Sustained-release and swelling characteristics of xanthan gum/ethylcellulose-based injection moulded matrix tablets: in vitro and in vivo evaluation

Sustained-release matrix tablets were developed by injection moulding using metoprolol tartrate (MPT) and ethylcellulose (EC) as sustained-release agent. Dibutyl sebacate was selected as plasticiser. The influence of matrix composition, plasticiser concentration, and drug load on drug release was evaluated. The influence of plasticiser addition was assessed on processability and drug release: Dibutyl sebacate was added to a dichloromethane/EC solution and subsequently spray-dried, or was mixed as a liquid with EC powder. Hydrated tablets were evaluated by frequency sweep and creep rheological tests to correlate the results with drug release. Xanthan gum (XG) was added to the formulation because drug release was too slow (< 50%, 24 h) from EC/MPT matrices (70%/30%, w/w). Increasing XG concentrations provided faster MPT release rates characterised by zero-order release kinetics, no burst release was observed. Lower plasticiser concentrations and higher drug loads increased drug release substantially. The plasticiser addition method did not affect drug release. Matrix composition, drug load, and plasticiser level affected the rheological properties of the swollen matrix tablets. X-ray diffraction demonstrated the formation of solid dispersions. Formulations composed of XG/EC (ratio 1:1.5) and 30% (w/w) MPT had a low relative bioavailability compared with the commercial product Lopressor®, which significantly improved at higher MPT concentration (50%, w/w).     

Impact of wearing personal protective equipment on the performance and decision making of surgeons during the COVID-19 pandemic: An observational cross-sectional study

During the coronavirus disease 2019 (COVID-19) pandemic, the mandatory use of personal protective equipment (PPE) has resulted in a significant reduction in the infection rate among health care workers (HCWs). However, there are some ongoing concerns about the negative impact of using PPE for prolonged periods.This study examined the impact of wearing PPE on surgeons’ performance and decision making during the COVID-19 pandemic.In this cross-sectional study, an anonymous online questionnaire was created and disseminated to surgeons all over the Eastern Province of Saudi Arabia. The questionnaire included the demographic data, the local hospital policies, the non-technical skills (e.g., communication, vision, and comfort) and the technical skills, and the process of decision making.From June 2020 to August 2020, 162 surgeons participated in this questionnaire. Of them, 80.2% were aged from 26 to 45 years, 70.4% have received a special training for PPE, and 59.3% of participants have operated on COVID-19 confirmed cases. A negative impact of wearing PPE was reported on their overall comfort, vision, and communication skills (92.6%, 95.1%, and 82.8%, respectively). The technical skills and decision making were not significantly affected (60.5% and 72.8%, respectively). More preference for conservative approach, damage control procedures, and/or open approach was reported.Despite its benefits, PPE is associated with a significant negative impact on the non-technical skills (including vision, communication, and comfort) as well as a non-significant negative impact on technical skills and decision making of surgeons. Extra efforts should be directed to improve PPE, especially during lengthy pandemics.     

Scaling up cancer care for children without medical insurance in developing countries: The case of Mexico

Background

In 2006, the Mexican government launched the Fund for Protection Against Catastrophic Expenditures (FPGC) to support financially healthcare of high cost illnesses. This study aimed at answering the question whether FPGC improved coverage for cancer care and to measure survival of FPGC affiliated children with cancer.

Procedure

A retrospective cohort study (2006–2009) was conducted in 47 public hospitals. Information of children and adolescents with cancer was analyzed. The coverage was estimated in accordance with expected number of incident cases and those registered at FPGC. The survival was analyzed by using Kaplan–Meier survival curves and Cox proportional hazards regression modeling.

Results

The study included 3,821 patients. From 2006 to 2009, coverage of new cancer cases increased from 3.3% to 55.3%. Principal diagnoses were acute lymphoblastic leukemia (ALL, 46.4%), central nervous system (CNS) tumors (8.2%), and acute myeloid leukemia (AML, 7.4%). The survival rates at 36 months were ALL (50%), AML (30.5%), Hodgkin lymphoma (74.5%), Non‐Hodgkin lymphoma (40.1%), CNS tumors (32.8%), renal tumors (58.4%), bone tumors (33.4%), retinoblastoma (59.2%), and other solid tumors (52.6%). The 3‐year overall survival rates varied among the regions; children between the east and south‐southeast had the higher risks (hazard ratio 3.0; 95% CI: 2.3–3.9) and 2.4; 95% CI: 2.0–2.8) of death from disease when compared with those from the central region.

Conclusion

FPGC has increased coverage of cancer cases. Survival rates were different throughout the country. It is necessary to evaluate the effectiveness of this policy to increase access and identify opportunities to reduce the differences in survival. Pediatr Blood Cancer 2013;60:196–203. © 2012 Wiley Periodicals, Inc.     

Guidelines for the management of vitiligo: the European Dermatology Forum consensus

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence‐based and expert‐based recommendations (S1 level).     

A comprehensive intervention for adverse drug reactions identification and reporting in a Pediatric Emergency Department

Background Physicians identify from 45.7 to 96.2 % of Adverse Drug Reactions (ADRs) in their patients, with under-reporting ranging from 6 to 100 %. In order to improve ADR reporting, several interventions have been evaluated in different studies, but not with regard to ADR identification. In addition, it is not known whether some patient characteristics might influence on ADR identification and reporting by physicians. Objectives (a) To assess the effectiveness of a comprehensive intervention directed to Emergency Department physicians and coordinated by a pharmacist in a tertiary care pediatric hospital on ADR identification and reporting. (b) To assess if some of the children’s characteristics might influence on ADR identification and reporting. Setting The Emergency Department of the Hospital Infantil de México “Federico Gómez”, which is a national pediatric institute of health in México. Methods A Quasi-experimental, pre-post test trial was designed. During the intervention, the pharmacist gave talks on Pharmacovigilance and on the program for electronic capture of data, took part in patient visits, left reminders, improved accessibility to ADR report format and performed feedback activities. To classify and quantify correctly identified ADRs and ADRs reported to the Institutional Pharmacovigilance Center (IPC), 1136 clinical records were reviewed. The models were adjusted for patient variables. Main outcome measures Total ADRs, ADRs correctly identified by physicians, ADRs reported to the IPC by physicians. Results Before the intervention, 97 % of ADRs were correctly identified and 6.1 % reported by physicians. During the intervention, 99.6 % were correctly identified and 41.2 % were reported, and after the intervention, 99.6 and 41.7 %, respectively. Identification during the intervention showed a sevenfold increase with regard to preintervention and was maintained post-intervention. ADR reporting during the intervention showed a 14-fold increase with regard to pre-intervention and was maintained during post-intervention. Conclusion Physicians do identify ADRs, but fail to report them. The intervention increased ADR correct identification and reporting. The effect was maintained after the intervention.     

Grover's disease in patients with chronic renal failure receiving hemodialysis: clinicopathologic review of 4 cases

In 4 patients undergoing hemodialysis for chronic renal failure, a transient or persistent, papular and keratotic eruption developed on the trunk and arms. Histologic examination disclosed focal acantholysis with dyskeratosis. The lesions were clinically and histologically indistinguishable from those of Grover's disease. A possible association with Grover's disease and chronic renal failure and/or hemodialysis is postulated. Possible implicated pathogenic mechanisms are discussed. We suggest that Grover's disease should be included in the differential diagnosis of cutaneous eruptions in patients with chronic renal failure.     

Adverse cutaneous reactions to anakinra in patients with rheumatoid arthritis: clinicopathological study of five patients

BACKGROUND: Anakinra, a recombinant human form of interleukin-1 receptor antagonist, is used to treat patients with active rheumatoid arthritis (RA). OBJECTIVES: To report five patients with cutaneous adverse drug reactions due to anakinra and to evaluate the histopathological and immunohistochemical findings with the aim of understanding the possible mechanisms involved. METHODS: Five patients of a series of 10 patients with RA undergoing treatment with anakinra in a clinical trial presented inflammatory lesions at the anakinra injection sites. In each case, clinical features were recorded and skin biopsy specimens were obtained. In one patient sequential biopsy specimens were obtained from skin lesions at different stages of development. Tissue sections of the biopsy specimens were stained with haematoxylin and eosin and May-Grünwald-Giemsa, and were immunoreacted with antibodies to leucocyte common antigen, CD68, CD3, CD45RO, CD20 and CD45RA. RESULTS: The onset of reaction was within the first month of treatment and appeared as well-defined erythema and oedema involving the injection sites. In two patients the treatment had to be discontinued because of the skin reaction, and in one patient it was associated with systemic involvement. All biopsy specimens exhibited marked dermal oedema and a lichenoid dermal infiltrate composed mainly of lymphomononuclear cells with prominent populations of eosinophils and large CD68+ dermal macrophages and an increase in the number of mast cells, which were spindle shaped in a significant proportion. CONCLUSIONS: Cutaneous toxicity is a frequent, usually well-tolerated complication of treatment with anakinra in patients with RA, although in some cases it can be associated with systemic involvement. The most relevant histopathological findings include dermal oedema and a lichenoid, perivascular and periadnexal predominantly lymphomononuclear infiltrate, with many eosinophils and the presence of enlarged CD68+ macrophages. These findings resemble those seen in skin reactions in patients receiving chemotherapy and colony-stimulating factors. We also found an increase in mast cell numbers that could be a specific effect of anakinra.     

Erythroderma due to ribostamycin

A 48-year-old man became erythrodermatous after intramuscular administration of ribostamycin, an aminoglycoside antibiotic in the same family as neomycin. Patch tests were positive to ribostamycin and neomycin, as well as to mercurials. There was no mercurial preservative in the injection solution. A lymphocyte transformation test was positive for ribostamycin and tobramycin, but not for gentamycin. Diagnostic and structure-activity relationship aspects of the case are discussed.