A paradigm shift for evaluating pharmacotherapy for Alzheimer's disease: the 10-patient screening protocol.

OBJECTIVE: Discuss etiology of Alzheimer's disease (AD) and offer a paradigm shift-a change in basic assumptions-from present standards in clinical trials. DATA SOURCE: PubMed search for studies into AD pathophysiology and assessment of disease progression. Searched terms: amyloid precursor protein/amyloid beta pathology, senile plaques, mitochondrial dysfunction, reactive oxygen species , advanced glycation end products, neuro-inflammation, dysfunctional microglia/astrocytes, proinflammatory cytokines, ApoE4 allele, Tau phosphorylation, Chlamydia pneumoniae, Dementia Severity Rating Scale, Clinical Dementia Rating Scale, Relative's Assessment of Global Symptomatology-Elderly, and Alzheimer's Disease Assessment Scale-cognitive. STUDY SELECTION: All prospective, randomized, placebo- or cohort-controlled, peer-reviewed English language publications from 1980 to 2012. Studies in animals, AD patients, and AD brain specimens. DATA EXTRACTION: Objectives, methods, statistical design, and results reviewed to assess soundness of trials and validity of results. Trials with flawed methods or uninterpretable results excluded. DATA SYNTHESIS: Primary pathophysiology comprises: amyloid precursor protein/amyloid beta pathology with deposition of senile plaques; mitochondrial dysfunction with insufficient ATP synthesis and release of reactive oxygen species; oxidative stress; and neuro-inflammation from dysfunction of microglia and astrocytes. Other factors include abnormal ApoE4 allele protein and aberrant Tau phosphorylation. Role of Chlamydia pneumoniae is unproven. Dementia Severity Rating Scale (DSRS) is optimal assessment tool for assessing AD progression. CONCLUSION: AD's complex pathophysiology may require polypharmacy to mitigate symptoms and progression. DSRS-driven, 10-patient pilot studies offer practical, valid, and reliable screening for potentially effective pharmacotherapy in AD. The simplicity of this paradigm shift should expedite research and may promote earlier discovery of effective pharmacotherapy for AD.

Case study: the link between hypertension and diabetes.

BACKGROUND: Many diabetics develop hypertension, and it is a major risk factor for cardiovascular and microvascular complications. OBJECTIVE: To review a case study of a patient with poorly controlled hypertension and diabetes. SUMMARY: Further assessment of this case study shows that the patient has poorly controlled hypertension, despite multiple medications. The patient also has metabolic syndrome complicated.by diabetes, microalbuminuria and peripheral arterial disease. The patient's hypertensive treatment options must be evaluated in light of the fact that polypharmacy has made it more difficult for her to achieve glycemic control. A panoply of drugs and drug classes are available from which to choose: diuretics, beta-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and aldosterone antagonists. New vasodilatory betablockers reduce adverse drug reactions and produce beneficial effects on arterial vasculature. Various beta~blockers' effects on insulin sensitivity are compared. CONCLUSION: Older beta-blockers have been shown to have detrimental effects on glucose or lipid parameters. Newer agents such as nebivolol do not impact lipid, glucose, insulin, or high-density lipoproteins. Instead, nebivolol stimulates endothelial nitric oxide release in renal arteries and improves renal function.

Pharmacoeconomic benefits of antihypertensive therapy.

BACKGROUND: Effective blood pressure reduction reduces cardiovascular risk and prevents later complications. OBJECTIVE: To consider the pharmacoeconomic benefits of antihypertensive therapy. SUMMARY: Every managed care pharmacist should consider the balance of cost and benefit of antihypertensive therapies, ensuring that best treatment options for patients with the lowest cost to the health care system are available and implemented. Pharmacists must also evaluate the direct and indirect cost associated with risk reduction for stroke and cardiovascular disease. CONCLUSION: Using an interdisciplinary approach to hypertension treatment, pharmacists can assume a major role in detection, management, and control of hypertensive patients. As the medical teams' drug expert, they will be expected to recommend best treatment options for effective blood pressure control and cardiovascular risk reduction.

An economic assessment of inhaled formoterol dry powder versus ipratropium bromide pressurized metered dose inhaler in the treatment of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is debilitating and costly to manage. A recent clinical trial concluded that formoterol, a long-acting beta(2)-adrenoceptor agonist, was more clinically effective than inpratropium bromide in the management of COPD. OBJECTIVE: The aim of this study was to perform an economic assessment of the management of COPD with formeterol versus ipratropium bromide. METHODS: Assessment were based on the results of a previously published 12-week, multicenter, double-masked, randomized, parallel-group, placebo-controlled clinical trial comparing inhaled formoterol dry powder 12 and 24 microg BID with ipratropium bromide 40 microg QID pressurized metered dose inhaler and with placebo in 780 COPD patients. Treatment costs for study drugs and rescue medications were estimated from resource utilization and average wholesale prices. Costs were assessed with respect to forced expiratory lung volume in 1 second (FEV(1)) and patient-reported quality of life (QOL) as assessed via the St. George's Respiratory Questionnaire. Cost-effectiveness ratios were calculated for each treatment arm and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment relative to the next best alternative. Economic efficiency frontiers were identified. Sensitivity analysis was conducted. RESULTS: Cost analysis with respect to FEV(1) revealed an economic efficiency frontier formed by placebo, ipratropium bromide 40 microg, and formoterol 12 microg at their respective FEV(1) levels, with cost-effectiveness ratios of $30.18, $53.50, and $142.04, respectively, per FEV(1). The ICER for ipratropium over placebo was $273.03; for formoterol 12 microg over ipratropium, $1611.32. Cost analysis with respect to QOL showed an economic efficiency frontier formed by placebo and formoterol 12 microg at their respective QOL outcomes, with cost-effectiveness ratios of $25.96 and $32.56, respectively, per QOL score change. The cost-effectiveness ratio for ipratropium was $69.40,which was not on the QOL economic efficiency frontier. The ICER for formoterol 12 microg over placebo was $34.51 per QOL score point. CONCLUSIONS: Formoterol 12 microg provided greater QOL outcome than ipratropium bromide at an additional cost of $554.28 per year. Further research would be necessary to assess whether the differences in outcomes, particularly QOL, observed in the short term with formoterol would lead to favorable long-term health and economic outcomes.

Neonatal nutrition: a focus on parenteral nutrition and early enteral nutrition.

No population has benefited more from the development and advancement of specialized nutrition support than pediatric patients. Today, neonates comprise the largest group of pediatric patients receiving parenteral nutrition (PN). Nutrient needs of neonates differ substantially from other populations, presenting unique challenges in optimizing nutrition care. Neonates are highly susceptible to catabolic stress because of reduced energy stores and markedly increased energy needs. Immature organ systems and metabolic pathways further complicate the delivery of adequate nutrition in the preterm neonate. Early nutrition support is essential to improve survival, reduce catabolism, promote growth, and limit developmental complications. This article discusses feeding strategies for PN and early enteral nutrition in neonates, particularly the preterm neonate.