Potentially inappropriate drug use in older people: a nationwide comparison of different explicit criteria for population-based estimates

Aims

The aim was to investigate the prevalence of potentially inappropriate medication use among older people in Sweden according to five different published sets of explicit criteria from Europe and the US.

Methods

This was a nationwide cross-sectional, register-based study across the whole of Sweden in 2008. All individuals aged 65 years and older were included (n = 1 346 709, both community-dwelling and institutionalized persons). We applied all drug-specific criteria included in the 2012 Beers Criteria, the Laroche’s list, the PRISCUS list, the NORGEP criteria and the Swedish National Board of Health and Welfare criteria. The main outcome was the potentially inappropriate drug use according to each set of criteria, separately and combined. Multivariate logistic regression models were used to identify individual factors associated with the use of potentially inappropriate drugs.

Results

The prevalence of potentially inappropriate medication use varied between the explicit criteria from 16% (NORGEP criteria) to 24% (2012 Beers criteria). Overall, 38% of the older people were exposed to potentially inappropriate drug use by at least one of the five sets of criteria. While controlling for other possible covariates, female gender, institutionalization and polypharmacy were systematically associated with inappropriate drug use, regardless of the set of explicit criteria we considered.

Conclusion

Although explicit criteria for inappropriate drug use among older people have been reported to be quite different in their content, they provide similar measures of the prevalence of potentially inappropriate drug use at the population level.     

新型抗胆碱能药物盐酸戊乙奎醚及其光学异构体的细胞毒性评价

目的:评价新型抗胆碱能药物盐酸戊乙奎醚(PHC)及其4个光学异构体R-1、R-2、S-1和S-2的细胞毒性。方法:不同浓度的PHC及其光学异构体作用HepG2细胞24 h后,采用MTT法和中性红吸收法测定细胞毒性:结果:PHC及其光学异构体均能浓度依赖性地降低细胞存活率。根据半数抑制浓度(IC_(50))比较这5个抗胆碱能化合物的细胞毒性:MTT法所测定的细胞毒性强弱次序为PHC>R-2>R-1>S-2>S-1,中性红吸收法所测定的细胞毒性强弱次序为R-2>PHC≈R-1>S-2>S-1。结论:就HepG2细胞而言,R构型异构体的细胞毒性强于S构型。并且,在PHC的4个光学异构体中,R-2的细胞毒性相对最强,而S-1相对最弱。     

Estimation of lean body weight in older community-dwelling men

AIMS

Lean body weight (LBW) decreases with age while total body fat increases, altering drug pharmacokinetics. The aim of this study was to evaluate the ability of the LBW equation to predict dual-energy X-ray absorptiometry (DXA)-derived fat free mass (FFM_DXA) in older community-dwelling males compared with that of two existing FFM equations: the Heitmann and Deurenberg equations.

METHODS

Data were obtained from 1655 older men enrolled in the Concord Health and Ageing in Men Project. The predictive performance of the LBW and FFM equations to predict FFM_DXA accurately was assessed graphically using Bland–Altman plots and quantitatively for precision and bias using the method of Sheiner and Beal in all participants and in frailty and body mass index (BMI) subgroups.

RESULTS

The LBW and Heitmann equations consistently overestimated FFM_DXA for all frailty and BMI subgroups with a mean difference [95% confidence interval (CI)] of 5.5 kg (−0.65, 11.63 kg) and 3.34 kg (−2.84, 9.64 kg), respectively. The Deurenberg equation overestimated FFM_DXA for overweight participants but underestimated FFM_DXA for not-frail participants, with a mean difference (95% CI) of 1 kg (−7.23, 5.25 kg) for all participants.

CONCLUSION

LBW and FFM estimated using these equations give results comparable to DXA-derived FFM. The LBW and Heitmann equations provide a more consistent estimate of FFM_DXA in all frailty and BMI groups despite the Deurenberg equation having the smallest mean difference. Further studies to determine whether the LBW equation is a clinically useful substitute for weight when determining drug dose in older people appear warranted.     

Drugs with anticholinergic effects and cognitive impairment,falls and all-cause mortality in older adults: A systematic review and meta-analysis

AimThe aim was to investigate associations between drugs with anticholinergic effects (DACEs) and cognitive impairment, falls and all-cause mortality in older adults.MethodsA literature search using CINAHL, Cochrane Library, Embase and PubMed databases was conducted for randomized controlled trials, prospective and retrospective cohort and case-control studies examining the use of DACEs in subjects ≥65 years with outcomes on falls, cognitive impairment and all-cause mortality. Retrieved articles were published on or before June 2013. Anticholinergic exposure was investigated using drug class, DACE scoring systems (anticholinergic cognitive burden scale, ACB; anticholinergic drug scale, ADS; anticholinergic risk scale, ARS; anticholinergic component of the drug burden index, DBI_AC) or assessment of individual DACEs. Meta-analyses were performed to pool the results from individual studies.ResultsEighteen studies fulfilled the inclusion criteria (total 124 286 participants). Exposure to DACEs as a class was associated with increased odds of cognitive impairment (OR 1.45, 95% CI 1.16, 1.73). Olanzapine and trazodone were associated with increased odds and risk of falls (OR 2.16, 95% CI 1.05, 4.44; RR 1.79, 95% CI 1.60, 1.97, respectively), but amitriptyline, paroxetine and risperidone were not (RR 1.73, 95% CI 0.81, 2.65; RR 1.80, 95% CI 0.81, 2.79; RR 1.39, 95% CI 0.59, 3.26, respectively). A unit increase in the ACB scale was associated with a doubling in odds of all-cause mortality (OR 2.06, 95% CI 1.82, 2.33) but there were no associations with the DBI_AC (OR 0.88, 95% CI 0.55, 1.42) or the ARS (OR 3.56, 95% CI 0.29, 43.27).ConclusionsCertain individual DACEs or increased overall DACE exposure may increase the risks of cognitive impairment, falls and all-cause mortality in older adults.     

Alcohol and other drug prevention for older adolescents: It's a no brainer

Older adolescence represents a critical period of brain development whereby the prefrontal cortex, responsible for higher level thinking and emotional regulation, is under construction. During this period, the brain is wired to underestimate risk and overestimate pleasure, which primes young people towards risky, pleasure‐oriented experiences. Substance use during this time can hinder brain maturation and lead to development related disorders. However, young people are the most likely to drink at risky quantities, use cannabis, MDMA and cocaine in the previous 12 months than any other age group. Despite this, there are no validated, age‐appropriate prevention programs targeting school leavers, which leaves a group of young people to navigate a landscape where drug use is the most common, without formal support. Drug and alcohol prevention programs should be developed for this age group that combine features of universal prevention programs and targeted intervention programs to support the wider range of drug use behaviours relevant to this older audience. This article outlines potential evidence‐based strategies that programs could focus on in the future.     

Clinical implications from drug–drug and drug–disease interactions in older people

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Effect of inhalation exposure to toluene on the activity of organic anion transporting polypeptide (Oatp) using pravastatin as a probe drug in rats

1.?Toluene, used as a pure substance or in solvent mixtures, is the cause of occupational exposures of large numbers of workers in the world. The organic anion transporting polypeptides (OATP: human; Oatp: rodents) are drug carriers which have been frequently associated to drug–drug interactions. The objective of this study was to evaluate the influence of inhalation exposure to toluene in Oatp in vivo activity using pravastatin as a probe drug in rats.

2.?Male Wistar rats ((n?=?6 per sampling time) were exposed to 85 mg/m³ toluene by inhalation or air in a nose only exposure system for 6 h/d, 5 d/week during 4 weeks, in order to simulate the occupational exposure to toluene at level slightly above the occupational exposure limit proposed by the American Conference of Governmental Industrial Hygienists (ACGIH). After 4 weeks of exposure, animals received a single dose of 20 mg/kg pravastatin orally.

3.?Areas under concentration × time curves extrapolated to infinite (AUC^0–∞) were calculated by Gauss Laguerre quadrature. Non-exposed animals showed AUC^0–∞ of 726.0 (261.8) ng h/mL for pravastatin and rats exposed to toluene 85 mg/m3 showed AUC^0–∞ of 681.8 (80.1)?ng?h/mL [data presented as mean (standard error of the mean)]. No significant difference was observed in pravastatin kinetic disposition between groups in terms of 95% confidence interval for the difference between means.

4.?Toluene exposure by inhalation did not change the in vivo activity of Oatp evaluated by pravastatin kinetic disposition in rats.     

The effect of admission to a geriatric ward on medication use: 2002 versus 1985

PURPOSE: To investigate the changes in pharmacotherapy of patients during and after admission to a geriatric ward in 2002 and to investigate if this goes along with reduction of drugs. To describe the differences of the admitted patients and their medication in 2002 compared to 1985. METHODS: Included patients were admitted to the geriatric ward of a general hospital in the Netherlands during 2002 (n = 258, mean age 84.2 years). Medication at admission, during admission and at discharge were described after retrospective reviewing of medical charts. A comparable study was performed at the same ward in 1985. RESULTS: In 2002, most frequently used medication at admission was acetylsalicylic acid (30.2%). Pantoprazole was during admission used in 38.8% of patients and at discharge in 31.8%. Folic acid that was at admission used by 11.6% of patients was at discharge increased to 23.4%. At discharge, vitamin D was used in 21.5% of patients, whereas lisinopril was used in 17.8% of patients. Both in 1985 and 2002 vitamins were added and use of antibiotics was increased during admission. A mean addition of 1.0 drug in 1985 and of 0.7 drugs in 2002 was observed. CONCLUSIONS: Geriatric hospital admission resulted both in 1985 and 2002 in addition of medication. In both periods reductions in medication were nullified by addition of medication for reason of therapy optimisation. Compared to 1985 admitted patients receive more medication resulting from new insights into pharmacotherapy and more use of preventive medicine.     

An update on the clinical consequences of polypharmacy in older adults: a narrative review

ABSTRACT

Introduction: Polypharmacy, the use of multiple medications by one individual, is increasingly common among older adults. Caring for the growing number of older people with complex drug regimens and multimorbidity presents an important challenge in the coming years.

Areas covered: This article reviews the international trends in the prevalence of polypharmacy, summarizes the results from previous reviews on polypharmacy and negative health outcomes, and updates a previous review on the clinical consequences of polypharmacy by focusing on studies published after 2013. This narrative review, which is based on a literature search in MEDLINE and EMBASE from January 1990 to June 2018, was undertaken to identify relevant articles. Search terms included variations of polypharmacy and multiple medications.

Expert opinion: The prevalence of polypharmacy is increasing worldwide. More than half of the older population is exposed to polypharmacy in some settings. Polypharmacy is associated with a broad range of clinical consequences. However, methods to assess the dangers of polypharmacy should be refined. In our opinion, the issue of ‘confounding by multimorbidity’ has been underestimated and should be better accounted for in future studies. Moreover, researchers should develop more clinically relevant definitions of polypharmacy, including measures of inappropriate or problematic polypharmacy.