Drugs & Aging最新文献

Background

The unfavorable effect of proton pump inhibitors (PPIs) on cardiovascular (CV) outcomes and mortality was reported in the general population. We investigated the impact of PPIs on CV outcomes and total mortality in older people with diabetes mellitus (DM) for whom evidence is missing.

Methods

Using administrative health databases of the Lombardy Region, we analyzed the risk of myocardial infarction (MI), ischemic stroke and total mortality in individuals with DM (≥65 years of age) exposed to PPIs in 2015 and followed up to 2021. The outcomes were analyzed using a multivariable-adjusted Cox proportional hazards model to compute hazard ratios (HRs) with 95% confidence intervals (CIs). HRs between PPI users and non-users were also estimated in selected subgroups. A sensitivity analysis was also performed in a 1:1 propensity score matching population.

Results

A total of 284,068 patients were included in the analysis (49.4% PPI users, 50.6% non-PPI users). A higher prevalence of comorbidities and medications was reported in PPI users as compared with non-users. During a median follow-up of 6.7 years, the use of PPIs was associated with a higher risk for ischemic stroke (HR 1.14, 95% CI 95% 1.08–1.20), MI (HR 1.36, 95% CI 1.31–1.41) and total mortality (HR 1.24, 95% CI 1.22–1.26). These risks were higher in PPI users regardless of the PPI type. Among sexes, previous CV diseases, and insulin subgroups, the use of PPIs was correlated with a statistically significant increased risk of ischemic stroke in men, in individuals without a history of CV disease, and in those who were not treated with insulin. A significantly higher risk of MI was associated with PPIs for all subgroups, as well as for total mortality, with the exception of patients with a previous history of CV diseases. The sensitivity analysis confirmed the results of the unmatched cohort.

Conclusions

Our findings confirmed an increased risk of CV events and all-cause mortality in a large population of older adults with DM exposed to PPIs. This could have an important impact on public health and costs for National Health Service, therefore a regular assessment of PPI appropriateness is recommended, particularly in this population.

Graphical abstract

Sarcopenia is a skeletal muscle disorder characterized by progressive and generalized decline in muscle mass and function. Although it is mostly known as an age-related disorder, it can also occur secondary to systemic diseases such as malignancy or organ failure. It has demonstrated a significant relationship with adverse outcomes, e.g., falls, disabilities, and even mortality. Several breakthroughs have been made to find a pharmaceutical therapy for sarcopenia over the years, and some have come up with promising findings. Yet still no drug has been approved for its treatment. The key factor that makes finding an effective pharmacotherapy so challenging is the general paradigm of standalone/single diseases, traditionally adopted in medicine. Today, it is well known that sarcopenia is a complex disorder caused by multiple factors, e.g., imbalance in protein turnover, satellite cell and mitochondrial dysfunction, hormonal changes, low-grade inflammation, senescence, anorexia of aging, and behavioral factors such as low physical activity. Therefore, pharmaceuticals, either alone or combined, that exhibit multiple actions on these factors simultaneously will likely be the drug of choice to manage sarcopenia. Among various drug options explored throughout the years, testosterone still has the most cumulated evidence regarding its effects on muscle health and its safety. A mas receptor agonist, BIO101, stands out as a recent promising pharmaceutical. In addition to the conventional strategies (i.e., nutritional support and physical exercise), therapeutics with multiple targets of action or combination of multiple therapeutics with different targets/modes of action appear to promise greater benefit for the prevention and treatment of sarcopenia.

Background: Adverse anticholinergic drug reactions are common, yet evidence on how to reduce exposure to anticholinergic activity and reliably measure successful deprescribing is still scant. This study proposes an algorithm-based approach to evaluate and reduce anticholinergic load, and reports the results of its pilot testing.

Methods: Based on published evidence and expert opinion, a list of 85 anticholinergic drugs and 21 algorithms for reducing anticholinergic load, e.g., by recommending alternative drugs with lower risk, were developed. An accompanying test battery was assembled by focusing on instruments that sensitively reflect anticholinergic load and may be sensitive to depict changes (Neuropsychological Assessment Battery to measure memory and attention, validated assessments for constipation, urinary symptoms, and xerostomia, as well as blood biomarkers). The approach was pilot-tested in a geriatric rehabilitation unit, with clinician feedback as the primary outcome and characterization of anticholinergic symptoms as the secondary outcome. The intervention was delivered by a pharmacist and a clinical pharmacologist who used the algorithms to generate personalized recommendation letters.

Results: We included a total of 20 patients, 13 with anticholinergic drugs and 7 without. Recommendations were made for 22 drugs in nine patients from the intervention group, of which seven letters (78%) were considered helpful and 8/22 (36%) anticholinergic drugs were discontinued, reducing anticholinergic load in seven patients. In contrast to patients without drug change, memory assessment in patients with reduced anticholinergic load improved significantly after 2 weeks (6 ± 3 vs. -1 ± 6 points).

Conclusions: The approach was well received by the participating physicians and might support standardized anticholinergic deprescribing.

Microscopic colitis, a diagnosis under the umbrella term of inflammatory bowel disease, is a prevalent cause of watery diarrhea, often with symptoms of urgency and bloating, typically observed in older adults aged ≥ 60 years. Its incidence has been reported to exceed those of ulcerative colitis and Crohn's disease in some geographical areas. Although nonpathognomonic endoscopic abnormalities, including changes of the vascular mucosal pattern; mucosal erythema; edema; nodularity; or mucosal defects, e.g., "cat scratches" have been reported, a colonoscopy is typically macroscopically normal. As reliable biomarkers are unavailable, colonoscopy using random biopsies from various parts of the colon is compulsory. Based on the histological examination under a microscope, the disease is divided into collagenous (with a thickened subepithelial collagenous band) and lymphocytic (with intraepithelial lymphocytosis) colitis, although incomplete forms exist. In routine clinical settings, the disease has a high risk of being misdiagnosed as irritable bowel syndrome or even overlooked. Therefore, healthcare providers should be familiar with clinical features and rational management strategies. A 6-8-week oral budesonide treatment course (9 mg/day) is considered the first-line therapy, but patients often experience relapse when discontinued, or might become intolerant, dependent, or even fail to respond. Consequently, other therapeutic options (e.g., bismuth subsalicylate, biologics, loperamide, bile acid sequestrants, and thiopurines) recommended by available guidelines may be prescribed. Herein, clinically meaningful data is provided based on the latest evidence that may aid in reaching a diagnosis and establishing rational therapy in geriatric care to control symptoms and enhance the quality of life for those affected.

Background: Hip fracture (HF) mostly affects older adults and is responsible for increased morbidity and mortality. Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the peri-operative multimodal analgesic management, but their use could be associated with adverse events in older adults. This systematic review aimed to assess outcomes associated with NSAIDs use in the peri-operative period of HF surgery.

Methods: This systematic review was conducted according to the PRISMA guidelines. Three databases (PubMed/EMBASE/Cochrane Central) were used to search for clinical trials and observational studies assessing efficacy, safety and impact of NSAIDs use on non-specific post-operative outcomes, such as functional status and post-operative complications.

Results: Among the 1320 references initially identified, four provided data on efficacy, four on safety and six on non-specific post-operative outcomes (three randomized controlled clinical trials, three observational studies). Mean study population ages ranged from 68 to 87 years. Two studies found that NSAIDs were effective on pain control, but two studies found conflicting results on opioid sparing. No increased risk of acute kidney injury was observed, while results concerning bleeding risk and delirium were conflicting. No study has found any effect of NSAIDs use on walk recovery. Quality of evidence was high for pain control, but low to very low for all the other studied outcomes.

Conclusions: The use of NSAIDs may be effective for pain control in the peri-operative period of HF surgery. However, safety data were conflicting with low levels of certainty. Further studies are needed to assess their benefit-risk balance in this context. The research protocol was previously registered on PROSPERO (registration number: CRD42021237649).

Helicobacter pylori is the main etiopathogenetic factor of chronic gastritis, peptic ulcer disease and gastric cancer. The world's population is shifting towards older people, who have the highest prevalence of H. pylori. Aging-related peculiarities could have an impact on the treatment of H. pylori and there is still a lack of research data in the older population. The aim of this review was to summarize the findings of the most recent information, publications and studies on the issues relating to H. pylori infection in older patients. H. pylori eradication offers gastrointestinal and extra gastrointestinal benefits in older patients. Based on the main guidelines, H. pylori should be eradicated independent of the patient's age, only reconsidering cases with terminal illness and low life expectancy. Proton pump inhibitors are generally safe and well tolerated. Some antibiotics require dose adjustment only in advanced renal insufficiency and the risk of hepatotoxicity is very low. Special precautions should be taken in patients with polypharmacy and those taking aspirin or non-steroidal anti-inflammatory drugs. In older patients, H. pylori eradication treatment frequently causes only mild and short-term adverse events; however, treatment compliance is usually still very good. H. pylori treatment in older patients does not increase the risk of Clostridium difficile infection. Optimal eradication effectiveness (> 90%) is mostly achieved with bismuth- and non-bismuth-based quadruple therapies. Susceptibility-guided treatment of H. pylori can contribute to increasing the effectiveness of eradication regimens in older adults. To achieve optimal H. pylori eradication effectiveness in older patients, the same guidelines, which are applied to adults, also apply to this population: avoiding repetitive treatment prescriptions, choosing quadruple therapies, prescribing longer treatment duration and administering high-dose proton pump inhibitors twice daily.

Background and objectives: Physicians often face difficulties in selecting appropriate medications for older adults with multiple comorbidities. As people age, they are more likely to be living with a number of chronic conditions (multimorbidity) and be prescribed a high number of medications (polypharmacy). Multimorbidity is frequent in nursing home (NH) residents and the use of potentially inappropriate medications, especially psychotropic drugs, is widespread. This retrospective cross-sectional cohort study examined the frequency of potentially inappropriate psychotropic drugs using the Beers, Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) and Fit fOR The Aged (FORTA) criteria, and their association with mortality.

Methods: This retrospective cross-sectional cohort study was conducted on a sample of long-term care NHs across Italy. Of the 34 NHs with an electronic medical records system, 27 met the inclusion criteria, with complete web-based case report forms (CRFs). Residents under the age of 65 years were excluded. We calculated the prevalence of potentially inappropriate psychotropics drugs (antipsychotics, antidepressants and anxiolytics/hypnotics) according to three criteria for prescriptive appropriateness. Univariate and multivariate correlations were examined, taking into account age, sex, comorbidities, and the number of psychotropic drugs, to analyse the relationship between inappropriate psychotropic use and mortality rates. The rate of inappropriate psychotropic prescriptions was calculated with the prevalence of residents receiving potentially inappropriate psychotropic drugs according to the three criteria. We used a logistic model to check for a possible predictive relationship between inappropriate use of psychotropics and mortality. The study evaluated differences in prescriptive appropriateness among NHs by analysing the proportions of potentially inappropriately treated residents at the last visit. Differences were compared with the overall sample mean using confidence intervals (CIs) calculated using Wald's method.

Results: This study involved 2555 residents, of whom 1908 (74.7% of the total) were treated with psychotropic drugs; 186 (7.3% of the total) were exposed to at least one psychotropic drug considered potentially inappropriate according to the FORTA criteria. Analysis using the Beers criteria showed that 1616 residents (63.2% of the total) received at least one psychotropic drug considered potentially inappropriate. In line with the Beers recommendation, patients receiving at least three psychotropic drugs were also included and 440 were identified (17.2% of the total sample). According to the STOPP criteria, 1451 residents (56.8% of the total sample) were prescribed potentially inappropriate psychotropic drugs. No correlation was found between potentially inappropriate use of psychotro

Background: Prescribing cascades occur when a drug-induced adverse event is treated with a new medication. Identifying clinical scenarios in which prescribing cascades are more likely to occur may help determine ways to prevent prescribing cascades.

Objective: To understand the extent to which discordant providers and discordant pharmacies contribute to the dihydropyridine calcium channel blocker (DH CCB)-loop diuretic prescribing cascade.

Study population and design: A retrospective cohort study using Medicare Fee-For-Service data (2011-2018) of adults aged ≥ 66 years.

Exposures: Patients who initiated DH CCB with subsequent initiation of loop diuretic (DH CCB-loop diuretic dyad) within 90 days or patients who initiated angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with subsequent initiation of a loop diuretic (ACEI/ARB-loop diuretic dyad; control).

Main outcomes: The primary outcomes were provider and pharmacy discordance for prescribing cascades and control drug pairs. Baseline clinical and socio-demographic characteristics were balanced using inverse probability of treatment weighting with propensity scores.

Results:  Overall, we identified 1987 DH CCB-loop diuretic dyads and 3148 ACEI/ARB-loop diuretic dyads. Discordant providers occurred in 64% of DH CCB-loop diuretic dyads and 55% of ACEI/ARB-loop diuretic dyads, while discordant pharmacies occurred in 19% of DH CCB-loop diuretic dyads and 16% of ACEI/ARB-loop diuretic dyads. After adjustment, the risk of having discordant providers was 20% {Relative Risk (RR) 1.20 [95% confidence interval (CI), 1.14-1.26]} higher in the DH CCB-loop diuretic dyad compared with the ACEI/ARB-loop diuretic dyad. Moreover, pharmacy discordance was 17% (RR 1.17 [95% CI 1.02-1.33]) higher.

Conclusion: Our findings suggest that discordant providers and discordant pharmacies were more commonly involved in the potential prescribing cascade when compared with a similar control dyad of medications. Opportunities for enhanced care coordination and medication reconciliation should be explored to prevent unnecessary polypharmacy.

Introduction: Atrial fibrillation (AF) is a common condition among older adults, requiring anticoagulation therapy to prevent thromboembolic events. Direct oral anticoagulants (DOACs) are now recommended as first-line therapy for this purpose. Apixaban and rivaroxaban are two direct-factor Xa inhibitors whose dosing is based on various factors (age, weight, creatinine, and creatinine clearance) that can affect the pharmacokinetics of the medication. This study aimed to evaluate factors associated with inappropriate dosing of apixaban or rivaroxaban based on the summary of product characteristics.

Methods: A retrospective, single-center study included 777 hospitalizations of patients treated with apixaban or rivaroxaban for AF between 1 January 2018 and 31 December 2022. Primary endpoint assessed whether the dose of apixaban or rivaroxaban was within the summary of product characteristics used by European Medicine Agency (EMA).

Results: Inappropriate dosing of apixaban or rivaroxaban is noted for approximately 30% of hospitalizations mostly underdosing. Factors associated with the risk of inappropriate dosing were the presence of cognitive impairment [adjusted odds ratio (OR*) 1.65, 95% confidence interval (CI) 1.19-2.29, p value (p) = 0.002], weight per kilogram increase (OR* 1.03, 95% CI 1.01-1.04, p < 0.0001), and history of bleeding under apixaban or rivaroxaban (OR* 1.94, 95% CI 1.24-3.03, p = 0.003).

Conclusion: This study highlighted the high prevalence of inappropriate apixaban or rivaroxaban doses in older adults, particularly underdosing, which increases the risk of thromboembolism.