- Epidemiological and clinical features of visceral leishmaniasis in children in Alicante Province, Spain. [Journal Article]
- PIPaediatr Int Child Health 2018 May 23; :1-6
- Background Visceral leishmaniasis (VL) is endemic to the Mediterranean basin. In children, VL often presents with non-specific symptoms and can be life-threatening without proper treatment. Aim To de...
Background Visceral leishmaniasis (VL) is endemic to the Mediterranean basin. In children, VL often presents with non-specific symptoms and can be life-threatening without proper treatment. Aim To describe the epidemiological and clinical features of pediatric VL in children in Alicante, Spain. Methods The study included all paediatric (<15 years) cases admitted to three hospitals in the province of Alicante from May 1992 to May 2015 with diagnosis of VL (detection was either by anti-Leishmania antibodies in serology or Leishmania in blood and/or bone marrow aspirates). Results There were 38 cases of pediatric VL (18 aged <24 months, 15 aged 24-59 months and 5 aged ≥5 years). The main symptoms were fever (97.4%), followed by pallor (75.0%) and loss of appetite (46.4%). Eighty-seven per cent of patients were anaemic (haemoglobin < 9 g/dL), 73.7% had neutropenia and 68.4% had thrombocytopenia. Before 2004, 92.3% of patients were treated with meglumine antimoniate (MA) and 7.7% with liposomal amphotericin B (LAmB); after 2004, 84% were treated with LAmB and just one (16%) with MA (p < 0.001). LAmB performed better than MA in terms of mean treatment length (7.4 days vs 25.9 days, p < 0.001), time to becoming afebrile (1.7 vs 13.7 days, p < 0.001), and length of hospital stay (10.9 vs 19.4 days, p = 0.001). Conclusion Paediatric VL in Alicante mainly affects children under five. Children aged ≤24 months present with a lower haemoglobin and white blood cell count. Treatment with LAmB reduces treatment length, time to becoming afebrile and length of hospital stay.
- Gemcitabine and cisplatin regimen facilitates prognosis of advanced nasopharyngeal carcinoma. [Journal Article]
- CMCancer Med 2018 May 23
- This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. ...
This study was conducted to assess the efficacy and adverse effects of GP (gemcitabine + cisplatin) regimen and FP (fluouracil + cisplatin) regimen in treatment of advanced nasopharyngeal carcinoma. Systematic online searches were performed in PubMed, Web of Sciences, China Knowledge Infrastructure and Weipu from the inception to November 15, 2017. Potential studies were assessed using the Cochrane risk of bias scale. Statistical analyses were performed on Stata 14.0 and RevMan 5.3. Finally, twelve studies entered final qualitative synthesis and quantitative analysis. The GP regimen compared with the FP regimen had significantly higher 1-year survival rate (relative risk (RR) = 1.07, 95% confidence interval (CI): 1.01-1.13), significantly better performance in the fixed-effect model (RR = 1.16, 95%CI: 1.04-1.30) and significantly higher remission rate (RR = 1.17, 95%CI: 1.05-1.29). Significant differences between regimens were found in gastrointestinal effects (RR = 0.58, 95%CI: 0.45-0.74). No significant differences between regimens were found in reduced hemoglobin rate (RR = 0.55, 95%CI: 0.36-1.21), neutropenia (RR = 1.84, 95%CI: 0.93-5.02), or reduced platelet (RR = 1.25, 95%CI: 0.85-1.75) and mucosal inflammation (RR = 0.81, 95%CI: 0.57-1.16). Sensitivity analysis indicated the results remained stable. The funnel plot indicated some publication bias. In conclusion, the GP regimen outperforms the FP regimen in treatment of advanced nasopharyngeal carcinoma with no difference in adverse effects. We may consider the GP regimen a better choice, but this conclusion should be confirmed by high-quality trials.
- Antiviral combination therapy for cytomegalovirus infection in high-risk infants. [Journal Article]
- ATAntivir Ther 2018 May 23
- CONCLUSIONS: Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.
- Failure of voriconazole therapy due to acquired azole resistance in Aspergillus fumigatus in a kidney transplant recipient with chronic necrotizing aspergillosis. [Case Reports]
- AJAm J Transplant 2018 May 22
- Invasive aspergillosis (IA) affects lungs and disseminates mostly in patients with neutropenia and/or receiving immunosuppressive and steroid therapies. Despite progress in diagnosis and therapy of I...
Invasive aspergillosis (IA) affects lungs and disseminates mostly in patients with neutropenia and/or receiving immunosuppressive and steroid therapies. Despite progress in diagnosis and therapy of IA, it is still characterized by a high mortality rate. Currently, voriconazole is considered as the standard therapy for invasive aspergillosis. Over the recent years, triazole resistant Aspergillus fumigatus isolates have emerged in the environment due to the use of fungicidal agricultural products with the risk of developing IA related to a resistant isolate. However, resistance may also develop in patient under long-term triazole therapy, particularly in the setting of chronic forms of pulmonary aspergillosis. We here describe a kidney transplant recipient who failed voriconazole therapy due to acquired resistance secondary to the appearance of a de novo mutation (Y121F) in the cyp51A gene during chronic necrotizing pulmonary aspergillosis. The infecting isolate acquired voriconazole resistance in eight months despite plasma concentrations within recommended range of the drug necessitating lobectomy in association with a new antifungal strategy consisting of liposomal amphotericin and caspofungin with a good outcome over 36 months. This article is protected by copyright. All rights reserved.
- Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial. [Journal Article]
- JHJ Hematol Oncol 2018 May 22; 11(1):69
- CONCLUSIONS: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations.
- TPMT testing in azathioprine: a 'cost-effective use of healthcare resources'? [Journal Article]
- PMPer Med 2009; 6(1):103-113
- This study aimed to critically appraise the current level of economic evidence available for thiopurine S-methyltransferase (TPMT) testing of thiopurine drugs, such as azathioprine. Six economic eval...
This study aimed to critically appraise the current level of economic evidence available for thiopurine S-methyltransferase (TPMT) testing of thiopurine drugs, such as azathioprine. Six economic evaluations of testing were identified, which all recommended that TPMT testing is a cost-effective use of healthcare resources. Critical appraisal, using published guidelines, showed potential limitations in model structures, approaches to data analysis and input parameters, which were mainly based on expert opinion. Where data did exist these were from retrospective studies. To conduct economic evaluations with more robust findings, decision analysts need good quality data for the following key parameters: current prevalence of profound neutropenia among patients prescribed thiopurine drugs; mean length of related hospitalization and clinical outcome; impact of introducing the test on clinical pathways in terms of resource use; and clinical effectiveness data in terms of number of cases of neutropenia averted and subsequent impact on mortality and health-related quality of life. An iterative approach may be used to stimulate the production of a sufficient evidence base for innovative technologies, such as pharmacogenetic testing. Such an iterative approach involves starting with simple models using available existing clinical and resource use data, as in the case of TPMT testing. The use of formal value of information methods may guide the decision whether prospective studies are required to address uncertainties in the key parameters driving the model results. The results from well-designed prospective studies can then be used to populate more complex economic models.
- Phase I study of the checkpoint kinase 1 inhibitor GDC-0575 in combination with gemcitabine in patients with refractory solid tumors. [Journal Article]
- AOAnn Oncol 2018 Feb 23
- CONCLUSIONS: GDC-0575 can be safely administered as a monotherapy and in combination with gemcitabine; however, overall tolerability with gemcitabine was modest. Hematological toxicities were frequent but manageable. Preliminary antitumor activity was observed but limited to a small number of patients with a variety of refractory solid tumors treated with GDC-0575 and gemcitabine.
- PEGylated IL-11 (BBT-059): A Novel Radiation Countermeasure for Hematopoietic Acute Radiation Syndrome. [Journal Article]
- HPHealth Phys 2018; 115(1):65-76
- Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed ...
Interleukin-11 was developed to reduce chemotherapy-induced thrombocytopenia; however, its clinical use was limited by severe adverse effects in humans. PEGylated interleukin-11 (BBT-059), developed by Bolder Biotechnology, Inc., exhibited a longer half-life in rodents and induced longer-lasting increases in hematopoietic cells than interleukin-11. A single dose of 1.2 mg kg of BBT-059, administered subcutaneously to CD2F1 mice (12-14 wk, male) was found to be safe in a 14 d toxicity study. The drug demonstrated its efficacy both as a prophylactic countermeasure and a mitigator in CD2F1 mice exposed to Co gamma total-body irradiation. A single dose of 0.3 mg kg, administered either 24 h pre-, 4 h post-, or 24 h postirradiation increased the survival of mice to 70-100% from lethal doses of radiation. Preadministration (-24 h) of the drug conferred a significantly (p < 0.05) higher survival compared to 24 h post-total-body irradiation. There was significantly accelerated recovery from radiation-induced peripheral blood neutropenia and thrombocytopenia in animals pretreated with BBT-059. The drug also increased bone marrow cellularity and megakaryocytes and accelerated multilineage hematopoietic recovery. In addition, BBT-059 inhibited the induction of radiation-induced hematopoietic biomarkers, thrombopoietin, erythropoietin, and Flt-3 ligand. These results indicate that BBT-059 is a promising radiation countermeasure, demonstrating its potential to be used both pre- and postirradiation for hematopoietic acute radiation syndrome with a broad window for medical management in a radiological or nuclear event.
- Meta-analysis examining the epidemiology of clozapine-associated neutropenia. [Journal Article]
- APActa Psychiatr Scand 2018 May 21
- CONCLUSIONS: Severe neutropenia associated with clozapine is a rare event and occurs early with a substantial decline in risk after one year of exposure. Death from clozapine-associated neutropenia is extremely rare. Implications for haematological monitoring are discussed.
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- Comparison of efficacy and toxicity of second-line combination chemotherapy regimens in patients with advanced urothelial carcinoma. [Journal Article]
- IJInt J Clin Oncol 2018 May 21
- CONCLUSIONS: Combination chemotherapy with either GP or GD was a favorable and well-tolerated second-line treatment regimen for patients with advanced or metastatic UC following the failure of a platinum-based regimen. Further study using a large prospective cohort is needed to identify patients who will benefit from second-line combination therapy.