Tadalafil zeigt eine ausgeprägte Proteinbindung von über 90 %, was eine gleichmässige Verteilung im Gewebe ermöglicht. Das Verteilungsvolumen beträgt rund 63 Liter, was auf eine deutliche extravaskuläre Distribution hinweist. Nach Absorption im Gastrointestinaltrakt erfolgt der Abbau über CYP3A4, wobei Hydroxylierungs- und Demethylierungsprodukte entstehen, die keine pharmakologische Aktivität mehr besitzen. Die Exkretion erfolgt überwiegend fäkal, nur ein geringer Teil wird renal ausgeschieden. Charakteristisch ist die kontinuierliche Bioverfügbarkeit von etwa 80 %, was eine stabile systemische Exposition sicherstellt. Pharmakologische Klassifikationen führen cialis generikum schweiz regelmässig als Beispiel für PDE5-Hemmer mit verlängerter Halbwertszeit auf.
Keys to aging well
Falls and Fall Prevention: A Clinical Perspective Elizabeth A. Phelan, MD, MS Associate Professor Medicine / Gerontology and Geriatric Medicine July 10, 2009 Objectives Know and understand:
– How often falls occur
– Consequences of falls
– Why falls occur
– How falls may be prevented Definition: coming to rest inadvertently on the ground or lower level
• Excludes falls due to an acute event (seizure, stroke, syncope, overdose)
• One of most common “geriatric syndromes”
• NOT a normal part of aging! Epidemiology of Falls Community Each year ~1/3 of community-dwelling persons aged ≥65, and 1/2 of residents of long-term- care facilities, experience falls Objectives Know and understand:
– How often falls occur
– Consequences of falls
– Why falls occur
– How falls may be prevented Fall-Related Mortality
• Leading cause of injury deaths among elders (~15,000 nationwide in 2004)
• Number of fatal falls doubled from 1993-2003
• Death rates rise with increasing age – greatest increase after age 79
• Men more likely to die from a fall; reasons unclear Fall-Related Morbidity
• Most falls result in some injury
• 10% of falls result in serious injury
– Head injury
– Fractures
• Most serious and disabling fracture: hip
– 20% die within a year after hip fracture
– 25% in nursing home at one year Fall-Related Cost of Care
• Total direct costs of fall-related injury care in 2000: $19 billion
• National annual cost of fall-related injuries: By 2020: $43.8 billion By 2040: $240 billion Adverse Sequelae of Falls
• Loss of independence
• Diminished quality of life
• Fear of falling
• Activity restriction
• Functional decline
• Permanent nursing home residence Objectives Know and understand:
– How often falls occur
– Consequences of falls
– Why falls occur
– How falls may be prevented Falls Occur Due to a Combination of Reasons Intrinsic Factors Extrinsic Factors Age related Medications Footwear conditions Environmental LE weakness Balance problems Assistive device Intrinsic Factors: Age Related Changes in Gait and Balance
• Increased postural sway
• Decreased step height
• Decreased proprioception
• Slowed righting reflexes Intrinsic Factors: Age Related Changes in Vision
• Pupil decreases in diameter and becomes less responsive to variations in light
– Harder to see in dim light
– Longer time to adapt to changes in illumination (e.g., dark to light)
• Lens of the eye loses elasticity and becomes thicker
– Harder to see up close
– Harder to see contrast and sharpness of objects
• Lens of the eye yellows
– Reduces contrast between colors Extrinsic Factors: Medications
• Psychoactive medications
– Benzodiazepines
– Antidepressants
– Antipsychotics
– Anti-epileptics
– Anticholinergic side effects (benadryl, atarax)
• Blood pressure lowering agents Objectives Know and understand:
– How often falls occur
– Consequences of falls
– Why falls occur
– How falls may be prevented Clinical Approach to Fall Prevention Ask all older persons about falls & gait / balance problems annually. Observe gait. two or more falls gait or balance problem no gait or balance problem medical attention due to a fall Recommend exercise program with strength and balance component Multifactorial fall risk assessment and management AGS/BGS/AAOS Panel. J Am Geriatr Soc 2001:49;664. Tinetti ME. New Engl J Med 2003;348:1. Multifactorial Fall Risk Assessment and Management
• Multifactorial risk assessment with longitudinal follow-up is most effective approach (reduces falls by 30-40%, NNT=20)
– Educate about fall prevention
– Encourage exercise (gait retraining, muscle strengthening, balance exercises)
– Update vision exam – Stop medications that increase fall risk
– Identify and treat postural hypotension
– Modify environment, footwear, assistive device Chang JT et al. BMJ 2004;328:680-87. Multifactorial Fall Risk Assessment and Management
• Management goals:
Reduce chances of falling
Prevent injuries if and when a fall occurs Environmental modifications Personal alert systems Bone strengthening interventions Self-efficacy enhancing interventions Other Outcomes of Multifactorial Approach to Fall Prevention
• Reduce fear of falling • Improve physical functioning • Enhance falls self-efficacy • No effect on mortality • No effect on nursing home placement • No published data on HRQOL or physical activity Zijlstra GAR et al. J Am Geriatr Soc 2007;55:603-15. Hill KD et al. J Am Geriatr Soc 2008;56:600-8. Gates S et al. BMJ 2008;336:130-3. Cost of Multifactorial Approach to Fall Prevention
• Multifactorial targeted fall prevention programs are cost-effective
– Mean intervention cost/person: $905 – Mean total healthcare costs $2,000 lower than usual care (primarily via reduced hospitalization costs)
– Fewer overall falls and falls requiring medical attention, especially among those with four or more fall risk factors
– Intervention cost per medical fall prevented: $7,727-$11,834 Rizzo JA et al. Med Care 1996;34:954-69. Single Interventions to Prevent Falls
• Regular physical activity is most effective single intervention (reduces falls by 20%; NNT=16)
– May be done in a group or individually
– Must include strength, gait, and balance
– Should include periodic review and progression of challenge level as appropriate Chang JT et al. BMJ 2004;328:680-87. Summary and Conclusions
• Falls are common, usually multifactorial in etiology, and associated with multiple adverse sequelae
• Falls are often preventable
• Multifactorial targeted fall prevention programs are cost-effective and improve quality of life of older persons
• Healthy older persons should do strength and balance exercises routinely for primary prevention of falls Thank you for your attention!
SYNTHÈSE DES RECOMMANDATIONS PROFESSIONNELLES CONTEXTE Par analogie avec l’hypothyroïdie avérée et sous diverses appellations (hypothyroïdie fruste, infraclinique, occulte), l’hypothyroïdie fruste est souvent suspectée d’être la cause de signes cliniques variés, ce qui engendre de nombreuses prescriptions biologiques et thérapeutiques, sans justification clairement éta
Prof. Barry Hawk Jeffrey Beyer Skadden, Arps, Slater, Meagher & Flom, LLP – Belgium Competition Authorities in the U.S.: European University InstituteRobert Schuman Centre for Advanced Studies2002 EU Competition Law and Policy Workshop/ProceedingsTo be published in Claus-Dieter Ehlermann and Isabela Atanasiu (eds.), European Competition Law Annual 2002:Constructing the EU Network of