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1.
Ann Clin Microbiol Antimicrob ; 18(1): 30, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31629409

RESUMO

OBJECTIVES: To analyse the effectiveness of dalbavancin (DBV) in clinical practice as consolidation therapy in patients with bloodstream infection (BSI) and/or infective endocarditis (IE) produced by gram-positive cocci (GPC), as well as its safety and pharmacoeconomic impact. METHODS: A multicentre, observational and retrospective study was conducted of hospitalised patients with IE and/or BSI produced by GPC who received at least one dose of DBV. Clinical response was assessed during hospitalization, at 3 months and at 1 year. RESULTS: Eighty-three patients with median age of 73 years were enrolled; 73.5% were male; 59.04% had BSI and 49.04% IE (44.04% prosthetic valve IE, 32.4% native IE, 23.5% pacemaker lead). The most frequently isolated microorganism was Staphylococcus aureus in BSI (49%) and coagulase-negative staphylococci in IE (44.1%). All patients with IE were clinically cured in hospital; at 12 months, there was 2.9% loss to follow-up, 8.8% mortality unrelated to IE, and 2.9% therapeutic failure rate. The percentage effectiveness of DBV to treat IE was 96.7%. The clinical cure rate for BSI was 100% during hospital stay and at 3 months; there were no recurrences or deaths during the follow-up. No patient discontinued treatment for adverse events. The saving in hospital stay was 636 days for BSI (315,424.20€) and 557 days for IE (283,187.45€). CONCLUSIONS: DBV is an effective consolidation antibiotic therapy in clinically stabilized patients with IE and/or BSI. It proved to be a cost-effective treatment, reducing the hospital stay, thanks to the pharmacokinetic/pharmacodynamic profile of this drug.


Assuntos
Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Sepse/tratamento farmacológico , Teicoplanina/análogos & derivados , Idoso , Antibacterianos/efeitos adversos , Análise Custo-Benefício , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Teicoplanina/efeitos adversos , Teicoplanina/uso terapêutico , Resultado do Tratamento
2.
AIDS Rev ; 21(3): 126-134, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31532397

RESUMO

Persistent coinfection with the hepatitis B/D viruses (HDV) represents the most severe form of viral hepatitis. Hepatitis D often leads to liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. The current treatment options are limited as only pegylated interferon-alpha (PEG-IFNa) has efficacy against HDV. However, treatment response is still unsatisfactory with 25-40% HDV RNA suppression after 1-2 years. In addition, late HDV RNA relapses have been described during long-term follow-up. Fortunately, new treatment options for patients with chronic hepatitis delta are now on the horizon. The hepatocyte entry inhibitor bulevirtide (formerly myrcludex B) and the farnesyl transferase inhibitor lonafarnib are currently explored in patients with chronic hepatitis delta in Phase 3 clinical studies. The nucleic acid inhibitor REP-2139-Ca and PEG-IFN-lambda are studied in Phase 2 trials. We here summarize data on the efficacy of these new antiviral drugs and the existing safety data on the treatment of HDV infection.


Assuntos
Antivirais/administração & dosagem , Hepatite D/tratamento farmacológico , Interferon-alfa/administração & dosagem , Lipopeptídeos/administração & dosagem , Ácidos Nucleicos/administração & dosagem , Piperidinas/administração & dosagem , Polímeros/administração & dosagem , Piridinas/administração & dosagem , Antivirais/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Coinfecção/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Hepatite B Crônica/tratamento farmacológico , Vírus Delta da Hepatite/efeitos dos fármacos , Humanos , Interferon-alfa/efeitos adversos , Lipopeptídeos/efeitos adversos , Ácidos Nucleicos/efeitos adversos , Piperidinas/efeitos adversos , Polímeros/efeitos adversos , Piridinas/efeitos adversos , Recidiva , Resultado do Tratamento
3.
J Ovarian Res ; 12(1): 88, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533857

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is the majority ovarian cancer (OC) type with a poor prognosis. This present study aimed to investigate potential prognostic factors including albumin-to-fibrinogen ratio (AFR) for advanced EOC patients with neoadjuvant chemotherapy (NAC) followed by debulking surgery. METHODS: A total of 313 advanced EOC patients with NAC followed by debulking surgery from 2010 to 2017 were enrolled. The predictive value of AFR for the overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. The univariate and multivariate Cox proportional hazards regression analyses were applied to investigate prognostic factors for advanced EOC patients. The association between preoperative AFR and progression free survival (PFS) or OS was determined via the Kaplan-Meier method using log-rank test. RESULTS: The ROC curve analysis showed that the cutoff value of preoperative AFR in predicting OS was determined to be 7.78 with an area under the curve (AUC) of 0.773 (P < 0.001). Chemotherapy resistance, preoperative CA125 and AFR were independent risk factors for PFS in advanced EOC patients. Furthermore, chemotherapy resistance, residual tumor and AFR were significant risk factors for OS by multivariate Cox analysis. A low preoperative AFR (≤7.78) was significantly associated with a worse PFS and OS via the Kaplan-Meier method by log-rank test (P < 0.001). CONCLUSIONS: A low preoperative AFR was an independent risk factor for PFS and OS in advanced EOC patients with NAC followed by debulking surgery.


Assuntos
Carcinoma Epitelial do Ovário/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Fibrinogênio/metabolismo , Albumina Sérica/metabolismo , Adulto , Idoso , Antígeno Ca-125/sangue , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Procedimentos Cirúrgicos de Citorredução , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Tratamento Farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
4.
Future Microbiol ; 14: 1087-1097, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31512522

RESUMO

Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Peptídeos/farmacologia , Venenos de Vespas/farmacologia , Animais , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/toxicidade , Queratinócitos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Peptídeos/administração & dosagem , Peptídeos/efeitos adversos , Peptídeos/toxicidade , Venenos de Vespas/administração & dosagem , Venenos de Vespas/efeitos adversos , Venenos de Vespas/toxicidade , Peixe-Zebra
5.
Parasit Vectors ; 12(1): 433, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492168

RESUMO

BACKGROUND: The safety of ProHeart® 12 (PH 12; extended-release injectable suspension; 10% moxidectin in glyceryl tristearate microspheres) was evaluated in four studies using Beagle dogs and one study using ivermectin-sensitive Collies. The recommended dose is 0.5 mg/kg subcutaneously once yearly. METHODS: Study 1: safety margin was evaluated as 3 treatments of PH 12 (0× (control); 1× (recommended dose); 3× (3 times recommended dose) and 5× (5 times recommended dose) in 12 months via clinical observations, body weights, food consumption, injection site observations, physical examinations, moxidectin tissue assay, pharmacokinetics, and clinical and anatomic pathology. Study 2: safety in breeding-age males was demonstrated by semen testing at 14-day intervals from Day 7 to Day 91 post-treatment (0× or 3×). Study 3: reproductive safety in females was demonstrated by monitoring dams and litters following treatments (0× or 3×) administered during breeding, gestation, or lactation. Study 4: safety in dogs surgically implanted with adult heartworms was evaluated by clinical and laboratory monitoring following treatment with 0× or 3× administered 61 days post-implantation. Study 5: safety in ivermectin-sensitive dogs (120 µg/kg SC) was by clinical monitoring for 1 week after administering 1×, 3× or 5×. RESULTS: Study 1: slight swelling clinically detectable at some 3× and 5× injection sites was characterized microscopically as granulomatous inflammation, like tissue responses to medical implants, interpreted as non-adverse. Pharmacokinetics were dose-proportional and there was little or no systemic accumulation. Residual moxidectin mean (range) at 1× injection sites after 1 year was 16.0% (0.045-37.6%) of the administered mass. Studies 2 and 3: no effects were identified in reproductive indices (females) or semen quality characteristics (males). Study 4: PH 12 produced marked reductions in circulating microfilariae and lower numbers of adult heartworms, but no adverse clinical signs were identified. Study 5: there were no abnormal clinical signs at 1×, 3× or 5× overdoses of PH 12 in ivermectin-sensitive dogs. CONCLUSIONS: PH 12 has a > 5× safety margin in both normal and ivermectin-sensitive dogs, has no effects on canine reproduction, and is well tolerated in heartworm-positive dogs. The only treatment-related finding was non-adverse, granulomatous inflammation at the injection site.


Assuntos
Antinematódeos/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Injeções/efeitos adversos , Macrolídeos/efeitos adversos , Suspensões/efeitos adversos , Animais , Antinematódeos/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Doenças do Cão/tratamento farmacológico , Cães , Hidropericárdio/tratamento farmacológico , Macrolídeos/administração & dosagem , Suspensões/administração & dosagem , Resultado do Tratamento
6.
Anticancer Res ; 39(8): 4337-4342, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366527

RESUMO

BACKGROUND: Induction therapy with docetaxel, cisplatin and fluorouracil (TPF) is a treatment option for locally advanced head and neck cancer (LAHNC), but it is not known which patients are appropriate for TPF. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with LAHNC who underwent induction TPF, and evaluated factors predictive of the completion of TPF treatment (defined as ≥3 cycles administered). RESULTS: Of the total 93 enrolled patients, 73 (78.5%) achieved therapy completion. In a multivariate analysis, hypolaryngeal/ laryngeal primary tumor site was a negative predictive factor (hazard ratio(HR)=0.32, 95% confidence interval(CI)=0.11-0.96, p=0.041) and body mass index ≥22 kg/m2 was a positive predictive factor (hazard ratio=3.51, 95% confidence intervaI=1.04-11.83, p=0.043) of TPF completion. CONCLUSION: For patients with LAHNC, oropharyngeal primary tumor site and high body mass index can be used to predict TPF completion and may contribute to decisions on the indications for TPF in terms of safety and tolerability.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Quimioterapia de Indução/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia
7.
Anticancer Res ; 39(8): 4555-4560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366559

RESUMO

BACKGROUND/AIM: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy. PATIENTS AND METHODS: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated. RESULTS: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1. CONCLUSION: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved.


Assuntos
Anorexia/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Ingestão de Alimentos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Adulto , Idoso , Anorexia/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/patologia , Vômito/induzido quimicamente , Vômito/epidemiologia , Vômito/patologia
8.
Int J Antimicrob Agents ; 54(4): 410-422, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404620

RESUMO

Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA), is an important aetiological cause of community-acquired pneumonia (CAP) and associated with significant morbidity and mortality. Empiric therapy for CAP frequently consists of ß-lactam monotherapy or ß-lactam/macrolide combination therapy. However, such agents are often ineffective against S. aureus and do not reflect the emergence and increasing prevalence of MRSA in the community setting. Ceftaroline fosamil is a fifth-generation parenteral cephalosporin with broad-spectrum activity against Gram-positive pathogens - such as S. aureus (including MRSA), Streptococcus pneumoniae and Streptococcus pyogenes - and typical Gram-negative pathogens, including Haemophilus influenzae and Moraxella catarrhalis. The approval of ceftaroline fosamil in the United States and Europe for the treatment of adults with moderate-to-severe CAP was based on two phase 3 trials (FOCUS 1 and 2), which demonstrated that ceftaroline fosamil was non-inferior to ceftriaxone, a standard empiric treatment for CAP, while exhibiting a comparable safety profile. Although head-to-head trials of ceftaroline fosamil versus comparators against MRSA CAP are lacking, the effectiveness of ceftaroline fosamil in subpopulations of patients not covered by phase 3 trials (e.g. those with MRSA CAP or severe renal impairment) has been demonstrated in the Clinical Assessment Program and Teflaro Utilization Registry (CAPTURE) study. As ineffective empiric therapy is associated with adverse outcomes, including mortality and increased costs, ceftaroline fosamil, with its extended spectrum of activity, is an attractive alternative to standard antibiotic CAP regimens.


Assuntos
Antibacterianos/uso terapêutico , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Pneumonia Estafilocócica/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ensaios Clínicos Fase III como Assunto , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Resultado do Tratamento
9.
Mycoses ; 62(10): 969-978, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355956

RESUMO

This randomised, double-blind, placebo-controlled trial assessed the efficacy, safety and tolerability of voriconazole+anidulafungin (combination) or voriconazole+placebo (monotherapy) for invasive aspergillosis (IA; NCT00531479). We present a post hoc analysis of Korean and non-Korean patients with IA (including baseline positive serum galactomannan [GM]). Immunocompromised patients ≥ 16 years with IA were randomised 1:1, combination or monotherapy, for ≥ 2 weeks' treatment. The primary endpoint was 6- and 12-week all-cause mortality (Korean modified intent-to-treat [mITT] population). Overall, 454 patients enrolled (Koreans: 56 [combination: 28, monotherapy: 28], non-Koreans: 398 [combination: 200, monotherapy: 198]). The mITT population comprised 40 Koreans (combination: 23; monotherapy: 17) and 237 non-Koreans (combination: 112; monotherapy: 125). Week 6 treatment difference in mortality rate between combination and monotherapy was -6.4% in non-Koreans. This reduction was more marked in Koreans (-22.4%). Week 12 difference in all-cause mortality between combination and monotherapy was -17.7% (Koreans) and -20.2% at Week 6 (Koreans; positive baseline GM). Week 6 mortality (Koreans [mITT]; baseline GM >0.5-2.0) was 0/13 (combination) and 2/6 (monotherapy). Serious adverse events were numerically higher for combination than monotherapy (Koreans: 57.1%, 46.4%; non-Koreans: 49.5%, 46.0%). In Koreans, combination therapy was associated with marginally better outcomes than monotherapy and more so than in non-Koreans.


Assuntos
Anidulafungina/uso terapêutico , Antifúngicos/uso terapêutico , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Voriconazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidulafungina/efeitos adversos , Antifúngicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Voriconazol/efeitos adversos , Adulto Jovem
12.
Eur J Clin Microbiol Infect Dis ; 38(10): 1849-1856, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280481

RESUMO

The incidence of nosocomial invasive fungal infections involving Candida spp. has increased markedly in recent years in patients undergoing abdominal surgery. This post hoc analysis aimed to determine the efficacy and safety of anidulafungin treatment in patients with intra-abdominal candidiasis (IAC) from five prospective studies (one comparative and four open-label) of adult surgical patients with microbiologically confirmed Candida intra-abdominal infection. Patients received an intravenous (IV) loading dose of anidulafungin 200 mg, followed by a daily 100-mg maintenance dose. Per study protocols, some patients could be switched to an oral azole after ≥ 5 or ≥ 10 days of IV treatment. Antifungal treatment was maintained for ≥ 14 days after the last positive Candida culture and resolution of symptoms. The global response rate (GRR) at the end of IV treatment (EOIVT) was the primary endpoint. GRR at the end of therapy (EOT), all-cause mortality at days 14 and 28, and safety was also evaluated. Seventy-nine patients had IAC from peritoneal fluid or hepatobiliary tract. C. albicans (72.2%) and C. glabrata (32.9%) were the most common pathogens. Overall GRR was 73.4% and 67.1% at EOIVT and EOT, respectively. All-cause mortality was 17.7% at day 14 and 24.1% at day 28 in the modified intent-to-treat population. Anidulafungin was well tolerated in this population, with most adverse events mild or moderate in severity. In these patients with IAC, anidulafungin showed a GRR at EOIVT similar to the anidulafungin registrational trial, and the results of our analysis confirmed the known safety profile of anidulafungin. ClinicalTrials.gov registration number NCT00496197, registered July 3, 2007, https://clinicaltrials.gov/ct2/show/study/NCT00496197 ; ClinicalTrials.gov registration number NCT00548262, registered October 19, 2007, https://clinicaltrials.gov/ct2/show/record/NCT00548262 ; ClinicalTrials.gov registration number NCT00537329, registered September 25, 2007, https://clinicaltrials.gov/ct2/show/record/NCT00537329 ; ClinicalTrials.gov registration number NCT00689338, registered May 29, 2008, https://clinicaltrials.gov/ct2/show/study/NCT00689338 ; ClinicalTrials.gov registration number NCT00805740, registered November 26, 2008, https://clinicaltrials.gov/ct2/show/NCT00805740.


Assuntos
Anidulafungina/administração & dosagem , Antifúngicos/administração & dosagem , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Infecções Intra-Abdominais/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidulafungina/efeitos adversos , Antifúngicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
13.
PLoS One ; 14(6): e0218487, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211809

RESUMO

BACKGROUND: Hypothyroidism is one of the adverse drug reactions that associated with Multidrug Resistant Tuberculosis (MDR-TB) medications. Extremely variable magnitude of hypothyroidism in MDR-TB patients has been reported from different parts of the world. However, there is no evidence that tried to estimate the pooled prevalence of hypothyroidism to confirm the rareness of hypothyroidism in MDR-TB patients on treatment. Therefore, we did a systematic review and meta-analysis to estimate the prevalence of hypothyroidism in MDR-TB patients on treatment, and to summarize the demographic and clinical characteristics of the patients. METHODS: We conducted a systematic review and meta-analysis on studies reported around the world on the prevalence of hypothyroidism in MDR-TB patients on treatment. We searched electronic databases: PubMed/Medline, EMBASE, CINAHL, Science Direct, Academic Search Complete and Google scholar for English language articles without limiting publication year. We also reviewed the bibliographies of relevant studies and conducted an electronic search for relevant conference abstracts. Eligible studies were cross-sectional and cohort studies that included at least five participants. We used a random-effects model to estimate the pooled prevalence of hypothyroidism. The registration number of this review study protocol is CRD42018109237. RESULTS: We included 30 studies and pooled data on a total of 6,241 MDR-TB patients. The crude prevalence of hypothyroidism was extremely heterogeneous. The pooled prevalence of hypothyroidism in MDR-TB patients on treatment was 17.0% (95% CI: 13.0-20.0). Ethionamide and para-aminosalicylic acid (PAS) were the most frequently reported drugs that associated with the occurrence of hypothyroidism. CONCLUSION: This review revealed that hypothyroidism is not a rare adverse drug reaction in MDR-TB patients on treatment. Ethionamide and PAS were the most frequently reported drugs that associated with the occurrence of hypothyroidism. Screening of hypothyroidism in MDR-TB patients on treatment is important while targeting patients on Ethionamide and PAS based treatment regimen.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Hipotireoidismo/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Ácido Aminossalicílico/efeitos adversos , Ácido Aminossalicílico/uso terapêutico , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Etionamida/efeitos adversos , Etionamida/uso terapêutico , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/microbiologia , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
14.
Semin Oncol ; 46(2): 160-172, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31204004

RESUMO

INTRODUCTION: Taste and smell alteration is a frequent side effect of chemotherapy. However, little is known about their influence on patients' food behavior and the mechanisms underpinning their occurrence. This lack of clarity is likely due to a series of factors among which heterogeneity in chemotherapy-induced taste and smell modifications may play a prominent role. The present review provides a critical overview of the evidence on the association between taste and smell alterations and food behavior modifications in cancer patients undergoing chemotherapy. DESIGN: The literature search was performed using PubMed and Google Scholar databases and restricted to literature for English-language articles published between 1990 and June 2018. Sensory-related terms were combined with food behavior-related terms to identify the studies that examined the association between these two terms. The retrieved studies were grouped based on the taste and smell assessment outcomes. RESULTS: Thirteen eligible articles were included in the review. The studies varied in design, length, methodology of assessment, and studied population. The categorization of studies depending on taste and smell assessment outcomes allowed the definition of three patient profiles: unaltered, hypo- and hyperchemosensation (taste and/or smell). Alterations were significantly correlated with patients' energy intake and macronutrient preferences suggesting that sensitivity of each patient to olfactory and gustatory stimuli is likely to play a role in food behavior modulation during cancer and chemotherapy. CONCLUSION: The review summarizes and provides relevant associations between taste/smell alterations and food behavior while receiving chemotherapy considering existing individual variations. Given the sensory influence on food behavior modulation, a better characterization of smell and taste alterations before the launch of chemotherapy seems important for a better understanding and management of patients' food behavior trajectory over the treatment.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias/tratamento farmacológico , Olfato/efeitos dos fármacos , Paladar/efeitos dos fármacos , Comportamento/efeitos dos fármacos , Humanos , Neoplasias/complicações , Neoplasias/patologia
15.
J Biol Regul Homeost Agents ; 33(4): 1241-1242, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31250616

RESUMO

We present the case of an 80-year-old man in good general condition. The patient was hospitalized for a complaint about the appearance of highly itchy plaques in the area of both lower legs for several months.


Assuntos
Dermatite/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Púrpura/induzido quimicamente , Idoso de 80 Anos ou mais , Humanos , Extremidade Inferior/patologia , Masculino
16.
Jpn J Infect Dis ; 72(5): 299-305, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31155600

RESUMO

Human papillomavirus (HPV)-associated disease is common among men with HPV infection. A quadrivalent HPV (qHPV) vaccine has demonstrated 85.9% efficacy against HPV6/11/16/18-related, persistent (≥ 6 month) infection in a study of Japanese men aged 16-26 years old. Here, we report the results of an open-label study of the immunogenicity and tolerability of the qHPV vaccine (NCT02576054), conducted to bridge findings from Japanese men to Japanese boys aged 9-15 years old. A total of 100 boys completed a three-vaccination regimen (Day 1, and Months 2 and 6), and 99 boys were included in the primary analysis population. The rate of seroconversion at one month after vaccine Dose 3 (Month 7) was high for each type of HPV (anti-HPV6/11/16/18 seroconversion rates [95% CI]: 94.9% [85.5%, 98.3%], 99.0% [94.4%, 100.0%], 99.0% [94.5%, 100.0%], and 99.0% [94.4%, 100.0%], respectively). Moreover, anti-HPV6/11/16/18 geometric mean titers were 482.9 mMU/mL, 1052.8 mMU/mL, 3878.3 mMU/mL, and 1114.5 mMU/mL, respectively. Immune responses to the qHPV vaccine were non-inferior among Japanese boys included in the current study and compared with young Japanese men from a separate study. Injection-site reactions were the most common adverse events, and administration of the vaccine was well tolerated in Japanese boys.


Assuntos
Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/efeitos adversos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Adolescente , Anticorpos Antivirais/sangue , Grupo com Ancestrais do Continente Asiático , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Humanos , Masculino , Soroconversão
17.
Lipids Health Dis ; 18(1): 134, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31170997

RESUMO

Low-density lipoprotein cholesterol (LDL-C) has been recommended as the primary treatment target on lipid management in coronary heart disease (CHD) patients for past several decades. However, even by aggressive LDL-C lowering treatment, patients still present a significant residual risk of major adverse cardiovascular events (MACE). Non-high-density lipoprotein cholesterol (non-HDL-C) contained all the atherogenic lipoproteins, such as chylomicron, very-low density lipoprotein (VLDL), LDL, intermediate density lipoprotein (IDL). Many prospective observation studies have found that non-HDL-C was better than LDL-C in predicting risks of MACE. Since non-HDL-C appears to be superior for risk prediction beyond LDL-C, current guidelines have emphasize the importance of non-HDL-C for guiding cardiovascular prevention strategies and have flagged non-HDL-C as a co-primary therapeutic target. The goals of non-HDL-C were recommended as 30 mg/dl higher than the corresponding LDL-C goals, but the value seemed inappropriate. This review provide evidence for changing lipid management strategy to focus on non-HDL-C and appropriate values for adding to LDL-C goals would be proposed.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Quilomícrons/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/antagonistas & inibidores , Doença das Coronárias/complicações , Doença das Coronárias/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/antagonistas & inibidores , Lipídeos/genética , Fatores de Risco
18.
Helicobacter ; 24(5): e12606, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31168941

RESUMO

BACKGROUND: Several studies have shown that Pylera® (three-in-one capsules containing 140 mg bismuth potassium subcitrate, 125 metronidazole, and tetracycline 125 mg) in association with omeprazole or esomeprazole is a good option in the treatment of Helicobacter pylori infection. In particular, the adjunction of a PPI to Pylera® may be useful to overcome metronidazole resistance. However, omeprazole and its derivatives can promote greater bismuth absorption and enhance its toxicity. The H2 receptor antagonist (H2RA) ranitidine seems to induce less bismuth absorption and as a consequence less systemic toxicity. AIM: To evaluate whether Pylera® in combination with esomeprazole or with ranitidine is equally effective in the treatment of H. pylori infection. MATERIAL AND METHODS: Two separate groups of patients were treated simultaneously. One group was treated with Pylera® three capsules qid plus esomeprazole 40 mg bid for 10 days (group A), and the other group was treated with Pylera® three capsules qid plus ranitidine 300 mg bid for 10 days (group B). H. pylori eradication was defined as a negative result in 13 C urea breath test performed at least 8 weeks after the end of treatment with a delta-over-baseline value less than 5. RESULTS: Thirty-two patients were recruited for group A and thirty-three patients in group B. Eradication rates were 93.7% (30/32) and 90.9% (30/33), respectively, at intention-to-treat analysis, and 96.6% (29/30) and 93.3% (28/30), respectively, at per-protocol analysis. Adverse events occurred in 26 patients and led to the suspension of treatment in one patient in group A and in one patient in group B. CONCLUSION: The results showed that Pylera® plus a PPI or ranitidine were equally effective in the population studied. The high cure rates of bismuth triple therapy (without an antisecretory drug) and the lack of susceptibility testing make it impossible to exclude the possibility that the results would have been similar if neither the PPI nor the ranitidine were given.


Assuntos
Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Ranitidina/administração & dosagem , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antiulcerosos/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Esomeprazol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ranitidina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
J Exp Clin Cancer Res ; 38(1): 209, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31113478

RESUMO

Growing preclinical evidence shows that short-term fasting (STF) protects from toxicity while enhancing the efficacy of a variety of chemotherapeutic agents in the treatment of various tumour types. STF reinforces stress resistance of healthy cells, while tumor cells become even more sensitive to toxins, perhaps through shortage of nutrients to satisfy their needs in the context of high proliferation rates and/or loss of flexibility to respond to extreme circumstances. In humans, STF may be a feasible approach to enhance the efficacy and tolerability of chemotherapy. Clinical research evaluating the potential of STF is in its infancy. This review focuses on the molecular background, current knowledge and clinical trials evaluating the effects of STF in cancer treatment. Preliminary data show that STF is safe, but challenging in cancer patients receiving chemotherapy. Ongoing clinical trials need to unravel if STF can also diminish toxicity and increase efficacy of chemotherapeutic regimes in daily practice.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Jejum , Neoplasias/dietoterapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Neoplasias/patologia , Qualidade de Vida
20.
Biomed Res Int ; 2019: 1283824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119149

RESUMO

Drug-induced liver injury (DILI) is a major concern in clinical studies as well as in postmarketing surveillance. It is necessary to establish an animal model of DILI for thorough investigation of mechanisms of DILI and searching for protective medications. This article reviews the current status and future perspective on establishment of DILI models based on different hepatotoxic drugs, as well as the underlying mechanisms of liver function damage induced by specific medicine. Therefore, information from this article can help researchers make a suitable selection of animal models for further study.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Humanos , Imunossupressão/efeitos adversos , Fígado/patologia , Tetraciclina/efeitos adversos , Tetraciclina/uso terapêutico
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