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1.
Medicine (Baltimore) ; 99(35): e21825, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871904

RESUMO

OBJECTIVE: To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an evidence-based medical strategy. METHODS: Randomized controlled trials (RCTs) comparing the effect of pegylated interferon (Peginterferon) combined with ribavirin (PR) alone and its combination with TCM were manually retrieved from the Weipu Information Resources System (VIP), Wan Fang Database, PubMed, and the Chinese Journal Full Text Database (CNKI). Studies meeting the inclusion criteria were selected and analyzed using the Review Manager 5.3 software. Suitable tests were also performed to determine the quality, heterogeneity, and sensitivity of the studies included in the meta-analysis. RESULTS: Twenty-eight RCTs met the inclusion criteria. The combination therapy or intervention group showed significantly greater HCV-RNA negative rate post-treatment compared to the monotherapy or the control group (P < .05). In addition, the serum levels of the liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were significantly improved after the combination therapy compared to PR alone (P < .05), while total bilirubin (TB) and r-glutamyltransferase (GGT) levels were not affected by TCM (P > .05). Finally, the parameters of liver fibrosis were also reduced by the combination therapy more effectively than the monotherapy. CONCLUSION: The combination of TCM and PR can improve the Comprehensive Clinical Efficacy of hepatitis C and have a better negative rate of HCV-RNA with a better benefit in the liver function. The effect of TCM + PR is better than that of PR alone in treating hepatitis C.


Assuntos
Antivirais/uso terapêutico , Hepatite C/terapia , Medicina Tradicional Chinesa , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Terapia Combinada , Quimioterapia Combinada , Hepacivirus/genética , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Albumina Sérica , gama-Glutamiltransferase/sangue
2.
Zhonghua Zhong Liu Za Zhi ; 42(8): 617-623, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867451

RESUMO

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/análogos & derivados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Síndrome Mão-Pé/complicações , Neoplasias/tratamento farmacológico , Estomatite/complicações , Antibióticos Antineoplásicos/uso terapêutico , Consenso , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Guias de Prática Clínica como Assunto
3.
BMC Infect Dis ; 20(1): 590, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778058

RESUMO

BACKGROUND: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. METHODS: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. RESULTS: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05). CONCLUSIONS: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.


Assuntos
Antivirais/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Fígado/patologia , Polietilenoglicóis/uso terapêutico , Adulto , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Fígado/metabolismo , Masculino , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Recombinantes/uso terapêutico , Adulto Jovem
4.
Medicine (Baltimore) ; 99(30): e21251, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791701

RESUMO

INTRODUCTION: Cranioplasty following decompressive craniectomy is routinely performed to restore integrity of skull and improve neurological function. However, reconstructing the cranial defect brings many challenges to neurosurgeons and search for ideal implant materials is one of the most controversial issues. Although many studies have compared the outcomes of titanium and polyetheretherketone (PEEK) cranioplasty, yet no prospective study exists to guide the choice of titanium and PEEK materials. METHODS/DESIGN: A non-randomized, partially blinded, prospective cohort study is described that comprehensively compares the long-term outcomes of titanium cranioplasty versus PEEK cranioplasty. One hundred forty-five patients for each group will be recruited. Eligible patients are those with cranial defect due to traumatic brain injury (≥ 16 years), defect size is over 25 cm and they must agree to participate in the trial. Each participant is evaluated before surgery, on discharge, 3, 6, and 12 months after cranioplasty. The primary outcome is the infection, implant failure and implant deformation requiring revision surgery within 12 months. Secondary outcomes include postoperative complication rate, neurological outcomes, motor function, and cosmetic outcome over a 6-month period. DISCUSSION: Search for ideal implant materials is throughout the history of cranioplasty. This study will provide robust evidence for the choice of cranioplasty materials. TRIAL REGISTRATION NUMBER: ChiCTR2000033406.


Assuntos
Lesões Encefálicas Traumáticas/cirurgia , Craniectomia Descompressiva/métodos , Titânio/uso terapêutico , Humanos , Cetonas/uso terapêutico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados não Aleatórios como Assunto , Polietilenoglicóis/uso terapêutico , Estudos Prospectivos
5.
Jpn J Clin Oncol ; 50(11): 1274-1281, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-32700733

RESUMO

OBJECTIVE: The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. The guideline committee for clinical care of extra-abdominal desmoid-type fibromatosis in Japan conducted a systematic review of treatment with doxorubicin-based chemotherapy for desmoid-type fibromatosis. METHODS: We searched the pertinent literature. Two reviewers evaluated and screened it independently for eligibility and extracted data. They rated each report according to the grading of recommendations development and evaluation methodology. Based on the 'body of evidence', which the reviewers created, the clinical guideline committee decided a recommendation for the clinical question, 'Is doxorubicin-based chemotherapy effective for patients with extra-abdominal desmoid-type fibromatosis?' RESULTS: Fifty-three articles were extracted by the literature search, and one from hand search. After the first and second screenings, five articles were subjected to the final evaluation. There were no randomized controlled trials. According to response evaluation criteria in solid tumors criteria, the response rates of doxorubicin-based regimens and liposomal doxorubicin were 44% (28.6-54) and 33.3% (0-75) on average, respectively. In two reports, the response rates of doxorubicin-based regimens were higher than those of non-doxorubicin-based ones; 54% vs 12%, 40% vs 11%, respectively. The rates of G3 or G4 complications according to common terminology criteria for adverse events were 28% and 13% with doxorubicin-based and liposomal doxorubicin chemotherapy, respectively, including neutropenia or cardiac dysfunction. None of the reports addressed the issue of QOL. CONCLUSION: Although the evidence level was low in the evaluated studies, doxorubicin-based and liposomal doxorubicin chemotherapy was observed to be effective. However, doxorubicin-based chemotherapy is associated with non-ignorable adverse events, and is not covered by insurance in Japan. We weakly recommend doxorubicin-based chemotherapy for patients with extra-abdominal desmoid-type fibromatosis in cases resistant to other treatments.


Assuntos
Abdome/patologia , Doxorrubicina/análogos & derivados , Fibromatose Agressiva/tratamento farmacológico , Antineoplásicos/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Japão , Polietilenoglicóis/uso terapêutico , Resultado do Tratamento
6.
BMC Infect Dis ; 20(1): 522, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677900

RESUMO

BACKGROUND: Hepatitis E virus (HEV) may be resistant to immunosuppression reduction and ribavirin treatment in kidney transplant recipients because of mutant strains and severe side effects of ribavirin which conduct to dose reduction. Sofosbuvir efficacy is controversial. Peg-interferon 2 alpha (PEG-IFN) is currently contraindicated due to a high risk of acute humoral and cellular rejection. The present study assessed, for the first time, the effect of PEG-IFN in a kidney transplant recipient infected with HEV. CASE PRESENTATION: The patient had chronic active HEV that was resistant to immunosuppression reduction and optimal ribavirin treatment. He developed significant liver fibrosis. PEG-IFN was administered for 10 months, and it was well tolerated and did not induce rejection. A sustained virological response was obtained. CONCLUSIONS: We conclude that prolonged treatment with PEG-IFN in kidney transplant recipients infected with HEV could be considered as a salvage option.


Assuntos
Farmacorresistência Viral/efeitos dos fármacos , Hepatite E/tratamento farmacológico , Hepatite Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Rim , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Transplantados , Hepatite E/virologia , Vírus da Hepatite E/efeitos dos fármacos , Vírus da Hepatite E/fisiologia , Hepatite Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Resposta Viral Sustentada , Resultado do Tratamento
7.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680878

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.


Assuntos
Síndrome da Liberação de Citocina/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Pirazóis/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Criança , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada , Febre/etiologia , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/congênito , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Janus Quinases/antagonistas & inibidores , Masculino , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Pirazóis/farmacologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Carga Viral
8.
Mayo Clin Proc ; 95(8): 1671-1683, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32499125

RESUMO

OBJECTIVE: To evaluate the effect and safety of acupuncture for the treatment of irritable bowel syndrome (IBS) through comparisons with those of polyethylene glycol (PEG) 4000 and pinaverium bromide. PATIENTS AND METHODS: This multicenter randomized controlled trial was conducted at 7 hospitals in China and enrolled participants who met the Rome III diagnostic criteria for IBS between May 3, 2015, and June 29, 2018. Participants were first stratified into constipation-predominant or diarrhea-predominant IBS group. Participants in each group were randomly assigned in a 2:1 ratio to receive acupuncture (18 sessions) or PEG 4000 (20 g/d, for IBS-C)/pinaverium bromide (150 mg/d, for IBS-D) over a 6-week period, followed by a 12-week follow-up. The primary outcome was change in total IBS-Symptom Severity Score from baseline to week 6. RESULTS: Of 531 patients with IBS who were randomized, 519 (344 in the acupuncture group and 175 in the PEG 4000/ pinaverium bromide group) were included in the full analysis set. From baseline to 6 weeks, the total IBS-Symptom Severity Score decreased by 123.51 (95% CI, 116.61 to 130.42) in the acupuncture group and 94.73 (95% CI, 85.03 to 104.43) in the PEG 4000/pinaverium bromide group. The between-group difference was 28.78 (95% CI, 16.84 to 40.72; P<.001). No participant experienced severe adverse effects. CONCLUSION: Acupuncture may be more effective than PEG 4000 or pinaverium bromide for the treatment of IBS, with effects lasting up to 12 weeks. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR-IOR-15006259.


Assuntos
Terapia por Acupuntura/métodos , Síndrome do Intestino Irritável/terapia , Terapia por Acupuntura/efeitos adversos , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Morfolinas/administração & dosagem , Morfolinas/uso terapêutico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Pol Merkur Lekarski ; 48(285): 147-151, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32564036

RESUMO

Every year, 3-4 million people become infected with HCV, most of them are asymptomatic. In more than 20-30 years from infection, it leads to 10-20% of patients with cirrhosis, followed by hepatocellular carcinoma. Cardiological complications of the antiviral treatment are relatively rare, but force us to take additional diagnostic or discontinuation of therapy. AIM: The aim of study was to assess the cardiovascular safety of chronic hepatitis C treatment of genotype 1 in a triple regimen containing pegylated interferon-α in combination with ribavirin and boceprevir based on analysis of 24-hour ECG Holer monitoring, as well as changes in the concentration of cardiac fraction of fatty acid binding proteins (h-FABP). MATERIALS AND METHODS: 14 hepatitis C patients and 15 healthy people were included. The participants had an ambulatory 24-hour ECG-Holter recording at home condition and the determined level of h-FABP at baseline, after 4 and 12-16 weeks of treatment and 2 weeks after the end of therapy. The HRV parameters, AC/DC and QTc was calculated. RESULTS: At baseline there were no statistically significant differences in the HRV parameters, DC/AC, and QTc-interval. Absolute DC/AC values, HRV parameters: SDNN-ix, rMSDD, TP, HF, VLF and ULF were significantly lower in the treated group. LF/HF ratio was higher in this group (p=0.047). These changes persisted during the follow-up and disappeared after treatment. QTc was the shortest in the 4th week and withdrew during further follow-up. H-FABP levels did not differ statistically significantly between any subsequent determinations. CONCLUSIONS: At baseline there were no statistically significant differences in the HRV parameters, DC/AC, and QTc-interval. Absolute DC/AC values, HRV parameters: SDNN-ix, rMSDD, TP, HF, VLF and ULF were significantly lower in the treated group. LF/HF ratio was higher in this group (p=0.047). These changes persisted during the follow-up and disappeared after treatment. QTc was the shortest in the 4th week and withdrew during further follow-up. H-FABP levels did not differ statistically significantly between any subsequent determinations.


Assuntos
Eletrocardiografia Ambulatorial , Hepatite C Crônica , Interferon-alfa , Polietilenoglicóis , Antivirais/uso terapêutico , Biomarcadores/análise , Proteína 3 Ligante de Ácido Graxo/análise , Frequência Cardíaca , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico
10.
Medicine (Baltimore) ; 99(25): e20820, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569231

RESUMO

INTRODUCTION: Interferon alpha (IFNα) has been used for a long time in patients with functionally active neuroendocrine tumors (NET). However, due to the unfavorable toxicity profile of interferon, the perceived limited efficacy as well as the development of novel substances, IFNα is only used sparingly in the treatment of NET to date. PATIENTS CONCERNS AND DIAGNOSIS: We describe the case of a 63-year-old male patient with highly differentiated, functional NET of the ileum and synchronous liver metastasis. INTERVENTIONS: After failure of classical therapies including dose-intensified somatostatin analog treatment and palliative primary tumor resection, a therapy with pegylated IFNα2a (135 µg/wk) was initiated. Following this treatment, the patient fully recovered from signs of hypersecretion and demonstrated an impressive tumor response. OUTCOMES: Thirty months after initiating IFNα, the patient is still free of clinical symptoms and shows a sustained tumor response. Notably, no relevant side effects were observed. CONCLUSION: Our case report supports the use of IFNα in patients with functional NET refractory to classical treatments.


Assuntos
Neoplasias do Íleo/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Tumores Neuroendócrinos/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Humanos , Neoplasias do Íleo/patologia , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Proteínas Recombinantes/uso terapêutico , Falha de Tratamento , Resultado do Tratamento
11.
Ann Hematol ; 99(6): 1331-1339, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32382775

RESUMO

Autologous stem cell transplantation (ASCT) is the only curable therapy for multiple myeloma (MM), while its success primarily relies on mobilization to obtain sufficient hematopoietic stem/progenitor cells (HPC). Although the role of Pegfilgrastim (PEG), a novel PEGylated form of the recombinant G-CSF filgrastim (FIL), in mobilization has been demonstrated, it remains unclear whether this approach is cost-effective in MM treatment. Here, we performed a real-world analysis to evaluate the efficacy and cost of PEG for mobilization in a cohort of MM patients, of which 53% carried high-risk cytogenetic abnormalities. A total of 91 patients who received either a single dose of PEG (6 or 12 mg, n = 42) or multiple dosing of 10 µg/kg/day FIL (n = 49) after chemotherapy for HPC mobilization were included. The yield of MNCs and CD34+ cells per milliliter of blood collected via apheresis was significantly greater in the PEG group than that in the FIL group (P = 0.014 and P = 0.038). Mobilization with PEG yielded significantly higher median number of collected CD34+ cells than FIL (5.56 vs. 4.82 × 106/kg; P = 0.038). Moreover, the average time-to-recovery of leukocytes and platelets after transplantation was markedly shorter in the PEG group than that in the FIL group (leukocyte, 11.59 ± 1.98 vs 12.93 ± 2.83 days, P = 0.019; platelet, 12.86 ± 2.62 vs 14.80 ± 5.47, P = 0.085). However, the total cost of mobilization and apheresis using PEG or FIL was comparable (P = 0.486). Of note, mobilization with 12 mg PEG further shortened time-to-recovery of leukocytes (10.64 ± 0.51 vs. 12.04 ± 2.26 days, P = 0.05) and platelets (10.60 ± 2.89 vs. 13.33 ± 2.35 days, P = 0.031) compared with 6 mg PEG. Our results support a notion that PEG (especially 12 mg) combined with chemotherapy is a cost-effective and convenient regimen of mobilization, which might improve the outcome of ASCT in MM.


Assuntos
Filgrastim/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Análise Custo-Benefício , Feminino , Filgrastim/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Mobilização de Células-Tronco Hematopoéticas/tendências , Transplante de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/economia , Polietilenoglicóis/economia , Transplante Autólogo/economia , Transplante Autólogo/métodos , Transplante Autólogo/tendências , Resultado do Tratamento
12.
Cytokine Growth Factor Rev ; 53: 38-42, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32360420

RESUMO

Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Pneumonia Viral/patologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Terapia de Substituição Renal Contínua/métodos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/biossíntese , Feminino , Humanos , Interferon-alfa/uso terapêutico , Masculino , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos
13.
PLoS One ; 15(4): e0230893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275726

RESUMO

BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Internacionalidade , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/metabolismo , Humanos , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Segurança , Resultado do Tratamento
14.
Arthritis Rheumatol ; 72(7): 1067-1071, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32253823

RESUMO

OBJECTIVE: To compare uptake in the ordering of biosimilars at a Veterans Affairs Medical Center (VAMC) to that at an academic medical center, where institutional incentives for infused medications differ. METHODS: We performed a cross-sectional study of medical record data and estimated institutional financial incentives at 2 medical centers in Philadelphia: 1) the University of Pennsylvania Health System (UPHS), and 2) the local VAMC. All ordering events for filgrastim or infliximab products were quantified over time and stratified according to product (biosimilar versus reference product) and center. Financial incentives to the institutions over time were determined based on actual drug costs for the VAMC and average sales prices (ASPs) and Medicare Part B reimbursement rates for UPHS. RESULTS: There were 15,761 infusions of infliximab at UPHS, of which 99% were for the reference product. There was a sharper decline in the use of reference products at the VAMC; 62% of the 446 infliximab infusions ordered at the VAMC were for the reference product. ASPs were consistently lower for biosimilar infliximab products, but the estimated institutional financial incentives remained similar over time for biosimilar and reference infliximab at UPHS. At the VAMC, the costs for 100-mg vials of reference infliximab and infliximab-abda were $623.48 and $115.58, respectively: a $507.90 (81%) savings per vial. CONCLUSION: The uptake of infliximab biosimilars has been slow at an academic medical center compared to a nearby VAMC, where financial savings are realized by the institution from its use. Slow adoption of biosimilar medications may impact the rates of decline in costs.


Assuntos
Centros Médicos Acadêmicos , Antirreumáticos/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Filgrastim/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Infliximab/uso terapêutico , United States Department of Veterans Affairs , Antirreumáticos/economia , Medicamentos Biossimilares/economia , Redução de Custos , Custos de Medicamentos , Filgrastim/economia , Gastroenterologia , Fármacos Hematológicos/economia , Humanos , Infliximab/economia , Infusões Intravenosas , Medicare Part B , Motivação , Philadelphia , Polietilenoglicóis/economia , Polietilenoglicóis/uso terapêutico , Mecanismo de Reembolso , Reumatologia , Estados Unidos
15.
Am J Case Rep ; 21: e921301, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32251268

RESUMO

BACKGROUND Xeroderma pigmentosum (XP) is an autosomal recessive disease caused by mutations in DNA repair genes. Clinical manifestations include extreme sensitivity to ultraviolet (UV) rays, freckle-like pigmentation, ocular abnormalities, and an increased risk of developing neoplasms in sun-exposed areas of the skin, mucous membranes, and eyes. This paper describes the clinical outcome of pegylated interferon alpha 2b (PEG-IFN-alpha-2b) subconjunctival injections and topical mitomycin C (MMC) in the treatment of ocular surface squamous neoplasia (OSSN) in patients with XP. CASE REPORT A series of 3 patients with histopathologically-proven biopsy specimens of XP-associated neoplasia of the eyelids and ocular surface underwent subconjunctival injections of PEG-IFN-alpha-2 band topical cycles of MMC. There was a noticeable decrease in the size and severity of ocular surface squamous neoplasia, with minimal adverse effects of flu-like symptoms with mild fever and generalized malaise. Transient mental depression was reported in 2 of our patients, and only 1 patient developed autoimmune diabetes mellitus, which required insulin therapy after the discontinuation of the PEG-IFN-alpha-2b. CONCLUSIONS The literature on the specifics of ocular care using PEG-IFN-alpha-2b for XP-associated OSSN is sparse. However, according to our clinical experience, the combination of PEG-IFN-alpha-2b subconjunctival injection and the topical cycles of MMC is a promising long-term medical therapy to minimize the development and recurrence of OSSN in XP patients.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Oculares/tratamento farmacológico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Mitomicina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Xeroderma Pigmentoso/complicações , Adulto , Antibióticos Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Carcinoma de Células Escamosas/etiologia , Quimioterapia Combinada , Neoplasias Oculares/etiologia , Feminino , Humanos , Masculino , Proteínas Recombinantes/uso terapêutico
16.
Am J Gastroenterol ; 115(6): 895-905, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32324606

RESUMO

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.


Assuntos
Constipação Intestinal/tratamento farmacológico , Laxantes/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Bisacodil/uso terapêutico , Doença Crônica , Colonoscopia/estatística & dados numéricos , Constipação Intestinal/fisiopatologia , Fibras na Dieta/uso terapêutico , Ácido Dioctil Sulfossuccínico/uso terapêutico , Serviço Hospitalar de Emergência , Emprego , Grupos Étnicos/estatística & dados numéricos , Feminino , Gastroenterologistas , Fármacos Gastrointestinais/uso terapêutico , Agonistas da Guanilil Ciclase C/uso terapêutico , Humanos , Seguro Saúde/estatística & dados numéricos , Controle Interno-Externo , Lactulose/uso terapêutico , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Medicamentos sem Prescrição/uso terapêutico , Peptídeos/uso terapêutico , Médicos de Atenção Primária , Polietilenoglicóis/uso terapêutico , Senosídeos/uso terapêutico , Índice de Gravidade de Doença , Fatores Sexuais , Tensoativos/uso terapêutico , Inquéritos e Questionários , Estados Unidos
17.
Drugs Today (Barc) ; 56(3): 195-202, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32282866

RESUMO

Ropeginterferon alfa-2b is a novel mono-PEGylated alfa interferon. It is the first interferon approved for the treatment of patients with polycythemia vera (PV) and the first and only approved treatment for PV independent of previous hydroxyurea exposure. In contrast to other interferons, the drug has to be subcutaneously injected every 2 weeks only, with intervals of 4 weeks being possible after prolonged use. It is generally well tolerated and can lead to deep molecular responses. In this article, we provide a review of available preclinical and clinical data of ropeginterferon alfa-2b leading to its E.U. approval and give an outlook on future clinical trials involving this drug.


Assuntos
Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Humanos , Hidroxiureia , Interferon alfa-2/administração & dosagem , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
18.
J Clin Nurs ; 29(15-16): 2863-2871, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32320100

RESUMO

AIMS AND OBJECTIVES: To evaluate the efficacy and safety of a comprehensive protocol for constipation prevention. BACKGROUND: Constipation is a common problem for patients undergoing total hip arthroplasty (THA), yet sparse evidence is available to guide constipation prevention after THA. DESIGN: Randomised controlled superiority clinical trial. METHODS: This randomised controlled study was carried out according to the Consolidated Standards of Reporting Trials (CONSORT). A total of 80 THA patients were randomised to receive only preoperative education about lifestyle or the combination of education with postoperative abdominal massage and polyethylene glycol 4,000 (Forlax®). Efficacy outcomes included rates of postoperative constipation and enema rescue, as well as time to first postoperative defecation and readmission within 30 days. Safety outcomes were number and type of adverse events. RESULTS: Patients who received combination treatment showed a significantly lower rate of postoperative constipation during hospitalisation than patients who received only preoperative education (25% versus 55%), and they showed a significantly lower rate of enema rescue (12.5% versus 40%). Many more patients receiving combination treatment experienced their first defecation within two postoperative days than patients who received only preoperative education (62.5% versus 35.9%). In contrast, the two groups were similar in terms of constipation rate on postoperative days 15 and 30, rate of readmission within 30 days and rate of postoperative adverse events. CONCLUSIONS: These results suggest that our comprehensive protocol can relieve constipation after THA, reduce the need for enema rescue and shorten time to first defecation without sacrificing safety. More work is needed to optimise and develop this protocol further. RELEVANCE TO CLINICAL PRACTICE: Constipation is a distressing problem that frequently occurs after THA. This study confirmed that a comprehensive protocol including preoperative education, postoperative abdominal massage and polyethylene glycol 4,000 can effectively relieve constipation after THA without sacrificing safety.


Assuntos
Artroplastia de Quadril/efeitos adversos , Constipação Intestinal/prevenção & controle , Massagem/enfermagem , Polietilenoglicóis/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Cuidados Pré-Operatórios/métodos , Resultado do Tratamento
19.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: covidwho-606
20.
Nat Rev Drug Discov ; 19(3): 149-150, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127666
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