Characteristics and quality of adverse drug reaction reports by pharmacists in Norway

PURPOSE: To evaluate the characteristics and quality of adverse drug reaction (ADR) reports submitted by pharmacists, and thereby assess the possible contribution of pharmacists to the spontaneous reporting system for ADRs in Norway. METHODS: An open, prospective study was conducted where dispensing pharmacists from 39 pharmacies were encouraged to report ADRs over a 3-month period. The submitted ADR reports were compared to reports by physicians from the same time period. All reports were evaluated for selected characteristics, that is distribution of Anatomical Therapeutic Chemical (ATC) classification codes of suspected drugs, distribution of ADRs according to system-organ classes and the quality of the reports. RESULTS: A total of 118 reports covering 274 ADRs received from the pharmacists were compared to 109 ADR reports with 304 ADRs submitted by physicians. Pharmacists more often reported ADRs related to cardiovascular drugs, alimentary tract and metabolism drugs and respiratory drugs, whereas physicians more frequently reported ADRs related to musculoskeletal drugs and antineoplastic and immunomodulating agents. ADRs reported by pharmacists more frequently described gastrointestinal reactions while physicians reported more ADRs in relation to the cardiovascular and blood system. Whereas 68% of the physicians' reports were classified as serious, only 5% of the pharmacists' reports were serious. More than 50% of the reports submitted by pharmacists concerned ADRs following a generic substitution, in contrast to only 2% of the physicians' reports. The pharmacists' reports were found to be of a lower documentation grade. However, there was no substantial difference in a subjective assessment of the quality of information in the reports submitted by the two categories of health professionals. CONCLUSIONS: Pharmacists submit valuable ADR reports which provide information complimentary to physicians' reports. This emphasises that pharmacist ADR reporting might constitute an important addition to the spontaneous reporting system.     

Dlk1 in normal and abnormal hematopoiesis.

Dlk1 (Pref-1) is a transmembrane and secreted protein, which is a member of the epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We have found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10 of 12 MDS samples compared with CD34(+) cells from 11 normals. Also, Dlk1 mRNA was elevated in mononuclear, low density bone marrow cells from 11/38 MDS patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of Dlk1 mRNA markedly increased during megakaryocytic differentiation of both CMK megakaryoblasts as well as normal CD34(+) hematopoietic stem cells. High serum levels of Dlk1 occurred in RA (4/10) and essential thrombocythemia (2/10) patients. Functional studies showed that forced expression of Dlk1 enhanced proliferation of K562 cells growing in 1% fetal bovine serum. Analysis of hematopoiesis of Dlk1 knockout mice suggested that Dlk1 contributed to granulocyte, megakaryocyte and B-cell clonogenic growth and was needed for generation of splenic B-cells. In summary, Dlk1 is overexpressed in selected samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it appears to be associated with normal development of megakaryocytes and B cells.     

Outcomes of open versus laparoscopic surgery in patients with colon cancer

Objective

There is limited information on health service use or patient-reported outcomes when comparing the effectiveness of laparoscopic with that of open surgery. The aim was to compare the effectiveness of laparoscopic with that of open surgery up to 2 years after intervention in patients with colon cancer.

Differential regulation of RGS proteins in the prefrontal cortex of short- and long-term human opiate abusers

Opiate addiction is characterized by drug tolerance and dependence which involve adaptive changes in μ-opioid receptors (MORs) signaling. Regulators of G-protein signaling RGS9, RGS4 and RGS10 proteins negatively regulate G(αi/o) protein activity modulating MOR function. An important role of RGS proteins in drug addiction has been described but the status of RGS proteins in human brain of opiate addicts remains unknown. The present study evaluated the immunoreactivity levels of RGS4, RGS9 and RGS10 proteins in prefrontal cortex of short- (n = 15) and long-term (n = 21) opiate abusers and in matched control subjects. RGS4 protein was not altered in short-term opiate abusers but, in long-term abusers it was significantly up-regulated (Δ = 29 ± 6%). RGS10 protein expression was significantly decreased in short-term (Δ = -42 ± 7%) but remained unaltered in long-term opiate abusers. RGS9 protein levels in opiate abusers did not differ from matched controls either in the short-term or in the long-term opiate abuser groups. RGS4, RGS9 and RGS10 levels were also studied in brains (frontal cortex) of rats submitted to acute and chronic morphine treatment and to spontaneous and naloxone-precipitated opiate withdrawal. Chronic morphine treatment in rats was associated with an increase in RGS4 protein immunoreactivity (Δ = 28 ± 7%), which persisted in spontaneous (Δ = 35 ± 8%) and naloxone-precipitated withdrawal (Δ = 30 ± 9%) without significant changes in RGS9 and RGS10 proteins. The specific modulation of RGS4 and RGS10 protein expression observed in the prefrontal cortex of opiate abusers might be relevant in the neurobiology of opiate tolerance, dependence and withdrawal. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.     

Graft-vs-host disease after small bowel transplantation in children

Purpose

Graft-vs-host disease (GVHD) is a rare complication of transplantation of organs rich in immunocompetent cells. The goal of this study was to report the features of GVHD after small bowel transplantation (SBTx) in children.

Methods

The study involved a retrospective review of patients undergoing SBTx between 1999 and 2009 who had GVHD.

Results

Of 46 children receiving 52 intestinal grafts (2 liver-intestine and 3 multivisceral), 5 (10%) developed GVHD. Median age at transplant was 42 (19-204) months. Baseline immunosupression consisted of tacrolimus and steroids supplemented with thymoglobulin (n = 2) or basiliximab (n = 3) for induction. Median time between transplantation and GVHD was 47 (16-333) days. All patients had generalized rash, 2 had diarrhea, and 2 had respiratory symptoms. Other symptoms were glomerulonephritis (n = 1) and conjunctivitis (n = 1). Four developed severe hematologic disorders. The diagnosis was confirmed by skin biopsy in 4 patients and supported by chimerism studies in two. Colonoscopy and opthalmoscopic findings were also suggestive in one. Treatment consisted of steroids and decrease of tacrolimus, with partial response in four. Other immunosuppressants were used in refractory or recurrent cases. Three patients died within 4 months after diagnosis.

Conclusion

Graft-vs-host disease is a devastating complication of SBTx, with high mortality probably associated with severe immunologic dysregulation.     

Platelet-rich plasma,an adjuvant biological therapy to assist peripheral nerve repair

hTerapies such as direct tension-free microsurgical repair or transplantation of a nerve autogratf, are now-adays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. hTus, new biomedical engineering strategies based on tissue engineering approach-es through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and ifbrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinlfammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.