Advances In Drug Therapy Research Articles

Advances in drug therapy of osteoporosis

Advances in drug therapy of osteoporosis

SAT0144 The Causes of Discontinuation of Biologics(Bio)-Use in the Treatment of Rheumatoid Arthritis (RA) Under Practical Circumstances in Japan: from the “Ninja” Registry

BackgroundWith recent astonishing advances in drug therapy, “remission” has become a realistic therapeutic goal in RA. Among them the most powerful driving force might be the advent of “biologics (Bio)”...

AB1306 Isolated tenosynovitis is frequently detected by ultrasound in symptomatic ankles of RA patients with significantly shorter disease duration

BackgroundBecause recent advances in drug therapies for RA have increased the importance of early diagnosis, musculoskeletal ultrasonography (US) has become increasingly a part of daily rheumatologic practice as a sensitive...

Medication adherence issues in patients: focus on cost

Correspondence: Doreen Matsui Children’s Hospital, London Health Sciences Centre, 800 Commissioners Road East, London, Ontario, N6C 2V5 Canada, Tel +1 519 685 8268 Fax +1 519 684 8156 Email dmatsui@uwo.ca Abstract: Advances in drug therapy have resulted in efficacious treatments being available; however, the benefit may be lost if prescribed medications are not taken properly. Unfortunately, poor medication adherence is common and widespread, affecting all age groups and disease conditions. Adherence is a factor in health outcomes of pharmacotherapy with possible failure to achieve therapeutic goals and worsening of illness. Higher health care costs may result from more frequent physician and emergency department visits and increased hospitalization rates. The cost of medications may play a role in whether patients do or do not take their medication with increased cost sharing leading to poorer adherence with prescription drugs. Given the possible adverse consequences of nonadherence, interventions to improve medication-taking behavior are encouraged although not consistently successful. Surprisingly, there is relatively little information on the cost-effectiveness of these interventions and more methodologically sound research is needed in this area. Alternative strategies that have been proposed are valuebased insurance design and the use of financial incentives, although the former has not been widely accepted, and the latter is ethically controversial. This article reviews some of the main issues with regards to adherence with drug therapy including some of the cost implications of less than optimal medication adherence.

Percutaneous Sympathetic Renal Denervation

Arterial hypertension is a highly prevalent disease and is associated with increased cardiovascular risk. Despite great advances in drug therapy, a considerable number of patients do not have an effective control of the disease, despite the use of multiple drugs, usually in high doses. Renal sympathetic denervation (RSD) has proved to be a promising therapy, with high safety and eficacy in preliminary studies in patients with resistant hypertension. The role of the sympathetic nervous system in the physiopathology of hypertension is well known, and is the rationale for the ablation of sympathetic ibers by transluminal delivery of radiofrequenc y in the renal arteries. In the last few years, results from case series, non-controlled studies and one multicenter randomized trial with a limited number of patients have shown a signiicant decrease in short and mid-term blood pressure levels. The objective of this re view was to gather evidence on the use of RSD in the control of resistant hypertension and describe technical aspects and perspectives of the procedure.

Idiopathic Gastroparesis

Gastroparesis is a disorder characterized by a delay in gastric emptying of a meal in the absence of a mechanical gastric outlet obstruction. The most common etiologies include diabetes, postsurgical and idiopathic. Idiopathic Gastroparesis is at least as common as diabetic Gastroparesis in most case series. Diagnosis of Gastroparesis is based on the presence of symptoms such as nausea, vomiting, postprandial abdominal fullness, and on an objectively determined delay in gastric emptying. The true prevalence of Gastroparesis is unknown. Gastric emptying can be assessed by scintigraphy and stable isotope breath tests. Management of Gastroparesis consists of dietary and lifestyle measures, possible pharmacological interventions (prokinetics, antiemetics, intrapyloric botulinum toxin injection) and/or interventions that focus on adequate nutrient intake either through a nasoduodenal tube, percutaneous gastrostomy, or jejunostomy. New advances in drug therapy and gastric electrical stimulation techniques have been introduced and might provide new hope to patients. Presented here is an interesting case of idiopathic Gastroparesis along with its management and review of the literature.

Temporal trends in the surgical outcomes of patients with breast cancer

BackgroundThe incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer.MethodsWe evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009.ResultsThe number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted’s radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%.ConclusionThe survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.

Clinico-epidemiological profile and quality of life of PLWHA in Central India

Background Advances in drug therapy have dramatically extended the life of people living with HIV/AIDS (PLWHA). Empirical evidence shows that as the HIV disease progresses, quality of life deteriorates. PLWHA face physiological, physical, psychological and socio-cultural problems that are caused by these factors affect quality of life. The purpose of this study was to study the clinico-epidemiological profile and assess quality of life of PLWHA.

Sumário de atualização da II Diretriz Brasileira de Insuficiência Cardíaca Aguda 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Pediatric epilepsy: Five new things.

Epilepsy in children can be very different from epilepsy in adults, both in seizure type and epilepsy syndrome. The goal in treating children is seizure freedom, no treatment side effects, and function that is no different from the general population. In a significant percentage of patients, this goal remains unachievable, but many aspects of epilepsy are becoming clearer. This review will highlight 5 areas where progress is being made to achieve these goals in pediatric epilepsy. Specific research animal models are being developed to reflect the unique features of different pediatric epilepsies. As genetic syndromes are better identified, for some patients this has led to improved treatment. New advances in drug therapy have led to 3 new medications approved for children. More effective drug choices can now be recommended due to comparative drug trials and better overall care of children can be provided due to awareness of the comorbidities of epilepsy.

Recent advances in medicines for children and neonates

The European Society for Developmental, Perinatal and Paediatric Pharmacology held its 13th Biennial Congress in Oslo, Norway. The congress was attended by over 100 health professionals from all around the world. The focus of the congress was recent advances in drug therapy in neonates and children. Alongside invited speakers, there were a host of presentations by young investigators which consisted of oral and poster presentations.

Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by mutations in the SMN1 gene. The homologous copy (SMN2) is always present in SMA patients. SMN1 gene transcripts are usually full-length (FL), but exon 7 is spliced out in a high proportion of SMN2 transcripts (delta7) (Δ7). Advances in drug therapy for SMA have shown that an increase in SMN mRNA and protein levels can be achieved in vitro. We performed a systematic analysis of SMN expression in primary fibroblasts and EBV-transformed lymphoblasts from seven SMA patients with varying clinical severity and different SMN1 genotypes to determine expression differences in two accessible tissues (skin and blood). The basal expression of SMN mRNA FL and Δ7 in fibroblasts and lymphoblasts was analyzed by quantitative real-time PCR. The FL-SMN and FL/Δ7 SMN ratios were higher in control cells than in patients. Furthermore, we investigated the response of these cell lines to hydroxyurea, valproate and phenylbutyrate, drugs previously reported to upregulate SMN2. The response to treatments with these compounds was heterogeneous. We found both intra-patient and inter-patient variability even within haploidentical siblings, suggesting that tissue and individual factors may affect the response to these compounds. To optimize the stratification of patients in clinical trials, in vitro studies should be performed before enrolment so as to define each patient as a responder or non-responder to the compound under investigation.

Effect of Lipid-Lowering Treatment on Natural History of Heterozygous Familial Hypercholesterolemia in Past Three Decades

Long-term data on the effects of cholesterol-lowering regimens on low-density lipoprotein cholesterol levels and cardiovascular events in patients with familial hypercholesterolemia (FH) are lacking. The present study evaluated the effectiveness of long-term intensive lipid-lowering therapy on the natural history of FH. Of approximately 1,000 adult patients with heterozygous FH treated from 1974 to 2008, the charts of 327 were randomly selected for review. FH was defined according to the Simon Broome Registry Group criteria. The recorded data included age; gender; lipid levels with diet only, with each lipid-lowering regimen, and at the most recent visit during treatment; the length of follow-up; cardiovascular events; and revascularization procedures. The lipid assay calibrations and standardization were unchanged throughout the study period. Of the 327 patients, 60% were men, the mean age at diagnosis was 38 ± 14 years, and the mean follow-up was 15 ± 8 years. The baseline and most recent low-density lipoprotein cholesterol levels during treatment were 256 ± 60 mg/dl and 116 ± 46 mg/dl, respectively, for a mean reduction of 55% from baseline (p <0.0001). At their most recent visit, 24% of all subjects were treated with statin monotherapy, 55% with a statin plus another agent, and 21% with triple therapy; 44% received a statin-ezetimibe combination. The interval between recurrent cardiovascular events tended to increase from 5.3 ± 4.8 years before treatment to 7.4 ± 6.7 years after referral (p = 0.1303). In conclusion, advances in drug therapy during the past 3 decades has led to substantial reductions in low-density lipoprotein cholesterol levels and appears to diminish the cardiovascular risk in patients with FH.

Current and future treatment options in osteoporosis

The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. When prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. Currently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years. This review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.

Advances in drug therapy for gastroesophageal reflux disease

Advances in drug therapy for gastroesophageal reflux disease

Advances in drug therapy for systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that afflicts 500,000 people in the United States. There has not been a new SLE drug approved in the United States since 1958. However, a guidance document issued by the Food and Drug Administration in 2005 provided a roadmap for investigators which spawned numerous ongoing clinical trials. Among these, Belimumab, a monoclonal antibody to soluble B lymphocyte stimulator, met its primary endpoints in two large trials and will probably obtain FDA approval soon. Other promising agents targeting a variety of mechanisms of action are currently in development. This minireview highlights the latest therapies under investigation in SLE and gives an overview of the pathways that are specifically being targeted.

Interferons as potential adjuvants in prophylactic vaccines

Importance of the field: Vaccines are still one of the best approaches to manage infectious diseases. Despite the advances in drug therapies, prophylactic medicine is still more cost efficient and minimizes the burden in the heath system. Despite all the research in vaccine development, many infectious diseases are still without an effective vaccine. The use of adjuvants in vaccines has been one successful strategy to increase efficacy. IFNs are widely expressed cytokines that have potent antiviral effects. These cytokines are the first line of defense against viral infections and have important roles in immuno surveillance for malignant cells. One of the most promising uses of IFNs is as adjuvants that are co-applied with antigen in vaccines.Areas covered in this review: In this review, a cumulative analysis of many of the studies that have used IFN-α, -β, -γ and -λ as adjuvants between 1987 and the present suggests that many do possess the capacity to serve as potent immunoadjuvants for vaccination.What the reader will gain: This review provides a very large collection of studies involving all types of IFNs used as adjuvants in vaccines using different vaccination strategies and various animal models.Take home message: It is clear that the use of IFNs not only improved the efficacy and safety of most vaccines, but also had important immunomodulatory effect directing TH1 immune responses.

Non-surgical stem cell delivery strategies and in vivo cell tracking to injured myocardium

Heart failure is a major economic and public health problem. Despite the recent advances in drug therapy and coronary revascularization, the lost cardiomyocytes due to necrosis and apoptosis are not replaced by new myocardial tissue. Cell therapy is an interesting therapeutic option as it potentially improves contractility and restores regional ventricular function. Early clinical data demonstrated that cell transplantation, mainly delivered through non-surgical methods, is safe and feasible. However, several important issues need to be elucidated. This includes, next to determining the best cell type, the optimal delivery strategy, the biodistribution and the survival of implanted stem cells after transplantation. In this view, pre-clinical animal experiments are indispensable. Reporter genes, magnetic or radioactive labeling of stem cells have been developed to observe the fate and the distribution of transplanted cells using non-invasive imaging techniques. Several studies have demonstrated that these direct and non-direct labeling techniques may become an important tool in cell therapy. Integration of cell delivery and cell tracking will probably be a key for the success of cell therapy in patients. This review will provide a comprehensive overview on the various cell tracking and non-surgical cell delivery techniques, which are highly important in view of experimental and clinical studies.

Improved Hypertension Control

HYPERTENSION HAS LONG BEEN RECOGNIZED AS A MAjor risk factor for cardiovascular diseases. Advances in drug therapy have provided clinicians with the ability to lower blood pressure (BP) to goal levels in most persons with hypertension. In addition, many intervention trials have demonstrated large benefits of BP lowering in reducing the incidence of cardiovascular events independently of age, sex, type or severity of hypertension, or presence of comorbid conditions. Nevertheless, the control of hypertension in the United States and throughout the world has been grossly inadequate. The article by Egan and colleagues in this issue of JAMA provides new information on hypertension awareness, treatment, and control rates compiled from the 2007-2008 National Health and Nutrition Survey (NHANES). Data were derived from a representative sample of individuals aged 18 years or older and compared with the findings from NHANES surveys dating back to 1988. The results suggest considerable improvement in hypertension treatment and control rates in the period since the 1999-2004 survey, with awareness of hypertension increasing from 72% to 81%, treatment from 61% to 73%, and control (defined by systolic BP level of 140 mm Hg and diastolic BP level of 90 mm Hg) from 35% to 50%. The 50% control rate is particularly impressive and meets the Healthy People 2010 objective, which even recently seemed unachievable. The study by Egan et al also indicates a substantial reduction in BP in the hypertension group as a whole, the decrease averaging 7/4 mm Hg between these same periods. The percentage of individuals with the more severe category of stage 2 hypertension also decreased from 21% to 12%. The highest percentage of patients treated and not controlled for hypertension was in the group aged 60 years or older. These NHANES data have some limitations inherent in the study design. The hypertension sample size was relatively small, particularly in the group younger than 40 years. Blood pressures were obtained by a physician on a single visit and not confirmed subsequently; therefore, hypertension prevalence was probably overestimated. Individuals with diabetes were not considered to have hypertension if their BP was less than 140/90 mm Hg; however, they were included in the controlled hypertension group even if they did not receive antihypertensive therapy. Nevertheless, comparison of data between different periods would seem valid for demonstrating trends because the methods used in the different NHANES study periods appear broadly comparable, and appropriate age adjustments of data were made. The reasons for the accelerated improvement in hypertension control rates are unclear. Blood pressure control may be affected by factors such as inadequate access to health care, cost of therapy, poor adherence to medications, drug adverse effects, clinician inertia, disregard of treatment guidelines, inadequate education of clinicians and patients, and unhealthy lifestyles. The magnitude of the changes reported by Egan et al suggests that several factors probably were involved. Major changes toward healthier lifestyles have not occurred in the United States during the periods covered by this study and would not appear responsible for the observed improvement. Importantly, the proportion of individuals with hypertension receiving drug treatment increased substantially in concert with the increased percentage who achieved goal BP levels. The availability of a broad array of effective antihypertensive drugs with excellent tolerability has made treatment easier than in the past. Significant adverse effects are uncommon with many of the drugs, and cost has become less of an issue with the availability of generic preparations for most antihypertensive drug classes. In addition, many combination drugs have been introduced that can facilitate medication adherence for the patient. Other factors that may have been involved include increased use of electronic systems and other approaches to provide feedback reminders to patients and clinicians regarding patient appointments, prescription refills, the need to advance therapy based on existing national guidelines, auditing of records, and adherence to Health Plan Employer Data and Information Set performance standards and their enforcement by insurers and managed care organizations. Likewise, the increased use of nonphysician health care professionals such as nurse cli-

Atrial Fibrillation &amp;#x2013; Advances in Drug Therapy

The prevalence of atrial fibrillation (AF) continues to increase worldwide. It is projected that by 2050, between 5 and 15 million Americans will have AF. Such predictions necessitate new advances in drug therapy. AF is associated with changes in ionic currents. Atrial fibrosis, changes in gap junctions and cell membranes act in concert to initiate and maintain AF. Significant advances in understanding the pathophysiology of this condition have led to numerous new drug discoveries in the last decade. We discuss newly patented molecules that act as sodium and potassium channel blockers, gap junction and intracellular calcium modulators, stretch receptor antagonists, ischemic ion current inhibitors and adenosine receptor agonists.