Polypharmacy difference between older people with and without diabetes: evidence from the English Longitudinal Study of Ageing

Aim: To study the association between diabetes and the prevalence of and risk factors for polypharmacy among adults aged 50 and older in England. / Methods: A cross-sectional study (2012−2013) of the English Longitudinal Study of Ageing. Polypharmacy was defined as taking 5-9 long-term medications a day and heightened polypharmacy as 10 or more. Diabetes included diagnosed and undiagnosed cases (glycated haemoglobin ≥ 6.5% (48 mmol/mol)). / Results: Of 7729 participants, 1100 people had diabetes and showed higher prevalence rates of polypharmacy (41.1% vs 14.8%) and heightened polypharmacy (5.8% vs 1.7%) than those without diabetes, even when antihyperglycemic medications were excluded. Risk factors for polypharmacy also differed according to diabetes status. Among people with diabetes, risk factors for polypharmacy and heightened polypharmacy were having more long-term conditions (relative risk ratio (RRR) =1.86; 3.51) and being obese (RRR=1.68; 3.68), while females were less likely to show polypharmacy (RRR=0.51) and heightened polypharmacy (RRR=0.51) than males. Older age (RRR=1.04) was only related to polypharmacy among people without diabetes. / Conclusions: Adults with diabetes had higher prevalence rates of polypharmacy and heightened polypharmacy than those without diabetes, regardless of including antihyperglycemic drugs. Early detection of polypharmacy among older people with diabetes needs to focus on co-morbidities and obesity

The impact of high-risk medications on mortality risk among older adults with polypharmacy: evidence from the English Longitudinal Study of Ageing.

BACKGROUND: Polypharmacy is common among older people and is associated with an increased mortality risk. However, little is known about whether the mortality risk is related to specific medications among older adults with polypharmacy. This study therefore aimed to investigate associations between high-risk medications and all-cause and cause-specific mortality among older adults with polypharmacy. METHODS: This study included 1356 older adults with polypharmacy (5+ long-term medications a day for conditions or symptoms) from Wave 6 (2012/2013) of the English Longitudinal Study of Ageing. First, using the agglomerative hierarchical clustering method, participants were grouped according to the use of 14 high-risk medication categories. Next, the relationship between the high-risk medication patterns and all-cause and cause-specific mortality (followed up to April 2018) was examined. All-cause mortality was assessed by Cox proportional hazards model and competing-risk regression was employed for cause-specific mortality. RESULTS: Five high-risk medication patterns-a renin-angiotensin-aldosterone system (RAAS) inhibitors cluster, a mental health drugs cluster, a central nervous system (CNS) drugs cluster, a RAAS inhibitors and antithrombotics cluster, and an antithrombotics cluster-were identified. The mental health drugs cluster showed increased risks of all-cause (HR = 1.55, 95%CI = 1.05, 2.28) and cardiovascular disease (CVD) (SHR = 2.11, 95%CI = 1.10, 4.05) mortality compared with the CNS drug cluster over 6 years, while others showed no differences in mortality. Among these patterns, the mental health drugs cluster showed the highest prevalence of antidepressants (64.1%), benzodiazepines (10.4%), antipsychotics (2.4%), antimanic agents (0.7%), opioids (33.2%), and muscle relaxants (21.5%). The findings suggested that older adults with polypharmacy who took mental health drugs (primarily antidepressants), opioids, and muscle relaxants were at higher risk of all-cause and CVD mortality, compared with those who did not take these types of medications. CONCLUSIONS: This study supports the inclusion of opioids in the current guidance on structured medication reviews, but it also suggests that older adults with polypharmacy who take psychotropic medications and muscle relaxants are prone to adverse outcomes and therefore may need more attention. The reinforcement of structured medication reviews would contribute to early intervention in medication use which may consequently reduce medication-related problems and bring clinical benefits to older adults with polypharmacy

Dose-response relationships between polypharmacy and all-cause and cause-specific mortality among older people

BACKGROUND: Although medicines are prescribed based on clinical guidelines and expected to benefit patients, both positive and negative health outcomes have been reported associated with polypharmacy. Mortality is the main outcome, and information on cause-specific mortality is scarce. Hence, we investigated the association between different levels of polypharmacy and all-cause and cause-specific mortality among older adults. METHODS: The English Longitudinal Study of Ageing is a nationally representative study of people aged 50+. From 2012/2013, 6295 individuals were followed up to April 2018 for all-cause and cause-specific mortality. Polypharmacy was defined as taking 5-9 long-term medications daily and heightened polypharmacy as 10+ medications. Cox proportional hazards regression and competing-risks regression were used to examine associations between polypharmacy and all-cause and cause-specific mortality, respectively. RESULTS: Over a 6-year follow-up period, both polypharmacy (19.3%) and heightened polypharmacy (2.4%) were related to all-cause mortality, with hazard ratios of 1.51 (95% CI 1.05-2.16) and 2.29 (95% CI 1.40-3.75) respectively, compared with no medications, independently of demographic factors, serious illnesses and long-term conditions, cognitive function and depression. Polypharmacy and heightened polypharmacy also showed 2.45 (95% CI 1.13-5.29) and 3.67 (95% CI 1.43-9.46) times higher risk of cardiovascular disease (CVD) deaths, respectively. Cancer mortality was only related to heightened polypharmacy. CONCLUSION: Structured medication reviews are currently advised for heightened polypharmacy, but our results suggest that greater attention to polypharmacy in general for older people may reduce adverse effects and improve older adults' health

Transcribed ultraconserved noncoding RNAs (T-UCR) are involved in Barrett's esophagus carcinogenesis.

Barretts esophagus (BE) involves a metaplastic replacement of native esophageal squamous epithelium (Sq) by columnar-intestinalized mucosa, and it is the main risk factor for Barrett-related adenocarcinoma (BAc). Ultra-conserved regions (UCRs) are a class non-coding sequences that are conserved in humans, mice and rats. More than 90% of UCRs are transcribed (T-UCRs) in normal tissues, and are altered at transcriptional level in tumorigenesis. To identify the T-UCR profiles that are dysregulated in Barretts mucosa transformation, microarray analysis was performed on a discovery set of 51 macro-dissected samples obtained from 14 long-segment BE patients. Results were validated in an independent series of esophageal biopsy/surgery specimens and in two murine models of Barretts esophagus (i.e. esophagogastric-duodenal anastomosis). Progression from normal to BE to adenocarcinoma was each associated with specific and mutually exclusive T-UCR signatures that included up-regulation of uc.58-, uc.202-, uc.207-, and uc.223- and down-regulation of uc.214+. A 9 T-UCR signature characterized BE versus Sq (with the down-regulation of uc.161-, uc.165-, and uc.327-, and the up-regulation of uc.153-, uc.158-, uc.206-, uc.274-, uc.472-, and uc.473-). Analogous BE-specific T-UCR profiles were shared by human and murine lesions. This study is the first demonstration of a role for T-UCRs in the transformation of Barretts mucosa

Operationalisation of intrinsic capacity in older people and its association with subsequent disability, hospital admission and mortality: results from ELSA

Background Intrinsic capacity (IC) is a new concept in the healthy aging field and has many operationalized definitions. In this study, we operationalized IC using item response theory in the English Longitudinal Study of Ageing (ELSA) and tested the predictive value of the scale using a subsequent functional ability, mortality, and hospital admission. Methods IC was measured at baseline (2004, Wave 2) using 14 dichotomous indicators: word recall, orientation in time, balance, chair rises, walking speed, upper mobility, lower mobility, eyesight, hearing, grip strength, body mass index, waist circumference, depressive symptoms, and life satisfaction. A 2-parameter item response theory model was used to generate a scale of IC at baseline. Logistic regression was used for the prediction of subsequent difficulties, measured by difficulties with ≥1 activities of daily living (ADLs) and ≥1 instrumental activities of daily living (IADLs) at 4 and 8 years after baseline. Competing risk and Cox regressions were employed to test the prediction of hospital admission and mortality, respectively, over a 14-year follow-up. Results IC scores were generated for 4 545 individuals aged on average 70.8 years (standard deviation [SD] 7.93). Better baseline IC scores were associated with reduced risk of subsequent difficulties with ADLs and IADLs, hospital admission (subdistribution hazard ratios [SHR] = 0.99, 95% confidence interval [CI] 0.98–0.99), and mortality (hazard ratios [HR] = 0.98, 95% CI 0.98–0.99), when adjusted for sociodemographic and health-related covariates. Conclusion These results suggest the utility of this IC score as a measure of risk for future adverse outcomes in older people, potentially above that indicated by other sociodemographic and health-related factors

Glycated albumin for glycemic control in t2dm population: A multi-dimensional evaluation

Purpose: To investigate the glycated albumin (GA) introduction implications, as an add-on strategy to traditional glycemic control (Hb1Ac and fasting plasma glucose – FPG) instruments, considering insulin-naïve individuals with type 2 diabetes mellitus (T2DM), treated with oral therapies. Methods: A Health Technology Assessment was conducted in Italy, as a multi-dimensional approach useful to validate any innovative technology. The HTA dimensions, derived from the EUnetHTA Core Model, were deployed by means of literature evidence, health economics tools and qualitative questionnaires, filled-in by 15 professionals. Results: Literature stated that the GA introduction could lead to a higher number of individuals achieving therapeutic success after 3 months of therapy (97.0% vs 71.6% without GA). From an economic point of view, considering a projection of 1,955,447 T2DM insulinnaïve individuals, potentially treated with oral therapy, GA introduction would imply fewer individuals requiring a therapy switch (−89.44%), with a 1.06% in costs reduction, on annual basis, thus being also the preferable solution from a cost-effectiveness perspective (costeffectiveness value: 237.74 vs 325.53). According to experts opinions, lower perceptions on GA emerged with regard to equity aspects (0.13 vs 0.72, p-value>0.05), whereas it would improve both individuals (2.17 vs 1.33, p-value=0.000) and caregivers quality of life (1.50 vs 0.83, p-value=0.000). Even if in the short term, GA required additional investments in training courses (−0.80 vs 0.10, p-value = 0.036), in the long run, GA could become the preferable technology (0.30 vs 0.01, p-value=0.018) from an organisational perspective. Conclusion: Adding GA to traditional glycaemic control instruments could improve the clinical pathway of individuals with T2DM, leading to economic and organisational advantages for both hospitals and National Healthcare Systems

Body mass index as a predictor of healthy and disease-free life expectancy between ages 50 and 75 : a multicohort study

BACKGROUND: While many studies have shown associations between obesity and increased risk of morbidity and mortality, little comparable information is available on how body mass index (BMI) impacts health expectancy. We examined associations of BMI with healthy and chronic disease-free life expectancy in four European cohort studies. METHODS: Data were drawn from repeated waves of cohort studies in England, Finland, France and Sweden. BMI was categorized into four groups from normal weight (18.5-24.9 kg m(-2)) to obesity class II (>= 35 kg m(-2)). Health expectancy was estimated with two health indicators: sub-optimal self-rated health and having a chronic disease (cardiovascular disease, cancer, respiratory disease and diabetes). Multistate life table models were used to estimate sex-specific healthy life expectancy and chronic disease-free life expectancy from ages 50 to 75 years for each BMI category. RESULTS: The proportion of life spent in good perceived health between ages 50 and 75 progressively decreased with increasing BMI from 81% in normal weight men and women to 53% in men and women with class II obesity which corresponds to an average 7-year difference in absolute terms. The proportion of life between ages 50 and 75 years without chronic diseases decreased from 62 and 65% in normal weight men and women and to 29 and 36% in men and women with class II obesity, respectively. This corresponds to an average 9 more years without chronic diseases in normal weight men and 7 more years in normal weight women between ages 50 and 75 years compared to class II obese men and women. No consistent differences were observed between cohorts. CONCLUSIONS: Excess BMI is associated with substantially shorter healthy and chronic disease-free life expectancy, suggesting that tackling obesity would increase years lived in good health in populations.Peer reviewe