Relationship between beliefs about medicines and adherence in elderly patients with cardiovascular and respiratory diseases: A cross-sectional study in Romania

ObjectivesThe aim of this study was to explore elderly patients’ beliefs about medicines in general, and specific towards their treatment and the relationship between beliefs and adherence.MethodsA cross-sectional study was performed by administering a questionnaire developed to meet the study’s objectives. Elderly patients were recruited from three different settings.Results167 patients agreed to participate to our study, having a mean age of 73 years. Patients were aware of the necessity for treatment, but they also showed concern over the potential for the adverse outcomes. Only 15% of the patients were completely accepting their treatment having high necessity and low concerns, while 40% were ambivalent, having high necessity beliefs, but also high concerns, with 89% being adherent in this group. Overall, higher adherence was significantly correlated with higher necessity and with higher necessity-concern differential.ConclusionPatients beliefs have an impact on adherence, thus patients’ concerns and necessities should be addressed in order to improve adherence and treatment outcome.Practice implicationsHigher necessity positively influenced adherence to treatment, suggesting the fact that healthcare professionals could improve patients’ adherence by outlining and educating the patients on the necessity of the treatment, while also managing patients’ concerns.     

The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination

Objectives: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations.

Methods: The oral tablets were made by using a Christ freeze-dryer alpha 2–4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams.

Results: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets.

Conclusion: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the ‘codrug’ complex, which do not affect the release of the bioactive compounds.     

Natural killer cell–derived extracellular vesicles in cancer therapy

Cancer is a major cause of death in the industrialized world. New therapies are constantly being developed in order to reduce morbidity and mortality. NK cell–based cellular therapies have shown effect against haematological malignancies, but it has been difficult to target solid tumours due to low NK cell infiltration of the tumour and efficient tumour evasion strategies. NK cells release extracellular vesicles that naturally contain cytolytic proteins and tumour-targeting molecules. These vesicles can directly interact with and kill malignant cells, and their small size could allow more efficient extravasation into the tumour tissue. Extracellular vesicles are also less sensitive to the hostile tumour microenvironment compared to cells. Based on their features, NK cell–derived extracellular vesicles represent promising novel tools in oncology. In this review, we summarize the current available literature on NK cell–derived extracellular vesicles and discuss how they may be utilized in therapy for solid tumours.     

Acute diarrhea associated with Cyclospora cayetanensis

Acute diarrhea is a major problem with high morbidity and mortality rates in developing countries, especially in children. Complex laboratory investigations are required to define the etiology because of the broad spectrum of etiological agents and the non-specific clinical signs. In the last decade, Cyclospora cayetanensis--a new acid-fast coccidian species--was pointed to be the cause of watery self-limited or prolonged diarrhea in immunocompetent and immunocompromised patients, with very good evolution after treatment with co-trimoxazole. Unlike Cryptosporidium parvum, nonsporulated Cyclospora oocysts are eliminated in feces, with no risk of human to human transmission. Cyclospora cayetanensis is widely spread, producing endemic infections, in Asia and South America and was reported to produce infections in foreign travellers in these areas and epidemic outbreaks of foodborne diarrhea. We describe the first case of acute diarrhea associated with Cyclospora cayetanensis in an immunocompetent child admitted to Ia?i "Sf. Maria" Hospital.     

Dynamic changes in clinical features and cytokine/chemokine responses in SARS patients treated with interferon alfacon-1 plus corticosteroids

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged in early 2003 as a major international health crisis. We report on serum cytokine levels, viral load and clinical parameters over the course of the disease in a cohort of nine adult SARS patients treated with steroids and interferon alfacon-1 at North York General Hospital in Toronto, Ontario. Considerable variation among SARS patients with respect to circulating viral load and patterns of SARS-CoV-evoked cytokine responses was recorded. No single cytokine profile was observed in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels during the course of the disease in all patients. Expression levels for IL-10, IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL-12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently highest within 5 days of peak viral load. These results suggest that elevated levels of inflammatory cytokines are sensitive correlates of disease severity, including lung abnormalities and viral load in serum, and may provide a tool for monitoring disease progression in affected individuals.     

The concentration of alpha-1-antitrypsin in cerebrospinal fluid and serum in a series of 40 intracranial tumors.

Forty patients with histologically proved intracranial tumors were submitted to preoperative lumbar and venous punctures. The concentration of alpha-1-antitrypsin in the serum and in cerebrospinal fluid was determined by radial immunodiffusion technique. In the series, both serum and cerebrospinal fluid alpha-1-antitrypsin concentrations are significantly higher than the mean normal values. No statistical differences are observed in serum alpha-1-antitrypsin levels between benign and malignant tumors, but cerebrospinal fluid alpha-1-antitrypsin is significantly increased in the group of malignant tumors if cases undergoing steroid treatment are excluded. The diagnostic value of alpha-1-antitrypsin determinations in groups of patients with intracranial tumors is suggested.     

Indomethacin-loaded polymer nanocarriers based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane): preparation, in vitro and in vivo evaluation

The study is focused on the development of copolymers based on poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane). The macromolecular compounds were synthesized by dispersion polymerization in the presence of the radical initiator 4,4'-azobis(cyanopentanoic acid) and using sodium lauryl sulfate as tensioactive compound and poly(aspartic acid) (PAS) as protective colloid. PAS presents biocompatibility and biodegradability, and assures the increase of the absorbent character for the new synthesized network, and also, can supplement the hydrogen bonds contributing to the stability of the achieved complexes. The prepared polymeric networks were characterized by FTIR, SEM, and thermogravimetric analyses. The dependence on the pH of the swelling degree equilibrium was also evaluated correlated also with different temperature values. The poly(2-hydroxyethyl methacrylate-co-3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]-undecane) copolymers were evaluated as matrix for indomethacin (INN) as model drug loaded onto these polymeric networks. The evaluation of the homogeneity distribution of the INN drug in polymeric network was made by near infrared chemical imaging (NIR-CI) and correspondingly statistical analysis. The pharmacokinetic profile was achieved performing the in vitro release of the INN drug from the polymeric network. The data resulted from the in vivo experimental studies, respectively the biocompatibility tests, somatic nociceptive experimental model (Tail flick test) and visceral nociceptive experimental model (Writhing test)-are also reported in the study.     

Alloantibodies and the outcome of cadaver kidney allografts

The role of humoral immunity in causing antibody-mediated rejection (AMR) of organ allografts has been extensively documented. For this reason, negative complement-dependent cytotoxicity (CDC) cross-matches between recipient sera and donor T and B lymphocytes have become a mandatory requirement for cadaveric kidney transplantation. However, the significance of donor-specific antibodies (DSAs) detectable only by flow cytometry (FC) or solid phase assays (SPA) but not CDC is still controversial. We have performed a retrospective analysis of FC cross-matching results in 80 consecutive cadaver kidney allograft recipients. Antibodies against HLA class I and class II antigens were measured by CDC and SPA in sequential samples of sera obtained prior to transplantation. The preoperative cross-match was performed by CDC using magnetically sorted T and B cells from donor spleen. Sera obtained from each patient before and at the time of transplantation were included in the final cross-match. The sample of serum obtained at the time of transplantation was cross-matched retrospectively by FC and analyzed for anti-HLA antibody specificity on high resolution SPA. The actuarial kidney allograft survival at one year was 98%. Two of these eighty patients lost the graft, one due to AMR, the other for reasons unrelated to DSAs. Donor-specific antibodies were detected by FC in 17 of 80 patients, yet only 6 of 17 had an early episode of AMR. This episode was successfully reversed by desensitization therapy using intravenous immunoglobin (IVIG) and plasmapheresis. Flow cytomery cross-matching showed 95% specificity but only 35% sensitivity for prediction of AMR (p = 0.002). There was a significant correlation between high panel reactive antibodies (PRA) and positive FC cross-matching (p = 0 .0001), as well as high PRA and AMR (p = 0.0004 by CDC and 0.0011 by Luminex). Reversible AMR occurred 12-30 days post-transplantation in 8 patients. Of these 8 patients, 3 had no detectable DSAs in spite of C4d positivity, 4 had C4d deposition in conjunction with anti-HLA antibodies, and 1 patient had DSAs (anti-MICA) yet no C4d deposition. We conclude that early initiation of desensitization protocols can prevent transplant failure and that retrospective FC cross-matches may facilitate the diagnosis of AMR. Extensive analysis of patients' sera using a comprehensive set of tests may contribute to early treatment and better understanding of the mechanism underlying humoral rejection.     

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation,oxidative stress,and differential morphological changes in the mouse lung

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D.     

Development and validation of a pediatric laparoscopic surgery simulator

Background

Although a validated simulator exists for adult laparoscopy, there is no pediatric counterpart. The objective of this study is to develop and validate a pediatric laparoscopic surgery (PLS) simulator.

Methods

A PLS simulator was developed. Participants were stratified according to level of expertise and tested on the fundamentals of laparoscopic surgery (FLS) and PLS simulators. A subsequent group was tested exclusively on the PLS simulator.

Results

The PLS intracorporeal suturing score was lower than its adult counterpart (P = .02). The PLS pattern-cutting score was higher than in the FLS simulator (P < .001). If the latter was eliminated from the calculation, the revised total FLS score was significantly better than the revised PLS score. When all participants were combined, total PLS scores as well as performance on 3 of 5 tasks allowed differentiation between novice, intermediate, and expert.

Conclusions

The PLS simulator was able to discriminate between the novice, intermediate, and expert using the total PLS score and the performance on 3 of the 5 tasks, thus providing evidence for construct validity. The other 2 tasks will require formal modification or a change in the scoring metrics to establish their independent construct validity.