Purpose - Fused deposition modeling (FDM) is a layer by layer technology with the potential to create complex and individual parts from thermoplastic materials such as ABS. The use of Polylactic acid ...(PLA) and tricalcium phosphate (TCP) as resorbable composite is state of the art in tissue engineering and maxillofacial surgery. The purpose of this paper is to evaluate the processing conditions and the performance of parts (e.g. mechanical properties) manufactured with a FDM machine.Design methodology approach - In this paper, the general suitability of PLA for the processing with FDM is evaluated and material specific effects (e.g. crystallization and shrinkage) are shown. Therefore, the characterization of the semi-crystalline biodegradable material by thermal, mechanical and microscopic analysis is carried out.Findings - Facts, which affect the functional properties of the samples, are analyzed. Among them, the processing temperature and sample size significantly affect the morphology of the final components. Components from PLA TCP with sufficient mechanical properties for their potential use as scaffolds are obtained.Originality value - Thus, the paper shows that by thermal analysis it is possible to identify major influences on processing and part properties.
The high cost of fidaxomicin has restricted its use despite the benefit of a lower
Clostridioides difficile
infection (CDI) recurrence rate at 4 weeks of follow-up. This short follow-up represents ...the main limitation of pivotal clinical trials of fidaxomicin, and some recent studies question its benefits over vancomycin. Moreover, the main risk factors of recurrence after treatment with fidaxomicin remain unknown. We designed a multicentre retrospective cohort study among four Spanish hospitals to assess the efficacy of fidaxomicin in real life and to investigate risk factors of fidaxomicin failure at weeks 8 and 12. Two-hundred forty-four patients were included. Fidaxomicin was used in 96 patients (39.3%) for a first episode of CDI, in 95 patients (38.9%) for a second episode, and in 53 patients (21.7%) for a third or subsequent episode. Patients treated with fidaxomicin in a first episode were younger (59.9 years vs 73.5 years), but they had more severe episodes (52.1% vs. 32.4%). The recurrence rates for patients treated in the first episode were 6.5% and 9.7% at weeks 8 and 12, respectively. Recurrence rates increased for patients treated at second or ulterior episodes (16.3% and 26.4% at week 8, respectively). Age greater than or equal to 85 years and having had a previous episode of CDI were identified as recurrence risk factors at weeks 8 and 12. We conclude that the outcomes with fidaxomicin in real life are at least as good as those observed in clinical trials despite a more demanding evaluation. Be it 85 years of age or older, and the use after a first episode appears to be independent factors of CDI recurrence after treatment with fidaxomicin.
The adverse events associated with bevacizumab therapy are characterized, and the underlying pathophysiology, risk factors, frequency, and management of these events are described.
The adverse events ...associated with bevacizumab include hypertension, proteinuria, thromboembolism, impaired wound healing, bleeding, perforation, reversible leukoencephalopathy syndrome, skin rash, and infusion-related hypersensitivity reactions. Patients should be monitored for these events throughout the course of bevacizumab therapy. Hypertension is by far the most common adverse event associated with bevacizumab. Blood pressure should be routinely monitored, and hypertension should be medically managed with antihypertensive drugs as deemed appropriate during bevacizumab therapy. Patients should be monitored for proteinuria every three to four weeks, and bevacizumab should be discontinued with persistent proteinuria of >2+. Thromboembolic events, impaired wound healing, bowel and nasal septum perforation, and bleeding share similar pathophysiology. Thromboembolic events should be managed in accordance with guidelines established by the American College of Chest Physicians, and bevacizumab should be discontinued for new life-threatening venous or arterial thromboembolism. To minimize the risk of bleeding or impaired wound healing, bevacizumab should be started at least four weeks after surgery or discontinued for at least six to eight weeks before elective surgery. The management of other adverse events is more anecdotal, with relatively few reports of their occurrence with bevacizumab.
Many of the potential serious complications of bevacizumab can be averted by close monitoring of patient-specific variables, which should be measured at baseline and then at predetermined intervals throughout the course of therapy to maximize patient safety.
Interprofessional care is exhibited in outpatient oncology practices where practitioners from a myriad of specialties (e.g., oncology, nursing, pharmacy, health informatics and others) work ...collectively with patients to enhance therapeutic outcomes and minimize adverse effects. Historically, most ambulatory-based anticancer medication therapies have been administrated in infusion clinics or physician offices. Oral anticancer medications (OAMs) have become increasingly prevalent and preferred by patients for use in residential or other non-clinic settings. Self-administration of OAMs represents a significant shift in the management of cancer care and role responsibilities for patients and clinicians. While patients have a greater sense of empowerment and convenience when taking OAMs, adherence is a greater challenge than with intravenous therapies. This paper proposes use of a qualitative systems evaluation, based on theoretical frameworks for interdisciplinary team collaboration and systems science, to examine the social interactionism involved with the use of intravenous anticancer treatments and OAMs (as treatment technologies) by describing patient, organizational, and social systems considerations in communication, care, control, and context (i.e., Kaplan's 4Cs). This conceptualization can help the healthcare system prepare for substantial workforce changes in cancer management, including increased utilization of oncology pharmacists.
Tyrosine kinase inhibitor therapy is an established standard of care for patients with NSCLC with EGFR mutations, but a worse prognosis has been observed in patients with specific EGFR exon-20 ...insertion mutations. Mobocertinib (TAK-788) is a novel tyrosine kinase inhibitor developed to target EGFR exon-20 insertion and has exhibited promising response rates and acceptable safety in phase 1 and 2 trials. We report a case of a 59-year-old woman with metastatic NSCLC and EGFR exon-20 mutation responsive to mobocertinib therapy, who developed severe depression and catatonia approximately 4 months after mobocertinib initiation, ultimately necessitating its permanent discontinuation. Given the observed severe depression in this case report, we recommend that, for patients on mobocertinib who develop neuropsychiatric adverse effects, strong consideration should be given for dose interruption or discontinuation.
Abstract
Background
Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine ...estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.
Methods
Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.
Results
The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047, and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009, with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).
Conclusions
Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
The aim of this transversal study was to describe the virological and immunological features of HIV-infected youths transferred from pediatric to adult care units since 1997 vs. the non-transferred ...patients from the Madrid Cohort of HIV-infected children and adolescents in Spain. We included 106 non-transferred and 184 transferred patients under clinical follow-up in 17 public hospitals in Madrid by the end of December 2017. Virological and immunological outcomes were compared in transferred vs. non-transferred patients. ART drug resistance mutations and HIV-variants were analyzed in all subjects with available resistance pol genotypes and/or genotypic resistance profiles. Among the study cohort, 133 (72.3%) of 184 transferred and 75 (70.7%) of 106 non-transferred patients had available resistance genotypes. Most (88.9%) of transferred had ART experience at sampling. A third (33.3%) had had a triple-class experience. Acquired drug resistance (ADR) prevalence was significantly higher in pretreated transferred than non-transferred patients (71.8% vs. 44%; p = 0.0009), mainly to NRTI (72.8% vs. 31.1%; p < 0.0001) and PI (29.1% vs. 12%; p = 0.0262). HIV-1 non-B variants were less frequent in transferred vs. non-transferred (6.9% vs. 32%; p < 0.0001). In conclusion, the frequent resistant genotypes found in transferred youths justifies the reinforcement of HIV resistance monitoring after the transition to avoid future therapeutic failures.
Summary
Little data are available on renal toxicity exerted by direct‐acting antivirals (DAAs) in real life. The aim of this study was to assess the impact of direct‐acting antivirals against ...hepatitis C virus infection currently used in Spain and Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise. From an international, prospective multicohort study, patients treated with DAAs for at least 12 weeks and with eGFR ≥30 mL/min per 1.73 m2 at baseline were selected. eGFR was determined using the CKD‐EPI formula. A total of 1131 patients were included; 658 (58%) were HIV/HCV‐coinfected patients. Among the 901 patients treated for 12 weeks, median (interquartile range) eGFR was 100 (87‐107) at baseline vs 97 (85‐105) mL/min per 1.73 m2 at week 12 of follow‐up (FU12) post‐treatment (P < .001). For HIV‐coinfected subjects who received tenofovir plus a ritonavir‐boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104 (86‐109) vs 104 (91‐110) mL/min per 1.73 m2 (P = .913). Among subjects receiving ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented with eGFR <30 mL/min per 1.73 m2. In conclusion, eGFR slightly declines during therapy with all‐oral DAAs and this effect persists up to 12 weeks after stopping treatment in subjects with normal to moderately impaired renal function, regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to have an impact on eGFR.
An overview of therapeutic oncology biosimilars, the U.S. biosimilars regulatory pathway, and the clinical development of selected biosimilar products is provided, including discussion of ...considerations in adopting biosimilars into oncology practice.
Biosimilars are biologic agents that are highly similar to and have no clinically meaningful differences from an approved reference product in terms of safety, purity, and potency. There is a large market for cancer biologics, and approval of biosimilars has the potential to increase access to care and reduce costs. An abbreviated regulatory pathway for the development and approval of biosimilars defines a stepwise approach to demonstrating biosimilarity and conducting clinical comparative trials to confirm equivalent pharmacokinetics, efficacy, safety, and immunogenicity to the reference product. Three therapeutic biologics (bevacizumab, trastuzumab, and rituximab) have been used extensively in the treatment of a variety of cancers and are targets for biosimilar product development. Preclinical and clinical experience with 2 recently approved biosimilars to bevacizumab and trastuzumab is reviewed. Challenges faced by pharmacy and therapeutics committees when considering oncology biosimilars for formulary inclusion are discussed.
Increased adoption of biosimilars could potentially lower treatment costs and improve access to biologics for patients with cancer. Key considerations in formulary review of biosimilars include the quality and quantity of data from comparative clinical trials, economic factors, manufacturer reliability, and challenges associated with incorporating biosimilars into practice.
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