Showing papers in "Drugs & Aging in 2019"

Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

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

Pharmacological Management of Dementia with Lewy Bodies

Abstract: Dementia with Lewy bodies (DLB) is a complex disease that involves a variety of cognitive, behavioral and neurological symptoms, including progressive memory loss, visual hallucinations, parkinsonism, cognitive fluctuations and rapid eye movement sleep behavior disorder (RBD). These symptoms may appear in varying combinations and levels of severity in each patient who is seen in the clinic, making diagnosis and treatment a challenge. DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer’s disease and Parkinson’s disease (PD). The median age of onset for DLB (76.3 years) is younger than that seen in PD dementia (81.4 years). New pathological studies have shown that most DLB patients have variable amounts of Alzheimer’s changes in their brains, explaining the wide variability in this disease’s clinical presentation and clinical course. This review discusses the three cholinesterase inhibitors that have been shown to be effective in managing the cognitive and behavioral symptoms of DLB: rivastigmine, galantamine and donepezil. Memantine is able to improve clinical global impression of change in those with mild to moderate DLB. Levodopa can treat the parkinsonism of some DLB patients, but the dose is often limited due to the fact that it can cause agitation or worsening of visual hallucinations. A recent phase 2 clinical trial showed the benefit of zonisamide when it is added as an adjunct to levodopa for treating DLB parkinsonism. While atypical antipsychotic drugs may not always be helpful as monotherapy in managing the agitation associated with DLB, low doses of valproic acid can be effective when added as an adjunct to drugs like quetiapine. Pimavanserin may prove to be a useful treatment for psychosis in DLB patients, but like other antipsychotic drugs that are used in dementia patients, there is a small increased risk of mortality. RBD, which is a common core clinical feature of DLB, can be managed with either melatonin or clonazepam. Two agents targeting alpha-synuclein (NPT200-11 and ambroxol) currently hold promise as disease-modifying therapies for DLB, but they are yet to be tested in clinical trials. An agent (E2027) that offers hope of neuroprotection by increasing central cyclic guanosine monophosphate (cGMP) levels is currently being examined in clinical trials in DLB patients.

Medical Cannabis for Older Patients

Abstract: Interest in the medicinal use of cannabis and cannabinoids is mounting worldwide. Fueled by enthusiastic media coverage, patients perceive cannabinoids as a natural remedy for many symptoms. Cannabinoid use is of particular interest for older individuals who may experience symptoms such as chronic pain, sleep disturbance, cancer-related symptoms and mood disorders, all of which are often poorly controlled by current drug treatments that may also incur medication-induced side effects. This review provides a summary of the evidence for use of cannabinoids, and medical cannabis in particular, for this age group, with attention to efficacy and harms. Evidence of efficacy for relief of an array of symptoms is overall scanty, and almost all study participants are aged < 60 years. The risk of known and potential adverse effects is considerable, with concerns for cognitive, cardiovascular and gait and stability effects in older adults. Finally, in light of the paucity of clinical evidence and increasing patient requests for information or use, we propose a pragmatic clinical approach to a rational dialogue with older patients, highlighting the importance of individual benefit–risk assessment and shared patient–clinician decision making.

Effect of Vitamin B Supplementation on Cognitive Function in the Elderly: A Systematic Review and Meta-Analysis.

Abstract: Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval − 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval − 0.10 to 0.18) cognitive impairment compared to placebo. Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

Safety of symptomatic slow-acting drugs for osteoarthritis: outcomes of a systematic review and meta-analysis.

Abstract: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58–3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02–4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36–4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42–4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85–5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

Abstract: We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42–7.89); ER opioids (RR 4.22, 95% CI 3.44–5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87–18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22–5.18); ER opioids (RR 4.03, 95% CI 3.37–4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74–7.43; ER opioids: RR 7.87, 95% CI 5.20–11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90–4.02; ER opioids: RR 2.76, 95% CI 2.19–3.47) was found with all opioid formulations versus placebo. Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.

Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of the Literature and Practical Guide

Abstract: Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with increased localized and generalized osteoporosis (OP). Previous studies estimated that approximately one-third of the RA population experience bone loss. Moreover, RA patients suffer from a doubled fracture incidence depending on several clinical factors, such as disease severity, age, glucocorticoid (GC) use, and immobility. As OP fractures are related to impaired quality of life and increased mortality rates, OP has an enormous impact on global health status. Therefore, there is an urgent need for a holistic approach in daily clinical practice. In other words, both OP- and RA-related factors should be taken into account in treatment guidelines for OP in RA. First, to determine the actual fracture risk, dual-energy X-ray absorptiometry (DXA), including vertebral fracture assessment (VFA) and calculation of the 10-year fracture risk with FRAX®, should be performed. In case of high fracture risk, calcium and vitamin D should be supplemented alongside anti-osteoporotic treatment. Importantly, RA treatment should be optimal, aiming at low disease activity or remission. Moreover, GC treatment should be at the lowest possible dose. In this way, good fracture risk management will lead to fracture risk reduction in RA patients. This review provides a practical guide for clinicians regarding pharmacological treatment options in RA patients with OP, taking into account both osteoporotic-related factors and factors related to RA.

The FORTA (Fit fOR The Aged) List 2018: Third Version of a Validated Clinical Tool for Improved Drug Treatment in Older People

Abstract: Multimorbidity and widespread use of clinical guidelines are the main causes for highly prevalent polypharmacy in older people [1, 2]. Polypharmacy has been identified as a major risk factor for inappropriate drug treatment and adverse drug events in older patients [3–5], and is even associated with increased mortality [6, 7]. However, the use of multiple drugs to treat serious medical conditions is often vital, but should be differentiated into appropriate/beneficial or problematic applications by the critical review of medication schemes. Several listing approaches and tools have been developed to assist prescribers in choosing the appropriate drugs for their patients. The majority of these approaches (e.g., Beers criteria [8]) are drug-oriented listing approaches (DOLA) [9] and mostly focus on what not to prescribe in older patients. Their impact on relevant clinical outcomes (e.g., mortality or hospitalization) is still unclear [10], with the majority of randomized clinical trials failing to demonstrate improvement of clinical endpoints [9]. In contrast, a few listing approaches (e.g., the FORTA [Fit fOR The Aged] List) are patient-in-focus listing approaches (PILA); they recommend both what to do and what not to do, requiring intricate medical knowledge about patients. For PILA, the majority of randomized trials have been clinically successful [9]. The FORTA Lists 2012 and 2015 were published in Drugs & Aging [11, 12], and represent the first drug lists combining positive and negative labeling of drugs used for long-term drug treatment in older patients. Labels in the FORTA List range from A (indispensable) to B (beneficial), C (questionable) and D (avoid), depending on the state of evidence for safety, efficacy and age appropriateness [13]. So far, the clinical usefulness, implementability and teachability of the FORTA List have been validated in controlled clinical trials [14, 15], showing a significant impact on medication quality (reduction of overand undertreatment errors as totalized in the FORTA score) and adverse drug reactions [15, 16]. Driven by new evidence in the field of geriatric pharmacology and experiences with the previous versions, the FORTA List was updated in 2018 utilizing the same twostep Delphi process employed to generate its former versions [11, 12]. Twenty-two experts from Germany, Austria and Switzerland participated in the assessment. The metrics of changes are given in Table 1. The new list (https ://www.umm.uni-heide lberg .de/klini sche-pharm akolo gie/ forsc hung/forta -proje kt/; free access to PDFs and FORTA apps) now contains 296 entries in 30 indications; it thus adds 23 entries and one indication to its former version. The highest percentage of disease-related entries with changed FORTA classifications was observed for atrial fibrillation (33.3%, Table 1). In addition, the mean consensus coefficient for oncological diseases (solid tumors and hematological neoplasias) significantly increased (p < 0.01, Table 1). Over 99.66% (292 items) of the proposed 295 items received a consensus coefficient of ≥ 0.8 after the first round of the Delphi process, rendering the second round redundant. This demonstrates increased coherence between raters and initiators. The FORTA List 2018 now reflects the latest advances in drug therapy for older patients, and its changes demonstrate the necessity of frequent updates as a living document. It is supported by an even wider consensus among raters as compared to its last version, thus further increasing its validity for clinical use. It represents a clinical aid to ameliorate drug treatment in older patients by targeting both overand undertreatment. As a PILA, its use requires detailed knowledge of the patient [9, 17] and thus a patient-centered FORTA members are listed in the Acknowledgements section.

Safety of Paracetamol in Osteoarthritis: What Does the Literature Say?

Abstract: Osteoarthritis (OA) is a major cause of pain and physical disability in adults, and an increasingly common disease given its associations with aging and a growing obese/overweight population. Paracetamol is widely recommended for analgesia at an early stage in the management of OA, and, although frequently prescribed, evidence suggests the efficacy of paracetamol for OA pain is low. Furthermore, there have been recent concerns over the safety profile of paracetamol, with reports of gastrointestinal, cardiovascular, hepatic and renal adverse events. This narrative review summarizes recent literature on the benefits and harms of paracetamol for OA pain. Data on long-term paracetamol safety are derived largely from observational evidence, and are difficult to interpret given the potential biases of such data. Nonetheless, a considerable degree of toxicity is associated with paracetamol use among the general population, especially at the upper end of standard analgesic doses. Paracetamol is linked to liver function abnormalities and there is evidence for liver failure associated with non-intentional paracetamol overdose. Safety data for paracetamol use in the older population (aged >65 years) are sparse; however, there is some evidence that frail elderly people may have impaired paracetamol clearance. Given that the analgesic benefit of paracetamol in OA joint pain is uncertain and potential safety issues have been raised, more careful consideration of its use is required.

Influenza Vaccination in Older Adults: Recent Innovations and Practical Applications.

Abstract: Influenza can lead to serious illness, particularly for older adults. In addition to short-term morbidity and mortality during the acute infection, recovery can be prolonged and often incomplete. This may lead to persistent declines in health and function, including catastrophic disability, which has dramatic implications for the well-being and support needs of older adults and their caregivers. All of this means that prevention of infection and effective treatment when illness has occurred are of paramount importance. In this narrative review, we discuss the effectiveness of influenza vaccines for the prevention of influenza illness and serious outcomes in older adults. We review evidence of vaccine effectiveness for older adults in comparison with younger age groups, and also highlight the importance of frailty as a determinant of vaccine effectiveness. We then turn our attention to the question of why older and frailer individuals have poorer vaccine responses, and consider changes in immune function and inflammatory responses. This sets the stage for a discussion of newer influenza vaccine products that have been developed with the aim of enhancing vaccine effectiveness in older adults. We review the available evidence on vaccine efficacy, effectiveness and cost benefits, consider the potential place of these innovations in clinical geriatric practice, and discuss international advisory committee recommendations on influenza vaccination in older adults. Finally, we highlight the importance of influenza prevention to support healthy aging, along with the need to improve vaccine coverage rates using available vaccine products, and to spur development of better influenza vaccines for older adults in the near future.

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.

Safety of Cyclooxygenase-2 Inhibitors in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

Abstract: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09–1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03–1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08–1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01–2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80–1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22–2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21–2.29; 0%). In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis

Abstract: We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue. The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04–1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15–1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96–3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73–1.27). Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.

Approaches to Deprescribing Psychotropic Medications for Changed Behaviours in Long-Term Care Residents Living with Dementia.

Abstract: Psychotropic medications have a high risk of serious adverse events and small effect size for changed behaviours for people with dementia. Non-pharmacological approaches are recommended as first-line treatment for changed behaviours, yet psychotropic medications remain highly prevalent in long-term aged care settings. This narrative review describes the current evidence regarding deprescribing psychotropic medications for people with dementia in long-term care. Deprescribing psychotropic medications can be achieved without harm to the person with dementia, and most people experience no withdrawal symptoms. Interventions to deprescribe psychotropic medications should be multifactorial, including lowering the dose of the medication over time, educational interventions and psychological support. However, implementing this is a significant challenge due to the overreliance on psychotropic medications for behavioural management in long-term aged care. Facilitators to deprescribing psychotropic medications in long-term care include multidisciplinary teams with adequate training, education and managerial support, engaging residents and families and change 'champions'. Deprescribing practices should be person-centred, and an individualised deprescribing protocol should be in place, followed by careful monitoring of the individual. The person with dementia and their family, general practitioner, pharmacist, and allied health and direct care staff should all be involved throughout the deprescribing process. Direct care staff need adequate support, education and training, so they can effectively help the individual and implement person-centred approaches in the absence of psychotropic medications. Effective communication between residents and staff and amongst staff is consistently shown to be an important factor for deciding whether deprescribing of a medication should occur and the successful implementation of deprescribing psychotropic medications.

Drugs Contributing to Anticholinergic Burden and Risk of Fall or Fall-Related Injury among Older Adults with Mild Cognitive Impairment, Dementia and Multiple Chronic Conditions: A Retrospective Cohort Study

Abstract: It is not known whether drugs with different anticholinergic ratings contribute proportionately to overall anticholinergic score. Our objective was to assess the risk of falls or fall-related injuries as a function of the overall anticholinergic score resulting from drugs with different anticholinergic ratings among people with impaired cognition. This was a retrospective cohort study of adults aged ≥ 65 years with mild cognitive impairment (MCI) or dementia and two or more additional chronic conditions (N = 10,698) in an integrated delivery system. Electronic health record data, including pharmacy fills and diagnosis claims, were used to assess anticholinergic medication use, quantified using the anticholinergic cognitive burden (ACB) scale, falls and fall-related injuries. During a median follow-up of 366 days, 63% of the cohort used one or more ACB drug; 2015 (18.8%) people experienced a fall or fall-related injury. Among patients with a daily ACB score of 5, the greatest increase in risk of falls or fall-related injuries was seen when level 2 and level 3 drugs were used in combination [hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.51–2.83]. Multiple ACB level 1 drugs taken together also increased the hazard of a fall or fall-related injury (HR 1.16; 95% CI 1.03–1.32). The risk of fall or fall-related injury as a function of exposure to ACB level 2 drugs (HR 1.56; 95% CI 1.16–2.10) was higher than that for ACB level 1 or 3 drugs. The same daily ACB score was associated with a different degree of risk, depending on the ACB ratings of the individual drugs comprising the score. Combinations of level 2 and level 3 drugs had the greatest risk of fall or fall-related injury relative to other individuals with the same daily ACB score. Low-potency anticholinergic drugs taken together modestly increased the hazard of a fall or fall-related injury.

Qualitative Analysis of Cannabis Use Among Older Adults in Colorado

Abstract: Although the rate of cannabis use by older adults is increasing more quickly than all other age groups, little is known about the reasons why older adults use cannabis and the outcomes they experience. The objective of this study was to identify the most salient themes concerning the use of medical and recreational cannabis by older adults living in Colorado. Specifically, we sought to (1) characterize perceptions of cannabis use by users and non-users, (2) determine how older adults access cannabis, and (3) explicate both positive and negative outcomes associated with cannabis use. Between June and November 2017, we conducted 17 focus groups in senior centers, health clinics, and cannabis dispensaries in 15 Colorado cities. Participants included 136 persons aged over 60 years who were both users and non-users of cannabis. We coded and analyzed session transcripts using thematic analysis with NVivo software. We identified 16 codes from which five main themes emerged. These themes included: a lack of education and research about cannabis, a lack of provider communication, access to medical cannabis, the outcomes of cannabis use, and a reluctance to discuss cannabis use. Older adults want more information about cannabis and desire to communicate with their healthcare providers. Older adults who used cannabis for medical purposes reported positive outcomes but highlighted difficulties in accessing medical cannabis. Older adults in Colorado also revealed how a stigma continues to be attached to using cannabis.

Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

Abstract: Some controversy exists regarding the safety of intra-articular hyaluronic acid (IAHA) in the management of osteoarthritis (OA). The objective of this study was to re-assess the safety profile of IAHA in patients with OA, through a comprehensive meta-analysis of randomized, placebo-controlled trials. A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with IAHA in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, musculoskeletal, renal and urinary disorders, infections and infestations, and hypersensitivity reaction. Database searches initially identified 1481 records. After exclusions according to the selection criteria, 22 studies were included in the qualitative synthesis, and nine studies having adequate data were ultimately included in the meta-analysis. From the studies excluded according to the pre-specified selection criteria, 21 with other pharmacological OA treatments permitted during the trials were a posteriori included in a parallel qualitative synthesis, from which eight studies with adequate data were finally included in a parallel meta-analysis. Since this meta-analysis was designed to assess safety, the exclusion criterion on concomitant anti-OA medication was crucial. However, due to the high number of studies that allowed mainly concomitant oral non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a post hoc parallel analysis in order to compare the results from the two analyses. No statistically significant difference in odds was found between IAHA and placebo for all types of SOC-related disorders, except for infections and infestations, for which significantly lower odds were found with IAHA compared with placebo, both overall (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.40–0.93; I2 = 0%) and in studies without concomitant anti-OA medication (OR = 0.49, 95% CI 0.27–0.89). There were significant increased odds of reporting serious AEs with IAHA compared with placebo, both overall (OR = 1.78, 95% CI 1.21–2.63; I2 = 0%) and in studies with concomitant anti-OA medication (OR = 1.78, 95% CI 1.10–2.89), but not in studies without concomitant anti-OA medication (OR = 1.78, 95% CI 0.92–3.47). Using the available data on studies without any concomitant anti-OA medication permitted during clinical trials, IAHA seems not to be associated with any safety issue in the management of OA. However, this evidence was associated with only a “low” to “moderate” certainty. A possible association with increased risk of serious AEs, particularly when used with concomitant OA medications, requires further investigation.

Relation Between Delirium and Anticholinergic Drug Burden in a Cohort of Hospitalized Older Patients: An Observational Study

Abstract: Delirium is a neuropsychiatric syndrome which occurs on average in one out of five hospitalized older patients. It is associated with a number of negative outcomes, including worsening of cognitive and functional status, increasing the burden on patients and caregivers, and elevated mortality. Medications with anticholinergic effect have been associated with the clinical severity of delirium symptoms in older medical inpatients, but this association is still debated. The aim was to assess the association between delirium and anticholinergic load according to the hypothesis that the cumulative anticholinergic burden increases the risk of delirium. This retrospective, cross-sectional study was conducted in a sample of older patients admitted to the Acute Geriatric Unit (AGU) of the San Gerardo Hospital in Monza (Italy) between June 2014 and January 2015. Delirium was diagnosed on admission using the 4 ‘A’s Test (4AT), a validated screening tool for delirium diagnosis, which has shown good sensitivity and specificity to detect this condition in elderly patients admitted to an AGU. Each patient’s anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale, a ranking of anticholinergic medications to predict the risk of adverse effects on the central nervous system in older patients. Of the 477 eligible for the analysis, 151 (31.7%) had delirium. According to the ACB scale, 377 patients (79.0%) received at least one anticholinergic drug. Apart from quetiapine, which has a strong anticholinergic effect, the most commonly prescribed anticholinergic medications had potential anticholinergic effects but unknown clinically relevant cognitive effects according to the ACB scale (score 1). Patients with delirium had a higher anticholinergic burden than those without delirium, with a dose–effect relationship between total ACB score and delirium, which was significant at univariate analysis. A plateau risk was found in patients who scored 0–2, but patients who scored 3 or more had about three or six times the risk of delirium than those not taking anticholinergic drugs. The dose–response relationship was maintained in the multivariate model adjusted for age and sex [odds ratio (OR) 5.88, 95% confidence interval (CI) 2.10–16.60, p = 0.00007], while there was only a non-significant trend in the models adjusted also for dementia and Mini Nutritional Assessment (OR 2.73, 95% CI 0.85–8.77, p = 0.12). Anticholinergic drugs may influence the development of delirium due to the cumulative effect of multiple medications with modest antimuscarinic activity. However, this effect was no longer evident in multivariable logistic regression analysis, after adjustment for dementia and malnutrition. Larger, multicenter studies are required to clarify the complex relationship between drugs, anticholinergic burden and delirium in various categories of hospitalized older patients, including those with dementia and malnutrition.

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.

Safety and Tolerability of Pharmacotherapies for Parkinson's Disease in Geriatric Patients

Abstract: Parkinson's disease is a chronic neurodegenerative movement disorder affecting people mainly beyond their 50s. Geriatric patients with Parkinson's disease experience a specific profile of comorbidities. Multimorbidity and resulting polypharmacotherapy are frequent at this age. Comorbid diseases, widely spread, involve arterial hypertension, ischemic heart disease, heart failure, atrial fibrillation, polyneuropathy, diabetes mellitus, cerebrovascular disease, sarcopenia, and frailty. Following years of drug development, levodopa is still the most effective drug for the treatment of motor symptoms. However, a wide range of other drugs are available with specific effects, contraindications, and complications. The treatment of geriatric patients with Parkinson's disease is challenging and requires the cooperation of multidisciplinary teams. A careful assessment of a patient's Parkinson's disease symptoms, comorbidities, medication, vital signs, and resources is crucial for an effective and safe therapy. Laboratory tests can assist in the identification of contraindications for specific treatments. Identifying potentially inadequate drugs from prescription lists can lead to a better targeted treatment for geriatric patients with Parkinson's disease. Future research should help develop a more evidence-based therapy of geriatric patients with Parkinson's disease. For this purpose, randomized controlled trials of geriatric patients are urgently needed. An international register concerning issues of safer drug application and monitoring could help to implement a better treatment.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs) : Position on Knowledge Dissemination, Management, and Future Research

Abstract: Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Going Beyond the Guidelines in Individualising the Use of Antihypertensive Drugs in Older Patients.

Abstract: Hypertension is commonly diagnosed in older patients, with increasing cardiovascular (CV) risk as systolic blood pressure (BP) increases. Maximising CV risk reduction must be reconciled with minimising the risk of treatment-related harms and burden, especially among frail, multi-morbid and older old patients who have been excluded from most randomised trials. Contemporary clinical guidelines, based on such trials, differ in their recommendations as to threshold levels warranting treatment with antihypertensive drugs (AHDs) and target levels that should be achieved. In optimising AHD prescribing in older patients, we propose the following decision framework: decide therapeutic goals in accordance with patient characteristics and preferences; estimate absolute CV risk; measure and profile BP accurately in ways that account for lability in BP levels and minimise error in BP measurement; determine threshold and target BP levels likely to confer net benefit, taking into account age, co-morbidities, frailty and cognitive function; and consider situations that warrant AHD deprescribing on the basis of potential current or future harm. In applying this framework to older persons, and based on a review of relevant randomised trials and observational studies, individuals most likely to benefit from treating systolic BP to no less than 130 mmHg are those of any age who are fit and have high baseline systolic BP (≥ 160 mmHg); high CV risk, i.e. established CV disease or risk of CV events exceeding 20% at 10 years; previous stroke or transient ischaemic attack; heart failure; and stage 3-4 chronic kidney disease with proteinuria. Individuals most likely to be harmed from treating BP to target systolic < 140 mmHg are those who have no CV disease and aged over 80 years; moderate to severe frailty, cognitive impairment or functional limitations; labile BP and/or history of orthostatic hypotension, syncope and falls; or life expectancy < 12 months. Treatment should never be so intense as to reduce diastolic BP to < 60 mmHg in any older person. At a time when guidelines are calling for less conservative management of hypertension in all age groups, we contend that a more temperate approach, such as that offered here and based on the totality of available evidence, may assist in maximising net benefit in older patients.

Statins for Primary Prevention in Those Aged 70 Years and Older: A Critical Review of Recent Cholesterol Guidelines

Abstract: The risk of atherosclerotic cardiovascular disease rises with age and remains the leading cause of death in older adults. Evidence for the use of statins for primary prevention in older adults is limited, despite the possibility that this population may derive significant clinical benefit given its increased cardiovascular risk. Until publication of the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the Management of Blood Cholesterol, and the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease, guidelines for statin prescription in older adults remained unchanged despite new evidence of possible benefit in older adults. In this review, we present key updates in the 2018 and 2019 guidelines and the evidence informing these updates. We compare the discordant recommendations of the seven major North American and European guidelines on cholesterol management released in the past 5 years and highlight gaps in the literature regarding primary prevention of cardiovascular disease in older adults. As most cardiovascular events in older adults are nonfatal, we ask how clinicians should weigh the risks and benefits of continuing a statin for primary prevention in older adults. We also reframe the concept of deprescribing of statins in the older population, using the Geriatrics 5Ms framework: Mind, Mobility, Medications, Multi-complexity, and what Matters Most to older adults. A recent call from the National Institute on Aging for a statin trial focusing on older adults extends from similar concerns.

Ginkgo biloba Extract (EGb761), Cholinesterase Inhibitors, and Memantine for the Treatment of Mild-to-Moderate Alzheimer’s Disease: A Network Meta-Analysis

Abstract: Cholinesterase inhibitors (ChEIs) and memantine have been reported to provide modest benefits for cognition and aspects of functioning in Alzheimer’s disease (AD). Ginkgo biloba extract (EGb761), a phytomedicine, is widely used and expected to be well-tolerated. A few trials have compared EGb761 with ChEIs, and the results were inconclusive. A network meta-analysis was conducted to evaluate the therapeutic benefits and tolerability of EGb761, three ChEIs (donepezil, galantamine, and rivastigmine), and memantine in mild-to-moderate AD patients. Electronic databases were searched through 30 June 2017. We included randomized double-blinded trials with a minimum treatment duration of 22 weeks for EGb761 240 mg/day and 12 weeks for ChEIs or memantine. The study patients included AD or probable AD patients without other types of dementia or neurological disorders. Cognition, function, and behavior symptoms were compared between treatments using the standardized mean difference (SMD). Clinical global impression, treatment discontinuation, and adverse events were compared between treatments using the relative risk (RR). Statistical pooling of the individual trial results was conducted using a frequentist approach. The probability of being the best for a treatment was estimated using surface under the cumulative ranking. EGb761 and memantine showed no therapeutic benefits in all study outcomes. For cognition, all ChEIs were significantly better than placebo (SMD from − 0.52 to − 0.26), and galantamine was better than rivastigmine in the oral and patch forms, EGb761, and memantine (SMD [95% confidence interval (CI)]: − 0.22 [− 0.40 to − 0.05]; − 0.26 [− 0.45 to − 0.07]; − 0.34 [− 0.56 to − 0.12]; and − 0.42 [− 0.71 to − 0.13], respectively). Compared to placebo, galantamine, the rivastigmine patch, and oral rivastigmine provided modest functional benefits (SMD, from 0.21 to 0.24), and galantamine provided behavioral benefits (SMD [95% CI]: − 0.15 [− 0.26 to − 0.04]). All ChEIs provided a better improvement in clinical global impression than placebo (RR from 1.20 to 1.69). The global impression ratings were more improved with donepezil than with galantamine (RR [95% CI]: 1.40 [1.09–1.80]) or with EGb761 (RR [95% CI]: 1.40 [1.06–1.85]), with a 96% probability of donepezil being more effective than the other study agents. Rivastigmine in oral and patch forms, galantamine, and donepezil had a higher risk of being discontinued than placebo (RR [95% CI]: 2.14 [1.49–3.06]; 2.04 [1.30–3.20]; 1.79 [1.28–2.49]; 1.49 [1.03–2.17], respectively). Discontinuation of EGb761 was not statistically lower than that of the ChEIs, in which donepezil had the lowest probability (38%) of being discontinued. EGb761 and memantine showed no treatment benefits compared to placebo and ChEIs. Galantamine provided the highest beneficial effect on cognition and behavioral symptoms. Donepezil provided a better clinical global impression and tolerability than the other ChEIs and EGb761, with a similar benefit for cognition as galantamine.

Parkinson's Disease in the Era of Personalised Medicine: One Size Does Not Fit All.

Abstract: The concept of personalised medicine in Parkinson’s disease has arrived where the implications of findings made in research are certain to have an increasing impact upon clinical practice. Disease heterogeneity in Parkinson’s disease has been well described and lends itself to the construct of personalised medicine where it is hypothesised that a greater understanding of genetic and pathophysiological contributions may underpin the sub-groups described. This in turn has driven the development of potentially individualised disease-modifying therapies where, for example, we are beginning to see treatments that target patients with Parkinson’s disease with specific genetic mutations. Furthermore, clinicians are increasingly recognising the need to tailor their management approach to patients depending on their age of presentation, acknowledging differential side-effect profiles and responses especially when considering the use of device-assisted technologies such as infusion or surgery. Clearly, individualising the treatment of both motor and non-motor symptoms will remain imperative but, in the future, personalised medicine may provide clearer insights into various aspects of a patient’s symptomatology, disease course and thus the best therapeutic approaches.

The Relationship Between Anticholinergic Exposure and Falls, Fractures, and Mortality in Patients with Overactive Bladder.

Abstract: Understanding risk factors associated with falls is important for optimizing care and quality of life for older patients. Our objective was to determine the relationship between anticholinergic exposure and falls, fractures, and all-cause mortality. 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. 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. 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.

Idiopathic Pulmonary Fibrosis: New and Emerging Treatment Options.

Abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive and debilitating, scarring lung disease with a worse prognosis than some cancers. The incidence of IPF is increasing and while current antifibrotic therapies slow disease progression, they do not offer a cure. The pathobiology of IPF is complex and is driven by aging-associated cellular dysfunction, epithelial injury, and an aberrant wound-healing response characterised by fibroblast activation and extracellular matrix accumulation (ECM) in the interstitium. As understanding of the underlying mechanisms has evolved, new targets for pharmacotherapy have emerged. Novel drugs currently in development for pulmonary fibrosis have diverse molecular properties and mechanisms of action, as well as different routes of administration. A shared primary goal of these agents is reduction of the profibrotic activity of fibroblasts and limitation of ECM deposition, which hinders gas exchange and ultimately leads to respiratory failure. This article provides an overview of some promising new therapeutic options for IPF and considers the challenges for future drug development.

Use of Cholinesterase Inhibitors in Non-Alzheimer's Dementias.

Abstract: Non-Alzheimer's dementias constitute 30% of all dementias and present with major cognitive and behavioral disturbances. Cholinesterase inhibitors improve memory by increasing brain acetylcholine levels and are approved symptomatic therapies for Alzheimer's disease (AD). They have also been investigated in other types of dementias with potential cholinergic dysfunction. There is compelling evidence for a profound cholinergic deficit in Lewy Body dementia (LBD) and Parkinson's disease dementia (PDD), even to a greater extent than AD. However, this deficit is difficult to objectivize in vascular dementia (VaD) given the increased comorbidity with AD. Furthermore, there is minimal to no evidence for cholinergic loss in frontotemporal dementia (FTD). Although cholinesterase inhibitors showed significant improvement in cognitive, behavioral, and functional measures in both LBD and PDD clinical trials, only rivastigmine is approved for PDD, due to the heterogeneity of the scales used, the duration of trials, and the limited sample sizes impacting data interpretation. Similarly, the interpretation of findings in VaD trials are limited by the lack of pre-defined inclusion criteria for 'pure VaD' and the wide heterogeneity of patients enrolled with respect to location and extent of cerebrovascular disease. In FTD patients, cholinesterase inhibitors were mostly associated with worsening of cognitive and behavioral symptoms. In non-AD dementias, cholinesterase inhibitors were well tolerated, with increased reports of mild to moderate cholinergic side effects and a non-significant trend for increased cardio and cerebrovascular events with rivastigmine in VaD, justifying their cautious use on a case-by-case basis, especially when there is evidence for cholinergic deficit.

Clinical Assessment and Management of Foot and Ankle Osteoarthritis: A Review of Current Evidence and Focus on Pharmacological Treatment.

Abstract: Foot and ankle osteoarthritis (OA) is a common and disabling problem that adversely affects physical function and significantly reduces quality of life. Although the knee was considered to be the lower-limb site most often affected by OA, recent population data showed foot OA is as prevalent as knee OA, and rates increase with advancing years. The most common foot OA sites include the first metatarsophalangeal joint and the midfoot, with the ankle affected less often. Despite the high prevalence and disabling nature of foot and ankle OA, the condition has been neglected by clinical researchers, and there are very few trials investigating non-surgical foot or ankle OA treatment options. There are no accepted clinical diagnostic criteria for foot or ankle OA so imaging remains common. Clinical guidelines based on knee and hip OA research recommend education, exercise, and weight loss in the first instance. Topical non-steroidal anti-inflammatory drugs (NSAIDs) or capsaicin may be used as an adjunct. Failing these approaches, acetaminophen (paracetamol) should be recommended; however, if there is inadequate symptomatic relief, then clinicians should trial an oral NSAID or a cyclo-oxygenase-2 inhibitor. Given that adverse events and co-morbidities are common in the elderly, older patients should be closely monitored. Some studies have investigated intra-articular injections for foot and ankle OA, and there is some evidence to suggest hyaluronic acid may be effective in the short term for ankle OA. With the lack of research on foot or ankle OA treatments, however, robust clinical trials are urgently needed.