Wednesday, February 24, 2010
catheterisation hart coronairen
Simple Measures Can Cut Catheter-Related Bloodstream Infections Significantly
Thousands of infections and deaths could be prevented.
Catheter-related bloodstream infections cause tens of thousands of deaths each year, and each infection costs tens of thousands of dollars to treat. In an earlier Michigan initiative (JW Gen Med Dec 27 2006) that involved 103 intensive care units (ICUs), rates of these infections were lowered dramatically after systematic implementation of five evidence-based interventions: washing hands, using full barrier precautions, cleaning the skin with chlorhexidine, avoiding the femoral site, and removing unnecessary catheters. Eighteen months after implementation, catheter-related bloodstream infections were reduced by two thirds from baseline. In this follow-up study that involved 90 of the original ICUs, investigators evaluated whether the lower incidence of such infections were sustained at 19 to 36 months after implementation (sustainability period).
Overall, data related to more than 1500 ICU months and 300,000 catheter-days during the sustainability period were reported. The mean rate of catheter-related bloodstream infections decreased from 7.7 per 1000 catheter-days at baseline to 1.3 per 1000 catheter-days at 16–18 months and to 1.1 per 1000 catheter-days at 34–36 months postimplementation. Compared with the baseline rate, mean bloodstream infection rates at 16–18 months and 34–36 months were significantly lower.
Comment: Implementing five simple evidence-based interventions significantly lowers catheter-related bloodstream infections. These results are sustainable after such interventions are integrated into practice. As the authors conclude, widespread implementation of these interventions could lower morbidity and costs associated with these infections substantially.
— Paul S. Mueller, MD, MPH, FACP
Published in Journal Watch General Medicine February 23, 2010
Monday, February 22, 2010
vitamine D
Weekly Vitamin D3 Improves Vitamin D Insufficiency but Not Neuromuscular Function in Older Adults
Laurie Barclay, MD
Authors and Disclosures
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February 18, 2010 — Weekly treatment with 8400 IU of vitamin D3 raises serum 25-hydroxyvitamin D [25(OH)D] concentrations in elderly, vitamin D–insufficient individuals, according to the results of a randomized controlled, double-blind trial reported online February 3 in the American Journal of Clinical Nutrition.
"Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls," write Paul Lips, from Vrije Universiteit Medisch Centrum, Amsterdam, Netherlands, and colleagues. "We examined the effects of a weekly dose of 8400 IU vitamin D3 on postural stability, muscle strength, and safety."
Participants 70 years or older with 25(OH)D concentrations of 20 ng/mL or less but at least 6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU of vitamin D3 or placebo. The main endpoint of the study was mediolateral body sway with eyes open, measured with use of the AccuSwayPLUS platform (Advanced Medical Technology Inc, Watertown, Massachusetts). The short physical performance battery and serum 25(OH)D concentrations were secondary outcomes. Safety and tolerability were evaluated, and treatments were compared by use of an analysis of covariance model.
Strength of Randomized Study Design
"An increasing number of studies report on significant associations between low serum levels of 25-hydroxyvitamin D (25-(OH)D) and a multitude of extra-skeletal diseases and pathological conditions," Meinrad Peterlik, PhD, MD, professor emeritus of pathophysiology at Medical University Vienna in Vienna, Austria, told Medscape Nutrition when asked for independent comment.
"However, these mostly observational studies are rarely controlled for potential confounders, and interventional trials that would prove a causative relation between a compromised vitamin D status and disease incidence are rare. The main strength of the study by Lips et al. thus lies in the fact that it was designed as a randomized controlled multicenter trial to evaluate the effect of vitamin D3 supplementation on a well defined neuromuscular functional parameter, i.e., body sway, in a group of elderly people with sub-optimal vitamin D supply."
In patients treated with 8400 IU of vitamin D3 (n = 114) but not in patients receiving placebo (n = 112), serum 25(OH)D concentrations increased significantly from 13.9 to 26.2 ng/mL (P < .001). Mediolateral sway and short physical performance battery at 16 weeks were not significantly different between treatment groups.
Treatment with 8400 IU of vitamin D3 was associated with significantly decreased sway vs treatment with placebo (P = .047) in patients with elevated baseline sway but not in patients with normal baseline sway, based on a post hoc analysis of patients subgrouped by baseline sway (≥ 0.46 vs <>
"Weekly treatment with 8400 IU vitamin D3 raised 25(OH)D concentrations in elderly, vitamin D–insufficient individuals," the study authors write. "Treatment with 8400 IU vitamin D3 did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D3 reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D3 was well tolerated."
Parathyroid hormone levels decreased significantly in the vitamin D3 group but not in the placebo group. Both groups had similar adverse events and incidences of hypercalcemia, hypercalciuria, and elevated creatinine levels.
Limitations of the Study
"Although the results are straightforward, their interpretation is hampered by a number of facts, most of which are appropriately addressed by the authors themselves," Dr. Peterlik told Medscape Nutrition. "However, they fail to discuss what impact the optimization of calcium intake in the entire study group could have had on the outcome of the study. It could well be that at high calcium intake levels vitamin D supplementation is only minimally effective. This would not be surprising since a recent study by one of the coauthors (Pfeifer et al., Osteoporosis Int. 20:315-322, 2009) shows a positive effect of combined vitamin D and calcium supplementation on parameters of muscle function in elderly people."
Limitations acknowledged by the study authors include small size and unusually healthy condition of the elderly participants. In addition, a substantial number of participants had mediolateral sway values at baseline that were consistent with participants who did not fall, suggesting that their balance as measured by sway was adequate. There may have been little room for improvement of sway and physical performance with treatment in these patients.
"It is clear that elderly individuals with an increased body sway will benefit from a daily dose of 1200 IU vitamin D3 in combination with intake of > 1000 mg calcium per day," Dr. Peterlik concluded. "Additional studies with fracture rates as endpoint are necessary to prove that the observed reduction of body sway actually has a substantial impact on the incidence of falls and osteoporotic fractures in elderly people."
Merck & Co Inc supported this study, employs 5 of the study authors, and provided research grants to 4 other study authors. Dr. Peterlik has disclosed no relevant financial relationships.
Am J Clin Nutr. Published online February 3, 2010.
Thursday, February 18, 2010
statins
J Epidemiol Community Health 2010;64:109-113 doi:10.1136/jech.2009.091033 - Evidence-based public health policy and practice
Adherence and chemoprevention in major cardiovascular disease: a simulation study of the benefits of additional use of statins
- A Shroufi1,
- J W Powles2
+ Author Affiliations
- 1NHS Mid Essex, Chelmsford, Essex, UK
- 2Institute of Public Health, Cambridge, UK
- Correspondence to Dr A Shroufi, NHS Mid Essex, Swift House, Chelmsford, Essex CM2 5PF, UK; amir.shroufi@doctors.org.uk
Abstract
Background In everyday practice, adherence to preventive medication for cardiovascular disease (CVD) is lower than in clinical trials and appears to decline to ~50% by about 5 years. The UK body for the evaluation of health technologies, NICE, currently recommends that persons with a >20% 10-year risk of incident cardiovascular disease receive statins.
Methods Publications on adherence to statin medication in clinical trials and in normal practice were systematically reviewed. Data on CVD-free members of a large southern hemisphere cohort study were used to simulate the expected benefits of contrasting strategies to increase the use of statins. Risks of incident CVD and death from CVD were estimated.
Results A strategy to enhance statin adherence among cohort members meeting NICE statin-prescribing guidelines resulted in about twice as large a reduction in the aggregate risk of CVD death as did a strategy to lower treatment thresholds.
Conclusions The benefits from increased spending on statin medication will be much greater if they result from enhanced adherence rather than from lowering the medication threshold.
Friday, February 12, 2010
marokko
Kritiek op namenlijst Marokko
Gepubliceerd: 12 februari 2010 12:23 | Gewijzigd: 12 februari 2010 12:24
Door onze correspondent
Casablanca, 12 febr. Vrijheid van naamkeuze en wederkerigheid bij valutaverkeer. Dat heeft minister Eberhard van der Laan (Integratie, PvdA) deze week in Marokko bepleit bij Marokkaanse collega’s.
Minister Eberhard van der Laan (WWI, PvdA).
Foto Roel Rozenburg
De minister bracht een vijfdaags bezoek aan het land, waarbij de aandacht uitging naar de integratie van Marokkanen in Nederland.
Bij minister Ameur, verantwoordelijk voor Marokkanen in het buitenland, kaartte Van der Laan de omstreden lijst aan van toegestane namen voor Marokkaanse Nederlanders die hun kind inschrijven op het Marokkaanse consulaat. Officieel bestaat zo’n lijst niet, aldus Ameur, maar er bestaat wel een informele lijst. Niet inschrijven van een kind kan gevolgen hebben voor onder meer het erfrecht.
Van der Laan eiste volkomen wederkerigheid voor het geldverkeer tussen Nederland en Marokko. Die geldstroom is van levensbelang voor Marokko: volgens de Wereldbank stuurden Marokkanen in het buitenland in 2008 zo’n 6,7 miljard euro naar het vaderland op. Dat geld opnieuw uit Marokko krijgen is bijzonder moeilijk: vanaf 915 euro is toestemming vereist. Van der Laan voorziet groeiende problemen met erfenissen naarmate meer Marokkanen overlijden die uit Nederland zijn teruggekeerd.
Marokko heeft beloofd beide thema’s te onderzoeken. Nederland zal het probleem van de vrije naamkeuze in kaart brengen. Komend najaar bezoeken Marokkaanse ministers Nederland. „We geven hun het vertrouwen”, zei Van der Laan, „maar we gaan hen hier wel elke maand aan herinneren.” Is er tegen het najaar geen vooruitgang, „dan hoeft minister Ameur niet naar Nederland te komen”.
Een aanbod van Marokko om Nederland te „helpen” met Marokkaanse probleemjongeren heeft Van der Laan „beleefd afgeblokt”. „Dat is iets wat Nederland samen met de Marokkaanse gemeenschap moet oplossen.”
Op andere punten, zoals een verbod op huwelijken tussen neven en nichten, wacht Nederland niet op Marokko. „Dat gaan we gewoon doen”, aldus Van der Laan.
Thursday, February 11, 2010
Anthonius met het varken. Het vuur wijst op het koudvuur, het gevolg van moederkoorn
Rechts: bedevaart gangers naar Santiago
Jaren die erg vochtig verliepen waren gunstig voor het ontwikkelen van de schimmel De gevolgen waren dan vaak catastrofaal. In 922, 944 en 1129 heerste ergotisme over grote delen van Europa. Vooral in in het departement Sologne waren de gevolgen zeer ernstig en men noemt de ziekte daarom wel maladie de Sologne. In 1736 was de ziekte rond de stad Hannover endemisch. De ziekte heette officieel "morbus miserabilis et terribilis".
Het verband tussen ergotamine en de nadelige gevolgen werden pas in 1676 door de Fransman Dr.
Thaillier ontdekt. Hij deed veel onderzoek en zag dat het in de steden veel minder voorkwam dan
op het platte land. Soms kwam het bij de ene familie voor en bij de buurman niet. Hij zag dat het
meestal armen mensen waren, die aan de ziekte leden, die zich alleen roggebrood konden permitteren. Rogge is een gewas dat zonder veel bemesting op arme zandgrond toch nog redelijke opbrengsten heeft. Hij kwam tot de conclusie dat de veel voorkomende ziekte, die wel het Anthonius vuur of "holy fire" of "hell fire" in het Engels genoemd werd, veroorzaakt werden door het eten van roggebrood. Hij wist dat
extracten van moederkoren medisch gebruikt werden om bevallingen te bespoedigen en zo kon hij
de link leggen tussen het eten van moederkoren in het roggebrood en de gevolgen daarvan. Het
duurde toch nog meer dan l00 jaar voordat de ontdekking van Dr. Thaillier algemeen
aanvaard werd.
Het voorkomen van Anthonius vuur wordt voor het eerst vermeld in de tiende eeuw na Christus. In
944 stierven 40.000 mensen in Zuid Frankrijk aan het Anthonis vuur. Vanaf die tijd is het een ware
pest geweest tot de zeventiende eeuw toe. Omdat het ergotamine de weerstand sterk aantastte kreeg
gelijktijdig ook de pest haar kans en we zien de pest vaak gepaard gaan met het voorkomen van
moederkoren. De ziekte verspreidde zich over geheel Europa. De ledematen werden gangreneus
(koudvuur) en stierven tenslotte af..
De heilige Anthonis (251-356) was een asceet, die leefde op het einde van de derde eeuw. Omdat
St. Athanasius het leven van Anthonius in het Grieks nauwkeurig beschreef, is het in de vroege Middeleeuwen de voornaamste heilige geworden, die patroon was voor allerlei ziekten bij mens en dier. Hij was de eerste monnik die in armoede en alleen als kluizenaar in een grot leefde. Hij vaste streng en
"kastijdde" zich zoals ook nu nog bij de Shiieten in de Islam en strenge katholieken gebruikelijk is. In 305 kwam hij uit zijn eenzaamheid te voorschijn om als voorbeeld te dienen voor zijn volgelingen. Anthonis is daarom de stamvader van alle monnikenordes.
Vanwege zijn bekendheid werd hij de patroonheilige van de mensen die aan koudvuur (Anthonius vuur) leden.
In 1093 werd er vanuit de Benedictijner orde een afdeling gesticht, die zich de Anthonieten
noemde. De orde werd opgericht in de Dauphine, Zuid Frankrijk door een edelman met de naam
Gaston de la Valloire. Zijn zoon had aan de Anthonis ziekte geleden en men geloofde dat hij op voorspraak van Anthonius genezen was. Ook nu nog kan men het stichtings klooster in Frankrijk bezoeken in een
plaatsje met de naam Saint Antoine in de buurt van Grenoble. De monniken bestonden
aanvankelijk uit leken-broeders, die een zwarte toog droegen met een blauwe tau kruis, maar later
voegden zich ook priesters bij de orde. In 1227 werd de orde officieel door de paus erkend. Men trok
rond in heel Europa met bepaalde ijzeren instrumenten, waarmede men de lijders aan koudvuur de
aangetaste ledematen amputeerden en de wonden dicht brandde. Het leven van die patiënten werd
zo gespaard. De paus juichte een en ander toe en gaf de broeders toestemming (dispensatie) om
varkens in de steden en dorpen vrij te laten rondlopen. De varkens droegen een bel zodat iedereen
kon zien dat het varkens van de broeders waren. Daarom wordt de heilige Anthonis nog altijd
afgebeeld met een varken en een bel, hoewel zowel het varken als de bel niets met de oude heilige te
maken hebben.
De broeders bouwden een soort ziekenhuizen met rode daken, De lijders aan Anthonis vuur, die vaak op bedevaart naar Santiago de Compostella gingen, konden zien dat zij daar terecht konden voor hulp.
Tuesday, February 09, 2010
C-RP c-reactive protein
Articles
The
Lancet,
Volume 375, Issue 9709, Pages 132 - 140,
9 January
2010 doi:10.1016/S0140-6736(09)61717-7
Cite or Link Using DOI C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis
Original Text
The Emerging Risk Factors Collaboration‡ Summary
Background
Associations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances.
Methods
We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1·31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk factor levels.
Results
Loge CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher loge CRP concentration (three-fold higher) were 1·63 (95% CI 1·51—1·76) when initially adjusted for age and sex only, and 1·37 (1·27—1·48) when adjusted further for conventional risk factors; 1·44 (1·32—1·57) and 1·27 (1·15—1·40) for ischaemic stroke; 1·71 (1·53—1·91) and 1·55 (1·37—1·76) for vascular mortality; and 1·55 (1·41—1·69) and 1·54 (1·40—1·68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1·23 (1·07—1·42) for coronary heart disease; 1·32 (1·18—1·49) for ischaemic stroke; 1·34 (1·18—1·52) for vascular mortality; and 1·34 (1·20—1·50) for non-vascular mortality.
Interpretation
CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are each of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation.
Funding
British Heart Foundation, UK Medical Research Council, BUPA Foundation, and GlaxoSmithKline.
Saturday, February 06, 2010
posttraumatic stress disorder
From Reuters Health Information
Noninvasive Brain Stimulation Effective for Posttraumatic Stress Disorder
NEW YORK (Reuters Health) Jan 29 - Noninvasive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex relieves the core symptoms of posttraumatic stress disorder (PTSD), according to an online report in the Journal of Clinical Psychiatry.
Repetitive TMS (rTMS) has been tested in several small studies and is emerging as a potentially effective treatment for PTSD, the authors explain.
Led by Dr. Felipe Fregni, from Beth Israel Deaconess Hospital in Boston, Brazilian and American researchers studied 30 patients to evaluate the effect of high-frequency rTMS on core PTSD symptoms - such as hyperarousal, flashbacks, vigilance, intrusive thoughts, emotional numbness, and withdrawal - as well as on anxiety and depression.
Patients were randomized either to right-side rTMS, left-side rTMS, or sham procedures. The treatments were given in 10 sessions every weekday for 2 weeks. The 3 groups were similar in terms of medications.
At 5 and 10 days, right or left rTMS induced significant decreases in PTSD symptoms, whereas sham treatments had no significant effect.
Improvements in the PTSD Checklist and the Treatment Outcome PTSD Scale were greater after right rTMS than after left rTMS, but the differences were only marginally significant.
The improvement in avoidance and hyperarousal was larger after right rTMS than after left rTMS, the investigators say, whereas the improvement in reexperiencing was similar for the two sides.
Depression scores were significantly improved only after left rTMS treatment, and anxiety scores were significantly improved only after right rTMS treatment.
Performance in verbal fluency (as measured by the Controlled Oral Word Association Test) improved only after right rTMS, but other changes in cognitive function did not differ significantly between right and left rTMS.
The beneficial effects persisted to last follow-up (at 3 months) for both the PTSD Checklist and the Treatment Outcome PTSD Scale.
"This study supports the continuation of clinical investigation of brain stimulation for the treatment of PTSD," the authors conclude.
"Our results confirm that high-frequency rTMS over the right dorsolateral prefrontal cortex may be the best approach in most patients," they add, "yet we suggest that patients with high levels of depression may show greater benefit from high-frequency rTMS applied over the left dorsolateral prefrontal cortex."
J Clin Psychiatry 2009.
Friday, February 05, 2010
osteoarthritis artrose
Developments in the Scientific Understanding of Osteoarthritis
Steven B Abramson; Mukundan Attur
Authors and Disclosures
Posted: 01/27/2010; Arthritis Research & Therapy. 2009;11(3) © 2009
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Abstract and Introduction
Abstract
Osteoarthritis is often a progressive and disabling disease, which occurs in the setting of a variety of risk factors – such as advancing age, obesity, and trauma – that conspire to incite a cascade of pathophysiologic events within joint tissues. An important emerging theme in osteoarthritis is a broadening of focus from a disease of cartilage to one of the 'whole joint'. The synovium, bone, and cartilage are each involved in pathologic processes that lead to progressive joint degeneration. Additional themes that have emerged over the past decade are novel mechanisms of cartilage degradation and repair, the relationship between biomechanics and biochemical pathways, the importance of inflammation, and the role played by genetics. In this review we summarize current scientific understanding of osteoarthritis and examine the pathobiologic mechanisms that contribute to progressive disease.
Introduction
Osteoarthritis (OA) is characterized by a progressive loss of articular cartilage accompanied by new bone formation and, often, synovial proliferation that may culminate in pain, loss of joint function, and disability. A variety of etiologic risk factors and pathophysiologic processes contribute to the progressive nature of the disease and serve as targets of behavioral and pharmacologic interventions. Risk factors such as age, sex, trauma, overuse, genetics, and obesity can each make contributions to the process of injury in different compartments of the joint. Such risk factors can serve as initiators that promote abnormal biochemical processes involving the cartilage, bone, and synovium, which over a period of years result in the characteristic features of OA: degradation of articular cartilage, osteophyte formation, subchondral sclerosis, meniscal degeneration, bone marrow lesions, and synovial proliferation.
Thursday, February 04, 2010
aspirine Harrie
Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial.
Sung JJ; Lau JY; Ching JY; Wu JC; Lee YT; Chiu PW; Leung VK; Wong VW; Chan FK
Institute of Digestive Disease, Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong. joesung@cuhk.edu.hk
BACKGROUND: It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin. OBJECTIVE: To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases. DESIGN: A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725) SETTING: A tertiary endoscopy center. PATIENTS: Low-dose aspirin recipients with peptic ulcer bleeding. INTERVENTION: 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up. MEASUREMENTS: The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks. RESULTS: 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, -3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]). LIMITATIONS: The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy. CONCLUSION: Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.
Monday, February 01, 2010
osteo-artrose statins
Abstract
There have been numerous efforts to alter the lipid content of cardiovascular tissues. Although equally important, only limited information is available about musculoskeletal tissues. I characterized joint and bone marrow lipids in patients having joint replacement surgery and explored the effects of fish oils and statins on lipid composition in bone marrow and joint fluid. Joint drainage catheters were used to collect marrow lipids from 84 patients having 128 hip and knee replacements for osteoarthritis, osteonecrosis, and femoral neck fractures (osteoporosis). Statins reduced the amount of lipid by 22% in patients with osteoporosis, 26% in patients with osteoarthritis, and 41% in patients with osteonecrosis compared with pretreatment lipid levels in the same patients. Taking fish oils reduced the amount of lipid in bone marrow by 20%. Lipid profiles of disturbed marrow and joint fluid from patients who took statins or dietary fish oil showed an increase in the proportion of unsaturated fatty acids and longer-chain fatty acids relative to pretreatment profiles. The ability to change the amount and character of bone and joint lipids may have major importance for strengthening bone, reducing the severity or preventing osteonecrosis, and enhancing joint lubrication.
Level of Evidence: Level I, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.
celecoxib flutter Arytmia haert
Good Pharma Bad PharmaRe: Good Pharma Bad Pharma
Post by bigbunny on Jan 17, 2008, 10:01am
Celecoxib Can Adversely Affect Heart Rhythm, Study Suggests
![[image]](http://img90.imageshack.us/img90/9281/080114173854cn7.jpg)
The attached image shows the larval heart from Drosophila on which many of the experiments were done. The arrows point to the walls of the heart. The upper frame shows the heart in its dilated form and the lower frame shows the heart after contraction. (Credit: Satpal Singh)
ScienceDaily (Jan. 17, 2008) —
COX-2 inhibitors like Celecoxib have come under scrutiny lately due to adverse cardiovascular side-effects stemming from COX-2 reduction. In both fruit fly and rat models, researchers reveal another adverse effect of Celecoxib; this drug can induce arrhythmia. More interestingly, this effect is independent of the COX-2 enzyme.
Satpal Singh and colleagues tested various Celecoxib doses on the heart rate of Drosophila, a good model for human cardiac pharmacology. To their surprise, administering 3 ƒÝm Celecoxib (not much higher than the plasma levels in humans taking the drug) reduced heart rate and increased beating irregularities, while 30 ƒÝm was enough to stop the heart within a minute.
The surprise arises from the fact that Drosophila do not have COX-2 enzymes. Rather, Celecoxib could directly inhibit the potassium channels that help generate the electric current that drives heartbeat.
The researchers could achieve similar heart-stopping results in rat cardiac cells, whereas aspirin, another potent COX-2 inhibitor, had no effect, confirming that another mechanism is at work. The drug also inhibited rat and human potassium channels expressed in a human cell line.
Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. They also stress it is too early to speculate on human effects, although their results suggest Drosophila are a valuable tool to investigate other COX-2 drugs.
http://www.sciencedaily.com/releases/2008/01/080114173854.htm
DEMENTIA
Some Blood Pressure Drugs May Stave Off Dementia
TUESDAY, Jan. 12 -- Blood pressure drugs that block the protein angiotensin appear to reduce the risk of developing Alzheimer's disease and other forms of dementia, a new study finds.
"We think it [angiotensin] is one of the most important factors determining healthy blood vessels and also acts in the brain to help neurons to be a little more resilient," said Dr. Benjamin Wolozin, a professor of pharmacology and neurology at Boston University and senior author of a report on the findings, published online Jan. 13 in BMJ.
That report describes a study of more than 819,000 U.S. veterans, nearly all men, that found that those taking blood pressure medications that block cell receptors for angiotensin had a lower risk for dementia than those taking other cardiovascular medicines.
A similar but smaller protective effect was found for a related drug, lisinopril (Prinivil, Zestril), which blocks production of the active form of angiotensin.
Angiotensin causes blood vessels to constrict, raising blood pressure. It is produced when enzymes act to convert a precursor molecule, angiotensinogen. Lisinopril is a member of a drug family called ACE (angiotensin-converting enzyme) inhibitors. Other examples of ACE inhibitors are benazepril (Lotensin), enalapril (Vasotec) and ramipril (Altace).
Reducing angiotensin production by giving ACE inhibitors can lower blood pressure. The same effect can be achieved with drugs that block the cell receptors through which angiotensin acts. Called angiotensin receptor blockers, these drugs have a greater protective effect against dementia than ACE inhibitors, the study found. Such drugs include candesartan (Atacand), irbesartan (Avapro), losartan (Cozaar) and valsartan (Diovan).
In the study, men taking an angiotensin receptor blocker had a 24 percent lower incidence of dementia than those taking other cardiovascular drugs. The risk was 19 percent lower for men taking ACE inhibitors. The risk was nearly halved for those taking both angiotensin-targeting drugs.
In men with Alzheimer's disease, use of an angiotensin receptor blocker reduced admission to nursing homes by half. Combined angiotensin medication therapy reduced nursing home admissions by two-thirds.
Wolozin said that it's not clear why the drugs would have a beneficial effect on the brain, but improved blood flow probably plays a role.
"If you get no blood to the brain, you're not going to think well," he said. "Also, in brain cells there is more than one kind of angiotensin receptor. By blocking bad receptors, you are left with the good ones so that helps neurons become more resilient."
But the evidence is not sufficient to support routine use of angiotensin receptor blockers to prevent Alzheimer's disease, Wolozin said. The new report describes an observational study, one that lacks the strict controls that are needed for convincing proof.
"Any study like this is hypothesis-generating," he said. "You only know for sure when you have done clinical prospective trials."
His advice for anyone considering angiotensin receptors blockers to reduce dementia risk: "They should consult with their physicians." There are potential hazards, such as too-low blood pressure that can lead to damaging falls, Wolozin said.
Caution was urged by Dr. Richard B. Lipton, vice chairman of neurology at Albert Einstein College of Medicine in New York City, who has done work on the genetics of Alzheimer's disease.
The angiotensin hypothesis makes sense, Lipton said, because improved blood flow to the brain helps nerve cells and reduces formation of Alzheimer's-related amyloid protein.
But there have been a number of observational studies implicating various molecules, including estrogens, in dementia, he said. "The sequence is that when you do the randomized trial, you don't get the same effect," Lipton said.
On the other hand, such randomized trials usually include people who are close to having Alzheimer's disease, and "it could be different if you gave the drugs earlier," Lipton said.
More information
The U.S. Food and Drug Administration has more on blood pressure medications.
