Retraction Note: Three-year Experience with Alendronate Treatment in Postmenopausal Osteoporotic Japanese Women with or without Renal Dysfunction: A Retrospective Study The Editor has retracted this article [Iwamoto J, Sato Y, Uzawa M, Takeda T, Matsumoto H. Three-year Experience with Alendronate Treatment in Postmenopausal Osteoporotic Japanese Women with or without Renal Dysfunction: A Retrospective Study. Drugs Aging 2012; 29(2): 133-142.]. After publication, serious concerns were raised with respect to the reporting of the study design, methodology, data and authorship, and the Editor no longer has confidence in this article. Hideo Matsumoto and Tsuyoshi Takeda agree with this retraction. Jun Iwamoto and Mitsuyoshi Uzawa have not responded to correspondence about this retraction. Yoshihiro Sato is deceased.

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.

The Relationship Between Anticholinergic Exposure and Falls, Fractures, and Mortality in Patients with Overactive Bladder Abstract Background Understanding risk factors associated with falls is important for optimizing care and quality of life for older patients. Objective Our objective was to determine the relationship between anticholinergic exposure and falls, fractures, and all-cause mortality. Methods An observational retrospective cohort study was conducted using administrative claims data from 1 January 2007 to 30 September 2015. Individuals aged 65–89 years newly diagnosed or treated for overactive bladder (OAB) were identified. Index date was the first OAB diagnosis or OAB medication prescription claim. Follow-up began on the index date and continued until death, disenrollment, or end of study period. The Anticholinergic Cognitive Burden (ACB) scale was used to define and quantify daily anticholinergic exposure and intensity. The primary study outcome was a combined endpoint of falls or fractures. All-cause mortality was a secondary endpoint. Results There were 113,311 patients with mean age of 74.8 ± standard deviation (SD) 6.2 years included. Current anticholinergic exposure was associated with a 1.28-fold increased hazard of a fall/fracture (95% confidence interval [CI] 1.23–1.32) compared with unexposed person-time, and past exposure was associated with a 1.14-fold increased hazard of a fall/fracture (95% CI 1.12–1.17). Compared with unexposed person-time, low-, moderate-, and high-intensity anticholinergic exposure was associated with a 1.04-fold (95% CI 1.00–1.07), 1.13-fold (95% CI 1.09–1.17), and 1.31-fold (95% CI 1.26–1.36) increased hazard of falls/fractures, respectively. A similar pattern was observed for all-cause mortality. Conclusions Anticholinergic exposure is associated with an increased risk of falls or fractures in older patients and is an important consideration when evaluating treatment options for such patients with OAB.

Efficacy and Adverse Events of Immunotherapy with Checkpoint Inhibitors in Older Patients with Cancer Abstract The number of older patients with cancer is increasing as a result of the ageing of Western societies. Immune checkpoint inhibitors have improved cancer treatment and are associated with lower rates of treatment-related toxicity compared with chemotherapy in the general population. Nonetheless, immune checkpoint inhibitors have potentially serious immune-related adverse events, which might have a greater impact on older and more vulnerable patients and potentially influence treatment efficacy and quality of life. Previous clinical trials have shown no major increase in immune-related adverse events; however, older patients are underrepresented and relatively healthy in these trials. Observational studies suggest that older and more vulnerable patients may be at a higher risk of immune-related adverse events and early treatment discontinuation. Geriatric assessment could help identify older patients who will benefit from immune checkpoint inhibitors.

Late-Onset and Elderly Psoriatic Arthritis: Clinical Aspects and Management Abstract Psoriatic arthritis (PsA) can start in subjects aged over 60 years, defined as late-onset PsA. In late-onset PsA, the weight of family history and genetic background appears less significant when compared with younger onset PsA, whereas obesity and smoking have been suggested as potential risk factors. In patients with late-onset PsA, erosive polyarticular or oligoarticular patterns are more frequent than other phenotypes. Laboratory findings usually show an increase in levels of acute phase reactants, including erythrocyte sedimentation rate and C-reactive protein. The drugs used for the management of young PsA subjects represent the same therapeutic armamentarium used in patients with late-onset disease. However, in elderly subjects, these anti-inflammatory, immunomodulatory and immunosuppressive therapies, including newer biologic therapies, represent an important challenge due to age aspects, increased frequency of comorbidities and associated polypharmacotherapy. There is a need for more evidence around treatment strategy for these patients in order to identify the best balance between the benefits and risks of pharmacological agents. This is important for establishing how treatment should ideally be tailored to the characteristics of any single patient and to the presence of complex age- and disease-related aspects. The objective of this review is to focus on pathogenetic, clinical and therapeutic aspects of late-onset PsA and the management of elderly PsA patients.

Potential Statin Overuse in Older Patients: A Retrospective Cross-Sectional Study Using French Health Insurance Databases Abstract Background Although compelling evidence exists supporting statins (HMG-CoA reductase inhibitors) for secondary prevention in older patients with clinical atherosclerotic diseases, the same cannot be said for primary prevention. Objectives The objectives of this study were to estimate the frequency of potential statin overuse in older patients, the potential drug cost savings if corrected, and the associated factors. Methods A retrospective cross-sectional study was conducted in Alsace and Lorraine (France) from 1 January to 30 April 2017. All statin users aged 80 years or over living in the community (including nursing homes) and identified from the French health insurance database were analyzed. Potential statin overuse was defined according to the STOPP/START (Screening Tool of Older People’s Prescriptions/Screening Tool to Alert to Right Treatment) criteria. Results Among the 38,268 aged insured, 23,228 (60.7%) had potential statin overuse. Of those living in the community, 22,132 (60.0%) patients had potential statin overuse: 12,352 (55.8%) for primary and 9780 (44.2%) for secondary prevention. Among nursing home residents, 1096 (79.0%) had potential statin overuse: 394 (35.9%) for primary and 702 (64.1%) for secondary prevention. The potential drug cost savings associated with the adjustment of potential statin overuse were €924,100 for the study period. Living in nursing home [adjusted odds ratio (ORadjusted) 3.91, 95% confidence interval (CI) 2.82–5.41] and being a female (ORadjusted 2.84, 95% CI 2.54–3.17) were the main risk factors associated with potential statin overuse. Conclusion The frequency of potential statin overuse is very high among older people aged 80 years or over, highlighting the need to re-evaluate statin therapy and consider deprescribing, particularly for primary prevention and in nursing homes.

Drug Treatment of Restless Legs Syndrome in Older Adults Abstract Restless legs syndrome (RLS) has a high prevalence in the elderly and can impact sleep quality and sleep quantity, reduce quality of life (QoL), and increase the risk of falls during episodes of night-time ambulation. In patients unable to verbalize their sensory symptoms, certain behavioral cues may help with the diagnosis. A state of brain iron deficiency could play a central role in the pathophysiology of RLS and be upstream to a series of dysfunctions that are not limited to the dopaminergic system. Management should initially emphasize lifestyle modifications and reduction of all possible iatrogenic contributors while maintaining a state of normal–high peripheral iron stores. Oral iron, in patients with ferritin levels < 75 μg/dL, appears to be effective, although iron infusions should be considered when more immediate benefit or oral iron have not been effective. When other attempts fail and patients continue to experience chronic RLS symptoms substantially interfering with QoL, pharmacological agents may present a favorable benefit versus risk profile. Such agents may include α-2-δ drugs or dopaminergic agents, after careful consideration of the risk of RLS augmentation with the latter class. In patients with established RLS augmentation from the use of dopaminergic drugs, the addition of α-2-δ agents or low-dose opioids, with subsequent slow tapering of dopaminergic agents, is recommended. With any of these agents, caution should be made with regard to the risk of drug–drug interactions and altered pharmacokinetics in this fragile population. Although showing excellent long-term safety data in non-elderly adults with RLS, studies are needed to ascertain that such treatments are effective and well tolerated in older adults.

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.

Management of Secondary Hyperparathyroidism in Chronic Kidney Disease: A Focus on the Elderly Abstract Secondary hyperparathyroidism (SHPT) is a major complication of chronic kidney disease (CKD), responsible for skeletal and vascular damage with increased risk of bone fractures, cardiovascular events, and mortality. However, the optimal serum parathormone (PTH) levels for improving clinical outcomes remain uncertain. Treatment of SHPT is based on nutritional therapy, phosphate binders, vitamin D, and calcimimetics, but none of these interventions has ever been tested against placebo in randomized controlled trials. Treatment of SHPT in the elderly should consider the many peculiarities of aging in terms of physiopathology, quality of life, symptoms, subjective perception of disease, drug load, and the modifying effect of treatment on disease-related outcomes. Unfortunately, peculiarities of SHPT among elderly CKD patients are mainly unexplored. The present review aims to provide a reasonable merging of evidence regarding the management of SHPT in CKD, with more actual concepts on how to care for older patients.

Suitable Use of Injectable Agents to Overcome Hypoglycemia Risk, Barriers, and Clinical Inertia in Community-Dwelling Older Adults with Type 2 Diabetes Mellitus Abstract The management of type 2 diabetes mellitus in older adults requires a comprehensive understanding of the relationship between the disease (medical) and the functional, psychological/cognitive, and social geriatric domains, to individualize both glycemic targets and therapeutic approaches. Prevention of hypoglycemia is a major priority that should be addressed as soon as its presence or risk is detected, adjusting the target and therapeutics accordingly. Nonetheless, treatment intensification should not be neglected when applicable, consistent with recommendations from organizations such as the American Geriatrics Society and the American Diabetes Association, to reduce not only long-term macrovascular and microvascular complications (individualization), but also short-term complications from hyperglycemia (polyuria, volume depletion, urinary incontinence). Such complications can negatively impact the physical and cognitive function of older adults, worsen their quality of life, and additionally affect their families and society. We emphasize individualization, utilizing the multiple classes of antihyperglycemic agents available. Metformin remains as first-line therapy, and additional agents offer advantages and disadvantages that ought to be considered when developing a patient-centric plan of care. For selected cases, injectable therapies such as long-acting basal insulin analogs and glucagon-like peptide-1 receptor agonists can offer advantages to counter hypoglycemia risk, patient-related barriers, and clinical inertia. Furthermore, some injectable agents could potentially simplify regimens while providing safe and effective glycemic control. In this review, we discuss the use of injectable therapies for selected community-dwelling older adults, barriers to transition to injectable therapy, and measures aimed at removing these barriers and assisting physicians and their teams to transition older patients to injectable therapies when appropriate.