Adverse drug reactions in patients with Alzheimer's disease and related dementia in France: a national multicentre cross-sectional study.

PURPOSE: To assess the prevalence of adverse drug reactions (ADRs) occurring in patients with Alzheimer's disease (AD) or other dementia in France. METHODS: A cross-sectional multicentre study was conducted by the French network of the 31 regional pharmacovigilance centres on a given day. The subjects were selected by random draw to be a representative sample of French patients with dementia: consultations of dementia clinics, nursing-homes, acute and long care geriatric units, rehabilitation care geriatric units. The staff of each medical structure together with that of the pharmacovigilance centre defined a day for including the patients. Socio-demographic data, history, ADR and drugs given were registered. RESULTS: There were 1332 subjects included, 51.1% living at home, 48.8% in institutions, aged 82.0 ± 8.0 years (46-108); 61.3% suffered from AD. Mean number of drugs was 6.3 ± 3.1. Anti-dementia drugs were given to 66.4% subjects. ADR prevalence was 5.0% (95% CI: 3.9-6.2) without a significant difference between at home and institutionalized patients. ADR consisted of gastro-intestinal (23.2%), central nervous system (17.4%) and psychiatric disorders (8.7%). Of the ADR, 31.9% were serious, and 47.8% preventable. The drugs most often involved were anti-dementia (28.9%), cardio-vascular (28.9%) and psychotropic drugs (26.4%, anxiolytics, hypnotics, antidepressants, neuroleptics). CONCLUSION: This national scale study showed that iatrogenesis in patients with AD and related dementia can at times be serious and preventable. Therefore, special attention is required when prescribing psychotropic and anti-dementia drugs, as they are frequently used and induce half of the ADR in this population.

The clinical status and survival in elderly dialysis: example of the oldest region of France.

BACKGROUND: The number of elderly (≥75 years) patients with end-stage renal disease (ESRD) has increased markedly, including in the Limousin region, which has the oldest population in France. We retrospectively compared outcomes in elderly and non-elderly ESRD patients who started dialysis during two time periods. METHODS: Baseline clinical characteristics, care, and survival rates were assessed in 557 ESRD patients aged ≥75 and <75 years who started dialysis in 2002-2004 and 2005-2007. Survival curves and Cox proportional hazards model were used to assess survival and factors associated with survival. RESULTS: Of the 557 patients, 343 and 214 were <75 years and ≥75 years, respectively. Dialysis was started in 2002-2004 and 2005-2007 by 197 and 146 patients <75 years, respectively, and by 96 and 118 patients ≥75 years, respectively. Median age (73.4 years [interquartile range [IQR] 61.7-79.5 years] vs 69.5 years [IQR 57.4-77.4 years] p = 0.001) and the proportion aged ≥75 years (44.7% vs 32.8%, p = 0.004) were significantly higher in 2005-2007 than in 2002-2004. Improved initial status during 2005-2007 was observed only in patients ≥75 years, with a decrease in some co-morbidities, improved walking and better preparation for dialysis. Mortality rates were significantly lower in 2005-2007 than in 2002-2004 (hazard ratio 0.81, 95% confidence interval 0.69-0.95; p = 0.008), with the difference due to factors associated with clinical status and care. CONCLUSIONS: Improved initial clinical status and better preparation for dialysis, accompanied by increased survival, were observed for patients ≥75 years who started dialysis more recently, perhaps because of early referral to a nephrologist.

Potentially inappropriate medications in the elderly: a French consensus panel list.

OBJECTIVE: To evaluate drug-related problems in the elderly, various lists of potentially inappropriate medications have been published in North America. Unfortunately, these lists are hardly applicable in France. The purpose of this study was to establish a list of inappropriate medications for French elderly using the Delphi method. METHOD: A two-round Delphi method was used to converge to an agreement between a pool of 15 experts from various parts of France and from different backgrounds (five geriatricians, five pharmacologists, two pharmacists, two general practitioners, one pharmacoepidemiologist). In round one, they were sent a questionnaire based on a literature review listing medications and clinical situations. They were asked to comment on the potential inappropriateness of the criteria proposed using a 5-point Likert scale (from strong agreement to strong disagreement) and to suggest therapeutic alternatives and new criteria. In round two, the experts confirmed or cancelled their previous answers from the synthesis of the responses of round one. After round two, a final list of potentially inappropriate drugs was established. RESULTS: The final list proposed 36 criteria applicable to people >/=75 years of age. Twenty-nine medications or medication classes applied to all patients, and five criteria involved medications that should be avoided in specific medical conditions. Twenty-five medications or medication classes were considered with an unfavourable benefit/risk ratio, one with a questionable efficacy and eight with both unfavourable benefit/risk ratio and questionable efficacy. CONCLUSION: This expert consensus should provide prescribers with an epidemiological tool, a guideline and a list of alternative therapies.

Is inappropriate medication use a major cause of adverse drug reactions in the elderly?

AIM: To study the occurrence of adverse drug reactions (ADRs) linked to inappropriate medication (IM) use in elderly people admitted to an acute medical geriatric unit. METHODS: All the elderly people aged > or = 70 years admitted to the acute medical geriatric unit of Limoges University hospital (France) over a 49-month period were included, whatever their medical condition. For all the patients, clinical pharmacologists listed the medications given before admission and identified the possible ADRs. The appropriateness of these medications and the causal relationship between drugs (either appropriate or not) and ADRs were evaluated. RESULTS: Two thousand and eighteen patients were included. The number of drugs taken was 7.3 +/- 3.0 in the patients with ADRs and 6.0 +/- 3.0 in those without ADRs (P < 0.0001). Sixty-six percent of the patients were given at least one IM prior to admission. ADR prevalence was 20.4% among the 1331 patients using IMs and 16.4% among those using only appropriate drugs (P < 0.03). In only 79 of the 1331 IM users (5.9%) were ADRs directly attributable to IMs. The IMs most often involved in patients with ADRs were: anticholinergic antidepressants, cerebral vasodilators, long-acting benzodiazepines and concomitant use of two or more psychotropic drugs from the same therapeutic class. Using multivariate analysis, after adjusting for confounding factors, IM use was not associated with a significant increased risk of ADRs (odds ratio 1.0, 95% confidence interval 0.8, 1.3). CONCLUSION: Besides a reduction in the number of drugs given to the elderly, a good prescription should involve a reduction in the proportion of IMs and should take into consideration the frailty of these patients.

Impact of hospitalisation in an acute medical geriatric unit on potentially inappropriate medication use.

BACKGROUND AND OBJECTIVE: Potentially inappropriate medication use is a major safety issue in the elderly and may cause a substantial proportion of drug-related hospital admissions. Hospitalisation could result in a change in the quantity and type of drugs, but its effect on potentially inappropriate drug use is still unknown. The aim of this study was to estimate the potentially inappropriate medication prevalence in patients > or =70 years of age at admission to and at discharge from an acute medical geriatric unit, and to identify the factors associated with no longer being a potentially inappropriate drug user at hospital discharge. METHODS: A prospective drug surveillance study was undertaken in 2018 elderly patients (> or =70 years of age) admitted to an acute medical geriatric unit in Limoges University Hospital, France. Prescribing patterns were established at admission and at discharge. Potentially inappropriate medication use was evaluated according to a list derived from the Beers criteria and adapted to French practice. "To be no longer a potentially inappropriate drug user at discharge" was defined as using at least one potentially inappropriate medication at admission and not using it at discharge. RESULTS: The numbers of drugs used at admission/discharge were 6.2 +/- 3.1/5.4 +/- 2.5. The prevalence of potentially inappropriate medication use decreased from 66% (95% CI 63.8, 68.0) at admission to 43.6% (95% CI 41.3, 45.9) at discharge. At discharge, 535 subjects were no longer potentially inappropriate medication users. Multivariate analysis showed that no longer being a potentially inappropriate medication user was associated with the number of drugs used (4-6 drugs vs < or =3 odds ratio [OR] 1.20; 95% CI 0.86, 1.68; 7-9 drugs vs < or =3 OR 1.37; 95% CI 0.97, 1.93; > or =10 drugs vs < or =3 OR 1.64; 95% CI 1.10, 2.44), age (80-89 years vs 70-79 years OR 1.38; 95% CI 1.03, 1.85; > or =90 years vs 70-79 years OR 1.69; 95% CI 1.22, 2.83), cerebral vasodilator use (OR 2.87; 95% CI 2.31, 3.57), analgesic use (OR 1.54; 95% CI 1.06, 2.25) and concomitant use of psychotropic drugs of the same therapeutic class (OR 1.94; 95% CI 1.29, 2.92). CONCLUSION: Hospitalisation in geriatric services results in a reduction in potentially inappropriate medication use. Improved pharmacological education of practitioners, especially with regard to drug adverse effects, is desirable to improve management of geriatric patients.

Predicting and preventing adverse drug reactions in the very old.

The size of the elderly population has been increasing steadily for several years. Individuals in this age group often have several concomitant diseases that require treatment with multiple medications. These drugs, for various reasons and especially as a consequence of potential accumulation, may be associated with adverse reactions. Of the numerous factors that can favour the occurrence of these adverse drug reactions, the most important are the pathophysiological consequences of aging, particularly as these apply to the very old. Although absorption of drugs is not usually reduced in the elderly, diffusion, distribution and particularly elimination decline with age. Furthermore, while hepatic metabolic function is fairly normal, renal function is usually markedly depressed in very old individuals, and this can translate into clinical consequences if it is not taken into account. This is why, before administration of any drug in the elderly, evaluation of glomerular filtration rate is essential. Validated estimations such as those obtained from the classical Cockcroft-Gault formula or from more recent methodologies are required. In addition to reductions in various organ functions, factors connected with very old age such as frailty, falls, abnormal sensitivity to medications and polypathology, all of which tend to be more common in the last years of life, all directly impact on adverse drug reaction occurrence. Given these characteristics of the elderly population, the best way to reduce the prevalence of adverse drug reactions in this group is to limit drug prescription to essential medications, make sure that use of prescribed agents is clearly explained to the patient, give drugs for as short a period as possible, and periodically re-evaluate all use of drugs in the elderly.

Paraoxonase 1 activity: a new vascular marker of dementia?

Paraoxonase 1 (PON1), an A-esterase with peroxidase-like activity present on the surface of HDL, decreases the peroxidation of LDL. Serum PON1 activity (PON1a) decreases with aging and in disorders associated with a high risk of adverse cardiovascular events (acute myocardial infarction, diabetes mellitus, and chronic renal failure). The implication of vascular factors in Alzheimer-type dementia (ATD) is strongly suspected. We measured PON1a by spectrophotometry using the paraoxon substrate in 180 healthy subjects (controls; mean age: 75.3 +/- 8.9 years; 98 women) and 154 patients admitted for cognitive testing. According to criteria, 45 patients had mild cognitive impairments (MCI; mean age: 75.6 +/- 9.3 years; 28 women), 60 had ATD (mean age: 75.6 +/- 8.3 years; 47 women), and 49 had vascular dementia (VaD; mean age: 77.5 +/- 7.2 years; 33 women). Mean PON1a was lower in VaD (0.25 +/- 0.1 U/mL) than in controls or ATD (both 0.41 +/- 0.2 U/mL, p < 0.01). Mean PON1a values in MCI (0.34 +/- 0.2 U/mL) and ATD (0.41 +/- 0.2 U/mL) were not significantly different. In multiple linear regression, PON1a was negatively correlated with male sex, age, and VaD, and positively correlated with ATD (each correlation p < 0.001). As shown in other high-risk cardiovascular disorders, PON1a seems to be a reliable marker of VaD. Its modification in Alzheimer's disease supports the implication of vascular risk factors in this type of dementia.

Paraoxonase 1 192/55 gene polymorphisms in Alzheimer's disease.

An esterase, paraoxonase 1 (PON1), protects against organophosphate neurotoxicity and decreases lipoprotein oxidation. Two polymorphisms of PON1 [192 (R or Q) and 55 (M or L)] exist and are associated with coronary artery disease. We have previously shown that serum PON1 activity (PON1a) is lower in vascular dementia (VaD) than in Alzheimer's disease (AD), suggesting that PON1a may distinguish VaD from AD. As PON1 polymorphism modifies PON1a, we determined 192 and 55 PON1 polymorphisms by sequence-specific primer PCR in 64 healthy subjects (HS; mean age: 79.5 +/- 6.3 years; 38 women) and in 72 patients (mean age: 80.2 +/- 6.8 years; 51 women) undergoing cognitive evaluations. According to DSM-IV/NINCDS/ADRDA/NINDS/AIREN criteria, 45 patients (mean age: 80.0 +/- 7.2 years, 34 women) had AD and 27 patients (mean age: 79.8 +/- 6.6 years, 16 women) had VaD. We also measured serum PON1a by spectrophotometry. No significant differences in phenotype distributions among the three study groups were detected by chi(2) test. Among the variables, age, sex, and phenotypes 192 and 55, logistic regression selected only polymorphism 192, but not 55, as a discriminating factor between AD and VaD (p < 0.05). Substitution of serum PON1a for genotype yielded a similar result. PON1 polymorphism 192 appears to be a reliable marker to distinguish patients with AD from patients with VaD and from healthy subjects. Changes in 192 polymorphism distributions in AD and in VaD may at least partially explain the significant difference in PON1a in these two types of dementia.