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To examine the association of (1) high and low blood pressure (BP) and (2) antihypertensive (AH) drug use with incident frailty.We conducted a secondary analysis of data from the Multidomain Alzheimer Preventive Trial (MAPT), in which 1394 non-frail community-dwelling participants aged ≥70 years were followed up for 5 years. BP was measured once at baseline in a lying position using a validated electronic device. High BP was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, and low BP as systolic BP ≤ 110 mm Hg and/or diastolic BP ≤ 70 mm Hg. AH drugs were assessed at baseline and classified according to the Anatomical Therapeutic Chemical (ATC) code.Incident frailty over the 5 years was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses.Low BP was associated with a greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p = 0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and those on two or more AH drugs were at the greatest risk of frailty. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p = 0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p = 0.22) was independently associated with incident frailty.Low BP could be used as a new marker for identifying older adults at higher risk of frailty.gov registration number: NCT00672685.

Aim: Oral anticoagulants are the first-line drugs for treating thrombotic disorders related to nonvalvular atrial fibrillation and for treating deep vein thrombosis, diseases that increase in prevalence with age. Older patients have a greater risk of thrombotic and hemorrhagic events and are more prone to drug interactions. Given this backdrop, we wanted to determine the factors associated with the prescription of direct oral anticoagulants and vitamin K antagonists in older patients. Methods: We performed a cross-sectional observational study using a hospital prescription database. The study population consists of 405 older patients who were given oral anticoagulants. The 2 variables of interest were the prescription of 1 of the 2 classes of oral anticoagulants (direct oral anticoagulants vs vitamin K antagonists) and appropriateness of oral anticoagulant prescribing according to Summary of Product Characteristics (potentially inappropriate vs appropriate). Results: The factors associated with direct oral anticoagulant prescribing were the female gender (odds ratio [OR]: 1.87, 95% confidence interval [CI]: 1.22-2.88) and initiation during hospital stay (OR: 2.56, 95% CI: [1.52-4.32]). Stage 4 and 5 chronic kidney diseases (OR: 0.39, 95% CI: [0.19-0.79] and OR: 0.07, 95% CI: [0.01-0.53]) were factors favoring vitamin K antagonist prescription. Being 90 years of age or more (OR: 2.05, 95% CI: [1.06-3.98]) was a factor for potentially inappropriate anticoagulant prescribing. The gastroenterology department (OR: 2.91, 95% CI: [1.05-8.11]) was associated with potentially inappropriate anticoagulant prescribing. Conclusions: Direct oral anticoagulants are the drugs of choice for anticoagulant treatment, including in older adults. The female gender and the initiation during hospital stay increased the chances of being prescribed a direct oral anticoagulant in older adults. Stage 4 and 5 chronic kidney disease increased the likelihood of having a vitamin K antagonist prescribed. Our study also revealed a persistence of potentially inappropriate oral anticoagulant prescriptions in older patients.

To investigate the impact of visit-to-visit systolic blood pressure variability (BPV), diastolic BPV, mean arterial pressure variability, and pulse pressure variability on cognitive decline and incident dementia in noninstitutionalized patients aged ≥65 years. A total of 3319 subjects from the S.AGES (Sujets AGÉS—Aged Subjects) cohort underwent clinical examinations every 6 months during 3 years. Variability was evaluated using standard deviation (SD), coefficient of variation, average real variability, successive variation, variation independent of mean, and residual SD. Cognition was assessed using the Mini-Mental State Examination and dementia with the Diagnostic Statistical Manual of Mental Disorders. Linear mixed models and Cox proportional hazards models were used. Higher systolic BPV was associated with poorer cognition independently of baseline SBP: adjusted 1-SD increase of coefficient of variation: β (SE)=−0.12 (0.06), P =0.04. Similar results were observed for diastolic BPV and mean arterial pressure variability: β (SE)=−0.20 (0.06), P P =0.02). Among the 3319 subjects, 93 (2.8%) developed dementia. Higher systolic BPV was associated with greater dementia risk (adjusted 1-SD increase of coefficient of variation: hazard ratios=1.23 [95% CI, 1.01–1.50], P =0.04). Similar results were found for diastolic BPV and mean arterial pressure variability ( P

Dental caries is defined as a pathological breakdown of the tooth. It is an infectious phenomenon involving a multifactorial aetiology. The impact of drugs on cariogenic risk has been poorly investigated. In this study, we identified drugs suspected to induce dental caries as adverse drug reactions (ADRs) and then studied a possible pathogenic mechanism for each drug that had a statistically significant disproportionality. We extracted individual case safety reports of dental caries associated with drugs from VigiBase® (the World Health Organization global individual case safety report database). We calculated disproportionality for each drug with a reporting odds ratio (ROR) and 99% confidence interval. We analysed the pharmacodynamics of each drug that had a statistically significant disproportionality. In VigiBase®, 5229 safety reports for dental caries concerning 733 drugs were identified. Among these drugs, 88 had a significant ROR, and for 65 of them (73.9%), no information about dental caries was found in the summaries of the product characteristics, the Micromedex® DRUGDEX, or the Martindale databases. Regarding the pharmacological classes of drugs involved in dental caries, we identified bisphosphonates, atropinic drugs, antidepressants, corticoids, immunomodulating drugs, antipsychotics, antiepileptics, opioids and β2-adrenoreceptor agonist drugs. Regarding possible pathogenic mechanisms for these drugs, we identified changes in salivary flow/composition for 54 drugs (61.4%), bone metabolism changes for 31 drugs (35.2%), hyperglycaemia for 32 drugs (36.4%) and/or immunosuppression for 23 drugs (26.1%). For nine drugs (10.2%), the mechanism was unclear. We identified 88 drugs with a significant positive disproportionality for dental caries. Special attention has to be paid to bisphosphonates, atropinic drugs, immunosuppressants and drugs causing hyperglycaemia.

Summary Introduction Faced with the increasing number of pharmaceutical products on the market, several pharmacovigilance notifications regarding confusion between look-alike and sound-alike drugs have been reported. This study of perception among patients, family physicians and pharmacists aims to evaluate drug identification factors and the risk of errors of confusion for patients. Material and methods Patients were systematically approached in randomly selected pharmacies within the Midi-Pyrenees region in France and invited to complete a questionnaire. Two other questionnaires were respectively sent to family physicians and pharmacists in the same region asking for their opinion on patients’ perception of the identification of prescribed medicines. Results Of the 768 patients interviewed, most report identifying their medications by name (brand name: 50%; generic: 21%), while a smaller number cite physical appearance (box: 16%, tablet: 7% and blister packaging: 3%). In practice the factors considered most likely to cause confusion by patients relate to drug appearance (look-alike tablets: 28%, look-alike boxes: 20% and look-alike blister packaging: 13%). In contrast, look-alike and sound-alike names (generic and brand names combined) were cited in 31% of cases. Physicians (n = 345) and pharmacists (n = 198) understimate that patients identify their treatment by name (physicians: 46%; pharmacists: 26% vs. patients: 71%), reporting instead that problems arise mainly from the appearance of medicines (physicians: identification: 52% and risk factors for confusion: 74%; pharmacists: identification: 74% and risk factors for confusion: 83%; versus patients: identification: 26%; risk factors for confusion: 61%). Discussion Our study highlights the critical role of medication name in identifying drugs among patients. However, confusion of look-alike tablets or pills figures prominently among fears surrounding medication errors. Despite several notifications of pharmacovigilance, this issue appears to be underestimated within the body of medical literature. Proper identification of medicines by patients is essential to improving medication safety and therapeutic compliance. Concrete measures can be undertaken to reach this goal.

To investigate the association between pulse wave velocity, intima-media thickness, carotid artery diameter, carotid plaques, and conversion from mild cognitive impairment to dementia. Three hundred and seventy-five elderly ambulatory subjects with mild cognitive impairment were followed yearly to examine potential conversion to dementia. Vascular function was assessed by carotid-femoral pulse wave velocity. Vascular structure was evaluated by intima-media thickness, carotid artery diameter, and carotid plaques using an ultrasonographic assessment of carotid arteries. One hundred and five patients (28%) converted to dementia during a mean follow-up period of 4.5 years. Higher pulse wave velocity was associated with greater risk of conversion to dementia (1-SD increase of pulse wave velocity: hazard ratio, 1.33; 95% CI, 1.04–1.71; P =0.02) independently of age, sex, educational level, systolic blood pressure, cardiovascular diseases, body mass index, calcium channel blockers intake, Mini–Mental State Examination at baseline, and apoE ε4 status. Intima-media thickness, carotid plaques, and carotid artery diameter did not predict conversion to dementia (1-SD increase of intima-media thickness: hazard ratio, 0.93; 95% CI, 0.73–1.18; P =0.55; presence of carotid plaques: hazard ratio, 1.08; 95% CI, 0.62–1.87; P =0.79; 1-SD increase of carotid artery diameter: hazard ratio, 1.08; 95% CI, 0.89–1.31; P =0.44). Pulse wave velocity was associated with conversion to dementia, whereas intima-media thickness, carotid plaques, or carotid artery diameter were not after controlling for age and other confounding factors. Arterial stiffness could identify mild cognitive impairment patients at higher risk of dementia and may be a therapeutic target to delay or prevent the onset of dementia.

International audience; Rationale, aim, and objective: There are several ways to establish an accurate medication list in the hospital admission medication reconciliation (MedRec). The challenge for MedRec lies in the availability, reliability, and completeness of the data used. In France, the Electronic Pharmaceutical Record (ePR) was developed to register each medication taken by ambulatory patients, primarily to make dispensation in community pharmacies safe. We evaluated the suitability of this tool in the MedRec when patients were admitted to the hospital. Method: We conducted a 6-month pilot study of 249 MedRec files from a hospital diabetology department. The analysis was supplemented by the ePR for any patient for whom this information was recorded. The study evaluated the ePR as a new MedRec tool, as well as the clinical impact (CI) of the new data collected. Results: The ePR was contributory for 28% of the patients. Discrepancies were associated with polypharmacy, most of which had a CI = 1. Medication omission was the most frequently found discrepancy (72%), but self-medication (8%) and lack of medication adherence (9%) were also observed. Conclusion: This tool provided added value for reconciliation, as it quickly identifies regular medications, adherence, and self-medication behaviour. The ePR is essential for conducting a thorough MedRec.

Describing the factors associated with direct oral anticoagulants (DOA) prescription in patients with atrial fibrillation (AF).This study was performed in Toulouse on a cohort of patients received in rhythmology consultation, treated with vitamin K antagonists (VKA) or DOA for AF. A multivariate model was performed using logistic regression to describe the factors associated with DOA prescription and secondly, those associated with discontinuation of the anticoagulant.Among the 140 patients included, 96 (66%) were treated with VKA and 48 (34%) with DOA. Recent AF diagnosis (OR 7.52, 95% CI [2.41;23.29], p = 0.001), previous exposure to VKA (OR 17.11, 95% CI [4.48;60.91], p0.001), and no current exposure to anti-platelet agents (APA) (OR 7.69, 95% CI [1.22; 50.00], p = 0.030) were associated to DOA prescription. Discontinuation of the anticoagulant (n=24) was associated to DOA intake (OR 2.71, 95% CI [1.21; 6.08], p = 0.016).DOA are less prescribed than VKA in patients treated with APA. DOA switch to VKA was not systematic in patients diagnosed for a long time. However, international normalized ratio (INR) values were stable in most of patients treated with VKA at the switching to DOA. A more powerful study would confirm the factors associated with DOA prescription.

A number of pre-clinical studies have demonstrated the value of adrenal medullary allografts in the management of chronic pain. The present longitudinal survey studied 15 patients transplanted for intractable cancer pain after failure of systemic opioids due to the persistence of undesirable side-effects. Before inclusion, all the patients had their pain controlled by daily intrathecal (I-Th) morphine administration. The main evaluation criteria of analgesic activity of the chromaffin cell allograft was the complementary requirement of analgesics and in particular the consumption of I-Th morphine required to maintain effective pain control. Out of the 12 patients who profited from enhanced analgesia with long-term follow-up (average 4.5 months), five no longer required the I-Th morphine (with prolonged interruption of systemic opioids as well), two durably decreased I-Th morphine intake and five were stabilized until the end of their follow-up. Durable decline and stabilization were interpreted as indicative of analgesic activity by comparison with the usual dose escalation observed during disease progression. In most cases, we noted a relationship between analgesic responses and CSF met-enkephalin levels. The results of this phase II open study demonstrate the feasibility and the safety of this approach using chromaffin cell grafts for long-term relief of intractable cancer pain. However, while analgesic efficacy was indicated by the reduction or stabilization in complementary opioid intake, these observations will need to be confirmed in a controlled trial in a larger series of patients.

To use two different techniques to assess adherence of patients treated with antiosteoporotic drug.This monocentric transversal study was performed on a 6 months period, on patients of a single French pharmacy treated with antiosteoporotic drugs. Adherence was assessed crossing 2 techniques (patient autoquestionnaire and medication possession ratio measurement). Statistical analysis consisted in a description of the population study and a multivariate logistic regression to identify the factors associated with a lack of observance.Using the two techniques, the lack of adherence was estimated to be between 14 and 55%. Adherence was better in patients who were given dietetic advice or information about the usefulness of physical activity and worse in patients who reached menopause less than 23 years ago.A better identification of patients with a lack of observance is possible by crossing several techniques to assess adherence of the patient to his antiosteoporotic drug.

Intracerebroventricular morphine analgesic for the treatment of cancer pain was administered, using implanted access ports, in 82 patients from 1984 to January 1994. All of the patients who were selected for treatment were no longer responsive and had developed drug side effects to oral or parenteral opiates in varying doses (60-400 mg/d). The mean follow-up was 66 days (range, 12-443 d) for this series of 82 patients. The effective control of pain was achieved in nearly all of the patients, with only two failures. During the treatment, the daily morphine doses were moderately increased. The initial doses of morphine were a mean of 0.30 mg (range, 0.10-2 mg), and the final doses were a mean of 2.5 mg (range, 0.10-60 mg). The results show that the ratio of the terminal dose to the initial dose increased more rapidly for patients who had a follow-up of over 60 days. However, the increase seems to have been because of the progress of the disease rather than because of drug tolerance.