[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

[Pathophysiology of detrusor underactivity in the elderly]. / Physiopathologie de l'hypoactivité détrusorienne de la personne âgée.

AIM: The aim of this study was to review the evidence regarding the pathophysiology of detrusor underactivity in the elderly. METHODS: A literature review was conducted in July 2016 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: The prevalence of detrusor underactivity has been reported to range from 8% to 48% depending on the definition used and the age of the population studied. Current data suggest that aging may itself be a causative factor of detrusor underactivity through myogenic dysfunctions (ultrastructural degeneration of the detrusor muscle) and neurogenic dysfunctions (by degeneration of efferent but mostly afferent innervation mechanisms). Beyond these inherently age-related mechanisms, many comorbidities whose prevalence increase with age (diabetes, bladder outlet obstruction, estrogen deficiency, atherosclerosis, etc.) may be implicated in the development of detrusor underactivity in the elderly. The role played by detrusor overactivity in the appearance of detrusor underactivity must be considered separately as both seem to be the expression of the same condition of the lower urinary tract responding to different stages and secondary to numerous etiopathogenic factors which modulate its progression and clinical expressions. CONCLUSION: Pathophysiology of detrusor underactivity remains poorly understood but seems to imply myogenic and neurogenic factors which are favored, besides the aging per se, by various and numerous comorbidities which prevalence increase with age (diabetes, bladder outlet obstruction…).

[Guidelines concerning urinary incontinence in elderly: construction and validation of GRAPPPA algorithm]. / Recommandations concernant l'incontinence urinaire de la personne âgée : construction et validation de l'algorithme décisionnel GRAPPPA.

OBJECTIVES: Provide guidelines presented as an algorithm for practical evaluation and first line therapy of urinary incontinence in elderly. PATIENTS AND METHODS: Guidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 40 experts quoting proposals, subsequently reviewed by an independent group of multidisciplinary experts (urologist, general practitioner, neurologist, gynecologist, geriatrist, specialist in physical medicine and rehabilitation). RESULTS: By means of 3 rounds of interrogation of the expert panel, GRAPPPA algorithm was constructed. This algorithm take in account both evaluation and first line therapeutic options in the different type of incontinences observed in this population (urge, stress and mixed incontinence). Initial evaluation consists to track down urinary retention (and subsequently fecal stool impaction, use of anticholinergic or morphinic drugs), urinary tract infection and cognitive impairment. Haematuria, bladder-pelvic pain, history of radiotherapy or recent pelvic surgery, lead to refer the patient to a specialized unit. First line therapy is in all the cases pelvic floor training, use of local oestrogenotherapy and dietetic measures. In urge incontinence, anticholinergic drugs may be used. CONCLUSIONS: Implementation of this algorithm may promote best practice in management of urinary incontinence in elderly.

[Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly]. / Traitement anticholinergique de l'hyperactivité vésicale de la personne âgée et ses impacts sur la cognition. Revue de la littérature.

OBJECTIVES: Describe the central nervous system (CNS) adverse effects of anticholinergic drugs used for the treatment of overactive bladder (OAB) in the elderly. PATIENTS AND METHODS: Relevant data from the literature were identified primarily through a Medline search of articles published through December 2013. The search terms included overactive bladder, central nervous system, elderly, anticholinergic, and antimuscarinic. Articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. RESULTS: Several anticholinergic drugs are available for the treatment of OAB, including oxybutinin, tolterodine, trospium chloride, solifenacine, fesoterodine. Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutinin, lower for tolterodine, solifenacine, and darifenacine, and lowest for fesoterodine and trospium chloride. Unwanted CNS adverse effects depend in part on patient specific variability in pharmacokinetic parameters, blood-brain barrier permeability, degree of cholinergic neuronal degeneration, total anticholinergic drug burden and patient's baseline cognitive status. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and coma. Among the different anticholinergic agents, oxybutinin has been associated with cognitive impairment and trospium chloride and fesoterodine have shown favorable CNS tolerability. CONCLUSIONS: Anticholinergic drugs improve significatively overactive bladder symptoms in older adults. However, potential CNS adverse effects of anticholinergic agents used in OAB must lead to a full evaluation before and during the treatment in order to evaluate benefice, risks and central side effects in this frail population.

[Consensus statement on severe dementia]. / Consensus sur la démence de type Alzheimer au stade sévère.

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

[Consensus statement on severe dementia]. / Consensus sur la démence de type Alzheimer au stade sévère.

Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary group of experts, including geriatricians, neurologists, epidemiologists, psychiatrists, pharmacologists, and public health specialists developed consensus recommendations about care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians, and specialists, based on the knowledge currently available (2005). The aim of care at all stages is to mitigate the quality-of-life of patient, caregiver, and family insofar as possible, combining care and future planning until the end of life. Management, to take into account problems including nutritional status, behavior disorders, and ability (or inability) to perform activities of daily living, must be global, multidisciplinary, and coordinated and must optimize use of local medical and social resources. The group also stressed the importance of clinical research to improve knowledge of disease course and assess management strategies and recommended specific area for research.

Comparison of racecadotril and loperamide in adults with acute diarrhoea.

METHODS: A multicentre, randomized, double-blind, double-placebo, parallel-group study was carried out to compare the efficacy, tolerability, and safety of racecadotril (100 mg three times daily) and loperamide (2 mg after each diarrhoeic stool) in 157 adults with acute diarrhoea. Patients were treated for 7 days or until recovery, if this took place earlier. RESULTS: Both groups of patients passed similar numbers (mean +/- S.E.M.) of stools before recovery (3.5 +/- 0.5 for racecadotril vs. 2.9 +/- 0.4 for loperamide), and the duration of diarrhoea (mean +/- S.E.M.) was similar in both groups (14.9 +/- 2.0 h for racecadotril and 13.7 +/- 2.2 h for loperamide). Both treatments reduced the incidence of associated symptoms and signs during the study, and both were similarly well tolerated. However, more patients on loperamide reported rebound constipation during treatment (18.7% vs. 9.8% with racecadotril). CONCLUSIONS: The enkephalinase inhibitor, racecadotril, and the intestinal transit inhibitor, loperamide, were similarly and rapidly effective in resolving the symptoms and associated signs of diarrhoea.

[Consensus statement of an interdisciplinary group of French experts on modalities of diagnosis and medical treatment of Alzheimer's disease at a treatable stage]. / Convergences d'un groupe pluridisciplinaire d'experts français sur les modalités du diagnostic et du traitement médicamenteux de la maladie d'Alzheimer au stade démentiel.

A group of French expert met on the 7th and 8th of February 1998 in order to establish a consensus attitude for Alzheimer's disease diagnosis and treatment. Members were drawn from primary care, geriatrics, neurology and psychiatry. They used the consensus statement of the American Association for Geriatrics, the Alzheimer's Association and the American Geriatrics Society published in JAMA, in October 1997 as a source of data for further consideration. Alzheimer's disease in the most common etiology of dementia. Main clinical features are cognitive impairment and psycho-behavioral disorders. Diagnosis must be one of inclusion and not exclusion. It is based on interviews of informants and family members and office-based clinical assessment. After a physical examination, cognitive function must be evaluated using the Mini-Mental State Examination. A laboratory evaluation should include a complete blood cell count, blood chemistry and determination of thyroid-stimulating hormone. In addition, noncontrast computed tomography head scans are adequate in most cases. Available pharmacologic treatments are not curative but are given to improve quality of life and enhance cognition and behavior. Two cholinesterases inhibitors, tacrine and donepezil, are the only agents officially authorized for treatment of the cognitive impairment in Alzheimer's disease. Mood and behaviour disorder also have to be treated by both pharmacologic and nonpharmacologic strategies. Only pharmacologic treatments will be detailed here. The consensus statements established by this group of experts will be reevaluated each year, considering the new available data on Alzheimer's disease.

[Clinical trials in Alzheimer disease. Methodological problems: what application for what indication?]. / Essais cliniques dans la maladie d'Alzheimer. Problèmes méthodologiques: quel dossier pour quelle indication?

For many years, all application dossiers sent to the Ministry of Health for use in Alzheimer's disease focused on the correction of cognitive disorders. Discussions were centered on the choice of cognitive evaluation scales and psychometric tests. The situation has since evolved and in addition to the cognitive disorders, applications must also consider daily life activities and comportmental disorders. Animal experiences remain classical, the use of aged animals not bringing much information and being extremely expensive. Phase I does not need to be modified at this stage. Phase II, however, must be done with extreme methodological rigor, and especially with an evaluation of pertinent clinical benefit in the cognitive and non-cognitive fields. The simple statistically significant improvement in one scale or another was not found sufficient by the Commission. The pharmaceutical company therefore has to find the benefit risk ratio that has real therapeutic interest. If this ratio seems pertinent to the Ministry, then phase III studies can be done to confirm longterm efficacy on enough patients. The study of drug action is very interesting to advance research or even in the application dossier, but in all cases, the ratio of pertinent clinical benefit to the risk of side effects remains the cornerstone of the decision.

[Geriatric hospital facilities]. / Les structures hospitalières gériatriques.

Nowadays (and prior to any hospital reform), geriatric hospital structures rest on medium or long length stay units and on acute geriatry departments when these are available. However, to limit relations between hospital and the elderly to these three structures would be an oversimplification. The organization of emergency admission units for the elderly, the medico-social preparation of these patients before they return home, the setting up of geriatric consultations in both out-patient clinics and specialized hospital departments are all major topics not to be neglected. Moreover, geriatric day-hospitals offer hospital treatment without accommodation which is a solution desired by many old people. What can be suggested for the mentally deficient or demented old patient admitted to a hospital, if not the cooperative efforts of geriatric and psychiatric teams working in suitable architectural structures? Finally, we must insist on the need for coordination between hospital and non-hospital structures, so that the entire "geriatric network" becomes reality without any break in care between structures.

[Therapeutic trials in outpatients. Apropos of triazolam trials]. / L'essai thérapeutique en ville. A propos de l'essai du triazolam.

Clinical trials conducted in general practice are more especially interesting as they enable to test a drug in the real conditions of use. On the other hand, these trials are beneficial to the G.P. (new image, rupture of his loneliness, change in his prescription habits, contact with hospitals). The methodology, as for hospital studies, must be rigorous. As a matter of fact, these two types of studies are additional and the cooperation between the G.P.'s and the pharmaceutical industry can conduct to the solution of specific problems: drug interaction--long-term therapeutic effect--new indications. This double blind cross over study comparing triazolam and nitrazepam conducted by G.P.'s on insomniacs is the first French clinical study intended for the registration application and done according to this methodology. This work is an exemple of the new opportunity offered to G.P.'s in future. The results have shown that: on 54 patients (23 male and 31 female) of an average age: 48, 32 have preferred triazolam, 13 have preferred nitrazepam, 9 have had no preference.

Effects of acetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea.

Acetorphan is an orally active inhibitor of enkephalinase (EC 3.4.24.11) with antidiarrhoeal activity in rodents apparently through protection of endogenous enkephalins and a purely antisecretory mechanism. Its antidiarrhoeal activity in man was assessed in an experimental model of cathartic induced secretory diarrhoea as well as in acute diarrhoea of presumed infectious origin. In six healthy volunteers receiving castor oil and pretreated with acetorphan or placebo in a crossover controlled trial, the drug significantly decreased the number and weight of stools passed during 24 hours. About 200 outpatients with severe acute diarrhoea (more than five stools per day) were included in a randomised double blind study of acetorphan against placebo. The significant antidiarrhoeal activity of acetorphan was established using a variety of criteria: (i) the duration of both diarrhoea and treatment were diminished; (ii) no acetorphan treated patient withdrew from the study whereas five dropped out because of worsening in the placebo group; (iii) the frequency of symptoms associated with diarrhoea--for example, abdominal pain or distension, nausea and anorexia--remaining after two weeks was nearly halved; (iv) using visual analogue scales acetorphan treatment was found more effective than placebo by both investigators and patients. There was statistically no significant difference between acetorphan and placebo in respect of side effects, particularly constipation, which often accompanies the antidiarrhoeal activity of mu opioid receptor agonists this difference is attributable to the lack of antipropulsive activity of acetorphan in man. The efficacy and tolerance of acetorphan suggest that enkephalinase inhibition may represent a novel therapeutic approach for the symptomatic management of acute secretory diarrhoea without impairing intestinal transit.