Burden of Inappropriate Prescription of Direct Oral Anticoagulants at Hospital Admission and Discharge in the Elderly: A Prospective Observational Multicenter Study Abstract Introduction Direct oral anticoagulants (DOACs) were developed to overcome some of the limitations associated with vitamin K antagonists (VKAs), such as interindividual variability or the need for therapeutic drug monitoring. However, the complexity of DOAC dose regimens can still lead to dosing errors and potential bleeding-related or thromboembolic adverse events, especially in the elderly. Objective Our objective was to evaluate the rate of inappropriate preadmission DOAC prescriptions at hospital and to evaluate the ability of hospitals to correct them. Methods An observational prospective study was conducted in elderly patients (aged ≥ 65 years) hospitalized in six acute units of three Parisian university hospitals between February and July 2018. DOAC prescriptions prior to admission and at discharge were analyzed according to the guidelines in the summaries of product characteristics. Results A total of 157 patients were included in the study, with a median age of 84 years (interquartile range [IQR] 77–89). The median glomerular filtration rate, determined with the Cockcroft–Gault equation, was 48 mL/min (IQR 35–61). Apixaban was the most frequently prescribed drug, mainly for atrial fibrillation. Overall, 48 (30.6%) and 34 (22.4%) prescriptions were inappropriate prior to admission and at discharge, respectively, showing a significant decrease (p < 0.001). Hospitals significantly corrected more inappropriate prescriptions (37.5%) than they generated (4.6%) (p < 0.05). The nature of the inappropriate prescribing was underdosing (68.8% and 76.5% prior to admission and at discharge, respectively), followed by overdosing (stable rate at almost 20%) and indication errors. No risk factors for inappropriate use were identified by our analysis. Conclusion One-third of DOAC preadmission prescriptions for elderly patients were inappropriate, indicating that a need remains to strengthen DOAC prescribing guidelines in ambulatory clinical practice. However, the rate of inappropriate prescriptions decreased at patient discharge. Future studies are needed to test actions to promote the proper use of DOACs.

Appropriate Use of Laxatives in the Older Person Abstract Constipation is a common condition, affecting up to half of all older adults during their lifetime. Untreated constipation has significant impacts, decreasing quality of life and potentially leading to urinary and/or faecal incontinence, faecal impaction and, in severe cases, hospitalisation. The increased constipation prevalence among older populations is multifactorial, with a number of age-related factors contributing to the rise in prevalence with aging. Laxatives are the mainstay of constipation management and are commonly used among older populations for both treatment and prevention of constipation. A range of laxative types including bulk forming agents, softeners and emollients, osmotic agents, stimulants, and the newer prokinetic and secretory agents are available. Despite laxatives being freely available without prescription in many countries and commonly used by older individuals, evidence regarding the effectiveness or safety of most laxatives in older populations is lacking. Additionally, age-related changes increase the risk of adverse effects associated with laxatives, such as electrolyte disturbances, among older persons. Caution must be taken when extrapolating recommendations for general adult populations to older populations. Laxative choice for older individuals should be tailored after careful assessment and consideration of comorbid conditions, concomitant medications and the potential for adverse effects.

Is Testosterone Replacement Therapy in Older Men Effective and Safe? Abstract The number of older adults over 65 years of age is expected to increase to almost 100 million in the US by 2050, more than double the current figure of 46 million. Advanced age is associated with increased frailty among older Americans and often leads to increased disability, hospitalization, institutionalization, and, eventually, mortality. In search of means to improve age-related risks for adverse health outcomes, the question of restoring diminishing sex hormones has gathered much interest and has led to the practice of sex hormone replacement therapies in older men. Recent data suggest that androgen prescription rates in the US for men older than 60 years of age quadrupled from the years 2001 to 2011. While prescription sales of testosterone have increased from $150 million in 2000 to $1.8 billion in 2011, a significant portion of men prescribed testosterone replacement therapy did not meet the laboratory criteria for hypogonadism. While some clinical trials reported an association between testosterone insufficiency in older men and increased risk of death, the exact effects and consequences of testosterone replacement therapy, specifically in older men, remain unclear. This review is aimed at discussing the possible benefits and complications of testosterone replacement therapy in older men over 60 years of age.

Proton Pump Inhibitors and Infection-Related Hospitalizations Among Residents of Long-Term Care Facilities: A Case–Control Study Abstract Objective Our objective was to investigate associations between proton pump inhibitor (PPIs) use and infection-related hospitalizations among residents of long-term care facilities (LTCFs). Methods This was a case–control study of residents aged ≥ 65 years admitted to hospital between July 2013 and June 2015. Residents admitted for infections (cases) and falls or fall-related injuries (controls) were matched for age (± 2 years), sex, and index date of admission (± 6 months). Conditional logistic regression was used to estimate crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between PPI use and infection-related hospitalizations. Analyses were adjusted for age, sex, polypharmacy, diabetes, heart failure, chronic obstructive pulmonary disease, myocardial infarction, cerebrovascular accident, and concomitant use of cancer and immunosuppressant medications. Subgroup analyses were performed for high- and low/moderate-intensity PPIs and for respiratory and non-respiratory infections. Logistic regression was used to compare the odds of infection-related hospitalizations among users of high- and low/moderate-intensity PPIs. Results Overall, 181 cases were matched to 354 controls. Preadmission PPI use was associated with infection-related hospitalizations (aOR 1.66; 95% CI 1.11–2.48). In subgroup analyses, the association was apparent only for respiratory infections (aOR 2.26; 95% CI 1.37–3.73) and high-intensity PPIs (aOR 1.93; 95% CI 1.23–3.04). However, the risk of infection-related hospitalization was not significantly higher among users of high- versus low/moderate-intensity PPIs (aOR 1.25; 95% CI 0.74–2.13). Conclusion Residents who use PPIs may be at increased risk of infection-related hospitalizations, particularly respiratory infections. Study findings provide further support for initiatives to minimize unnecessary PPI use in the LTCF setting.

Age-Related Resistance to Thyroid Hormone Action Abstract The age-related resistance to thyroid hormones (THs) explains the paucity of symptoms and signs of hyperthyroidism in older adults and may partly explain the myriad of symptoms and signs of hypothyroidism in biochemically euthyroid older people. This review considers the available data on the mechanisms underlying TH resistance with aging and compares these physiologic changes with the changes observed in congenital TH resistance syndromes. Aging is associated with alterations in TH economy along with a host of changes in the responsiveness of various tissues to THs. The age-related resistance to THs can be attributed to decreased TH transport to tissues, decreased nuclear receptor occupancy, decreased activation of thyroxine to triiodothyronine, and alterations in TH responsive gene expression. Although an increase in serum TH levels is expected in syndromes of TH resistance, unchanged serum TH levels in the euthyroid elderly is the result of increased sensitivity to TH negative feedback with increased suppression of thyroid-stimulating hormone, decreased thyroidal sensitivity to thyroid-stimulating hormone, and decreased TH production and secretion. The current clinical evidence suggests that the age-related TH resistance is mostly an adaptive response of the aging organism. It is tempting to speculate that similar changes can occur prematurely in a group of younger people who present with signs and symptoms of hypothyroidism despite normal serum thyroid function tests.

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study Abstract Background Synthetic oral cannabinoids (nabilone and dronabinol) may have adverse respiratory effects. Our purpose was to describe the scope, pattern, and patient characteristics associated with incident off-label synthetic oral cannabinoid use among older adults with chronic obstructive pulmonary disease (COPD) compared to older adults without COPD. Methods This was a retrospective, population-based, cohort study using Ontario, Canada, heath administrative data. Individuals aged 66 years or older were included, and physician-diagnosed COPD was identified using a previously validated, highly specific algorithm. Incident off-label oral cannabinoid use was examined between April 1, 2005 and March 31, 2015. Descriptive statistics were used to describe drug use patterns. Multiple logistic regression was used to identify patient characteristics associated with incident drug use. Results There were 172,282 older adults with COPD and 1,068,256 older adults without COPD identified between April 1, 2005 and March 31, 2015. Incident synthetic oral cannabinoid use during this period occurred with significantly greater (p < 0.001) frequency among older adults with COPD (0.6%) versus older adults without COPD (0.3%). Compared to those without COPD, older adults with COPD used synthetic cannabinoids for significantly longer durations and more frequently at higher doses. Conclusions Although incident off-label oral cannabinoid use was relatively low among all older Ontarian adults, this drug class was used with greater frequency and more often in potentially concerning ways among older adults with COPD. These findings raise possible safety concerns, but further research on the respiratory safety of oral cannabinoids among individuals with COPD is needed.

Pathogenesis, Diagnosis and Management of Polymyalgia Rheumatica Abstract Polymyalgia rheumatica is an inflammatory rheumatic disease of the elderly characterised by pain and stiffness in the neck and pelvic girdle, and is the second most common inflammatory rheumatic condition in this age group, after rheumatoid arthritis. Polymyalgia rheumatica can occur independently or in association with giant cell arteritis, which is the most common form of primary vasculitis. The diagnosis of polymyalgia rheumatica is usually based on clinical presentation and increase of inflammatory markers. There are no pathognomonic findings that can confirm the diagnosis. However, different imaging techniques, especially ultrasonography, can assist in the identification of polymyalgia rheumatica. Glucocorticoids are the cornerstone of the treatment of polymyalgia rheumatica, but they might be associated with different adverse events. A subgroup of patients presents with a refractory disease course and, in these cases, adding methotrexate as a steroid-sparing agent could be useful. In this review, we summarise the latest findings regarding the pathogenesis, diagnosis and management of polymyalgia rheumatica and try to highlight the possible pitfalls, especially in elderly patients.

Precautions and Monitoring of Patients Taking Phosphodiesterase Type 5 Inhibitors Who are at Risk of Increased Intraocular Pressure Abstract Phosphodiesterase type 5 inhibitors (PDE5Is) may increase intraocular pressure (IOP) by increasing blood flow to the ciliary body. Although clinical studies of changes in IOP after single and multiple doses of PDE5Is show variable results, most are limited by small sample sizes, absence of control groups and blinding, and use of normal patient volunteers who have no risk factors for glaucoma. However, multiple case reports of glaucoma have been published, and one epidemiologic analysis of the National Health and Nutrition Examination Survey (NHANES) database of US respondents suggested a significant association of prolonged sildenafil use and self-reported glaucoma. With the widespread use of PDE5Is for treatment of erectile dysfunction in males with risk factors for glaucoma, and the potential of PDE5Is to worsen optic nerve damage in patients with glaucoma, we recommend a vision screening exam prior to the initiation of the PDE5I and careful follow-up thereafter, particularly if the patient is taking tadalafil, a long-acting PDE5I, if the patient is taking high doses of a PDE5I daily and persistently, and if the patient has risk factors for glaucoma or if the patient is at risk of worsening glaucoma.

Local Anesthetic Toxicity in the Geriatric Population Abstract This article provides a concise overview of local anesthetic systemic toxicity, its history, mechanisms, risk factors, prevention, clinical presentation, and treatment, with a special emphasis on issues specific to the geriatric population. The authors used MEDLINE, Scopus, and Google Scholar to search for original research articles (human and animal studies), registries data, case reports, review articles, and pertinent online publications using the combinations of the following search terms: local anesthetics, local anesthetic systemic toxicity, intralipid, lipid emulsion, Exparel, ultrasound-guidance, regional anesthesia, lidocaine, bupivacaine, ropivacaine, cocaine, procaine, tetracaine, levobupivacaine, liposomal bupivacaine, lignocaine. Local anesthetic systemic toxicity continues to occur despite the use of putatively less cardiotoxic formulations of local anesthetics and more common use of ultrasound guidance. The elderly appear to be at a disproportionately increased risk for toxicity owing to the presence of relevant comorbidities and decreased muscle mass. Examination of recent case reports involving patients over the age of 65 years demonstrates that inadvertent overdosing is responsible for some cases of local anesthetic systemic toxicity. Elderly patients are at increased risk of local anesthetic systemic toxicity. When considering use of local anesthetics in older patients, special attention should be paid to the presence of systemic disease and muscle wasting. The safety of regional anesthesia and multi-modal analgesia among these at-risk patients will be improved by educating physicians and staff to recognize and manage local anesthetic systemic toxicity.

Does Deprescribing Improve Quality of Life? A Systematic Review of the Literature Abstract Background Deprescribing has been shown to reduce potentially inappropriate or unnecessary medications; however, whether these benefits translate into improved quality of life (QOL) is uncertain. Objective The objective of this study was to isolate the impact of deprescribing on patient or designated representative reported QOL; satisfaction with care (SWC) and emergency department (ED) visits and hospitalizations were also investigated to further explore this question. Methods This systematic review searched the Cochrane Library, Cumulative Index to Nursing and Allied Health (CINAHL), MEDLINE, and EMBASE from database inception until November 2017. Randomized controlled trials and non-randomized prospective studies of older adults (> 65 years or older) and older persons with life-limiting conditions were included. Two reviewers independently assessed the search results and performed risk of bias assessments. Data on QOL, SWC, and ED visits and hospitalizations were extracted from all identified studies. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration. Results Screening of 6543 eligible records identified 12 studies within 13 articles. In ten studies investigating the reduction of at least one medication deprescribed, compared with usual care, all but two found no difference in QOL. To date there has only been one study examining the impact of deprescribing on SWC, which was found to be not statistically significant. Four studies exploring the impact of deprescribing on ED visits and hospitalizations also found no significant difference. However, many studies were found to have a higher performance, detection, or other bias. We found considerable heterogeneity in patient populations, targeted medications for deprescribing, and QOL measurements used in these studies. Conclusion Based on a limited number of studies with varying methodological rigor, deprescribing may not significantly improve QOL or SWC; however, it may not contribute to additional ED visits and hospitalizations. Future controlled studies are needed.