Drugs & Aging最新文献

{"title":"Clinician and Family Caregiver Perspectives on Deprescribing Chronic Disease Medications in Older Nursing Home Residents Near the End of Life","authors":"Loren J. Schleiden, Gloria Klima, Keri L. Rodriguez, Mary Ersek, Jacob E. Robinson, Ryan P. Hickson, Dawn Smith, John Cashy, Florentina E. Sileanu, Carolyn T. Thorpe","doi":"10.1007/s40266-024-01110-3","DOIUrl":"https://doi.org/10.1007/s40266-024-01110-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Nursing home (NH) residents with limited life expectancy (LLE) who are intensely treated for hyperlipidemia, hypertension, or diabetes may benefit from deprescribing.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study sought to describe NH clinician and family caregiver perspectives on key influences on deprescribing decisions for chronic disease medications in NH residents near the end of life.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We recruited family caregivers of veterans who recently died in a Veterans Affairs (VA) NH, known as community living centers (CLCs), and CLC healthcare clinicians (physicians, nurse practitioners, physician assistants, pharmacists, registered nurses). Respondents completed semi-structured interviews about their experiences with deprescribing statin, antihypertensive, and antidiabetic medications for residents near end of life. We conducted thematic analysis of interview transcripts to identify key themes regarding influences on deprescribing decisions.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Thirteen family caregivers and 13 clinicians completed interviews. Key themes included (1) clinicians and caregivers both prefer to minimize drug burden; (2) clinical factors strongly influence deprescribing of chronic disease medications, with differences in how clinicians and caregivers weigh specific factors; (3) caregivers trust and rely on clinicians to make deprescribing decisions; (4) clinicians perceive caregiver involvement and buy-in as essential to deprescribing decisions, which requires time and effort to obtain; and (5) clinicians perceive conflicting care from other clinicians as a barrier to deprescribing.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Findings suggest a need for efforts to encourage communication with and education for family caregivers of residents with LLE about deprescribing, and to foster better collaboration among clinicians in CLC and non-CLC settings.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":"26 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140600234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Scleritis in Older Adults.","authors":"Laura Butler, Oren Tomkins-Netzer, Or Reiser, Rachael L Niederer","doi":"10.1007/s40266-024-01105-0","DOIUrl":"10.1007/s40266-024-01105-0","url":null,"abstract":"<p><p>Scleritis, an inflammatory disease of the eye affecting scleral tissue, presents unique challenges in the older adult population. Unlike their younger counterparts, older individuals manifest a distinct spectrum of the disease with different underlying etiologies, co-morbidities, altered immune function, and an increased risk of systemic side effects from medication choices. Addressing these complexities necessitates a comprehensive and multidisciplinary approach. Treatment of choice will depend on any underlying cause but generally involves non-steroidal anti-inflammatory drugs, systemic or local corticosteroids, and potentially disease-modifying anti-rheumatic drugs. Utilization of these therapeutic agents in older adults warrants careful consideration because of their potential side-effect profiles. This article critically examines the specific concerns for the use of these drugs in older patients and reviews the existing literature on their use in this specific cohort.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"287-302"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of Comorbidities and Prescribing and Dispensing of Non-steroidal Anti-inflammatory Drugs (NSAIDs) Among Patients with Osteoarthritis in the USA: Real-World Study.","authors":"Joshua Ide, Azza Shoaibi, Kerstin Wagner, Rachel Weinstein, Kathleen E Boyle, Andrew Myers","doi":"10.1007/s40266-024-01108-x","DOIUrl":"10.1007/s40266-024-01108-x","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a major cause of chronic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are analgesics commonly used for musculoskeletal pain; however, NSAIDs can increase the risk of certain adverse events, such as gastrointestinal bleeding, edema, heart failure, and hypertension.</p><p><strong>Objective: </strong>The objective of this study was to characterize existing comorbidities among patients with OA. For patients with OA with and without a coexisting medical condition of interest (CMCOI), we estimated the prevalence of prescribing and dispensing NSAIDs pre-OA and post-OA diagnosis.</p><p><strong>Methods: </strong>Data from three large administrative claims databases were used to construct an OA retrospective cohort. Databases leveraged were IBM MarketScan Medicare Supplemental Database (MDCR), IBM MarketScan Commercial Database (CCAE), and Optum's de-identified Clinformatics^® Data Mart Database (Optum CDM). The OA study population was defined to be those patients who had an OA diagnosis from an inpatient or outpatient visit with at least 365 days of prior observation time in the database during January 2000 through May 2021. Asthma, cardiovascular disorders, renal impairment, and gastrointestinal bleeding risks were the CMCOI of interest. Patients with OA were then classified as having or not having evidence of a CMCOI. For both groups, NSAID dispensing patterns pre-OA and post-OA diagnosis were identified. Descriptive analysis was performed within the Observational Health Data Sciences and Informatics framework.</p><p><strong>Results: </strong>In each database, the proportion of the OA population with at least one CMCOI was nearly 50% or more (48.0% CCAE; 74.4% MDCR; 68.6% Optum CDM). Cardiovascular disease was the most commonly observed CMCOI in each database, and in two databases, nearly one in four patients with OA had two or more CMCOI (23.2% MDCR; 22.6% Optum CDM). Among the OA population with CMCOI, NSAID utilization post-OA diagnosis ranged from 33.0 to 46.2%. Following diagnosis of OA, an increase in the prescribing and dispensing of NSAIDs was observed in all databases, regardless of patient CMCOI presence.</p><p><strong>Conclusions: </strong>This study provides real-world evidence of the pattern of prescribing and dispensing of NSAIDs among patients with OA with and without CMCOI, which indicates that at least half of patients with OA in the USA have a coexisting condition. These conditions may increase the risk of side effects commonly associated with NSAIDs. Yet, at least 32% of these patients were prescribed and dispensed NSAIDs. These data support the importance of shared decision making between healthcare professionals and patients when considering NSAIDs for the treatment of OA in patients with NSAID-relevant coexisting medical conditions.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"357-366"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11021340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-Stroke Depression in Older Adults: An Overview.","authors":"Fabio Giuseppe Masuccio, Erica Grange, Rachele Di Giovanni, Martina Rolla, Claudio Marcello Solaro","doi":"10.1007/s40266-024-01104-1","DOIUrl":"10.1007/s40266-024-01104-1","url":null,"abstract":"<p><p>Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"303-318"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139939830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Pharmacological Urate-Lowering Therapy on Cardiovascular Disease in Older Adults with Gout.","authors":"Martijn Gerritsen, Mike T Nurmohamed","doi":"10.1007/s40266-024-01098-w","DOIUrl":"10.1007/s40266-024-01098-w","url":null,"abstract":"<p><p>Cardiovascular disease is an important cause of mortality in older patients. In addition to the traditional risk factors for cardiovascular disease, hyperuricemia has been increasingly associated with an elevated risk of cardiovascular disease. Uric acid itself has several unfavorable effects on the cardiovascular system, and hyperuricemia can lead to the development of gout. Gout is the most prevalent inflammatory rheumatic disease. Older patients with gout have an increased risk of cardiovascular morbidity and mortality due to an increased prevalence of traditional risk factors, as well as the inflammatory burden of gout activity. As the prevalence of traditional risk factors and the prevalence of both hyperuricemia and gout are increasing in older adults, cardiovascular risk management in these patients is very important. This risk management consists of, on the one hand, treatment of individual traditional risk factors and, on the other hand, of urate lowering, thereby decreasing inflammatory burden of gout. However, there is insufficient evidence to conclude that urate-lowering therapy reduces the risk of cardiovascular events. Moreover, from a cardiovascular point of view, there is no preference for one urate lowering drug over another in patients with gout, nor is there enough evidence to support a preference in patients with gout with increased cardiovascular risk. Personalized treatment in older patients with gout should be aimed at optimizing serum uric acid levels, as well as targeting traditional cardiovascular risk factors. Further prospective randomized trials are needed to support the hypothesis that urate lowering reduces cardiovascular risk in older patients with gout.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"319-328"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cumulative Anticholinergic Burden and its Predictors among Older Adults with Alzheimer's Disease Initiating Cholinesterase Inhibitors.","authors":"Ashna Talwar, Satabdi Chatterjee, Jeffrey Sherer, Susan Abughosh, Michael Johnson, Rajender R Aparasu","doi":"10.1007/s40266-024-01103-2","DOIUrl":"10.1007/s40266-024-01103-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cumulative anticholinergic burden refers to the cumulative effect of multiple medications with anticholinergic properties. However, concomitant use of cholinesterase inhibitors (ChEIs) and anticholinergic burden can nullify the benefit of the treatment and worsen Alzheimer's disease (AD). A literature gap exists regarding the extent of the cumulative anticholinergic burden and associated risk factors in AD. Therefore, this study evaluated the prevalence and predictors of cumulative anticholinergic burden among patients with AD initiating ChEIs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective longitudinal cohort study was conducted using the Medicare claims data involving parts A, B, and D from 2013 to 2017. The study sample included older adults (65 years and older) diagnosed with AD and initiating ChEIs (donepezil, rivastigmine, or galantamine). The cumulative anticholinergic burden was calculated based on the Anticholinergic Cognitive Burden scale and patient-specific dosing using the defined daily dose over the 1 year follow-up period after ChEI initiation. Incremental anticholinergic burden levels were dichotomized into moderate-high (sum of standardized daily anticholinergic exposure over a year (TSDD) score ≥ 90) versus low-no (score 0-89). The Andersen Behavioral Model was used as the conceptual framework for selecting the predictors under the predisposing, enabling, and need categories. A multivariable logistic regression model was used to evaluate the predictors of high-moderate versus low-no cumulative anticholinergic burden. A multinomial logistic regression model was also used to determine the factors associated with patients having moderate and high burdens compared to low/no burdens.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 222,064 older adults with AD with incident ChEI use (mean age 82.24 ± 7.29, 68.9% females, 83.6% White). Overall, 80.48% had some anticholinergic burden during the follow-up, with 36.26% patients with moderate (TSDD scores 90-499), followed by 24.76% high (TSDD score &gt; 500), and 19.46% with low (TSDD score 1-89) burden categories. Predisposing factors such as age; African American, Asian, or Hispanic race; and need factors included comorbidities such as dyslipidemia, syncope, delirium, fracture, pneumonia, epilepsy, and claims-based frailty index were less likely to be associated with the moderate-high anticholinergic burden. The factors that increased the odds of moderate-high burden were predisposing factors such as female sex; enabling factors such as dual eligibility and diagnosis year; and need factors such as baseline burden, behavioral and psychological symptoms of dementia, depression, insomnia, urinary incontinence, irritable bowel syndrome, anxiety, muscle spasm, gastroesophageal reflux disease, heart failure, and dysrhythmia. Most of these findings remained consistent with multinomial logistic regression.  CONCLUSION: Four out of five older adults with AD had s","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"339-355"},"PeriodicalIF":2.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140101292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Older Canadians’ Perceptions of the Safety, Effectiveness and Accessibility of Cannabis for Medicinal Purposes: A Cross-Sectional Analysis","authors":"Jennifer Bolt, Jacob Movold, Megan Behm, Jill Williamson, Melanie Fenton, Jennifer M. Jakobi","doi":"10.1007/s40266-024-01109-w","DOIUrl":"https://doi.org/10.1007/s40266-024-01109-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background and Objective</h3><p>Cannabis use is increasing among older adults, with use primarily for medicinal purposes. Much of the evidence on perceptions of cannabis is derived from younger populations and current users of cannabis. The purpose of this study was to describe community-dwelling older Canadians’ perceptions of cannabis effectiveness, safety and accessibility for medicinal purposes and to identify factors influencing cannabis perceptions.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>An online survey of older adults’ perceptions, knowledge and experiences with cannabis was completed between February and September 2022. The survey was open to English-speaking and French-speaking Canadians aged 50 years and older regardless of their cannabis use history.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 1615 Canadians completed the survey. Respondents identified primarily as men (49.7%) or women (48.5%) of Caucasian decent. The majority of participants viewed cannabis as a reasonable alternative (65.8%) and an effective (70.5%) treatment modality for symptom management in older adults. Few respondents (16.4%) felt that older adults compared to younger adults were at a higher risk of side effects and 34.5% felt that cannabis is safe to use with most medicines. Cannabis perceptions were influenced by gender, cannabis use history (prior use vs current use) and reasons for cannabis use (recreational purposes vs medicinal purposes vs both purposes).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Older Canadians have a positive view of the role of cannabis in symptom management. The perceptions of cannabis safety and effectiveness were influenced by gender, cannabis use history and reasons for cannabis use. Healthcare professionals should leverage these perceptions when discussing cannabis with their older patient populations.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":"153 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Difficulties of Managing Pain in People Living with Frailty: The Potential for Digital Phenotyping.","authors":"Jemima T Collins, David A Walsh, John R F Gladman, Monica Patrascu, Bettina S Husebo, Esmee Adam, Alison Cowley, Adam L Gordon, Giulia Ogliari, Hanneke Smaling, Wilco Achterberg","doi":"10.1007/s40266-024-01101-4","DOIUrl":"10.1007/s40266-024-01101-4","url":null,"abstract":"<p><p>Pain and frailty are closely linked. Chronic pain is a risk factor for frailty, and frailty is a risk factor for pain. People living with frailty also commonly have cognitive impairment, which can make assessment of pain and monitoring of pain management even more difficult. Pain may be sub-optimally treated in people living with frailty, people living with cognitive impairment and those with both these factors. Reasons for sub-optimal treatment in these groups are pharmacological (increased drug side effects, drug-drug interactions, polypharmacy), non-pharmacological (erroneous beliefs about pain, ageism, bidirectional communication challenges), logistical (difficulty in accessing primary care practitioners and unaffordable cost of drugs), and, particularly in cognitive impairment, related to communication difficulties. Thorough assessment and characterisation of pain, related sensations, and their functional, emotional, and behavioural consequences (\"phenotyping\") may help to enhance the assessment of pain, particularly in people with frailty and cognitive impairment, as this may help to identify who is most likely to respond to certain types of treatment. This paper discusses the potential role of \"digital phenotyping\" in the assessment and management of pain in people with frailty. Digital phenotyping is concerned with observable characteristics in digital form, such as those obtained from sensing-capable devices, and may provide novel and more informative data than existing clinical approaches regarding how pain manifests and how treatment strategies affect it. The processing of extensive digital and usual data may require powerful algorithms, but processing these data could lead to a better understanding of who is most likely to benefit from specific and targeted treatments.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"199-208"},"PeriodicalIF":2.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Immunosenescence in Older Kidney Transplant Recipients: Associated Clinical Outcomes and Possible Risk Stratification for Immunosuppression Reduction.","authors":"Borefore P Jallah, Dirk R J Kuypers","doi":"10.1007/s40266-024-01100-5","DOIUrl":"10.1007/s40266-024-01100-5","url":null,"abstract":"<p><p>The number of older individuals receiving a kidney transplant as replacement therapy has significantly increased in the past decades and this increase is expected to continue. Older patients have a lower rate of acute rejection but an increased incidence of death with a functioning graft. Several factors, including an increased incidence of infections, post-transplant malignancy and cardiovascular comorbidity and mortality, contribute to this increased risk. Notwithstanding, kidney transplantation is still the best form of kidney replacement therapy in all patients with chronic kidney disease, including in older individuals. The best form of immunosuppression and the optimal dose of these medications in older recipients remains a topic of discussion. Pharmacological studies have usually excluded older patients and when included, patients were highly selected and their numbers insignificant to draw a reasonable conclusion. The reduced incidence of acute rejection in older recipients has largely been attributed to immunosenescence. Immunosenescence refers to the aging of the innate and adaptive immunity, accumulating in phenotypic and functional changes. These changes influences the response of the immune system to new challenges. In older individuals, immunosenescence is associated with increased susceptibility to infectious pathogens, a decreased response after vaccinations, increased risk of malignancies and cardiovascular morbidity and mortality. Chronic kidney disease is associated with premature immunosenescent changes, and these are independent of aging. The immunosenescent state is associated with low-grade sterile inflammation termed inflammaging. This chronic low-grade inflammation triggers a compensatory immunosuppressive state to avoid further tissue damage, leaving older individuals with chronic kidney disease in an immune-impaired state before kidney transplantation. Immunosuppression after transplantation may further enhance progression of this immunosenescent state. This review covers the role of immunosenescence in older kidney transplant recipients and it details present knowledge of the changes in chronic kidney disease and after transplantation. The impact of immunosuppression on the progression and complications of an immunosenescent state are discussed, and the future direction of a possible clinical implementation of immunosenescence to individualize/reduce immunosuppression in older recipients is laid out.</p>","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"219-238"},"PeriodicalIF":2.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy of Cenobamate for the Treatment of Focal Seizures in Older Patients: Post Hoc Analysis of a Phase III, Multicenter, Open-Label Study.","authors":"Rebecca O'Dwyer, Sean Stern, Clarence T Wade, Anuradha Guggilam, William E Rosenfeld","doi":"10.1007/s40266-024-01102-3","DOIUrl":"10.1007/s40266-024-01102-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cenobamate is an antiseizure medication (ASM) approved in the US and Europe for the treatment of uncontrolled focal seizures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This post hoc analysis of a phase III, open-label safety study assessed the safety and efficacy of adjunctive cenobamate in older adults versus the overall study population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Adults aged 18-70 years with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled in the phase III, open-label safety study; adults aged 65-70 years from that study were included in our safety analysis. Discontinuations due to adverse events and treatment-emergent adverse events (TEAEs) were assessed throughout the study in all patients who received one or more doses of cenobamate (safety study population). Efficacy was assessed post hoc in patients who had adequate seizure data available (post hoc efficacy population); we assessed patients aged 65-70 years from that population. Overall, 100% responder rates were assessed in the post hoc efficacy maintenance-phase population in 3-month intervals. Concomitant ASM drug load changes were also measured. For each ASM, drug load was defined as the ratio of actual drug dose/day to the World Health Organization defined daily dose (DDD).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 1340 patients (mean age 39.7 years) in the safety study population, 42 were ≥ 65 years of age (mean age 67.0 years, 52.4% female). Median duration of exposure was 36.1 and 36.9 months for overall patients and older patients, respectively, and mean epilepsy duration was 22.9 and 38.5 years, respectively. At 1, 2, and 3 years, 80%, 72%, and 68% of patients overall, and 76%, 71%, and 69% of older patients, respectively, remained on cenobamate. Common TEAEs (≥ 20%) were somnolence and dizziness in overall patients, and somnolence, dizziness, fall, fatigue, balance disorder, and upper respiratory tract infection in older patients. Falls in older patients occurred after a mean 452.1 days of adjunctive cenobamate treatment (mean dose 262.5 mg/day; mean concomitant ASM drug load 2.46). Of 240 patients in the post hoc efficacy population, 18 were ≥ 65 years of age. Mean seizure frequency at baseline was 18.1 seizures/28 days for the efficacy population and 3.1 seizures/28 days for older patients. Rates of 100% seizure reduction within 3-month intervals during the maintenance phase increased over time for the overall population (n = 214) and older adults (n = 15), reaching 51.9% and 78.6%, respectively, by 24 months. Mean percentage change in concomitant ASM drug load, not including cenobamate, was reduced in the overall efficacy population (31.8%) and older patients (36.3%) after 24 months of treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Results from this post hoc analysis showed notable rates of efficacy in older patients taking adjunctive cenobamate. Rates of several individual TEAEs occurred more frequently in older patien","PeriodicalId":11489,"journal":{"name":"Drugs & Aging","volume":" ","pages":"251-260"},"PeriodicalIF":2.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}