Cost-effectiveness of a clinical medication review in vulnerable older patients at hospital discharge,a randomized controlled trial

International Journal of Clinical Pharmacy - Background Drug-related problems (DRP) following hospital discharge may cause morbidity, mortality and hospital re-admissions. It is unclear whether a...     

Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue

Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology.     

Genotoxicity of synthetic amorphous silica nanoparticles in rats following short‐term exposure. Part 1: Oral route

Synthetic amorphous silica (SAS) in its nanosized form is now used in food applications although the potential risks for human health have not been evaluated. In this study, genotoxicity and oxidative DNA damage of two pyrogenic (NM‐202 and 203) and two precipitated (NM‐200 and ‐201) nanosized SAS were investigated in vivo in rats following oral exposure. Male Sprague Dawley rats were exposed to 5, 10, or 20 mg/kg b.w./day for three days by gavage. DNA strand breaks and oxidative DNA damage were investigated in seven tissues (blood, bone marrow from femur, liver, spleen, kidney, duodenum, and colon) with the alkaline and the (Fpg)‐modified comet assays, respectively. Concomitantly, chromosomal damage was investigated in bone marrow and in colon with the micronucleus assay. Additionally, malondialdehyde (MDA), a lipid peroxidation marker, was measured in plasma. When required, a histopathological examination was also conducted. The results showed neither obvious DNA strand breaks nor oxidative damage with the comet assay, irrespective of the dose and the organ investigated. Similarly, no increases in chromosome damage in bone marrow or lipid peroxidation in plasma were detected. However, although the response was not dose‐dependent, a weak increase in the percentage of micronucleated cells was observed in the colon of rats treated with the two pyrogenic SAS at the lowest dose (5 mg/kg b.w./day). Additional data are required to confirm this result, considering in particular, the role of agglomeration/aggregation of SAS NMs in their uptake by intestinal cells. Environ. Mol. Mutagen. 56:218–227, 2015. © 2014 Wiley Periodicals, Inc.     

Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers.

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 microg of SCT orally, a placebo, and a 10-microg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5-1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 microg exceeding those of 10 microg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.     

Frequency, nature and determinants of pharmaceutical consultations provided in private by Dutch community pharmacists

OBJECTIVE: According to a report published by the federation of Dutch patients' associations, patients would like to see a pharmacist, who acts more as a personal adviser. This raised the question, how often Dutch community pharmacists have personal consultations with their patients in daily practice, on which factors this depends, and what kind of topics are discussed during these meetings. SETTING: Community pharmacies in the Netherlands. METHOD: A questionnaire was distributed among 800 randomly selected pharmacies. Questions were restricted to consultations characterized by one-to-one contact, drug therapy related content, and adequate privacy. These consultations were labelled as pharmaceutical consultations in private to distinguish them from other contacts between pharmacists and patients. MAIN OUTCOME MEASURE: Number, content, and character of consultations. RESULTS: 198 (24.8%) community pharmacies responded. The pharmacists provide an average of roughly 1.2 consultations in private per working day. The vast majority of respondents provided face-to-face and telephone consultations (94.4 and 91.9%, respectively), only a minority gave consultations by e-mail (30.8%). These consultations primarily dealt with topics related to medication safety. The mean overall time spent was 290 min per month. A relatively high frequency of personal consultations was significantly associated with the absolute number of full-time equivalent pharmacists in the pharmacy. CONCLUSION: The frequency of pharmaceutical consultations in private is low, but may be improved by reorganisation of the pharmacist's activities. The possibility of personal consultations by e-mail is not yet well-developed. Further research is needed to assess the patient's view of pharmaceutical consultations in private.     

Serial order short-term memory capacities and specific language impairment: No evidence for a causal association

This study re-explored the nature of verbal short-term memory (STM) deficits in children with specific language impairment (SLI), by distinguishing item and serial order STM processes. Recent studies have shown serial order STM capacity to be a critical determinant of language development, relative to item STM. In Experiment 1, 12 children with SLI, 12 age-matched children and 12 language-matched children were administered serial order recognition and reconstruction tasks. Experiment 2 assessed implicit serial learning abilities via a Hebb learning task. The SLI group showed impaired performance for the serial order reconstruction and recognition tasks, relative to language-matched and/or age-matched control groups. However, normal serial position effects were observed in all SLI children in the serial order reconstruction task, suggesting normal coding of serial position information. Similarly, performance on the Hebb serial learning task was at chronological age appropriate levels. Experiment 3 showed that the group differences observed for the serial order STM tasks in Experiment 1 disappeared when the SLI group was compared to a mental age-matched control group. Experiment 4 showed similar performance levels in the SLI group and the mental age-matched control group for a nonword recognition task assessing item STM capacities. This study shows that children with SLI have no specific impairments for serial order and item STM components but that poorer general cognitive efficiency is related to functional limitations in verbal STM tasks. The data are in line with limited information processing accounts of SLI.     

Downregulation of osteoblast markers and induction of the glial fibrillary acidic protein by oncostatin M in osteosarcoma cells require PKCdelta and STAT3.

The effects of OSM on proliferation and differentiation of osteosarcoma and nontransformed osteoblasts were analyzed. OSM downregulates osteoblast markers but induces the glial fibrillary acidic protein by the combined activation of PKCdelta and STAT3, offering new lines of therapeutic investigations. INTRODUCTION: Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family implicated in embryonic development, differentiation, inflammation, and regeneration of various tissues, mainly the liver, bone, and the central nervous and hematopoietic systems. One particularity of OSM relies on its growth inhibitory and pro-differentiating effects on a variety of tumor cell lines such as melanoma, providing arguments for a therapeutic application of OSM. The objective of this study was to analyze the effects of OSM on osteosarcoma cell lines proliferation and differentiation. MATERIALS AND METHODS: Proliferation was analyzed by 3H thymidine incorporation. Differentiation was analyzed by semiquantitative RT-PCR and immunocytochemistry for various markers. Alizarin red S staining was used to evaluate bone nodule formation. Morphological changes were studied by confocal and electron microscopy. Western blotting, kinases inhibitors, and dominant negative STAT3 were used to identified the signaling pathways implicated. RESULTS: OSM inhibits the growth of rat osteosarcoma cell lines as well as normal osteoblasts, in correlation with induction of the cyclin-dependent kinases inhibitor p21WAF1. However, OSM reduces osteoblast markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein, leading to strong inhibition of mineralized nodule formation. This inhibitory effect is restricted to mature osteoblasts and differentiated osteosarcoma because OSM effectively stimulates osteoblast markers and bone nodule formation in early, but not late, bone marrow mesenchymal stem cell (BMSC) cultures. In osteosarcoma cells or BMSC, OSM induces expression of the glial fibrillary acidic protein (GFAP) as well as morphological and ultrastructural changes, for example, elongated shape and bundles of microfilaments in cell processes. Rottlerin (PKCdelta inhibitor), and to a lesser degree UO126 (MEK/ERK inhibitor), prevents the loss of osteoblastic markers by OSM, whereas dominant negative STAT3 prevents GFAP induction. CONCLUSIONS: These results highlight the particular gene expression profile of OSM-treated osteosarcoma cells and BMSCs, suggesting either a osteocytic or a glial-like phenotype. Together with the implication of PKCdelta, ERK1/2, and STAT3, these results offer new lines of investigations for neural cell transplantation and osteosarcoma therapy.