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1.
Isr Med Assoc J ; 23(1): 38-42, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33443341

RESUMO

BACKGROUND: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines. OBJECTIVES: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel. METHODS: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result. RESULTS: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment. CONCLUSIONS: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.


Assuntos
Antibacterianos , Claritromicina/administração & dosagem , Infecções por Helicobacter , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Humanos , Israel/epidemiologia , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Retratamento/métodos , Retratamento/estatística & dados numéricos , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(40): e22542, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019463

RESUMO

BACKGROUND: The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD: The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT: Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION: Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).


Assuntos
Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Fosfatase Alcalina/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Colágeno Tipo I/efeitos dos fármacos , Creatinina , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Raloxifeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/uso terapêutico , Fraturas da Coluna Vertebral/epidemiologia , Fosfatase Ácida Resistente a Tartarato/efeitos dos fármacos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
4.
Cancer Discov ; 10(10): 1514-1527, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32699031

RESUMO

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias/mortalidade , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Fatores Etários , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Betacoronavirus/patogenicidade , Tomada de Decisão Clínica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Seguimentos , Glucocorticoides/uso terapêutico , Mortalidade Hospitalar , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento , Estados Unidos/epidemiologia
5.
J Urol ; 204(5): 969-975, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32519913

RESUMO

PURPOSE: American Urological Association (AUA) antibiotic prophylaxis recommendations may be insufficient for covering organisms commonly found in penile prosthesis infections. In this study we assess the difference between AUA recommended antibiotic prophylaxis and nonstandard prophylaxis in preventing device infections in penile prosthesis surgery performed in diabetic patients. MATERIALS AND METHODS: A multicenter, retrospective cohort study of diabetic patients undergoing primary penile prosthesis surgery was performed between April 2003 and August 2018. Eighteen institutions from the United States, Europe and Korea contributed. The association between antibiotic prophylaxis type and postoperative penile prosthesis infections, device explantations and revision surgeries was assessed. RESULTS: Standard AUA antibiotic prophylaxis was followed in 48.6% (391) of cases while nonstandard prophylaxis was used in 51.4% (413). Common nonstandard antibiotic prophylaxis included vancomycin-gentamycin-fluoroquinolone, clindamycin-fluoroquinolone, and vancomycin-fluoroquinolone among other combinations. Patients who received AUA prophylaxis had significantly more postoperative device infections (5.6% vs 1.9%, p <0.01) and explantations (8.3% vs 2.0%, p <0.001) compared to those who received nonstandard prophylaxis. Patients who received AUA prophylaxis had significantly higher odds of a postoperative device infection (OR 2.8, 95% CI 1.1-7.3) and explantation (OR 3.6, 95% CI 1.4-9.1) compared to those who received nonstandard prophylaxis. CONCLUSIONS: Diabetic men with erectile dysfunction who received standard AUA prophylaxis for penile prosthesis surgery had significantly greater odds of experiencing a postoperative device infection and device explantation compared to patients who received nonstandard prophylaxis. Our study provides a strong rationale for a prospective investigation to establish the most appropriate prophylaxis strategy in penile prosthesis surgery.


Assuntos
Antibioticoprofilaxia/normas , Diabetes Mellitus/imunologia , Disfunção Erétil/cirurgia , Prótese de Pênis/efeitos adversos , Guias de Prática Clínica como Assunto , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Implantação de Prótese/instrumentação , Infecções Relacionadas à Prótese/imunologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , República da Coreia/epidemiologia , Estudos Retrospectivos , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos/epidemiologia , Urologia/normas
6.
Br J Anaesth ; 125(2): 159-167, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32571568

RESUMO

BACKGROUND: Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of ∼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs. METHODS: National data from the Information Service Division, NHS Scotland were analysed for prescribing, sociodemographic, and mortality data from the Health Informatics Centre, University of Dundee. DRDs in which gabapentinoids were implicated were identified from National Records of Scotland and Tayside Drug Death Databases. RESULTS: From 2006 to 2016, the number of gabapentin prescriptions in Scotland increased 4-fold (164 630 to 694 293), and pregabalin 16-fold (27 094 to 435 490). In 2016 'recurrent users' (three or more prescriptions) had mean age 58.1 yr, were mostly females (62.5%), and were more likely to live in deprived areas. Of these, 60% were co-prescribed an opioid, benzodiazepine, or both (opioid 49.9%, benzodiazepine 26.8%, both 17.1%). The age-standardised death rate in those prescribed gabapentinoids was double that in the Scottish population (relative risk 2.16, 95% confidence interval 2.08-2.25). Increases in gabapentinoids contributing to cause of DRDs were reported regionally and nationally (gabapentin 23% vs 15%; pregabalin 21% vs 7%). In Tayside, gabapentinoids were implicated in 22 (39%) of DRDs, 17 (77%) of whom had not received a prescription. CONCLUSIONS: Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death (including DRDs). Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication.


Assuntos
Analgésicos Opioides/efeitos adversos , Benzodiazepinas/efeitos adversos , Overdose de Drogas/epidemiologia , Gabapentina/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Pregabalina/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Criança , Pré-Escolar , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Escócia/epidemiologia , Fatores Sexuais , Adulto Jovem
7.
Lancet ; 396(10244): 121-128, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32446323

RESUMO

BACKGROUND: Three drug classes (mineralocorticoid receptor antagonists [MRAs], angiotensin receptor-neprilysin inhibitors [ARNIs], and sodium/glucose cotransporter 2 [SGLT2] inhibitors) reduce mortality in patients with heart failure with reduced ejection fraction (HFrEF) beyond conventional therapy consisting of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and ß blockers. Each class was previously studied with different background therapies and the expected treatment benefits with their combined use are not known. Here, we used data from three previously reported randomised controlled trials to estimate lifetime gains in event-free survival and overall survival with comprehensive therapy versus conventional therapy in patients with chronic HFrEF. METHODS: In this cross-trial analysis, we estimated treatment effects of comprehensive disease-modifying pharmacological therapy (ARNI, ß blocker, MRA, and SGLT2 inhibitor) versus conventional therapy (ACE inhibitor or ARB and ß blocker) in patients with chronic HFrEF by making indirect comparisons of three pivotal trials, EMPHASIS-HF (n=2737), PARADIGM-HF (n=8399), and DAPA-HF (n=4744). Our primary endpoint was a composite of cardiovascular death or first hospital admission for heart failure; we also assessed these endpoints individually and assessed all-cause mortality. Assuming these relative treatment effects are consistent over time, we then projected incremental long-term gains in event-free survival and overall survival with comprehensive disease-modifying therapy in the control group of the EMPHASIS-HF trial (ACE inhibitor or ARB and ß blocker). FINDINGS: The hazard ratio (HR) for the imputed aggregate treatment effects of comprehensive disease-modifying therapy versus conventional therapy on the primary endpoint of cardiovascular death or hospital admission for heart failure was 0·38 (95% CI 0·30-0·47). HRs were also favourable for cardiovascular death alone (HR 0·50 [95% CI 0·37-0·67]), hospital admission for heart failure alone (0·32 [0·24-0·43]), and all-cause mortality (0·53 [0·40-0·70]). Treatment with comprehensive disease-modifying pharmacological therapy was estimated to afford 2·7 additional years (for an 80-year-old) to 8·3 additional years (for a 55-year-old) free from cardiovascular death or first hospital admission for heart failure and 1·4 additional years (for an 80-year-old) to 6·3 additional years (for a 55-year-old) of survival compared with conventional therapy. INTERPRETATION: Among patients with HFrEF, the anticipated aggregate treatment effects of early comprehensive disease-modifying pharmacological therapy are substantial and support the combination use of an ARNI, ß blocker, MRA, and SGLT2 inhibitor as a new therapeutic standard. FUNDING: None.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Volume Sistólico/efeitos dos fármacos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Morte , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Intervalo Livre de Progressão , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/fisiologia , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(9): e19295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118743

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Compostos de Platina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidrocarbonetos Aromáticos com Pontes/normas , Quimiorradioterapia/normas , Quimiorradioterapia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/normas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Taxoides/normas , Texas , Resultado do Tratamento
9.
Einstein (Sao Paulo) ; 18: eAO4995, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32074221

RESUMO

OBJECTIVE: To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the management of HIV infection. METHODS: Observational and descriptive study. Secondary data of the state of Paraná (Brazil) on drugs, treatment regimens, lines of treatment and number of individuals on treatment, from January to June 2018, were accessed at the Antiretroviral Agents Logistic Control System. Combinations of antiretroviral drugs (treatment regimens) were compared according to the current Clinical Protocol and Therapy Guidelines and non-compliances were classified and quantified. RESULTS: In Paraná, 35,127 individuals with HIV were treated with 253 different treatment regimens. Of the prescribed regimens, 19.1% were first-line, 27.4% second-line and 48.5% third-line. Among non-compliances, the most prevalent were absence of association of protease inhibitors and ritonavir (42.8%), low efficacy triple therapy (36.9%), double therapy (26.1%), monotherapy (20.3%), and triple therapy of nucleoside analog reverse transcriptase inhibitors (17.1%). CONCLUSION: Most individuals receiving HIV treatment in the state of Paraná are on treatment regimens established in the current Clinical Protocol and Therapy Guidelines, which contributes to successful therapy. However, associations not provided by the current Clinical Protocol and Therapy Guidelines were identified in the initial treatment lines, which could lead to ineffectiveness, virologic failure and viral resistance.


Assuntos
Antirretrovirais/administração & dosagem , Protocolos Clínicos/normas , Fidelidade a Diretrizes/normas , Adesão à Medicação , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Brasil , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Humanos , Adesão à Medicação/estatística & dados numéricos
10.
J Matern Fetal Neonatal Med ; 33(1): 92-95, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29886762

RESUMO

Background: Malaria in pregnancy carries a proven huge health burden; however, the economic challenges have not been properly evaluated in Nigeria.Methodology: The study was a descriptive cross-sectional hospital-based approach. A structured questionnaire was used to collect microeconomic data from pregnant women, on the medical and nonmedical cost of malaria to them.Results: A total of 371 questionnaires were analyzed (93%; 371/400), of 400 respondents interviewed. The average direct medical cost was N3581.78 naira (N) (US$11.86) with SD of N177.9 and mean direct nonmedical cost of N5741.5 (US$18.97). Of the patients, 86.8% received artemisinin-based combination therapy (ACTs) for the treatment of malaria. Nigeria has an estimated population of women of child-bearing age of 40 million and, the fertility rate of 124 per 1000. On the basis of estimation of 56.5% of pregnant women receiving at least one intermittent preventive therapy (IPT), will approximate to 22.8 billion naira (US$75.5 million) national annual expenditure for malaria in pregnancy. This approximates to 0.016% of the Nigerian gross domestic product of 481 billion USD of 2015. The major mechanism that was used to pay for treatment was out-of-pocket (OOP).Conclusions: Malaria carries high-economic burden both on individual and national levels, especially in Nigeria where OOPs is the major payment mechanism. Scaling up malaria control measures will not only improve the lives of pregnant women but will also improve the economy of the nation.


Assuntos
Antimaláricos/economia , Malária/tratamento farmacológico , Malária/economia , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/economia , Adulto , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/economia , Efeitos Psicossociais da Doença , Estudos Transversais , Quimioterapia Combinada/economia , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde , Humanos , Recém-Nascido , Malária/epidemiologia , Nigéria/epidemiologia , Gravidez , Complicações Parasitárias na Gravidez/epidemiologia , Inquéritos e Questionários , Adulto Jovem
11.
Eur J Pharmacol ; 868: 172889, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31870831

RESUMO

Previous studies have suggested the beneficial effects of vitamin C in patients with sepsis. However, the results could not be reproduced in the subsequent studies. This meta-analysis aimed to reevaluate the value of vitamin C treatment in patients with sepsis. Electronic databases were searched from inception to August 2019 for the studies comparing the effect of vitamin C versus non-vitamin C infusion in patients with sepsis. Data from 10 studies (4 randomized controlled trials [RCTs] and 6 retrospective studies) involving 1671 patients (495 in the vitamin C treatment group and 1176 in the control group) were included. The use of vitamin C did not reduce the risk of 28-day (OR = 0.84, P = 0.611, I2 = 56.3%), intensive care unit (ICU; OR = 0.79, P = 0.319, I2 = 46.2%), or in-hospital mortality (OR = 0.76, P = 0.251, I2 = 51.0%). No difference in the duration of vasopressor usage and the length of ICU or hospital stay was present. The subgroup analysis for two RCTs suggested that vitamin C treatment showed reduced 28-day mortality (OR = 0.22, P = 0.014, I2 = 35.7%), whereas this beneficial effect did not occur in subgroup analysis for three retrospective studies (OR = 1.11, P = 0.527, I2 = 0%). Retrospective meta-analysis could not reveal the beneficial effect of vitamin C on patients with sepsis. Therefore, in order to clarify the role of vitamin C in sepsis the high-quality RCTs will be required in the future study.


Assuntos
Ácido Ascórbico/uso terapêutico , Sepse/tratamento farmacológico , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/mortalidade , Fatores de Tempo , Resultado do Tratamento , Vasoconstritores/uso terapêutico
12.
Medicina (Kaunas) ; 55(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752240

RESUMO

Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG-CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG-CBD combination for further preclinical studies.


Assuntos
Canabinoides/normas , Quimioterapia Combinada/normas , Inflamação/prevenção & controle , Neurônios/efeitos dos fármacos , Canabidiol/normas , Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Técnicas de Cultura de Células/métodos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Humanos , Fatores de Proteção
13.
BMJ ; 366: l5125, 2019 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-31562117

RESUMO

OBJECTIVE: To investigate whether fenofibrate as add-on to statin treatment reduce persistent cardiovascular risk in adults with metabolic syndrome in a real world setting. DESIGN: Propensity matched cohort study. SETTING: Population based cohort in Korea. PARTICIPANTS: 29 771 adults with metabolic syndrome (≥40 years) receiving statin treatment. 2156 participants receiving combined treatment (statin plus fenofibrate) were weighted based on propensity score in a 1:5 ratio with 8549 participants using statin only treatment. MAIN OUTCOME MEASURE: Primary outcome was composite cardiovascular events including incident coronary heart disease, ischaemic stroke, and death from cardiovascular causes. RESULTS: The incidence rate per 1000 person years of composite cardiovascular events was 17.7 (95% confidence interval 14.4 to 21.8) in the combined treatment group and 22.0 (20.1 to 24.1) in the statin group. The risk of composite cardiovascular events was significantly reduced in the combined treatment group compared with statin group (adjusted hazard ratio 0.74, 95% confidence interval 0.58 to 0.93; P=0.01). The significance was maintained in the on-treatment analysis (hazard ratio 0.63, 95% confidence interval 0.44 to 0.92; P=0.02). The risk of incident coronary heart disease, ischaemic stroke, and cardiovascular death was lower in the combined treatment group than statin group but was not significant. Participant characteristics did not appear to be associated with the low risk of composite cardiovascular events with combined treatment. CONCLUSION: In this propensity weighted cohort study of adults with metabolic syndrome, the risk of major cardiovascular events was significantly lower with fenofibrate as add-on to statin treatment than with statin treatment alone.


Assuntos
Doenças Cardiovasculares , Fenofibrato/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Causas de Morte , Estudos de Coortes , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pontuação de Propensão , República da Coreia/epidemiologia , Fatores de Risco
14.
PLoS Negl Trop Dis ; 13(9): e0007709, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479442

RESUMO

BACKGROUND: Leprosy has a global presence; more than 180 thousand new cases were registered in 2013, 15% of which were found in the Americas. The elderly are a very susceptible demographic in terms of developing illnesses, mainly because of characteristics natural to the senescence of the human organism. This study's goals were to analyze leprosy in an elderly population from a hyperendemic region of the Brazilian Amazon in a historical series from 2004 to 2013 and to determine the clinical and epidemiological profile of a series of leprosy cases of elderly people in the period spanning from 2009 to 2013. METHODS: To achieve these goals, an observational, longitudinal, retrospective and descriptive study was put together to analyze leprosy in elderly people from data acquired from the Notification Aggravations Information System. Furthermore, a profile of the disease from a retrospective cohort based on data collected from medical records was developed. RESULTS: The number of new cases and the leprosy detection rate decreased across the observed period but remained stable among the elderly. The trend for the next ten years indicates decreases in the number of cases and in the detection rate in the general population and an increase in only the elderly. The overall profile was characterized by a predominance of males (64.32%), the multibacillary clinical form (87.57%), Type 1 reaction episodes (37.50%) and some physical incapacity at diagnosis (49.19%). The risk of reaction was greater in the first six months of multidrug therapy, and the positive result from the skin smear was associated with the greater chance of reactional condition development. CONCLUSIONS: The resulting data demonstrate that leprosy amongst the elderly deserves attention because of the increased susceptibility to disability in this age group, with their higher risk of reaction and their greater level of co-morbidity.


Assuntos
Quimioterapia Combinada/estatística & dados numéricos , Hansenostáticos/uso terapêutico , Hanseníase/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos de Coortes , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença
15.
PLoS Negl Trop Dis ; 13(9): e0007714, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31490925

RESUMO

BACKGROUND: Although leprosy is largely curable with multidrug therapy, incomplete treatment limits therapeutic effectiveness and is an important obstacle to disease control. To inform efforts to improve treatment completion rates, we aimed to identify the geographic and socioeconomic factors associated with leprosy treatment default in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Using individual participant data collected in the Brazilian national registries for social programs and notifiable diseases and linked as part of the 100 Million Brazilian Cohort, we evaluated the odds of treatment default among 20,063 leprosy cases diagnosed and followed up between 2007 and 2014. We investigated geographic and socioeconomic risk factors using a multivariate hierarchical analysis and carried out additional stratified analyses by leprosy subtype and geographic region. Over the duration of follow-up, 1,011 (5.0%) leprosy cases were observed to default from treatment. Treatment default was markedly increased among leprosy cases residing in the North (OR = 1.57; 95%CI 1.25-1.97) and Northeast (OR = 1.44; 95%CI 1.17-1.78) regions of Brazil. The odds of default were also higher among cases with black ethnicity (OR = 1.29; 95%CI 1.01-1.69), no income (OR = 1.41; 95%CI 1.07-1.86), familial income ≤ 0.25 times Brazilian minimum wage (OR = 1.42; 95%CI 1.13-1.77), informal home lighting/no electricity supply (OR = 1.53; 95%CI 1.28-1.82), and household density of > 1 individual per room (OR = 1.35; 95%CI 1.10-1.66). CONCLUSIONS: The findings of the study indicate that the frequency of leprosy treatment default varies regionally in Brazil and provide new evidence that adverse socioeconomic conditions may represent important barriers to leprosy treatment completion. These findings suggest that interventions to address socioeconomic deprivation, along with continued efforts to improve access to care, have the potential to improve leprosy treatment outcomes and disease control.


Assuntos
Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Fatores Socioeconômicos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Brasil/epidemiologia , Estudos de Coortes , Quimioterapia Combinada/estatística & dados numéricos , Grupos Étnicos , Feminino , Geografia , Humanos , Hanseníase/epidemiologia , Masculino
16.
J Clin Hypertens (Greenwich) ; 21(9): 1426-1428, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31441988

RESUMO

Several fixed dose combinations (FDCs) of antihypertensive drugs have recently been added to the World Health Organization model list of essential medications. FDCs have advantages in the management of hypertension compared to single drug tablets including improved adherence, greater blood pressure lowering and are associated with reduced cardiovascular complications. FDCs can also reduce ethnic, and age-related variation in blood pressure lowering and have similar or reduced adverse effects relative to single-drug therapy. Best hypertension control practices from the World Health Organization HEARTS program advocates the use of FDC in simple directive treatment protocols. FDC in simple directive protocols was viewed as a key success factor in the control of chronic infections (eg, tuberculosis, HIV). Unfortunately, implementing simple directive protocols with FDC has had substantial opposition from hypertension experts. Hypertension organizations and experts need to familiarize themselves with best practices in hypertension control, their supporting evidence and to become advocates.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Gerenciamento Clínico , Quimioterapia Combinada/estatística & dados numéricos , Humanos , Hipertensão/fisiopatologia , Adesão à Medicação , Guias de Prática Clínica como Assunto , Organização Mundial da Saúde/organização & administração
18.
J Parkinsons Dis ; 9(4): 749-759, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424419

RESUMO

BACKGROUND: Treatment patterns in Parkinson's disease (PD) have not been extensively studied for nearly two decades. Insurance claims are appropriate for such analysis. OBJECTIVE: To understand the standard of care use of symptomatic treatments in new cases of PD and factors associated with treatment choice. METHODS: Retrospective cohort study using claims data from the United States between 2008 and 2016. We used Kaplan-Meier methodology to estimate time to treatment start and switch or add-on therapy and Cox proportional hazards models to identify predictors. RESULTS: We identified 68,532 patients eligible for treatment pattern analyses. Median time from diagnosis until first treatment was 37 days (95% confidence interval: 36-38). Two distinct patterns of treatment initiation were identified: fast initiators and patients with delayed treatment start (or no recorded treatment). Levodopa therapies were the most commonly prescribed treatment class (52.6%). Increased age was associated with shorter time to start of treatment with levodopa. Younger age was associated with shorter time to initiation of dopamine agonists and other symptomatic treatments. Patients that initiated treatment with levodopa/combinations had the fewest switches/add-ons [30.4%; median time 7.29 (6.71, 8.13) years]. Older patients had fewer switch/add-on therapies, but only in the group that started with levodopa/combination therapy. CONCLUSIONS: Time from diagnosis to treatment start was relatively short, suggesting that PD diagnosis, as reflected in the database, is closely linked to start of symptomatic treatment. Levodopa treatment remains the most common treatment, especially for older patients. Delayed treatment start was associated with increased age and comorbidity.


Assuntos
Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , Idoso , Antiparkinsonianos/uso terapêutico , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Estimativa de Kaplan-Meier , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Estados Unidos
19.
J Affect Disord ; 257: 412-420, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306992

RESUMO

BACKGROUND: The study compared treatment failure when using three therapeutic strategies in bipolar disorders: (i) mood stabilizers (MSs: lithium, valpromide, divalproate, carbamazepine, lamotrigine) without second-generation antipsychotic (SGAP); (ii) SGAPs (aripiprazole, olanzapine, risperidone, quetiapine) without MS; (iii) combination of MSs and SGAPs. METHODS: A historical cohort study was conducted using the French national healthcare databases in 20,086 outpatients aged 21+, newly treated with one of the three treatment strategies in 2011-2012, and diagnosed with a bipolar disorder. A composite outcome was based on indicators of treatment failure identified over 12 months: treatment discontinuation, switch or addition, psychiatric hospitalisation, suicide attempt, and death. For each strategy, the cumulative incidence of treatment failure was calculated while adjusting for covariates by propensity score weighting. RESULTS: A total of 8,225 patients (40.9%) were newly dispensed MSs, 9,342 (46.5%) SGAPs, and 2,519 (12.5%) both MSs and SGAPs. The one-year adjusted cumulative incidence of treatment failure was 75.7% (95%CI 74.9;76.3) in patients using MSs, 75.3% (74.6;76.0) in patients using SGAPs, and 60.5% (58.3;62.6) in patients with the combination. The adjusted difference in incidence for SGAPs compared with MSs was -0.40% (-1.4;0.6 p = 0.4) in the whole population, -2.2% (-3.3; -1.2 p < 0.002) in patients under 65 years and +6.7% (4.1;9.1 p < 0.002) in patients 65 years and over. LIMITATIONS: Combinations of MSs and SGAPs could not be directly compared with MS or SGAP monotherapies. CONCLUSIONS: One-year treatment failure was high. Overall, no difference in treatment failure was observed between MS or SGAP strategy but differences might exist depending on age.


Assuntos
Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Falha de Tratamento , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Bases de Dados Factuais , Quimioterapia Combinada/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
J Manag Care Spec Pharm ; 25(6): 678-686, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31134857

RESUMO

BACKGROUND: Approximately 32% (75 million) of adults have hypertension in the United States, leading to 1,100 daily deaths and costing more than $48 billion annually in medical expenditures. Approximately 25% of patients with hypertension require triple combination therapy to reach recommended blood pressure. Currently, only 3 single-pill triple-combination therapies are available in the market for the treatment of hypertension. Medication adherence has become a major concern for the health care system, and nonadherence is associated with higher risks of morbidity and mortality. OBJECTIVE: To compare medication adherence rates among single-pill triple-combination therapy, free triple-combination therapy, and fixed-dose dual-combination therapy plus a third agent in hypertensive patients enrolled in a Medicare Advantage prescription drug plan using 2 adherence definitions. METHODS: A retrospective cohort study was conducted using Cigna-HealthSpring's medical claims database from January 2014 to December 2016. Antihypertensive combination therapy users were classified into a single-pill triple-combination group, a fixed-dose dual-combination plus a third agent group, and a free triple-combination group. Adherence rates using proportion of days covered (PDC) were calculated for each group within a 1-year follow-up period using 2 definitions: a strict one requiring all antihypertensive agents during follow-up and a more relaxed definition requiring any antihypertensive agent during follow-up. Descriptive statistics were examined, and group differences were assessed using chi-square and analysis of variance. Multivariate logistic regression was conducted to control confounders of adherence using both definitions. RESULTS: 10,836 triple-combination users were identified. In the multivariate model using the first definition, fixed-dose dual-combination plus a third agent was significantly associated with lower adherence compared with single-pill triple therapy (OR = 0.177; 95% CI = 0.119-0.263; P < 0.001). No significant difference was detected between single-pill triple-combination therapy in comparison with free-combination therapy. In the multivariate model using the second definition, fixed-dose dual-combination plus a third agent and free-combination therapy were significantly associated with better adherence in comparison with single-pill triple combination therapy (OR = 3.62, 95% CI = 2.59-5.05; OR = 4.31, 95% CI = 2.15-8.64, respectively). Younger age, female gender, language (Spanish), some comorbidities, and previous hospitalization had a negative effect on adherence. CONCLUSIONS: Measuring adherence to multiple concurrent regimens is complicated and different adherence definitions can result in significant variations in adherence measures. Future research evaluating clinical outcomes with various definitions is needed. DISCLOSURES: No outside funding supported this study. Abughosh reports grants from Sanofi, Regeneron, Valeant Pharmaceuticals, BMS/Pfizer, and PhRMA, not related to this study. Serna reports employement with CareAllies, a Cigna company. The other authors have no conflicts of interest to disclose.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/economia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Quimioterapia Combinada/economia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Hipertensão/economia , Masculino , Medicare Part C/economia , Medicare Part C/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Estados Unidos
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