Metatarsalgia

Abstract

Recognition of chronic obstructive pulmonary disease (COPD) is often missed or delayed in primary care. Once recognized, COPD is often undertreated or episodically treated, focusing on acute exacerbations without establishing maintenance treatment to control ongoing disease. Diagnostic and therapeutic pessimism result in missed opportunities to reduce exacerbations, maintain physical functioning, and reduce emergent health care requirements. Proactive diagnosis and evidence-based management can alleviate the impact of COPD on patients' lives. Smoking cessation has been proven to slow the rate of lung function decline. Maintenance pharmacotherapy and immunizations reduce exacerbations. Pulmonary rehabilitation improves respiratory symptoms and physical functioning and reduces rehospitalizations after exacerbations. Self-management education improves health-related quality of life and reduces inpatient and emergency care usage. Maintenance treatment with long-acting inhaled bronchodilators is appropriate beginning in moderate COPD to maintain airway patency and reduce exacerbations. Tiotropium is US Food and Drug Administration (FDA) approved to treat bronchospasm and reduce exacerbations in patients with COPD; salmeterol/fluticasone is FDA approved to treat airflow obstruction in COPD and reduce exacerbations in patients with a history of exacerbations. Other maintenance long-acting bronchodilators—salmeterol, formoterol, and budesonide/formoterol—are FDA approved to treat airway obstruction in COPD but lack an approved indication against exacerbations. FDA warnings on the use of long-acting beta-adrenergic agents (LABAs) in asthma specifically exempt COPD and do not apply to LABA/inhaled corticosteroid combinations used in COPD. The actual effectiveness achieved in practice with any COPD therapies depends on patients' inhaler technique, adherence, and persistence. Medication usage rates and inhaler proficiency may be improved by concordance, in which the health care provider and patient collaborate to make treatment plans sustainable in the patient's daily life. Practice redesign for whole-patient primary care provides additional tools for comprehensive COPD management. Innovations such as group visits and the patient-centered medical home provide newer ways to interact with COPD patients and their families. Patient-focused and evidence-based options enable primary care practices to manage COPD longitudinally and improve patient outcomes through the course of the disease.     

FDA drug safety communications: a narrative review and clinical considerations for older adults

BackgroundThe US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public.ObjectiveTo summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults.MethodsThe FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern.ResultsFDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose–response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose–response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older adults. Finally, several warnings were made about statins. Routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury from statin use; thus, liver enzymes are no longer recommended to be routinely monitored. Statin-induced cognitive changes are rare, and insufficient evidence is currently available to establish causality. Statins appear to moderately increase the risk of developing diabetes (versus placebo), and regular screening for diabetes should be considered, especially for patients taking high-dose statins and patients with multiple risk factors for diabetes.ConclusionFDA drug safety communications incorporate complex methodologies that investigate the risks (and relative benefits) of medication therapy. Clinicians caring for older adults need to be aware of the most current evidence behind these drug risks to effectively communicate with and care for their patients.     

Comorbidities,Age, and Polypharmacy Limit the Use by US Older Adults with Nocturia of the Only FDA-approved Drugs for the Symptom

PurposeThe goal of this study was to determine if the US adult population with nocturia (waking from sleep at night to void) can easily take medications (desmopressin acetate) approved by the US Food and Drug Administration for nocturia. The study examined: (1) the prevalence of comorbid conditions, laboratory abnormalities, and concomitant medications that increase risk of desmopressin use; and (2) whether these factors are associated with age or nocturia frequency.MethodsUsing a cross-sectional analysis of four US National Health and Nutrition Examination Survey (NHANES) waves (2005–2012), a total of 4111 participants aged ≥50 years who reported ≥2 nightly episodes of nocturia were identified. The main outcome was frequency of contraindications and drug interactions as described in US Food and Drug Administration–approved prescribing information. These prescribing concerns were matched to examination findings, medical conditions, concomitant medications, and laboratory results of NHANES participants. The associations between prescribing concerns and nocturia severity and age groups were examined.FindingsThe mean participant age was 65.7 years (95% CI, 65.3–66.1), and 45.5% were male. Desmopressin prescribing concerns were present in 80.5% (95% CI, 78.0–82.9) of those ≥50 years of age with nocturia; 50.0% (95% CI, 47.0–53.0) had contraindications, and 41.6% (95% CI, 39.3–44.0) took a concomitant drug that could increase risk of low serum sodium. Desmopressin contraindications were higher with older age (P < 0.001) and present in 73.2% (95% CI, 69.3–77.1) of those ≥80 years of age.ImplicationsUsing NHANES data, this study showed that older US adults with nocturia have a high prevalence of medical conditions, concomitant medications, and baseline laboratory abnormalities that likely increase the risk of potentially severe adverse side effects from desmopressin use. A medication designed and approved for a clinical symptom that is most common in older adults could not be taken by most of the older adults with the symptom.     

Medication errors in older adults: a review of recent publications

Objective:This paper reviews recent articles examining medication errors in the elderly.Methods:MEDLINE and International Pharmaceutical Abstracts were searched for articles published in 2006 using a combination of the terms medication errors, medication adherence, medication compliance, suboptimal prescribing, and aged. A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional publications. Those studies that described new measures of medication errors or had a randomized controlled design, evaluated the impact of an intervention on ≥1 measure of medication errors, and involved the community-dwelling elderly were included in the review.Results:The search identified 5 studies and a new set of explicit criteria for prescribing problems in nursing homes from the Centers for Medicare and Medicaid Services (CMS). One of the studies found a new instrument, the Medication Management Instrument for Deficiencies in the Elderly, to be a reliable and valid measure of medication management in older adults. A study in the ambulatory elderly found that 13.0% reported cost-related medication nonadherence. A randomized controlled trial of a pharmacist intervention in elderly patients at high risk for coronary events found the intervention was associated with improvements in both medication adherence and systolic blood pressure control. The report from the CMS described new explicit criteria for unnecessary drug use in elderly patients in long-term care facilities, including drugs to avoid, drugs that should be limited in dose or duration, drugs to be monitored, and drug-drug interactions. A modified Delphi survey of an expert panel reached consensus on 28 drug-disease interactions in older adults. Finally, a randomized controlled trial of computerized feedback in a health maintenance organization found improvements in inappropriate prescribing of target drugs in older adults.Conclusion:Data from recently published studies may provide guidance to practitioners and help direct future research.     

Strong Pharmacokinetic Drug-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2021: Mechanisms and Clinical Implications

PurposeThis analysis aimed to identify all strong drug-drug interactions (DDIs) associated with drugs approved by the US Food and Drug Administration (FDA) in 2021.MethodsDDI data for small molecular drugs approved by the FDA in 2021 (N = 36) were analyzed using the University of Washington Drug Interaction Database. The mechanism(s) and clinical magnitude of these interactions were characterized based on information available in the new drug application reviews. Clinical studies and simulation results with mean AUC ratios (AUCRs) ≥5 for inhibition DDIs and ≤0.2 for induction (ie, strong interactions) were then fully analyzed. A total of 7 drugs had an AUC change ≥5-fold as victim drugs, with inhibition and induction of cytochrome P450 (CYP) 3A explaining all interactions.FindingsSix drugs, namely atogepant, finerenone, ibrexafungerp, infigratinib, mobocertinib, and voclosporin, were sensitive substrates of CYP3A, with AUCRs of 5.45 to 18.55 when co-administered with the strong inhibitors itraconazole or ketoconazole, whereas avacopan was a moderate sensitive substrate of CYP3A, most sensitive to induction (>5-fold change). Only 1 drug, viloxazine, was a strong perpetrator (CYP1A2 inhibition with caffeine AUCR of 5.83). No drug had strong inhibition of transporters and no strong induction of enzymes or transporters was detected. No dominant therapeutic class was identified. As expected, all these strong DDIs triggered strict labeling recommendations.ImplicationsOverall, identifying strong DDIs with newly approved drugs and understanding their mechanisms are critical to provide effective management strategies in patients who often receive multiple comedications.     

Prescribing medications in pediatrics: concerns regarding FDA approval and pharmacokinetics

Prescribing medications "off-label" is a common practice in pediatric health care since many medications lack U.S. Food and Drug Administration (FDA) approval for pediatric drug labeling due to insufficient drug testing in children. This clinical paper reviews the FDA laws regarding approval of medications in children and the pharmacokinetic differences in absorption, distribution, metabolism and excretion between children and adults. Two commonly used pharmacology resources were reviewed to determine their identification of FDA approved indications in children and dosing recommendations by age or weight in children. Adhering to the "community's standard of care" is a common guideline for prescribing "off-label" in pediatrics, but must be used in combination with multiple respected pediatric resources and with full knowledge of pharmacokinetics in children, particularly in young children.     

Managing Stable COPD in 2009: Incorporating Results from Recent Clinical Studies into a Goal-Directed Approach for Clinicians

Abstract

Chronic obstructive pulmonary disease (COPD) is prevalent in primary care practice and an important cause of functional decline, hospitalizations, and death. Recent clinical trials of COPD therapy demonstrate the ability of bronchodilators (especially long-acting β₂-agonists and anticholinergics), either alone or in combination with inhaled corticosteroids, to achieve the goals of managing stable disease. These management goals include: symptom relief, improvement in exercise tolerance and health status, prevention of exacerbations and progression of disease, and reduction in mortality. Recent studies of COPD treatment also provide important safety information to help clinicians address patient concerns about treatment risks. We reviewed recent clinical trials to develop concepts of care for the non-specialist clinician managing patients with stable COPD.     

The short,the long and the “ultra-long”: Why duration of bronchodilator action matters in chronic obstructive pulmonary disease

Bronchodilators are the cornerstone of symptomatic treatment for all chronic obstructive pulmonary disease (COPD) severity stages when administered on a regular basis to prevent or reduce symptoms and exacerbations. The principal inhaled bronchodilator treatments are beta-2 agonists and anticholinergics, used singularly or in combination. There is good evidence that regular treatment with long-acting bronchodilators is more effective and convenient than treatment with short-acting bronchodilators. Long-acting agents include the twice-daily beta-2 agonists formoterol and salmeterol, the once-daily anticholinergic tiotropium, and, more recently, the once-daily beta-2 agonist indacaterol. Long-acting bronchodilators have been shown to improve multiple clinical outcomes in COPD in comparison to short-acting agents including lung function, symptoms, dyspnea, quality of life, and exacerbations. Studies of head-to-head comparisons of long-acting bronchodilators are scant but indicate superior bronchodilation of tiotropium over salmeterol, while preliminary data from trials with the novel once-daily beta-2 agonist indacaterol indicate superior bronchodilation and clinical efficacy over twice-daily long-acting beta-2 agonists and at least equipotent bronchodilation as once-daily tiotropium. These recent therapeutic developments in COPD represent a change of paradigm with a shift from short-acting bronchodilators with multiple dosing per day to reduced dosing frequency and prolonged duration of action including once-daily treatment. This review summarizes relevant data and landmark studies comparing the efficacy of short-acting versus longer-acting bronchodilators in COPD, including new data for once-daily indacaterol, and discusses potential mechanism underlying the improved efficacy of long-acting versus short-acting bronchodilators.     

Safety Considerations in Prescription of NSAIDs for Musculoskeletal Pain: A Narrative Review

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for the treatment of painful musculoskeletal conditions. When prescribing oral NSAIDs, clinicians must consider coexisting cardiovascular, cerebrovascular, gastrointestinal, and renal disease because oral NSAIDs are associated with a broad spectrum of adverse effects on these systems. The different safety profiles of NSAIDs can be attributed to differences in the extent to which the drug inhibits cyclo-oxygenase-1 vs -2 and their potential for drug-drug interactions. This narrative review intends to guide the clinician in prescribing oral NSAIDs while taking into consideration these comorbid conditions and drug interactions.

Cancer Pain Management Considerations in Older Adults

ObjectiveTo address the pharmacokinetics and pharmacodynamics of aging and its impact on the complexities of pain management in older adults with cancer. To describe assessment and nursing strategies for individualized care and side effect managementData SourcesPeer-reviewed articles.ConclusionCancer pain is a complex problem in older adults because of the variations in aging and alterations in pharmacokinetics and pharmacodynamics. Pain management must be based on thorough assessment, incorporating the unique factors of each patient. Ongoing follow-up is critical to ensure adequate pain control with optimization of functional status.Implications for Nursing PracticeAwareness of physiological changes of aging is important in caring for older adults. Oncology nurses can play a key role in the assessment of older adults with cancer and education of patients and caregivers regarding pain medications, side-effects, and oral adherence.     

Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection

In the era of increasing antibiotic resistance, development of new agents that could provide therapeutic options for difficult to treat pathogens is vital. Dalbavancin is a new lipoglycopeptide recently approved by the US FDA for the treatment of acute bacterial skin and skin structure infections. A derivative of the older glycopeptide class, chemical structure alterations resulted in a molecule with a similar mechanism of action, however, with a comparatively increased activity as reflected by organism MICs. These modifications also resulted in an antibiotic with distinctive properties that allow for once-weekly dosing in the treatment of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and drug resistant Streptococcus spp. As the first of these long acting compounds, understanding the pharmacokinetic and pharmacodynamic properties of agents like dalbavancin is essential for determining a place in therapy.     

Use of computer decision support interventions to improve medication prescribing in older adults: a systematic review

Background: Older adults take multiple medications and are at high risk for adverse drug effects.Objective: This systematic review was conducted to describe the impact of computer decision support (CDS) interventions designed to improve the quality of medication prescribing in older adults.Methods: PubMed and EMBASE databases were searched from January 1980 through July 2007 (English-language only); studies were eligible if they described a CDS intervention intended to improve medication prescribing in adults aged ≥60 years. Studies were retained if they were observational or experimental in design and reported ≥1 process or clinical outcome measurement related to medication prescribing. In the main analysis, study characteristics and major outcome results were extracted. A combination of searches was performed using relevant medical subject headings: aged; drug therapy, computer-assisted; medication errors; medication errors/prevention and control; decision making, computer-assisted; decision support systems, clinical; and clinical pharmacy information systems.Results: After review of study abstracts, 10 articles met the eligibility criteria. Of those 10 studies testing CDS interventions, 8 showed at least modest improvements (median number needed to treat, 33) in prescribing, as measured by minimizing drugs to avoid, optimizing drug dosage, or more generally improving prescribing choices in older adults (according to each study's intervention protocols). Findings for the impact of CDS interventions on clinical outcomes were mixed and were reported for only 2 studies.Conclusions: Various types of CDS interventions may be effective in improving medication prescribing in older adults, but few studies reported clinical outcomes related to changes in medication prescribing. Data from this study should help to guide refinement and testing of future CDS interventions that specifically target older adult populations that are taking multiple medications.     

Blueprint for Prescriber Continuing Education Program

EDITOR'S ABSTRACT

On October 25, 2011, the Center for Drug Evaluation and Research (CDER) of the Food and Drug Administration (FDA) posted online this Blueprint for Prescriber Continuing Education, labeled “final,” relating to extended-release and long-acting opioids. The pending FDA Risk Evaluation Management Strategy (REMS) requires prescriber education. This document provides guidance to sponsors of these dosage forms in developing the prescvriber education component of their REMS.

?This report was posted online by the federal agency on October 25, 2011 at: http://www.fda.gov/downloads/drugs/drugsafety/informationbydrugclass/ucm277916.pdf. It is in the public domain.     

Social transformation and social isolation of older adults: Digital technologies,nursing, healthcare

BackgroundThe incidence of social isolation among older adults is on the rise in today's health care climate. Consequently, preventing or ameliorating social isolation through technology in this age group is now being discussed as a significant social and health issue.AimThe purpose of the opinion paper is to clarify social transformation through technology and shed light on a new reality for older adults in situations of social isolation. Our goal is to persuade the reader that our position on this topic is a valid one. We support our claims with practice-based evidence and published research studies.MethodsTo do so, we checked the most recent literature, most of which came from the last decade. Our literature survey focused primarily on what is known about technology and how technology can affect social transformation and perceptions of social isolation.FindingsTwo dominant transformative realities became the focal points: the precarious implications of loneliness for older adults and the emerging reality of social change through digital technology central to eHealth and mHealth.DiscussionTo benefit from new technologies and reduce the detrimental effects of social isolation, we must engage older adults in a meaningful way and adapt the system of smart devices to reflect the specific physiological and psychological characteristics of the ageing population.ConclusionOlder adults need to comprehend the meanings of their social experiences to preserve their active lifestyle. Human interactions may be desirable, but technological dominance may also minimize the adverse effects of social isolation.     

Optimizing maintenance therapy for chronic obstructive pulmonary disease: strategies for improving patient-centered outcomes

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality. Published practice guidelines and treatment algorithms for COPD are designed to increase awareness of the problem and improve patient care; however, <40% of subjects diagnosed with COPD are receiving appropriate maintenance therapy. OBJECTIVE: This paper reviews the use of maintenance therapy in COPD and examines the optimal timing for initiating such therapy based on the available literature. METHODS: Relevant publications were identified through a search of MEDLINE (1995-May 2007) using the terms COPD, guidelines, treatment, maintenance therapy, bronchodilator, ipratropium, tiotropium, beta-agonist, salmeterol, and inhaled corticosteroid. English-language publications discussing pharmacologic maintenance therapy for COPD, including practice statements/guidelines, randomized controlled clinical trials, systematic reviews, and meta-analyses, with a focus on agents currently approved for use in the United States, were selected for inclusion. RESULTS: Although guidelines and algorithms agree on the importance of regularly scheduled maintenance therapy to reduce symptoms of COPD, minimize activity limitations, and improve health status, the timing of the initiation of such therapy is debatable. In most instances, maintenance medications, which include long-acting beta(2)-agonists, long-acting anticholinergics, and combination products, are prescribed late in the disease process and mainly for patients with severe disease. However, there is increasing evidence that the use of maintenance therapy early in the disease process may be associated with improvements in such outcomes as lung function, symptoms, exercise tolerance, exacerbations of COPD, and quality of life. CONCLUSION: The high burden associated with COPD highlights the need to initiate maintenance therapy before a substantial decline in lung function has occurred.     

Clinical characteristics of neutrophilic,eosinophilic and mixed-type exacerbation phenotypes of COPD

BackgroundChronic obstructive pulmonary disease (COPD) comprises a significant number of emergency department (ED) presentations, and hematological phenotypes may have prognostic significance. The aim of this study was to investigate the effect of hematological phenotypes on serious outcomes in COPD exacerbations.MethodsA prospective cohort study was carried out in patients with COPD exacerbation presenting to the ED. The patients were classified into three groups, including neutrophilic, eosinophilic, and mixed-type (including neutrophilic and eosinophilic features) COPD exacerbation. Outcome measures were defined as mortality, hospitalization, and need for intensive care unit (ICU) care within three months, and these outcomes were compared among groups.ResultsA total of 173 COPD patients were assessed for eligibility, and 147 of them were included in the final analysis. The study population consisted of 90 patients with neutrophilic exacerbation (61.2%), 26 patients with eosinophilic exacerbation (17.7%), and 31 patients with mixed-type exacerbation (21.1%). The neutrophilic exacerbation group was older, was more often tachycardic and desaturated, and had more sputum production compared with the eosinophilic exacerbation group. Mortality was seen in 35 patients in the neutrophilic exacerbation group (38.9%), whereas 5 patients in the eosinophilic group (19.2%) and 6 patients in the mixed-type group (19.4%) died (p = .044). No difference was observed among groups in terms of hospital and ICU admission.ConclusionCOPD exacerbations with neutrophilic phenotypes presented to the ED with more serious clinical findings compared with eosinophilic exacerbations. This may also have a possible effect on mortality.     

Recent advances in immunotherapy for the treatment of prostate cancer

Introduction: Prostate cancer vaccines attempt to induce cancer-specific systemic immune responses and represent a new class of targeted therapies, many of which are non-toxic. Several vaccine technologies are in development.

Areas covered: An autologous antigen presenting cell vaccine loaded with prostate acid phosphatase conjugated with GM-CSF, sipuleucel-T confers a survival advantage in men with metastatic castration-resistant prostate cancer (CRPC) and is now FDA approved based on the IMPACT trial. A poxvirus-based vaccine, PROSTVAC-VF TRICOM targeting prostate-specific antigen (PSA), has demonstrated improved survival in a randomized Phase II trial of patients with metastatic CRPC. Novel T lymphocyte checkpoint inhibitors of cytotoxic T lymphocyte antigen 4 and programmed death-1 are also emerging. Recognition of improved survival without an earlier clinical signal of activity by conventional criteria has led to new guidelines to evaluate immunotherapeutic agents. The clinical benefit of combining vaccines with chemotherapy, radiotherapy and other immunotherapeutic and biologic agents is being evaluated in the context of disappointing results of combination GVAX vaccine and docetaxel chemotherapy.

Expert opinion: To build on the success of early phase trials, efforts must be made to optimize vaccine approaches and patient selection.