found in 1.1% of all positive samples (90% mono-infections and 10% coinfections with P. falciparum). Although MDA/fMDA appeared to reduce P. malariae prevalence, P. ovale prevalence appeared unchanged.


Assuntos
Antimaláricos/administração & dosagem , Malária Falciparum/epidemiologia , Malária/epidemiologia , Administração Massiva de Medicamentos/métodos , Plasmodium falciparum , Reação em Cadeia da Polimerase em Tempo Real/métodos , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Quimioterapia Combinada/métodos , Humanos , Estudos Longitudinais , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/prevenção & controle , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/genética , Prevalência , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
14.
Am J Trop Med Hyg ; 103(2_Suppl): 3-6, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618265

RESUMO

From December 2014 to February 2016, a cluster randomized controlled trial was carried out in 60 health facility catchment areas along Lake Kariba in Zambia's Southern Province. The trial sought to evaluate the impact of four rounds of a mass drug administration (MDA) intervention with dihydroartemisinin-piperaquine (DHAP) or focal MDA with DHAP at the household level compared with a control population that received the standard of care. This study was the first randomized controlled trial with DHAP for MDA in sub-Saharan Africa and was conducted through a collaboration between the National Malaria Elimination Programme in the Zambian Ministry of Health, the PATH Malaria Control and Elimination Partnership in Africa, and the Center for Applied Malaria Research and Evaluation at Tulane University. This article serves as an introduction to a collection of articles designed to explore different aspects of the intervention. By describing the recent history of malaria control in Zambia leading up to the trial-from the scale-up of point-of-care diagnosis and treatment, vector control, and indoor residual spraying early in the twenty-first century, to the efforts made to sustain the gains achieved with that approach-it provides a rationale for the implementation of a trial that has informed a new national strategic plan and solidified malaria elimination as Zambia's national goal.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Erradicação de Doenças , Quimioterapia Combinada , Humanos , Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos/métodos , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
15.
Am J Trop Med Hyg ; 103(2_Suppl): 37-45, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618267

RESUMO

Mass drug administration (MDA) with artemisinin combination therapy is a potentially useful tool for malaria elimination programs, but its success depends partly on drug effectiveness and treatment coverage in the targeted population. As part of a cluster-randomized controlled trial in Southern Province, Zambia evaluating the impact of MDA and household focal MDA (fMDA) with dihydroartemisinin-piperaquine (DHAp), sub-studies were conducted investigating population drug adherence rates and effectiveness of DHAp as administered in clearing Plasmodium falciparum infections following household mass administration. Adherence information was reported for 181,534 of 336,821 DHAp (53.9%) treatments administered during four rounds of MDA/fMDA, of which 153,197 (84.4%) reported completing the full course of DHAp. The proportion of participants fully adhering to the treatment regimen differed by MDA modality (MDA versus fMDA), RDT status, and whether the first dose was observed by those administering treatments. Among a subset of participants receiving DHAp and selected for longitudinal follow-up, 58 were positive for asexual-stage P. falciparum infection by microscopy at baseline. None of the 45 participants followed up at days 3 and/or 7 were slide positive for asexual-stage parasitemia. For those with longer term follow-up, one participant was positive 47 days after treatment, and two additional participants were positive after 69 days, although these two were determined to be new infections by genotyping. High completion of a 3-day course of DHAp and parasite clearance in the context of household MDA are promising as Zambia's National Malaria Programme continues to weigh appropriate interventions for malaria elimination.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Adesão à Medicação , Aceitação pelo Paciente de Cuidados de Saúde , Plasmodium falciparum , Quinolinas/administração & dosagem , Adolescente , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Entrevistas como Assunto , Malária Falciparum/epidemiologia , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/psicologia , Administração Massiva de Medicamentos/estatística & dados numéricos , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
16.
Lancet Oncol ; 21(6): 843-850, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32502444

RESUMO

BACKGROUND: Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events. INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. FUNDING: Center for Clinical Trials, Japan Medical Association.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Timoma/enzimologia , Timoma/mortalidade , Timoma/secundário , Neoplasias do Timo/enzimologia , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Fatores de Tempo
17.
Medicine (Baltimore) ; 99(25): e20596, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569187

RESUMO

BACKGROUND: Whether erlotinib plus tivantinib (ET) can achieve better clinical benefits than erlotinib plus placebo (EP) among participants with previously treated advanced non-small-cell lung cancer (NSCLC) is still disputed. We conducted a meta-analysis to evaluate the anticancer efficacy and safety of both regimens. MATERIALS AND METHODS: We searched for pertinent trials at PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar. Endpoints mainly included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: We included 1522 patients who previously received ≥1 systemic anti-cancer regimen that included platinum-based chemotherapy. Although ET failed to improve OS (hazard ratio [HR] = 0.91, 95% confidence interval [CI]: 0.75-1.10, P = .35), the ET group had better PFS (HR = 0.73, 95% CI: 0.67-0.80, P < .00001), higher ORR (HR = 1.50, 95% CI: 1.06-2.12, P = .02), and better DCR (HR = 1.38, 95% CI: 1.20-1.59, P < .00001). Our subanalysis suggested that the ET group may have had better OS among patients with high Mesenchymal to epithelial transition factor (MET) expression (HR = 0.76, 95% CI: 0.58-0.99, P = .04) and good VeriStrat (HR = 0.88, 95% CI: 0.83-0.93, P < .0001). AEs were roughly similar except for specific hematological toxicities: more neutropenia and febrile neutropenia were observed in the ET group, both of which should not be overlooked. CONCLUSIONS: ET appears to be superior to EP due to better PFS and higher response rates, especially for patients with high MET expression and good VeriStrat. The greater hematological toxicity in the ET regimen is non-negligible.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Pirrolidinonas/administração & dosagem , Quinolinas/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Erlotinib/efeitos adversos , Humanos , Intervalo Livre de Progressão , Pirrolidinonas/efeitos adversos , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Cochrane Database Syst Rev ; 6: CD012735, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32557581

RESUMO

BACKGROUND: Pitavastatin is the newest statin on the market, and the dose-related magnitude of effect of pitavastatin on blood lipids is not known. OBJECTIVES: Primary objective To quantify the effects of various doses of pitavastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in participants with and without cardiovascular disease. To compare the effect of pitavastatin on surrogate markers with other statins.  Secondary objectives To quantify the effect of various doses of pitavastatin on withdrawals due to adverse effects.  SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for trials up to March 2019: the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2019), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: RCT and controlled before-and-after studies evaluating the dose response of different fixed doses of pitavastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility criteria for studies to be included, and extracted data. We entered data from RCT and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data, respectively. Withdrawals due to adverse effects (WDAE) information was collected from the RCTs. We assessed all included trials using the Cochrane 'Risk of bias' tool under the categories of allocation (selection bias), blinding (performance bias and detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other potential sources of bias. MAIN RESULTS: Forty-seven studies (five RCTs and 42 before-and-after studies) evaluated the dose-related efficacy of pitavastatin in 5436 participants. The participants were of any age with and without cardiovascular disease, and pitavastatin effects were studied within a treatment period of three to 12 weeks. Log dose-response data over doses of 1 mg to 16 mg revealed strong linear dose-related effects on blood total cholesterol and LDL cholesterol and triglycerides. There was no dose-related effect of pitavastatin on blood HDL cholesterol, which was increased by 4% on average by pitavastatin. Pitavastatin 1 mg/day to 16 mg/day reduced LDL cholesterol by 33.3% to 54.7%, total cholesterol by 23.3% to 39.0% and triglycerides by 13.0% to 28.1%. For every two-fold dose increase, there was a 5.35% (95% CI 3.32 to 7.38) decrease in blood LDL cholesterol, a 3.93% (95% CI 2.35 to 5.50) decrease in blood total cholesterol and a 3.76% (95% CI 1.03 to 6.48) decrease in blood triglycerides. The certainty of evidence for these effects was judged to be high. When compared to other statins for its effect to reduce LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. For the placebo group, there were no participants who withdrew due to an adverse effect per 109 subjects and for all doses of pitavastatin, there were three participants who withdrew due to an adverse effect per 262 subjects. AUTHORS' CONCLUSIONS: Pitavastatin lowers blood total cholesterol, LDL cholesterol and triglyceride in a dose-dependent linear fashion. Based on the effect on LDL cholesterol, pitavastatin is about 6-fold more potent than atorvastatin, 1.7-fold more potent than rosuvastatin, 77-fold more potent than fluvastatin and 3.3-fold less potent than cerivastatin. There were not enough data to determine risk of withdrawal due to adverse effects due to pitavastatin.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Lipídeos/sangue , Quinolinas/administração & dosagem , Atorvastatina/administração & dosagem , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Controlados Antes e Depois , Esquema de Medicação , Feminino , Fluvastatina/administração & dosagem , Humanos , Masculino , Piridinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Rosuvastatina Cálcica/administração & dosagem , Fatores Sexuais , Triglicerídeos/sangue
20.
Lancet Oncol ; 21(8): 1057-1065, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32589866

RESUMO

BACKGROUND: Pembrolizumab, an anti-PD-1 antibody, results in tumour response in around 15% of patients with advanced gastric cancer who have a PD-L1 combined positive score of at least 1. Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased tumour-associated macrophages and increased infiltration of CD8 T cells, resulting in enhanced anti-tumour activity of PD-1 inhibitors in an in-vivo model. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced gastric cancer in a phase 2 study. METHODS: This study was an open-label, single-arm, phase 2 trial undertaken at the National Cancer Center Hospital East (Chiba, Japan). Eligible patients were aged 20 years or older and had metastatic or recurrent adenocarcinoma of the stomach or gastro-oesophageal junction, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), irrespective of the number of previous lines of treatment. Patients received 20 mg oral lenvatinib daily plus 200 mg intravenous pembrolizumab every 3 weeks until disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate according to RECIST, analysed in all patients who were eligible and received protocol treatment at least once. The safety analysis included all those who received protocol treatment at least once, regardless of eligibility. This study is registered at ClinicalTrials.gov, NCT03609359, and enrolment is complete. FINDINGS: Between Oct 15, 2018, and March 25, 2019, 29 patients were enrolled in the first-line or second-line settings. At data cutoff (March 20, 2020), the median follow-up was 12·6 months (IQR 10·5-14·3). 20 (69%, 95% CI 49-85) of 29 patients had an objective response. The most common grade 3 treatment-related adverse events were hypertension (in 11 [38%] patients), proteinuria (five [17%]), and platelet count decrease (two [7%]). No grade 4 treatment-related adverse events, serious treatment-related adverse events, or treatment-related deaths occurred. INTERPRETATION: Lenvatinib plus pembrolizumab showed promising anti-tumour activity with an acceptable safety profile in patients with advanced gastric cancer. On the basis of these results, a confirmatory trial will be planned in the future. FUNDING: Merck Sharp & Dohme.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
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