An analysis of returned medicines in primary care

Objective: The number of pharmaceutical items issued on prescription is continually rising and contributing to spiralling healthcare costs. Although there is some data highlighting the quantity, in terms of weight of medicines returned specifically to community pharmacies, little is known about the specific details of such returns or other destinations for wasted medications. This pilot study has been designed to investigate the types and amounts of medicines returned to both general practices (GPs) and associated local community pharmacies determining the reasons why these medicines have been returned. Method: The study was conducted in eight community pharmacies and five GP surgeries within East Birmingham over a 4-week period. Main outcome Measure: Reason for return and details of returned medication. Results: A total of 114 returns were made during the study: 24 (21.1) to GP surgeries and 90 (78.9) to community pharmacies. The total returns comprised 340 items, of which 42 (12.4) were returned to GPs and 298 (87.6) to pharmacies, with the mean number of items per return being 1.8 and 3.3, respectively. Half of the returns in the study were attributed to the doctor changing or stopping the medicine; 23.7 of returns were recorded as excess supplies or clearout often associated with patients' death and 3.5 of returns were related to adverse drug reactions. Cardiovascular drugs were most commonly returned, amounting to 28.5 of the total drugs returned during the study. Conclusions: The results from this pilot study indicate that unused medicines impose a significant financial burden on the National Health Service as well as a social burden on the United Kingdom population. Further studies are examining the precise nature of returned medicines and possible solutions to these issues. © Springer 2005

Plasma Levels of Transforming Growth Factor-β1 Reflect Left Ventricular Remodeling in Aortic Stenosis

Background: TGF-b1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-b1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-b1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function. Methodology/Principal Findings: The subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-b1 was determined by ELISA. Under pressure overload, TGF-b1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-b1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-b1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, b-myosin heavy chain) remodelling targets of TGF-b1, in TAC mice and in AS patients. Conclusions/Significance: A circulating TGF-b1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-b1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts

Pseudo-Synesthesia through Reading Books with Colored Letters

Background Synesthesia is a phenomenon where a stimulus produces consistent extraordinary subjective experiences. A relatively common type of synesthesia involves perception of color when viewing letters (e.g. the letter ‘a’ always appears as light blue). In this study, we examine whether traits typically regarded as markers of synesthesia can be acquired by simply reading in color. Methodology/Principal Findings Non-synesthetes were given specially prepared colored books to read. A modified Stroop task was administered before and after reading. A perceptual crowding task was administered after reading. Reading one book (>49,000 words) was sufficient to induce effects regarded as behavioral markers for synesthesia. The results of the Stroop tasks indicate that it is possible to learn letter-color associations through reading in color (F(1, 14) = 5.85, p = .030). Furthermore, Stroop effects correlated with subjective reports about experiencing letters in color (r(13) = 0.51, p = .05). The frequency of viewing letters is related to the level of association as seen by the difference in the Stroop effect size between upper- and lower-case letters (t(14) = 2.79, p = .014) and in a subgroup of participants whose Stroop effects increased as they continued to read in color. Readers did not show significant performance advantages on the crowding task compared to controls. Acknowledging the many differences between trainees and synesthetes, results suggest that it may be possible to acquire a subset of synesthetic behavioral traits in adulthood through training. Conclusion/Significance To our knowledge, this is the first evidence of acquiring letter-color associations through reading in color. Reading in color appears to be a promising avenue in which we may explore the differences and similarities between synesthetes and non-synesthetes. Additionally, reading in color is a plausible method for a long-term ‘synesthetic’ training program

Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation

Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4+CD25+FOXP3+ regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-β and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4+CD25+FOXP3+ T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase