Adeline Gallini

Slow-release oral morphine for opioid maintenance treatment: a systematic review

This review article summarizes the results of all available clinical trials considering the use of slow-release oral morphine (SROM) for opioid maintenance treatment (OMT). All studies published up to October 2010 and assessing SROM for OMT in adult patients are included. Three independent reviewers assessed the selected articles using a standardized checklist. Study design, study length and number of subjects included were recorded. Data about retention rate (proportion of participants remaining under maintenance treatment at the end of the study), quality of life, withdrawal symptoms, craving, additional drug consumption, driving capacity and adverse events were collected. We identified 13 articles corresponding to nine clinical trials considering the use of SROM for OMT. Among them, only one was a randomized trial and one was a controlled not randomized trial. All other studies were uncontrolled. Retention rates were good (from 80.6 to 95%) with SROM maintenance, but similar retention rates were obtained with methadone. Most of the studies showed that quality of life, withdrawal symptoms, craving and additional drug consumption improved with SROM. However, there was no comparison with other maintenance drugs. As most of the studies assessing SROM efficacy were uncontrolled, there is no definite evidence that SROM is an effective alternative to methadone for OMT.

Does memantine induce bradycardia? A study in the French PharmacoVigilance Database

To review the cardiovascular adverse drug reactions (ADRs) with memantine reported to the French PharmacoVigilance Database.

Evaluating the clinical relevance of a cognitive composite outcome measure: An analysis of 1414 participants from the 5-year GuidAge Alzheimer's prevention trial

Composite cognitive scores have been developed as primary outcome measures for preclinical/prevention trials for Alzheimers disease (AD), mainly using observational data and with little consideration of clinical relevance.

A Longitudinal Study of Transitions Between Informal and Formal Care in Alzheimer Disease Using Multistate Models in the European ICTUS Cohort.

BACKGROUND We aimed to describe longitudinal patterns of care in community-dwelling European patients with Alzheimer disease (AD), and determine patient-, caregiver-, and country-related predictors of transitions across different care levels. METHODS Two-year follow-up data from ICTUS cohort (1375 patients with AD, 12 countries) were analyzed using multistate Markov models to describe transitions across states of care and identify their predictors. RESULTS Of the patients, 61.3% stayed in the same state during follow-up, and only 9.5% experienced ≥2 changes between states. Six-month transition probabilities were 11% for informal to formal care and 13% for formal to informal care (in the community). Older age, male gender, poorer cognitive and behavioral scores, and country of residence were associated with transitioning from informal to formal care, but only country of residence was associated with the reverse transition. DISCUSSION Changes between different types of care were rare during follow-up, and country factors in particular influenced these transitions.

Platelet Adhesion and Thrombus Formation in Whole Blood at Arterial Shear Rate at the End of Pregnancy

Platelet reactivity has not been evaluated in integrated functional testing during normal pregnancy. Here, we analysed platelet functions under arterial shear rate in comparison with static conditions.

Weight-loss associated with anti-dementia drugs in a patient with parkinson's disease

Two main pharmacological classes of drugs are available for patients suffering from Alzheimer’s disease (AD): cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) and N-methyl-D-aspartate (NMDA) receptor inhibitors (memantine). Among adverse drug reactions (ADR) associated with cholinesterase inhibitors, anorexia and weight loss are expected and quite common. Prevalence of these cholinergic ADRs during clinical trials was up to 17%.1 With NMDA inhibitors, these ADRs remain relatively unknown. Common adverse effects with memantine include constipation, dizziness, headache, or somnolence.2 We report here the case of a 69-year-old woman with Parkinson’s disease (PD) and dementia, who experienced an important weight loss under galantamine then memantine. Her PD was diagnosed in 1982, and she was treated in February 2004 with levodopa associated with benserazide, trihexiphenidyl plus piribedil. She lived at home with her husband. In February 2004, because of a cognitive decline (Folstein’s mini-mental state examination MMSE 14/30), galantamine (Reminyl) was initiated progressively to a maximal posology of 4 mg three time a day. Few months after beginning galantamine, the patient experienced nausea and anorexia and lost 17 kg (from 52 kg before initiation of galantamine to 35 kg, for a 150 cm-height). Dosage of galantamine was then decreased to 2 mg twice a day, and the patient regained 4 kg. However, this improvement did not last and the patient reached a minimal weight of 33 kg. In spite of adjunction of ornithine oxoglutarate (Cetornan), weight status was still unsatisfactory and galantamine was discontinued in December 2005. The etiological inquiry eliminated hyperthyroidism, diabetes, inflammatory syndrome, or a qualitative or quantitative decrease in ingesta. In March 2006, memantine (Ebixa) was instaured (MMSE 12/30). The patient weighed 35 kg then. The medication was initiated progressively to a maximal dose of 15 mg (30 drops) a day during 3 months then decreased to 12.5 mg (25 drops) a day. At the end of 2006, the patient weighed 28 kg (a 7 kg-loss) and memantine was discontinued in January 2007. Two-month later, the patient weighed 34 kg. During this period (February 2004, January 2007), anti-Parkinsonian drugs remained unchanged. This report illustrates weight-loss with off-label utilization of galantamine and memantine in a Parkinsonian patient. This ADR is expected with cholinesterase inhibitors, whereas it has never been published with memantine. Memantine is a derivative of amantadine, a drug used in PD and influenza infections. Amantadine, and memantine to a less extent level, possesses dopaminergical properties, which can induce nausea, vomiting, or anorexia. Amantadine enhances dopamine transmission directly by inhibiting dopamine uptake and indirectly through NMDA blockade.3 It has also been suggested that amantadine was able to increase serotonine levels in rat hypothalamus.4 Because of this ability to modify dopamine and serotonin transmissions, amantadine has been assessed in a few clinical trials for limiting weight-gain associated with atypical antipsychotics.5–7 Anorexia, nausea, and vomiting are well-known ADRs with amantadine. With memantine, there is no report of weight-loss during clinical trials and any notifications in the French national pharmacovigilance database. To our knowledge, only 4 cases have been reported to the Swedish adverse reaction data registry.8 We use the French imputability method, which is based on two criteria: intrinsic or case-related imputability (I, graded from I0–I4), which takes into account chronological (C) and semiological (S) data and extrinsic imputability or bibliographic data (B, quoted from B0–B3). Using this method, we recorded these ADRs in the French pharmacovigilance database with an imputation I3 “likely” (C3S2B3) under galantamine and I1 “dubious” (C2S1B1) under memantine. This report illustrates an unknown, although explainable from a pharmacodynamic point of view, ADR with memantine. The present ADR was potentialized by the association of two dopamine agonists: levodopa and piribedil. This report brings an additional reason for careful risk-benefit analysis before prescribing AD medications and regular assessment of their effectiveness during the treatment, especially in PD dementia because of the lack of efficacy data. Practiciens should be aware of this ADR and should pay more attention to drug-induced weight-loss, which could provoke in a geriatric population dramatic damages, such as institutionalization10 and death.11

Effect of dementia on receipt of influenza vaccine: a cohort study in French older adults using administrative data: 2007‐2012

Despite guidelines stating the vaccine benefit in this population, older adults with dementia may be less likely to receive influenza vaccine than cognitively intact older adults. But no study has yet reported on vaccine uptake in patients newly diagnosed with dementia or whether years since dementia diagnosis influences vaccine uptake. We conducted a cohort study in the French Health Insurance database (Echantillon Généraliste de Bénéficiaires) which contains hospital data and claims for a 1/97th random sample of the French population. Diseased subjects were ≥65 years and had a new record of dementia diagnosis between September 1, 2007, and August 31, 2008. Vaccine receipt was measured via influenza vaccine dispensing in community pharmacies. We described influenza vaccination rates up to 2011–2012 and estimated adjusted relative risks (aRR) for vaccine receipt each year using multivariate modified Poisson models controlling for sociodemographics, comorbidities, and health resources use. Four hundred and seven subjects with dementia (mean age 81.8 years, 69.3% females) and 4862 subjects (mean age 75.2 years, 61.3% females) without dementia were included. In 2008–2009, influenza vaccination prevalence was 70.0% (95% CI = [65.3–74.4]) and 70.2% (95% CI = [68.9–71.4]) in subjects with and without dementia, respectively (aRR = 0.93; 95% CI = [0.87–1.00]). In 2009–2010, the aRR was of the same magnitude (aRR = 0.96, 95% CI = [0.90–1.03]), but in 2010–2011 and 2011–2012, the aRR was 1.02 (95% CI = [0.94–1.11]) and 1.05 (95% CI = [0.96–1.14]), respectively. Subjects with dementia had a slightly nonsignificant lower receipt of influenza vaccine in the year following dementia diagnosis than subjects without dementia. In subsequent years, divergent trends were observed in vaccine uptake according to dementia status.

Anticholinergic exposure and cognitive decline in older adults: Effect of anticholinergic exposure definitions in a 3‐year analysis of the Multidomain Alzheimer Preventive Trial (MAPT) study

The aim of the present study was to assess the association between anticholinergic (atropinic) burden and cognitive decline in older adults over the course of 3 years.

Optimization of drug therapy in elderly individuals admitted to a geriatric unit

Background A substantial share of adverse drug events involves inappropriate prescribing (IP). Specialized geriatric units are supposed to pay particular attention to prescribing appropriateness and to promoting a higher prescribing quality. Objective The objective of this study was to evaluate the reality of such assessment and optimization in real life (usual care) in a population of elderly individuals admitted to a geriatric unit. Method This is an observational study including all older patients admitted to an acute geriatric unit over a 6-month period. As part of usual care, the geriatrician is supposed to detect potentially inappropriate medication and potential prescribing omission using validated tools. The primary outcome was the prevalence rate of therapeutic modifications motivated by treatment optimization (stop, switch, or introduction). Multivariate logistic regression analyses were performed to identify the factors associated with therapeutic discontinuation. Results A total of 216 patients were included. The mean age was 85.7 years. Included patients had an average of 7.2±3.3 drugs at admission and 5.8±2.7 at discharge. IP was highly prevalent in our study where about 63% of the patients had experienced at least one modification because of overuse. The most commonly discontinued medications were drugs used to treat gastroesophageal reflux disease and peptic ulcer disease and serotonin reuptake inhibitor antidepressants. The most commonly introduced medications were analgesics and warfarin. By using multivariate analysis, we found that patient age and number of drugs on admission were significantly associated with medication discontinuation during hospital stay. Conclusion In this real-life study of all patients admitted to a Geriatric Post Emergency Unit, 83% of the patients had a treatment modification during hospital stay. The most original result of our study is the clear reduction in polypharmacy during hospitalization.