Bladder Antimuscarinics and Cognitive Decline in Elderly Patients

Introduction: The evidence on the impact of bladder antimuscarinics initiation on cognitive function in older adults is inconsistent. Methods: A retrospective analysis of data from the National Alzheimer\u27s Coordinating Center (NACC) on enrollees 65 years and older evaluated the association between antimuscarinic initiation and cognitive decline. We defined decline from baseline (yes/no) for cognitive assessments included in the NACC Uniform Data Set 2.0 battery. New users were matched on year of enrollment and time in the cohort to randomly selected nonusers. Analyses were conducted using inverse probability of treatment weights based on baseline propensity scores. Results: Our analyses included 698 new users and 7037 nonusers. The odds ratio (OR) and 95% confidence interval for cognitive decline in users as compared to nonusers was 1.4 (1.19–1.65) for Mini–Mental State Examination (MMSE), and 1.21 (1.03–1.42) for Clinical Dementia Rating; in addition, the odds of decline were 20% higher in users compared to nonusers for semantic memory/language and executive function. The effect estimate for MMSE was 1.94 (1.3–2.91) for those with mild cognitive impairment, 1.26 (0.99–1.62) in those with normal cognition, and 1.44 (1.04–1.99) in those with dementia at baseline. Discussion: Our results show that antimuscarinic initiation is associated with cognitive decline and raise questions about their use, especially in those with impaired cognition

The Association of Gabapentin Initiation and Neurocognitive Changes in Older Adults with Normal Cognition

Background: Gabapentin is increasingly prescribed to older adults, which raises concerns about its potential to cause neurocognitive changes. Therefore, we aimed to examine the association of gabapentin use with neurocognitive changes (i.e., cognitive decline, functional status decline, and motor function change) in older adults. Methods: We conducted a retrospective cohort study using the National Alzheimer’s Coordinating Center Uniform Data Set (UDS; September 2005-March 2021 data freeze). From the eligible sample (≥age 65 years), we identified cognitively normal new-users of gabapentin and the visit they initiated gabapentin (i.e., index visit). Initiators were matched to randomly selected nonusers on year of UDS enrollment and visit number from enrollment to index. Cognitive decline was defined as any increase in the Clinical Dementia Rating global score (CDRGLOB) and as a 1-point increase in CDR sum of boxes (CDR-SB). Functional status decline was defined as a 3-point increase in the sum of the Functional Activities Questionnaire (FAQ) and as 0.3-point increase in mean FAQ. Decline in motor function was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, we used joint stabilized inverse probability of treatment weights and stabilized inverse probability of censoring weights. All analyses were conducted comparing index to index+1 and index+2 visits. Results: From the eligible UDS participants (N = 23,059), we included 480 initiators (mean age [SD]: 78.7 [6.9]; male 34.4%); 4,320 nonusers (78.3 [7.0]; 34.4%). Gabapentin initiation was significantly associated with cognitive/functional status decline: worsening CDRGLOB at index+1 visit (odds ratio [95% confidence interval]: 1.55 [1.07, 2.25]); CDR-SB at index+1 visit (1.94 [1.22, 3.09]); and mean of FAQ at index+2 visit (1.78 [1.12, 2.83]). After excluding initiators with extant motor dysfunction (n = 21), we identified 459 initiators (78.7 [6.9]; 34.0%) and 4,131 nonusers (78.2 [6.9]; 34.7%); in this sample, gabapentin initiation was associated with increased falls at the index+2 visit (2.51 [1.19, 5.31]). Conclusion: Gabapentin initiation was significantly associated with deleterious neurocognitive changes among older adults with initially normal cognition. Further studies are needed to examine the risk/benefit of prescribing gabapentin in older adults

Framework for the Synthesis of Non-Randomised Studies and Randomised Controlled Trials: A Guidance on Conducting a Systematic Review and Meta-Analysis for Healthcare Decision Making

Introduction: High-quality randomised controlled trials (RCTs) provide the most reliable evidence on the comparative efficacy of new medicines. However, non-randomised studies (NRS) are increasingly recognised as a source of insights into the real-world performance of novel therapeutic products, particularly when traditional RCTs are impractical or lack generalisability. This means there is a growing need for synthesising evidence from RCTs and NRS in healthcare decision making, particularly given recent developments such as innovative study designs, digital technologies and linked databases across countries. Crucially, however, no formal framework exists to guide the integration of these data types. Objectives and Methods: To address this gap, we used a mixed methods approach (review of existing guidance, methodological papers, Delphi survey) to develop guidance for researchers and healthcare decision-makers on when and how to best combine evidence from NRS and RCTs to improve transparency and build confidence in the resulting summary effect estimates. Results: Our framework comprises seven steps on guiding the integration and interpretation of evidence from NRS and RCTs and we offer recommendations on the most appropriate statistical approaches based on three main analytical scenarios in healthcare decision making (specifically, ‘high-bar evidence’ when RCTs are the preferred source of evidence, ‘medium,’ and ‘low’ when NRS is the main source of inference). Conclusion: Our framework augments existing guidance on assessing the quality of NRS and their compatibility with RCTs for evidence synthesis, while also highlighting potential challenges in implementing it. This manuscript received endorsement from the International Society for Pharmacoepidemiology

An Overview on the Anticancer Activity of <i>Azadirachta indica</i> (Neem) in Gynecological Cancers

In recent years, a wide range of studies have pointed out the importance of nutraceuticals as reservoirs of therapeutic compounds for several diseases, including cancer. This study is centered on the role of some nutraceuticals as anticancer agents and on their efficiency in the oncological gynecological field. Gynecological cancers include cervical, ovarian, and breast neoplasia and these are the major causes of morbidity and mortality in the female population. Cervical neoplasia affects sexually active women aged between 30 and 40 years and is considered the second leading cause of death for women worldwide. Epidemiological studies have shown a strong association of this cancer with human papilloma virus (HPV) infection, independent of any others risk factors. Ovarian cancer represents about 4% of all women&#8217;s cancers and breast neoplasia registers 52.8 new cases per 100,000 women annually. Since ancient times, herbal therapies have shown a wide range of beneficial effects and a high potential for safeguarding human health. Azadirachta indica (Neem) is a medicinal plant of Indian origin, a tree with more of 140 isolated compounds and at least 35 biologically active principles that have shown an important influence as tumor suppressors by interfering with the carcinogenesis process. Used for centuries in Asia as a natural remedy for cancer, neem compounds present in bark, leaves, flowers, and seed oil have been shown to possess properties such as chemopreventive capacity, apoptotic activities, immunomodulatory effects, and induction of p53-independent apoptosis. The current study is a systematic literature review based on the anticarcinogenic potential of neem compounds in gynecological cancers