An update on medical management on Crohn’s disease

Introduction: The management of Crohn’s disease (CD) is continuously evolving. New issues emerging from more recent studies could influence the decision-making process in clinical practice.

Areas covered: The aim of this review article is to highlight critical issues on the management of CD, new evidence from clinical trials, long-term prospective studies and real life experience, beyond the current guidelines.

Expert opinion: The role of mucosal healing in clinical practice is uncertain, clinical remission remains the primary end point. The timing for the definition of steroid-resistant CD should be considered between 2 and 4 weeks. Early treatment strategy with immunomodulators is effective for inducing remission but no controlled data are available regarding long-term outcome. Combination therapy (anti-TNFs agents and immunosuppressors) is more effective than single therapy but there is a lack of long-term data and an increased risk of malignancy. The effect of mesalazine, metronidazole and azathioprine in reducing postoperative recurrence is not clinically relevant; biologics are effective, but the duration of treatment is unknown. New drugs are under investigation in order to find exit strategy for patients who no longer respond to biologics. Combination therapy set on anti-TNF-α is until now the best option both to achieve fistula healing and avoid recurrence     

Can statins put the brakes on Alzheimer’s disease?

Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which initiates the syntheses of cholesterol and isoprenoid lipids that are needed to provide amyloid peptides for the amyloid cascade. This cascade is believed to induce sporadic or late-onset Alzheimer’s disease, which accounts for 90 – 95% of Alzheimer’s disease sufferers. Cholesterol is also the prime driver of cerebrovascular disease that (along with amyloid peptides) increasingly appears to be linked to the cognitive deterioration of Alzheimer’s disease. Cholesterol is needed to make the lipid rafts that are the platforms for isoprenoid-dependent assembly and activation of raftophilic β- and γ-secretases that work in tandem to excise dangerous 40 and 42 amino acid amyloid-β (Aβ) fragments from amyloid precursor protein, the transmembrane amyloid precursor glycoprotein. When they are excessively produced and can no longer be effectively destroyed or otherwise cleared from the hypoperfused ageing brain, the Aβ42 fragments released from the active synaptic terminals of normally busy neurons (and from stressed neurons unsuccessfully trying to proliferate and producing disruptive tangles of hyperphosphorylated τ-proteins) aggregate into neuritic plaques, which activate glial cells. The pro-inflammatory cytokines and growth factors from the glial cells further damage and kill neurons. As statins strike at several parts of the Alzheimer’s disease mechanism (such as the infliction of cholesterol-dependent cerebrovascular damage) by inhibiting HMG-CoA reductase, their long-term use (starting as early as possible during Alzheimer’s disease development) should slow or even prevent the progression of Alzheimer’s disease. Indeed, there is some evidence of a significantly reduced incidence of Alzheimer’s disease among people who have been using statins to reduce hypercholesterolaemia and its cardiovascular effects. To be certain of this, there must be more multi-year trials to specifically assess the effects of statins on sporadic Alzheimer’s disease.     

GPs’ views on patient drug use and the pharmacist’s role in DRP management

Objective The aim of this study was to examine general practitioners’ (GPs’) views on (1) patients’ drug-related problems (DRPs) and noncompliance and (2) the role of pharmacy practitioners in DRP management. Method A brief questionnaire was designed and distributed to 224 GPs in Sweden. Results Totally 152 GPs responded (68%). Most felt that pharmacy practitioners could improve patients’ drug use by identifying DRPs. A majority of the GPs also found presentations and analyses of their local pharmacies’ DRP documentation valuable. According to the GPs’ experiences, adverse drug effects and therapy failure were the most salient problems in patients’ drug use. Half of the doctors believed that 50–75% of their patients were compliant with their prescribed drug treatments. A majority of the GPs found a 75–95% degree of compliance acceptable. Conclusion The surveyed GPs demonstrated very positive attitudes towards the role of pharmacy practitioners in improving patients’ drug use and managing DRPs. The GPs realised that many patients were not compliant with their prescribed drug treatments and accepted an imperfect compliance.     

It’s time

Statistical inference involves taking the results of models and knowledge about probability to make decisions about the relationship in question. This commentary explains the usefulness of statistical inference to the drug development process, as well as some common pitfalls. It also examines reasons why statistical inference does not seem to be fully integrated into pharmacometric modeling. An example is shown that demonstrates the inferential advantages of mechanistic models. Both statisticians and pharmacometricians ought to take note of these advantages and integrate their efforts in order to maximize the decision-making potential of clinical research.     

Cushing’s syndrome: an update on current pharmacotherapy and future directions

Introduction: Endogenous Cushing’s syndrome (CS) is characterized by chronic overproduction of cortisol and is associated with increased mortality and morbidity. It can be caused by a pituitary adenoma, ectopic adrenocorticotropic hormone (ACTH) production or primary adrenal disease. Successful tumor-directed surgery is the keystone treatment. When surgery is unsuccessful, contraindicated or in case of acute disease, pharmacotherapy is indicated to treat hypercortisolism.

Areas covered: In this review, pharmacotherapeutic options for CS will be covered discussing the different possible targets, that is: i) inhibition of ACTH secretion; ii) suppression of steroidogenesis; and iii) blockade of cortisol effects at tissue level. Preclinical and clinical studies will be discussed considering mono- and combination therapy, taking into account efficacy, toxicity and mechanism of action. Per CS entity, future directions of pharmacotherapies will be addressed.

Expert opinion: The number of medical treatment options for CS has increased in the past years. In contrast to decades ago, prospective trials are now being performed focusing on pituitary-directed drugs like pasireotide, the glucocorticoid receptor blocker mifepristone and ‘new generation’ steroid synthesis inhibitors. Future studies will focus on tumor-shrinking effects of neuromodulatory drugs, the optimal order and combination of pharmacotherapy, long-term efficacy and safety and new targets for medical treatment of CS.     

Impact of pharmacist’s intervention on reducing cardiovascular risk in obese patients

International Journal of Clinical Pharmacy - Background Obesity is a risk factor for cardiovascular disease, the leading cause of death. Health education, nutritional follow-up, and life style...     

IBC’s 6th Annual Conference on Angiogenesis: Novel Therapeutic Developments

Angiogenesis is a process that is dependent upon co-ordinate production of angiogenesis stimulatory and inhibitory (angiostatic) molecules. Any imbalance in this regulatory circuit may lead to the development of a number of angiogenesis-mediated diseases. Angiogenesis is a multi-step process including activation, adhesion, migration, proliferation and transmigration of endothelial cells across cell matrices to or from new capillaries and from existing vessels. Angiogenesis is a process involved in the formation of new vessels by sprouting from pre-existing vessels. In contrast, vessel rudiments are sorted by a process termed vasculogenesis. Endothelial heterogeneity and organ specificity might contribute to differences in the response to different anti-angiogenic mechanisms (cultured EC versus microvascular EC isolated from different tissues). Under normal physiological conditions in mature organisms, endothelial cell turnover or angiogenesis is extremely slow (from months to years). However, angiogenesis can be activated for a limited time in certain situations such as wound healing and ovulation. In certain pathological states, such as human metastasis (oncology) and ocular neovascularisation, disorders including diabetic retinopathy and age-related macular degeneration (ophthalmology), there is excessive and sustained angiogenesis. Hence, understanding the mechanisms involved in the regulation of angiogenesis could have a major impact in the prevention and treatment of pathological angiogenic processes. Additionally, endothelial cells play a major role in the modelling of blood vessels. The interplay of growth factors, cell adhesion molecules, matrix proteases and specific signal transduction pathways either in the maintenance of the quiescent state or in the reactivation of endothelial cells is critical in physiological and pathological angiogenic processes.     

The effects of one-year simvastatin therapy on women’s bone mineral density

Only few studies have reported that bone fracture risk is decreased in hypercholesterolemic postmenopausal women treated with statin therapy. Because of a lack of longitudinal studies on the effect of statins on bones, the aim of our investigation was to estimate the simvastatin therapy effects on bone mineral density in hypercholesterolemic postmenopausal women. Our investigation was carried out on 53 postmenopausal women with hypercholesterolemia. The women included in the study were divided into two groups. Group 1 was comprised of women with two or more (n=32) atherosclerosis risk factors, whereas group 2 had women with less than two (n=21) of these risk factors. All the women included in the study were placed on a hypocholesterolemic diet and the women in group 1 were additionally treated with 20 mg of simvastatin daily. The parameters of lipid status, body mass index, and L2–L4 densitometry were determined at baseline and then after one year. The simvastatin-treated group showed significant improvement of lipid parameters and increased bone mineral density. Finally, changes in bone mineral density between the groups showed significant differences (p<0.05). Although our investigation was carried out on a small group, our results showed a positive effect of the simvastatin therapy on the bone mineral density of postmenopausal women.     

Effect of Indigofera aspalathoides on complete Freund’s adjuvant-induced arthritis in rats

The effect of ethanol extract of stems of Indigofera aspalathoides Vahl (Papilionaceae) (EIA) was evaluated for anti-arthritic activity on complete Freund’s adjuvant-induced (CFA-induced) arthritis in rats. The EIA was administered orally at doses of 250 and 500?mg/kg daily for 30 days. The paw volume was measured on days 7, 14, 21 and 30. At the end of day 30, the rats were sacrificed and various biochemical parameters such as serum aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol and triglycerides were estimated. Antioxidant enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and lipid peroxide (LPO) in the liver and kidney of normal, arthritic control and EIA treated rats were studied. Oral administration of EIA effectively inhibits rat paw edema in a dose-dependent manner. EIA significantly (P?<0.01) altered the biochemical parameters which were affected in arthritic rats. There was significant alteration in LPO, SOD, catalase, and GPx levels when compared to arthritic control rats. Our findings showed a significant anti-arthritic effect of EIA against CFA-induced arthritis in rats.