Predictive value of the World falls guidelines algorithm within the AGELESS-MELoR cohort.

AIM: The World Falls Guidelines (WFG) Task Force published a falls risk stratification algorithm in 2022. However, its adaptability is uncertain in low- and middle-income settings such as Malaysia due to different risk factors and limited resources. We evaluated the effectiveness of the WFG risk stratification algorithm in predicting falls among community-dwelling older adults in Malaysia. METHODS: Data from the Malaysian Elders Longitudinal Research subset of the Transforming Cognitive Frailty into Later-Life Self-Sufficiency cohort study was utilized. From 2013-2015, participants aged ≥55 years were selected from the electoral rolls of three parliamentary constituencies in Klang Valley. Risk categorisation was performed using baseline data. Falls prediction values were determined using follow-up data from wave 2 (2015-2016), wave 3 (2019) and wave 4 (2020-2022). RESULTS: Of 1,548 individuals recruited, 737 were interviewed at wave 2, 858 at wave 3, and 742 at wave 4. Falls were reported by 13.4 %, 29.8 % and 42.9 % of the low-, intermediate- and high-risk groups at wave 2, 19.4 %, 25.5 % and 32.8 % at wave 3, and 25.8 %, 27.7 % and 27.0 % at wave 4, respectively. At wave 2, the algorithm generated a sensitivity of 51.3 % (95 %CI, 43.1-59.2) and specificity of 80.1 % (95 %CI, 76.6-83.2). At wave 3, sensitivity was 29.4 % (95 %CI, 23.1-36.6) and specificity was 81.6 % (95 %CI, 78.5-84.5). At wave 4, sensitivity was 26.0 % (95 %CI, 20.2-32.8) and specificity was 78.4 % (95 %CI, 74.7-81.8). CONCLUSION: The algorithm has high specificity and low sensitivity in predicting falls, with decreasing sensitivity over time. Therefore, regular reassessments should be made to identify individuals at risk of falling.

Anticholinergics and falls in older adults.

INTRODUCTION: The use of medications with anticholinergic (ACh) properties is associated with numerous adverse effects especially in older adults. Emerging evidence suggests the presence of long-term effects with ACh use. AREAS COVERED: Our article presents an overview of ACh effects and falls in older individuals including examination of emerging evidence on ACh use and cumulative exposure on short-term and long-term falls risk. The databases CINAHL, MEDLINE, EMBASE, and Web of Science were searched for articles published from January 2002 to December 2021. EXPERT OPINION: Anticholinergic side effects include muscle weakness, blurred vision, and mental confusion which are likely to lead to increased falls risk. Many commonly used medications such as beta-blockers, calcium-channel blockers, and antihistamines are now known to have mild ACh properties. With polypharmacy now considered unavoidable in older patients, the cumulative effects of the use of multiple drugs with mild ACh properties may also lead to increased falls risk. The relationship between ACh drugs and falls may also be irreversible as ACh effects may extend beyond the period of drug use, due to cognitive and physical deconditioning following the initial exposure to ACh drugs. Future long-term studies with accurate quantification of cumulative ACh exposure and measurement of actual falls outcomes are urgently required.

A five-year prospective evaluation of anticholinergic cognitive burden and falls in the Malaysian elders longitudinal research (MELoR) study.

BACKGROUND: While anticholinergic use is associated with stroke, dementia and mortality, few have evaluated its potential link with falls. To determine the relationship between anticholinergic cognitive burden (ACB) and falls over five years using the Malaysian Elders Longitudinal Research (MELoR). METHODS: Community-dwelling adults aged 55 years and over were recruited through electoral roll sampling. Data obtained at baseline and follow-up (FU) at two and five years were included. Falls in the preceding 12 months were recorded. RESULTS: Of the 1499 individuals (mean (SD) age= 68.9(7.5) yrs and 53.3% female) with information on baseline ACB exposure, 575(38.4%) had ACB scores of 1-2 and 117(7.8%) had ACB scores ≥3. Differences in age, ethnicity, smoking status, diabetes, hypertension, cardiovascular disease, arthritis and education existed between ACB groups. Fall occurrence differed between ACB groups at recruitment (p = 0.004) and 2-year FU (p = 0.001) but not at 5-year FU (p = 0.053). Logistic regression revealed an independent association between ACB 1-2 and falls at baseline (odds ratio, OR (95% confidence interval, CI) =1.412(1.035-1.926)) and ACB≥3 and falls at 2-yr FU (OR (95%CI) =2.098(1.032-4.263)) following adjustment for confounders. CONCLUSION: Low level exposure to drugs with anticholinergic properties was associated cross-sectionally with falls, while exposure to higher levels were prospectively associated with falls at 2-year but not at 5-year FU. Future studies should determine whether avoidance of drugs with anticholinergic effects will lead to reduction in falls.

Depletion of Pokemon gene inhibits hepatocellular carcinoma cell growth through inhibition of H-ras.

BACKGROUND: Pokemon is a transcription repressor which plays a critical role in cell transformation and malignancy. However, little is known about its effect on the development and progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the expression of Pokemon in human HCC tissues and the biological behavior of Pokemon in HCC cells in which it is overexpressed. We also explored the expression of potential downstream cofactors of Pokemon. MATERIALS AND METHODS: Reverse transcription polymerase chain reaction and Western blot analysis were used to investigate the expression of Pokemon in tissues of 30 HCC patients. We then examined cell proliferation or apoptosis and ß-catenin or H-ras expression in Pokemon-depleted HepG(2) cells using DNA vector-based RNA interference technology. RESULTS: Pokemon was markedly expressed in 22/30 (73.3%) HCC tissues, with expression levels higher than in adjacent normal liver tissues (p < 0.05); expression is correlated with tumor size. In contrast, depletion of Pokemon inhibited proliferation of HepG(2) or induced apoptosis. Also, H-ras expression decreased to a large extent. CONCLUSIONS: Pokemon exerts its oncogenic activity in the development of HCC by promoting cancer cell growth and reducing apoptosis, and the effect may be mediated by H-ras.