Urinary Incontinence in Chronic Obstructive Pulmonary Disease: A Common Co-morbidity or a Typical Adverse Effect? Abstract Urinary incontinence (UI) is defined as a loss of bladder control and is characterized by the complaint of any involuntary leakage of urine. Evidence suggests that the prevalence of UI is higher in subjects with chronic obstructive pulmonary disease (COPD) than in age-matched controls in both sexes. UI is classified as stress, urge, and mixed, and has a considerable impact on quality of life. However, the prevalence of UI in individuals with COPD is mostly unexplored in clinical research and often underestimated in clinical practice. Interestingly, although the involuntary leakage of a small amount of urine during coughing (e.g., stress UI) is among the most plausible causes of UI in patients with COPD, its importance has been questioned by some researchers. Moreover, UI as a respiratory drug-related adverse effect is largely overlooked; only a few randomized controlled trials have reported the presence of urinary symptoms, mainly as urinary retention due to anticholinergic agents. In this narrative review, we explored whether, and to what extent, UI occurs in COPD individuals, and what the proposed actions to improve this condition are. We found that the association between UI and COPD is largely unexplored, mostly because UI tends to be attributed to older age. We infer that the prevalence of UI in individuals with chronic respiratory symptoms is often underestimated in clinical practice. The misinterpretation of urinary symptoms as related to the respiratory condition can delay diagnostic and therapeutic approaches. The use of simple self-administered questionnaires to assess the presence of UI is encouraged.

Old Drugs, New Delivery Systems in Parkinson’s Disease Abstract Levodopa is the mainstay of treatment in Parkinson’s disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.

Treating Older Patients with Chronic Lymphocytic Leukemia: A Personalized Approach Abstract Median age at diagnosis for patients with chronic lymphocytic leukemia (CLL) is 72 years, and the number of older individuals affected by this condition is predicted to increase in the future as populations age. Contrary to common assumptions, CLL significantly affects the life expectancy of older individuals, frequently presenting at a more advanced stage and with more unfavorable features than in the younger population. Therefore, identifying the optimal treatment for these patients is a priority. Older patients with CLL are usually classified as fit, non-fit, or frail based on performance status and comorbidities, and several assessment tools can be used to make these evaluations. While supportive care is appropriate for frail patients, the remaining patients should be treated when indication criteria are met. Treatment options include chemoimmunotherapy, monoclonal antibody-based approaches (such as the use of rituximab, ofatumumab, or obinutuzumab) and, more recently, small molecules (such as ibrutinib, idelalisib, and venetoclax). The choice of treatment is guided by the patient’s performance status and co-morbidities and by the disease characteristics, such as chromosomal and molecular abnormalities, and in patients with recurrent disease also by the type of prior regimen, their tolerability, and duration of response.

Managing Chronic Non-Malignant Pain in the Elderly: Intrathecal Therapy Abstract Intrathecal drug delivery (IDD) was first described in 1981 by Onofrio, who used a pump for continuous and intrathecal delivery of morphine to treat cancer pain. Over the following four decades, many reports supported this treatment method with implanted pumps for cancer and non-cancer pain. To date, more than 300,000 pumps for pain therapy and spasticity have been implanted worldwide. This article reviews current knowledge regarding intrathecal opioid therapy, focusing particularly on the use of IDD in elderly patients. Current literature is presented, and the arguments in favor of and against this therapy in elderly patients are discussed.

Sex Differences in the Prevalent Use of Oral Formulations of Cholinesterase Inhibitors in Older Adults with Dementia Abstract Background Cholinesterase inhibitors (ChEIs) are one of only two drug therapies available to manage cognitive decline in dementia. Given sex-specific differences in medication access and effects, it is important to understand how ChEIs are used by women and men. Objective The objective of this study was to provide contemporary sex-stratified evidence on patterns of ChEI use by community-dwelling older adults with dementia to inform opportunities to optimize drug prescribing. Methods We conducted a population-based cross-sectional study examining ChEI use in older adults with dementia in Ontario, Canada. We identified all community-dwelling individuals aged 66 years and older with a pre-existing diagnosis of dementia as of 1 April, 2016. We examined the prevalence of ChEI use among women and men separately, and explored the association between ChEI use and age, sex, income status, geographic location of residence, use of palliative care services, comorbidity, and polypharmacy. Concurrent use of drugs known to impair cognition (including antipsychotics, benzodiazepines, and medications with strong anticholinergic properties) was separately assessed among women and men using multivariable analyses and prevalence risk ratios. Results Of 74,799 women and 52,231 men living with dementia in the community, nearly 30% currently were using a ChEI (29.3% women, 28.6% men). Close to 70% of users were receiving the target therapeutic dose. Compared to men, women were less often taking the target therapeutic dose (67.8% women vs. 71.6% men, p < 0.001). Over 20% of users also were using drugs known to impair cognition, while being treated for cognitive decline using ChEIs. Compared to men, women were more often concurrently using drugs known to impair cognition (23.9% women vs. 21.8% men, p < 0.001). Conclusions This is one of the first studies of ChEI use to account for important sex differences. The results remind clinicians and researchers that patterns of ChEI therapy use differ by sex, as women were less likely to receive target therapeutic doses and more vulnerable to potentially problematic polypharmacy than men.

Patient-Associated Characteristics Influencing the Risk for Non-Persistence with Statins in Older Patients with Peripheral Arterial Disease Abstract Background and Objectives Secondary prevention of peripheral arterial disease includes administration of statins regardless of the patient’s serum cholesterol level. Our study aimed to identify patient-associated risk factors for statin non-persistence and comparison of the explanatory power of models based on clusters of patient-associated characteristics. Methods Our study cohort (n = 8330) was assembled from the database of the largest health insurance provider in the Slovak Republic. Statin users aged ≥ 65 years in whom peripheral arterial disease was diagnosed during 2012 were included. Patients were followed for 5 years; those with a treatment gap period of at least 6 months without statin prescription were classified as “non-persistent”. The risk factors for non-persistence were identified within six models (sociodemographic, cardiovascular events, comorbid conditions, statin-related characteristics, cardiovascular co-medication and full model) using Cox regression. The explanatory power of models was assessed using Harrell’s C-index. Results At the end of the follow-up, 35.7% of patients were found to be non-persistent. The full model had the highest explanatory power (C = 0.632). Female sex, atorvastatin and rosuvastatin as initially administered statins, being a new statin user and an increasing co-payment were associated with an increased risk for non-persistence. Increasing age, history of ischaemic stroke, diabetes mellitus, general practitioner as index prescriber, increasing overall number of medications and co-administration of certain cardiovascular co-medications were associated with a lower likelihood for non-persistence. Conclusions Patients identified as high risk for non-persistence require special attention aimed at the improvement of their persistence with statin treatment.

Alpha-1 Antitrypsin Deficiency and Accelerated Aging: A New Model for an Old Disease? Abstract Alpha-1 antitrypsin (AAT) protects the lung by inhibiting neutrophil proteinases, but AAT has many other non-proteolytic functions that are anti-inflammatory, antiviral and homeostatic. Approximately 1 in 1600 to 1 in 5000 people have the homozygous Z mutation, which causes AAT misfolding, accumulation in (predominantly) liver cells and low circulating levels of AAT, leading to AAT deficiency (AATD). AATD is classically a disease of neutrophilic inflammation, with an aggressive and damaging innate immune response contributing to emphysema and other pathologies. AATD is one of the most common genetic disorders but considerably under-recognised. Most patients are diagnosed later in life, by which time they may have accumulated significant lung, liver and multisystem damage. Disease presentation is heterogeneous and not fully explained by deficiency levels alone or exposure to cigarette smoking. This suggests other factors influence AATD-associated pathological processes. Aging itself is associated with organ dysfunction, including emphysema and airflow obstruction, inflammation, altered immune cell responses (termed immunosenescence) and a loss of proteostasis. Many of these processes are present in AATD but at an earlier age and more advanced stage compared with chronological aging alone. Augmentation therapy does not completely abrogate the manifold disease processes present in AATD. New approaches are needed. There is emerging evidence that both age- and AATD-related disease processes are amenable to correction by targeting proteostasis, autophagy, immunosenescence and epigenetic factors. This review explores the impact of the aging process on AATD presentation and discusses novel therapeutic strategies to mitigate low levels of AAT or misfolded AAT in an aging host.

Efficacy and Safety of Etanercept in Elderly Patients with Rheumatoid Arthritis: A Post-Hoc Analysis of Randomized Controlled Trials Abstract Background Elderly individuals are disproportionately affected by rheumatoid arthritis (RA), but few studies have addressed the efficacy and safety of treatments in this population. Objective Our objective was to assess the efficacy and safety of etanercept in elderly patients (aged ≥ 65 years) with RA. Methods The efficacy analysis was a post hoc analysis of data from the open-label period of three phase IV clinical trials of etanercept for RA. Least squares (LS) change from baseline (cfb) in 28-joint Disease Activity Score (DAS28), Health Assessment Questionnaire Disability Index (HAQ-DI), and modified Total Sharp Scores (mTSS) were analyzed by age (< 65 vs. ≥ 65 years) for each study. The safety analyses were of data pooled from the double-blind, placebo-controlled periods of 19 phase I–IV randomized studies of etanercept in patients with RA. The percentage occurrence of adverse events (AEs) in placebo- and etanercept-treated patients was analyzed by age (< 65 vs. ≥ 65 years). Results There were no significant differences in LS mean cfb in DAS28 or mTSS between the two age groups. LS mean cfb in HAQ-DI scores was consistently lower in elderly than in non-elderly patients, although significant differences were not observed in all trials. Overall, AE occurrence was higher in elderly than non-elderly patients, regardless of treatment. In etanercept-treated patients, there were small yet statistically significant increases in the occurrence of congestive heart failure, serious infections, and non-melanoma skin cancers in elderly versus non-elderly patients. For most AEs, occurrence did not significantly differ between elderly and non-elderly patients. Conclusion Overall, there were no substantial differences in the efficacy or safety of etanercept between elderly and non-elderly patients with RA.

Practical Treatment Considerations in the Management of Genitourinary Syndrome of Menopause Abstract Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a result of the loss of sex steroids that occurs with menopause. It is a progressive condition that does not resolve without treatment and can adversely affect a woman’s quality of life. For a variety of reasons, many symptomatic women do not seek treatment and, of those who do, many are unhappy with their options. Additionally, many healthcare providers do not actively screen their menopausal patients for the symptoms of genitourinary syndrome of menopause. In this review, we discuss the clinical presentation of genitourinary syndrome of menopause as well as the treatment guidelines recommended by the major societies engaged in women’s health. This is followed by a review of available treatment options that includes both hormonal and non-hormonal therapies. We discuss both the systemic and vaginal estrogen products that have been available for decades and remain important treatment options for patients; however, a major intent of the review is to provide information on the newer, non-estrogen pharmacologic treatment options, in particular oral ospemifene and vaginal prasterone. A discussion of adjunctive therapies such as moisturizers, lubricants, physical therapy/dilators, hyaluronic acid, and laser therapy is included. We also address some of the available data on both the patient and healthcare providers perspectives on treatment, including cost, and touch briefly on the topic of treating women with a history of, or at high risk for, breast cancer.

The FORTA (Fit fOR The Aged)-EPI (Epidemiological) Algorithm: Application of an Information Technology Tool for the Epidemiological Assessment of Drug Treatment in Older People Abstract Background To improve drug treatment in older people, who often present with multimorbidity and related polypharmacy, the FORTA (Fit fOR The Aged) List was developed via a Delphi consensus procedure. As a patient-in-focus listing approach (PILA), it has been clinically validated (VALFORTA trial). Unlike drug-oriented listing approaches (DOLAs), its application requires knowledge of patients’ characteristics, including diagnoses and other details. As a drug list with discrete labels, application of FORTA seems particularly amenable to electronic support. Methods An information technology (IT) algorithm was developed to analyze bulk data on International Classification of Diseases (ICD)-coded diseases and Anatomical Therapeutic Chemical (ATC)-coded drugs. FORTA-labeled diagnoses and drugs were used to compute the FORTA score, an automatically generated score that describes medication quality by adding up points assigned for errors related to over- and under-treatment. The algorithm detects mismatches between diagnoses and drugs, suboptimal drugs, omitted drugs, and deficient medication escalation schemes. The read-out produces explanations for each error point. Results A total of 5603 and 7954 patients ≥ 65 years were included from two claims datasets (> 30,000 patients each, public health insurance). The FORTA scores were comparable (mean ± standard deviation 4.29 ± 3.37 vs. 4.17 ± 3.16), and similar to that determined in VALFORTA (pre-intervention 3.5 ± 2.7). Under-treatment was two times more prevalent than over-treatment. The main areas of under-treatment were pain, type 2 diabetes mellitus, and depression, and the main areas of over-treatment were gastrointestinal (proton pump inhibitors), pain (non-steroidal anti-inflammatory drugs), and arterial hypertension (β-blockers). The FORTA score is positively correlated with higher age, a higher Charlson Comorbidity Index, and more frequent hospitalizations. Patients in disease management programs run by public health insurers had higher scores than comparators. Conclusions The algorithm produces plausible analyses of medication errors in older people, pointing to established areas of therapeutic deficiencies. Though individual recommendations exist, the algorithm cannot employ the full potential of FORTA as important details (e.g., blood pressure values, pain intensity) are not (yet) included. However, it seems capable of detecting medication problems in large cohorts—FORTA-EPI (Epidemiological) is designed to support epidemiological analyses, e.g., on comparisons of large cohorts, interventional impact, or longitudinal trends.