Wednesday, February 22, 2012
PPI omeprazole clostridium difficile
From Medscape Gastroenterology > Johnson on Gastroenterology
PPIs and C difficile: Putting the Risk in Perspective
Posted: 02/16/2012
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Putting the Risk in Perspective
I would like to go through the process of evaluating this potential risk, to put it in perspective, and discuss how you might potentially respond to this warning for your patients taking PPIs. The way I evaluate this is to look at the scientific hypothesis -- what is the biologic plausibility, what is the evidence base, what does the literature say, and what do I see in my patients? So, it is a 4-step process for evaluating the risk/benefit profile of any pharmacologic or intervention strategy. Let's walk through the process for PPIs and CDAD and see what we can garner from this.
The biologic plausibility. The scientific hypothesis is that the gastric acidity protects the gastrointestinal tract from ingested bacteria. A gastric pH less than 4 is fairly profoundly bacteriocidal, so most things do not survive that level of gastric acidity under normal conditions. The scientific hypothesis is that if you impair the gastric acid by means of an acid-suppressive agent, that you may diminish the protective effect of the gastric acidity and thereby raise risk for gastrointestinal infection. The idea that PPIs and even H2-receptor antagonists may do this has been reported and evaluated in the literature.[2]
The scientific hypothesis is that gastric pH diminution may pose increased risk for infection by loss of the bacteriocidal barrier of the gastric acidity. C difficile has 2 forms. One is a vegetative form, and this is acid-sensitive, so, under a normal acidic pH, the vegetative form is fairly quickly killed by the normal gastric acidity. The other is a spore form that is not killed by the normal gastric acidity, and can potentially transit [through] the gastrointestinal tract and pose risks. These spores can turn into a vegetative form once they get into the small intestine and colon. So the biologic plausibility is that the diminishment of acidity may affect the ability to kill the vegetative form, but not the spore form, which is acid-resistant.
To add one more factor to this, we do know that PPIs have an effect on white blood cell function. In vitro studies suggest that there may be alterations of chemotaxis, phagocytosis, and expression of adhesion molecules. This in vitro evidence suggests that PPIs (acid inhibition) may alter white cell function. The biologic plausibility, therefore, makes some sense.
Weighing the evidence. The scientific evidence is very controversial. I found 27 articles in the world literature to date that have looked at the association of C difficile and PPI therapy; 17 of these have suggested harm/potential risk. The risk ratios range from 1.1 to nearly 5 with respect to the incremental risk for C difficile in patients taking PPIs. None of these are prospective trials. Ten studies showed no associated harm. Four of the 17 studies that showed harm suggested an association between recurrent C difficile infection and PPI use, and 3 studies showed an increased risk with higher than standard dose PPIs. So the scientific evidence is fairly mixed, but, clearly, there is more evidence of an association than of a lack of association. Recognizing that these are all retrospective studies, it is very difficult thereby to risk-stratify. These patients are perhaps sicker and they have multiple exposures. All but 5 of these studies were hospital-based, so these were not outpatients. Extrapolation to the normal population of outpatients that you and I see in our clinics is hard to do on the basis of the available evidence.
Assess your practice. The evidence is fairly mixed, so I return to the fourth tenet, which is, what do I see in my practice? When I see a patient with C difficile, do the alarms go off that this patient is more likely to be on a PPI? I don't necessarily see in my practice that the patients who are positive for C difficile are more likely to be on a PPI. I would ask you to do the same analysis in your practice to see if that plays out.
Talking With Patients About PPIs
How do we put this in perspective? The news is out there, so it potentially needs to be discussed with patients. If you see a patient with diarrhea who is on a PPI, if they have risk factors, you should screen them for C difficile. It is always a healthy point to reanalyze, and consider: does this patient need to be on a PPI?. Many of these patients are on therapies that they don't need. However, in patients who are taking the PPI for nonsteroidal antiinflammatory drug (NSAID) prophylaxis, severe gastroesophageal reflux disease, or recurrent upper gastrointestinal bleeding, clearly the risk ratios are in favor of continuing that PPI. Nonetheless, reevaluate, potentially stop, or reduce the dose if you can, or change to alternative therapies if appropriate. It is always a healthy discussion to have with patients, and we talk about multiple risks associated with PPIs: bone fractures, hypomagnesemia, the clopidogrel interaction. It gives us the opportunity to discuss whether they really need the medication.
The International Society of Travel Medicine warns that PPIs may increase risk for multiple enteric infections and traveler's diarrhea.[3] So, recognize that PPIs have received a lot of press with respect to enteric infections, the most recent of which is C difficile. The evidence base to support this is, I think, very tenuous at best, and very difficult to analyze using retrospective studies. If we wanted to study this in a prospective way, it would be helpful to also nest a cohort of achlorhydria patients (those with vagotomies or gastric surgeries, following which they make no acid, patients with pernicious anemia, or atrophic gastritis). Those patients would be the ones who would be potentially at greatest risk, with no acid production. At the best case, PPIs may prolong gastric pH reduction to a pH higher than 4 for up to 18 hours. We never make these patients achlorhydric or anything close to it.
Beware of the new evidence, and that this is something that has now been reported by the FDA in the United States and by Health Canada as well. Put this in perspective, look at the evidence base, and, hopefully, this will help you as you begin to discuss these new alerts with your patients. I will leave this to your best clinical judgment and I look forward to chatting with you again soon. I am Dr. David Johnson.
statines
From Journal of the American College of Cardiology
Meta-Analysis of Statin Effects in Women Versus Men
Posted: 02/14/2012; J Am Coll Cardiol. 2012;59(6):572-582. © 2012 Elsevier Science, Inc.
- Abstract and Introduction
- Methods
- Results
- Discussion
- Conclusions
Abstract and Introduction
Abstract
Objectives The aim of this study was to evaluate the effect of statins in decreasing cardiovascular events in women and men.
Background Published data reviews have suggested that statins might not be as effective in women as in men in decreasing cardiovascular events.
Methods Published data searches and contacts with investigators identified 18 randomized clinical trials of statins with sex-specific outcomes (N = 141,235, 40,275 women, 21,468 cardiovascular events). Odds ratios (ORs) and 95% confidence intervals (CIs) for cardiovascular events were calculated for women and men separately with random effects meta-analyses.
Results The cardiovascular event rate was lower among those randomized to statin intervention than in those randomized to control (low-dose statin in 4 studies, placebo in 11 studies, usual care in 3 studies) and similar in women and men (OR: 0.81, 95% CI: 0.75 to 0.89; p < 0.0001, and OR: 0.77, 95% CI: 0.71 to 0.83, p < 0.0001, respectively). The benefit of statins was statistically significant in both sexes, regardless of the type of control, baseline risk, or type of endpoint and in both primary and secondary prevention. All-cause mortality was also lower with statin therapy both in women and men without significant interaction by sex (p for interaction = 0.4457).
Conclusions Statin therapy is associated with significant decreases in cardiovascular events and in all-cause mortality in women and men. Statin therapy should be used in appropriate patients without regard to sex.
Introduction
Randomized controlled clinical trials and meta-analyses have shown a benefit of statins in decreasing morbid and mortal cardiovascular events in apparently healthy individuals and in those with clinically evident cardiovascular disease (CVD).[1–6] However, there is insufficient information on the benefits of statins in women especially in primary prevention.[7–9] Reviews and meta-analyses have shown improved outcomes with statins in both women and men without significant interaction by sex.[10–11] However, they did not show statistically significant effects in women. This could be related to under-representation of women in trials and underscores the need to explore sex-related differences that would provide a basis for clinical strategies to improve outcomes for women.[12–15]
The purpose of this report is to present a meta-analysis of sex-specific outcomes in controlled randomized clinical trials of statin therapy.
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Tuesday, February 21, 2012
AF dabigatran
From Medscape Education Cardiology
A Patient-Centered Approach to Atrial Fibrillation-Related Stroke CME
Faculty and Disclosures
In the United States, approximately 1 out of every 18 deaths is attributed to stroke, making it the third leading cause of death. Underutilization or inappropriate application of thromboprophylaxis for stroke prevention in atrial fibrillation (AF) is a relatively common finding in clinical practice. Furthermore, patient and physician concern about the use of warfarin has resulted in its underutilization, particularly among elderly individuals who are at the greatest risk for cardiovascular and cerebrovascular events. The limitations of warfarin have led to the investigation and approval of more convenient anticoagulant options with more predictable pharmacokinetics and more favorable benefit-to-risk ratios, including factor IIa, factor Xa, and direct thrombin inhibitors. Despite emerging evidence of their benefit in AF-related stroke prevention, knowledge of new oral anticoagulants among healthcare providers is generally lacking. Join Drs. Bruce Lindsay and Walid Saliba for a discussion on the challenges faced during stroke risk assessment and treatment of patients with AF.
Saturday, February 18, 2012
aspirine dabigatran
February 15, 2012 (Northbrook, Illinois) — New thrombosis guidelines from the American College of Chest Physicians have come down in favor of aspirin use for primary prevention in adults over 50 years old [1].
Lead author of the coronary artery disease chapter of the guidelines, Dr Per Vandvik (Gjøvik Hospital, Oslo, Norway), noted that these are thought to be the first major guidelines to come out after the studies suggesting a reduction in cancer risk and mortality with aspirin were reported, and "incorporating these data pushed us to give aspirin a weak recommendation in primary prevention."
Vandvik added: "I would say the cardiovascular benefit and the bleeding risk is pretty much well balanced, but the suggestion of a benefit in mortality may just swing the balance over to taking aspirin." But he stressed that this was not a blanket recommendation. "Doctors need to talk to their patients about it, and it is something they might want to consider."
The ninth edition of the Antithrombotic Therapy and Prevention of Thrombosis Guidelines, published in the February 2012 issue of Chest, states: "People who are averse to taking medication over a prolonged time period for very small benefits will be disinclined to use aspirin for primary prophylaxis. Individuals who value preventing an MI substantially higher than avoiding a GI bleed will be, if they are in the moderate or high cardiovascular risk group, more likely to choose aspirin."
Head of the guidelines committee, Dr Gordon Guyatt (McMaster University, Hamilton, ON), added: "We agonized over this recommendation endlessly, with some heated discussions. Some people thought we should recommend aspirin for everyone; others were adamant that no primary-prevention patient should take it. The right message is that there are trade-offs to be made and a lot of uncertainty. In this situation, it is inevitable that individual patient values and preferences will bear in the decision."
He noted that this approach of collaborating with the patient in making the decision to take antithrombotic therapy or not was a big feature throughout these guidelines. "In many cases, the trade-offs between benefit and risk are very small, so we need to ask the patient more questions, really push for information to make the decision as to whether antithrombotic treatment is the right way to go."
Opinion Leaders Less Involved Than Before
Guyatt also explained that there were big process changes in the way the guidelines were formulated this time. In particular, instead of having world experts in the field of antithrombotics in charge of each guideline section, it was decided this year to choose instead clinicians who were experts in methodology and interpretation of the evidence. "It was felt that the experts in the field were maybe a little too close to the information, and they often have intellectual and/or financial conflicts. While thrombosis experts were still included on the panel, they did not have the same weight as in previous occasions."
Vandvik added: "If you performed the study that we were referring to you could not participate in the final discussions of what recommendations should be made."
Asked what the antithrombotics experts on the panel thought of the new system, Guyatt said, "We made a lot of converts because our approach was so rigorous. Most acknowledged that it was a superior process. Some, however, were still a little grumpy!" Vandvik added: "This is somewhat an experiment, in terms of the academic conflict of interest, but I think it will catch on."
Less Strong Recommendations
Not surprisingly, this new process has resulted in a set of guidelines that recommends antithrombotic treatment less often and less strongly than before. "The guidelines panel felt that the strength of the evidence in favor of antithrombotic therapy was less than has been thought in the past. Consequently, our recommendations tend to be weaker than in previous guidelines," Guyatt says. "There is recognition that not everyone in the hospital needs antithrombotic therapy, and we need to individualize such therapy more.
"From an outside view, it appears that antithrombotics may have been used a little too much in North America, although the situation is very variable," he adds. "In many cases, the risk of thrombosis is very small, and this has to be balanced by the risk of bleeding, the cost, and the inconvenience," Guyatt noted.
He explained that in making this trade-off, one stroke was thought to be equal to three bleeds. He gave the example of an AF patient at a low risk of stroke. If a patient has a 1% risk of stroke over a year, and this risk is halved by antithrombotic treatment, 200 patients would need to be treated to prevent one stroke. But if the bleeding risk was 3%, that would mean six bleeds in the 200 patients, with the balance of six bleeds vs one stroke going against antithrombotic treatment.
However, in another patient with a 6% risk of stroke and a 3% risk of bleeding, this would translate into six strokes vs three bleeds, so antithrombotic therapy would be the right option in this case.
"We have got to be much more quantitative than we have been in the past. We may not have the greatest ways of assessing stroke and bleeding risk, but we have to offer clinicians something," Guyatt says. The guidelines have opted for the CHADS2 score for stroke, rather than the CHA2DS2-VASc score as the first choice. "We also need to consider the values and preferences of the patient. Some people are more stroke averse; others are more bleeding averse. Some will be better than others at managing warfarin."
The guidelines do not advise passengers on long-haul flights to take antithrombotic prophylaxis unless they have known risk factors. Guyatt says: "The risk is very small. If your risk of [venous thromboembolism] VTE is one in 1000 and a long-haul flight doubles this risk, then your risk is still very low. But if your baseline risk is one in 100, then it would become one in 50, and then you start to worry."
Dabigatran Recommended for AF
But the guidelines do appear to welcome the new oral anticoagulants as an alternative to warfarin. For patients with atrial fibrillation in whom oral anticoagulants are indicated (CHADS2 score of >1), they recommend dabigatran rather than warfarin as long as the patient does not have severe renal impairment.
Thursday, February 16, 2012
potassium kalium hyperkalemia
SUMMARY AND COMMENT
Dual Therapy with Aliskiren plus ACE Inhibitor or ARB Is Linked to Hyperkalemia
February 9, 2012 | Paul S. Mueller, MD, MPH, FACP | General Medicine
Risk was about 50% higher with dual therapy than with monotherapy.
Reviewing: Harel Z et al. BMJ 2012 Jan 9; 344:e42
gout jicht
SUMMARY AND COMMENT
Gout and Diuretics in Hypertensive Patients Free!
January 26, 2012 | Allan S. Brett, MD | General Medicine
Diuretic use raised risk for gout by several percentage points.
Reviewing: McAdams DeMarco MA et al. Arthritis Rheum 2012 Jan 64:121
gout jicht
SUMMARY AND COMMENT
February 7, 2012 | Paul S. Mueller, MD, MPH, FACP | General Medicine
Diuretics, β-blockers, angiotensin-converting–enzyme inhibitors, and non-losartan angiotensin-receptor blockers are associated with increased risk.
Reviewing: Choi HK et al. BMJ 2012 Jan 12; 344:d8190
dabigatran
Dabigatran and Acute Coronary Syndromes: Meta-Analysis Confirms RE-LY Findings
Dabigatran increases risk for acute coronary syndromes but decreases mortality.
Several alternatives to warfarin for prevention of venous thromboembolism and stroke are already approved for clinical use, and several more are in development. The principal advantage of these agents is their ease of use. Yet they also have known disadvantages — such as the lack of a rapid reversal agent and cost — and, possibly, unknown toxicities. By contrast, warfarin has been in use for millions of patient-years, and its effects (both beneficial and adverse) are very familiar.
Dabigatran was FDA-approved for treatment of atrial fibrillation after the landmark RE-LY study (JW Cardiol Sep 1 2009). A secondary finding from RE-LY showed a significant increase in myocardial infarction with dabigatran. To find out more, investigators conducted a meta-analysis of seven dabigatran studies. Control agents in the studies included warfarin, enoxaparin, and placebo.
The rate of acute coronary syndromes (including infarction) was significantly higher in the 20,000 dabigatran patients than in the 10,514 control patients (1.19% vs. 0.79%). These results were largely driven by RE-LY, which contributed 59% of the cohort and 74% of the events. Unlike the RE-LY trial, in which a decrease in overall mortality with dabigatran did not quite achieve statistical significance (P=0.051), the meta-analysis demonstrated a significant reduction in mortality with dabigatran (5.02% vs. 4.83%; P=0.04).
Comment: The confirmation of one adverse endpoint in the RE-LY study does not diminish the fact that dabigatran reduces the rates of venous thromboembolism and stroke. However, this meta-analysis does underline the need for continuing postapproval study of any new drug. I suspect that as data accumulate from registry and other observational studies, warfarin will fare poorly in overall safety comparisons with dabigatran and other new competitors.
Published in Journal Watch Cardiology February 15, 2012
Wednesday, February 15, 2012
bloeddruk HYVET diuretica
Atlanta, Georgia US, 4 May, 2009 - HYVET (HYpertension in the Very Elderly Trial)1 has been unanimously voted as 2008 Trial of the Year by the prestigious Project ImpACT (Important Achievements of Clinical Trials) and the Society for Clinical Trials. HYVET was judged a landmark clinical trial, in terms of design, execution, and results. Evidence that effective antihypertensive treatment with indapamide sustained release 1.5 mg (Natrilix SR) in patients aged 80 or more prevents the fatal and debilitating consequences of hypertension such as stroke, heart failure, and dementia is likely to impact on guidelines and change the clinical management of very elderly patients with hypertension. This is especially relevant as this age group is the fastest growing globally, with growth rates expected to triple by 2050.2 Emeritus Professor Christopher Bulpitt, the lead investigator on the HYVET study from the Care of the Elderly Group at Imperial College London, UK, said: “I am very grateful to all who either worked on the trial or supported it in some way. The trial was entirely a collaborative effort. Our results clearly show that many patients aged 80 and over could benefit greatly from treatment.’
Increasing systolic blood pressure is part of the ‘normal’ aging process. Almost all very elderly patients (80 or over) have systolic hypertension (systolic blood pressure ≥160 mm Hg). Before HYVET, doctors were unsure whether these patients would obtain the same benefits from treatment to lower their blood pressure as those observed in younger people, as these very elderly patients had been largely excluded from previous clinical trials.
HYVET was the largest ever clinical trial to address this question. In total, 3845 patients were randomized to once daily treatment with placebo or the diuretic indapamide sustained release 1.5 mg (Natrilix SR), with the addition of the angiotensin-converting enzyme inhibitor perindopril 2-4 mg as necessary. Natrilix SR was used as it has proven efficacy in lowering blood pressure, particularly systolic blood pressure, in the long term.3 In July 2007 the trial was stopped early on the recommendation of an independent data monitoring committee after observation of significant reductions in overall mortality and stroke in those receiving treatment. Final results showed reductions of 21% (p=0.02) in total deaths, 39% (p=0.05) in stroke-related death, 64% (p<0.001) in fatal and nonfatal heart failure, and 34% (p<0.001) in cardiovascular events.1 There was also evidence from the HYVET-COG substudy that blood pressure lowering may reduce or delay dementia.4 According to Nigel S. Beckett, M.D., the trial coordinator from the Care of the Elderly group at Imperial College London: ‘The results of HYVET will have important implications for the generation of future guidelines and mean that very elderly individuals with sustained systolic blood pressures of 160 mm Hg or more should now be appropriately assessed and treated in accordance with these findings.’
HYVET has received other important awards which reinforce its landmark status. In January 2009, the American Heart Association voted HYVET as among the top 10 major advances in heart disease and stroke research for 2008.5 According to Timothy Gardner, M.D., President of the American Heart Association: ‘The results of HYVET demonstrate that effective antihypertensive treatment with indapamide (Natrilix SR) in persons aged 80 years old or older, is beneficial in reducing the risk of cardiovascular events, and thus extends the patient group in whom prevention must be pursued.’
HYVET was also nominated as the most important clinical trial of the year by Medscape, an online resource for clinicians.6 Commenting on the trial on Medscape Cardiology, Professor Henry R. Black, M.D., Clinical Professor of Internal Medicine, New York University School of Medicine, Center for Prevention of Cardiovascular Disease, USA, and President of the American Society of Hypertension, said ‘HYVET has filled in the gap in clinical management of hypertension in the very elderly.’
Furthermore, HYVET was identified as exceptional among the All time Top 10 list for clinical trials compiled by Faculty of 1000 Medicine,7 an online resource provided by expert researchers and clinicians. Deepak Bhatt, M.D., Chief of Cardiology, Veterans Affairs Boston Healthcare System and Director, Integrated Interventional Cardiovascular Program at Brigham and Women’s Hospital and the Veterans Affairs Boston Healthcare System, USA, said: ‘HYVET is a landmark study that challenges current paradigms which question the risk to benefit of treating hypertension in patients older than 80 years of age. The results of this study should encourage practitioners to treat elevated systolic blood pressure in the very elderly.’
HYVET and NATRILIX SR
HYVET was a randomized, double-blind, placebo-controlled trial in 3845 patients with persistent hypertension (sustained sitting systolic blood pressure ≥160 mm Hg) aged 80 years of age or older. Active treatment was indapamide sustained release (NATRILIX SR) 1.5 mg, with the addition of perindopril 2-4 mg as necessary, to reach a target blood pressure of 150/80 mm Hg. NATRILIX SR is a thiazide-like diuretic, with proven efficacy in lowering blood pressure, particularly systolic blood pressure, in the long term.3 Additionally, NATRILIX SR does not significantly affect the glucose or lipid profile over the long term.3,8 The primary study end point was fatal or nonfatal stroke.
At 2 years, mean sitting blood pressure was decreased by 15.0/6.1 mm Hg with NATRILIX SR compared with placebo. Intention-to-treat analysis showed that treatment with NATRILIX SR led to relative risk reductions of:
• 21% for total mortality (p=0.019)
• 39% for stroke mortality (p=0.046)
• 30% for stroke (p=0.055)
• 64% for heart failure (p<0.001)
• 34% for all cardiovascular events, a composite of cardiovascular causes of stroke, myocardial infarction or heart failure, (p<0.001)
Based on these findings, one death would be avoided for every 40 very elderly patients treated with NATRILIX SR (± perindopril) for 2 years.
HYVET also provided a unique opportunity to assess any effects of blood pressure–lowering treatment on cognitive function and the development of dementia in the HYVET-COG substudy. Cognitive function was evaluated using the Mini Mental Sate Examination (MMSE), with a fall to <24 or of >3 points in one year prompting assessment for possible dementia using the Diagnostic Statistical Manual edition IV, computed tomography scanning, and the Modified Ischemic Score. All cases were reviewed by an expert committee who were blinded to treatment allocation.
HYVET was stopped before follow-up for cognitive function was complete. Despite this, there was a tendency for reduction in incident dementia with active treatment (by 14%, hazard ratio 0.86, 95% CI 0.67-1.09, p=0.21), which was considered to be of clinical significance. Furthermore, when the HYVET data were added to those of previous trials using a meta-analytic technique, the result was significantly in favor of treatment (hazard ratio 0.87, 95% CI 0.76-1.00). The ongoing HYVET extension may provide supplementary data.
For further information on HYVET refer to the HYVET website: http://www.hyvet.com, and for information on HYVET and NATRILIX SR refer to the Servier website: http://www.servier.com or contact Servier International – 35, rue de Verdun – 92284 Suresnes Cedex – France.
References
1. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-98.
2. United Nations. World population ageing 1950-2050. IV. Demographic profile of the older population. Available from http://www.un.org/esa/population/publications/worldageing19502050/pdf/90chapteriv.pdf.
3. Leonetti G, Emeriau J-P, Knauf H, et al. Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients. Curr Med Res Opin 2005;21:37-46.
4. Peters R, Beckett N, Forette F, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial. Lancet 2008;7:683-9
5. American Heart Association. News release. Top research advances include studies that influence medical care, apply science to ‘real world’ communities. January 21, 2009. Available from http://americanheart.mediaroom.com/index.php?s=43&item=648.
6. Medscape Cardiology. This Year's Awards for the Most Important Trials Go to... HYVET and ACCOMPLISH. March 2, 2009. Available from http://cme.medscape.com/viewarticle/588818
7. Faculty of 1000 Medicine. All time Top 10 by F1000 factor. All of Medicine. March 30, 2009. Available from http://www.f1000medicine.com/top10/classics/
8. Weidmann P. Metabolic profile of indapamide sustained-release in patients with hypertension. Drugs Safety 2001;24:1155-65.
bloeddruk
het volledige artikel is:
SUMMARY AND COMMENT
Benefits of Treatment in Very Old People with Hypertension
February 14, 2012 | Paul S. Mueller, MD, MPH, FACP, and Allan S. Brett, MD
Immediate benefits of antihypertensive treatment included lowered risk for stroke, heart failure, and CV events.
Reviewing: Beckett N et al. BMJ 2012 Jan 4; 344:d7541
Hoort bij het vorige summary.
What is already known on this topic
People aged 80 or more with sustained systolic blood pressures of 160 mm Hg or more benefit from blood pressure lowering treatment
What this study adds
Benefits in terms of a reduction in cardiovascular events appeared within one year of starting treatment
The benefit was achieved by lowering systolic blood pressure to 150 mm Hg; any benefit of lowering blood pressure further cannot be assumed
Free living, community based octogenarians should be screened for hypertension and offered blood pressure lowering treatment in line with HYVET
bloeddruk
Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial
Abstract
Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment.
Design One year open label active treatment extension of randomised controlled trial (Hypertension in the Very Elderly Trial (HYVET)).
Setting Hospital and general practice based centres mainly in eastern and western Europe, China, and Tunisia.
Participants People on double blind treatment at the end of HYVET were eligible to enter the extension.
Interventions Participants on active blood pressure lowering treatment continued taking active drug; those on placebo were given active blood pressure lowering treatment. The treatment regimen was as used in the main trial—indapamide SR 1.5 mg (plus perindopril 2-4 mg if required)—with the same target blood pressure of less than 150/80 mm Hg.
Main outcome measures The primary outcome was all stroke; other outcomes included total mortality, cardiovascular mortality, and cardiovascular events.
Results Of 1882 people eligible for entry to the extension, 1712 (91%) agreed to participate. During the extension period, 1682 patient years were accrued. By six months, the difference in blood pressure between the two groups was 1.2/0.7 mm Hg. Comparing people previously treated with active drug and those previously on placebo, no significant differences were seen for stroke (n=13; hazard ratio 1.92, 95% confidence interval 0.59 to 6.22) or cardiovascular events (n=25; 0.78, 0.36 to 1.72). Differences were seen for total mortality (47 deaths; hazard ratio 0.48, 0.26 to 0.87; P=0.02) and cardiovascular mortality (11 deaths; 0.19, 0.04 to 0.87; P=0.03).
Conclusion Very elderly patients with hypertension may gain immediate benefit from treatment. Sustained differences in reductions of total mortality and cardiovascular mortality reinforce the benefits and support the need for early and long term treatment.
Monday, February 13, 2012
statins statines
From Reuters Health Information CME
Benefits of Statins Outweigh Musculoskeletal Effects, Say Experts CME
Faculty and Disclosures
Clinical Context
Statins are usually well tolerated, but the most common adverse effects are musculoskeletal, including muscle aches and pain, weakness, cramps, or increases in creatine kinase levels. In the general population, little is known about the prevalence of musculoskeletal pain and statin use.
Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002 had suggested an association between statin use and musculoskeletal pain among individuals without arthritis, but the relatively small sample size precluded determination of whether statins increased musculoskeletal pain in those with arthritis.
The objective of this study by Buettner and colleagues was to evaluate the association between statin use and musculoskeletal pain in the general population, including those with and without arthritis, using 6 years of NHANES data.
Study Synopsis and Perspective
In a cohort of people without arthritis, musculoskeletal pain, most often in the legs and lower back, was reported 33% more often by those using statins.
"Although the majority of people who use statins do not experience statin-associated musculoskeletal side effects, about 6% (or one out of every 17 people) without arthritis have pain associated with statin use," Dr. Catherine Buettner, who led the study, told Reuters Health.
In people who do have arthritis, statins didn't seem to add to the pain burden — although the pain of arthritis could mask statin-associated pain, she and her colleagues say.
Dr. Buettner, from Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, added, "Our study did not allow us to discern why those with arthritis do not report higher pain when using statins. Statins are known to have some anti-inflammatory effects so, theoretically, it is possible statins may decrease arthritis pain by decreasing inflammatory processes."
"On the other hand," she said, "most arthritis is due to osteoarthritis (rather than inflammatory arthritis), so we need to consider other reasons; it could simply be that pain from arthritis is more severe and masks mild-moderate pain related to statin use; it may be that patients with arthritis are more reluctant to start a statin, or discontinue them more frequently, due to concerns that using a statin is adding to their pain; or it may be that doctors are less likely to prescribe a statin to patients with painful musculoskeletal conditions, such as arthritis."
Statin drugs are one of the most widely prescribed classes of medications. In 2003-2004, an estimated 24 million adults in the United States received a prescription for one. Although generally well tolerated, musculoskeletal side effects, including muscle aches, pain, weakness, cramps or creatine kinase elevations are the most common adverse effects of statins.
Asked for his thoughts on the new findings, Dr. Harlan Krumholz of Yale School of Medicine in New Haven, Connecticut, who was not involved in the study, said: "It's an observational study and has some limitations. Nevertheless, we know that statins can cause some muscular discomfort — and this article is consistent with that knowledge."
"The bottom line," he told Reuters Health, is that the "33% relative increase in risk translates to a few additional patients feeling discomfort for every 100 treated. This study should not deter patients from taking their medication — or shake their faith in the powerful risk reduction effect of statins — but people with these complaints should talk with their doctors."
Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, Dr. Buettner and colleagues estimated the prevalence of self- reported musculoskeletal pain according to statin use.
The analysis, reported in the February issue of the American Journal of Medicine, included 8,228 adults (representing 113 million US adults) aged 40 and older; 1,306 of them (representing 17 million US adults) reported using a statin in the past month.
Statin use increased significantly over the study period, with prevalence of use in the last 30 days estimated at 13% in 1999-2000, 15% in 2001-2002, and 18% in 2003-2004.
Musculoskeletal pain was assessed by asking participants: During the past month, have you had a problem with pain that lasted more than 24 hours? Those who answered "yes" were asked where the pain was.
In the overall sample, the unadjusted prevalence of musculoskeletal pain was significantly higher among statin users reporting pain in any area than nonusers (30% vs 26%; p=0.007); in the lower extremities (18% vs 14%; p=0.008); and in the lower back (14% vs 11%; p=0.02).
After controlling for confounding factors, among the 5,170 subjects without arthritis (about 63% of the complete cohort), statin use was associated with a significantly higher prevalence of musculoskeletal pain in any region, the lower back and the lower extremities. The adjusted prevalence ratios were 1.33, 1.47 and 1.59, respectively.
Conversely, there was no association between musculoskeletal pain and statin use among the 3,058 adults with arthritis.
"Being aware that statins may cause musculoskeletal pain is important and should be considered when new symptoms start in a patient who has recently started a statin, had an increase in statin dose, or started a medication that interacts with a statin," Dr. Buettner said.
"However, it is also important to recognize that the background prevalence of musculoskeletal pain is high among adults (more than 20% in non-statin users in this study). Therefore the majority of people using statins who have muscle symptoms are more likely to have symptoms due to another cause rather than due to use of a statin," she commented.
Dr. Krumholz agrees. "Many people have musculoskeletal pain, and for those on a statin the pain could be unrelated." However, the use of statins "is associated with an increased risk of muscle discomfort and that adverse side effect can be evaluated by discontinuing the statin and seeing if it goes away."
It should also be recognized, he said, that the musculoskeletal side effect "is not consistent across statins and people should try another one if they do have this side effect, in collaboration with their doctor."
The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Am J Med. 2012;125:176-182.
Saturday, February 11, 2012
colonoscopy
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Friday, February 10, 2012
dementia
Summary and Comment
Cognitive Decline Begins in Middle Age
The decline accelerated as years advanced.
Cognitive performance declines with advancing age. When this decline begins, however, is unclear. In this prospective cohort study, investigators estimated the 10-year decline in cognitive function in London civil servants (age, 
45).
At baseline, the 5200 men and 2200 women were divided into five age groups (45–49, 50–54, 55–59, 60–64, and 65–70) and underwent cognitive testing. Cognitive outcomes were tests of memory, reasoning, vocabulary, and phonemic and semantic fluency. Participants were assessed three times during the next 10 years. All cognitive outcomes, except vocabulary, declined significantly in all baseline age groups with evidence for faster decline in older participants. For example, in men who were 45 to 49 at baseline, the 10-year decline in reasoning scores was 3.6%, whereas in men who were 65 to 70, it was 9.6%. (Similar results were obtained for women.)
Comment: In this prospective study, cognitive decline occurred in all age quintiles between 45 and 70 and was faster among older participants. Whether these results can be generalized is unknown, but the results have important public health implications. As the authors note, "research needs to identify the determinants of cognitive decline and assess the extent to which the cognitive trajectories of individuals are modifiable." One issue not addressed by the authors is the distinction between "normal aging" and the cognitive decline that heralds dementia syndromes.
— Paul S. Mueller, MD, MPH, FACP
Published in Journal Watch General Medicine February 9, 2012
Thursday, February 09, 2012
dementia stroke
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75) who were free of dementia 3 months after stroke. Participants underwent neuropsychological testing annually; the investigators identified incident cases of dementia according to standard DSM-IV criteria. The researchers performed brain autopsies in 50 of the 176 participants who died.potassium kalium
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K Kalium potasium hypokalemia
SUMMARY AND COMMENT
U-Shaped Association Between Potassium Level and Acute-MI Mortality
February 8, 2012 | Joel M. Gore, MD
Hypokalemia was associated with increased mortality, but so were serum potassium levels 
4.5 mEq/L, suggesting that repletion measures should be moderated.
Reviewing: Goyal A et al. JAMA 2012 Jan 11; 307:157
Scirica BM and Morrow DA. JAMA 2012 Jan 11; 307:195
Friday, February 03, 2012
statins
January 30, 2012 (Boston, Massachusetts)— A large meta-analysis has shown that statins are as effective in women as in men for the reduction of cardiovascular outcomes and all-cause mortality, leaving investigators to conclude that statins should be used in all appropriate patients regardless of sex [1].
"There have been a large number of clinical trials looking at the benefits of statin use, but the ability for us to prove that the benefits extend to both men and women has been limited, in part because of numbers," lead investigator Dr William Kostis (Massachusetts General Hospital, Boston) told heartwire . "There have been studies that have shown benefits in men, and where they have shown a trend toward benefit in women they were unable to show a statistically significant difference. Because of this, we undertook the meta-analysis, and what we found was what we had hoped to find, and that was that the benefits of reducing cardiovascular outcomes and all-cause mortality extend to both men and women."
The meta-analysis, published in the February 7, 2012 issue of the Journal of the American College of Cardiology, included 18 clinical trials of statin therapy with clinical outcomes for men and women. The analysis included 141 235 subjects, including 40 275 women, from studies such as JUPITER, ALLHAT-LLT, ASCOT-LLA, Heart Protection Study, MEGA, PROVE-IT, and TNT, among others. Ten of the studies were secondary-prevention studies, and eight studies were designed as primary-prevention trials, although five of the primary-prevention studies did include a proportion of patients with cardiovascular disease.
In an editorial accompanying the study [2], Dr Lori Mosca (Columbia University Medical Center, New York) states that the finding of "no interaction by sex in this contemporary meta-analysis is concordant with prior meta-analyses that were limited by smaller numbers of women and suggests statin therapy has similar proportional benefits for men and women, regardless of the type of end point studied or the level of population risk."
Primary- and Secondary-Prevention Studies
In the meta-analysis, statin therapy significantly reduced the risk of cardiovascular events 19% in women and 23% in men. The treatment effect in women was more pronounced in the secondary-prevention studies, where a 22% reduction in the risk of cardiovascular events was observed, compared with the 15% reduction in outcomes found in the primary-prevention studies. The reduction in events was similar in studies that used placebo/usual care and low-dose statin therapy as the control arm.
Regarding all-cause mortality, the researchers report that treatment with statin therapy significantly reduced the risk of death in women by 10% in the primary- and secondary-prevention studies and by 13% when the primary-prevention studies were analyzed separately. The effect of statin therapy on all-cause mortality in women enrolled in the secondary-prevention studies was not statistically significant, and there was only a trend toward a reduction in all-cause mortality in men enrolled in the primary-prevention studies.
When investigators stratified patients by expected mortality, they found that statin therapy resulted in a significant reduction in cardiovascular outcomes in patients at low, medium, and high risk.
"This is a very large meta-analysis and it gives us good evidence to show that the benefit of statin use extends to both men and women," said Kostis. "It even extends to people considered low risk. I think going forward, as there will continue to be other statin trials and new agents, we want to make sure that women and people from all demographics are represented in the population studies, because it will allow us to show that benefits extend to all subpopulations, and if there are differences to see what they are with regard to safety and efficacy."
The Institute of Medicine has recently called for more sex-specific reporting of data for safety and efficacy outcomes. In the meta-analysis by Kostis and colleagues, there were not enough data to evaluate the adverse side effects of statin therapy in women, as just two studies reported sex-specific adverse-outcomes data. Future sex-specific results in cardiovascular medicine trials are needed to assess absolute and relative benefits, adverse outcomes, and cost-effectiveness.
Good for the Goose . . .
In her editorial, Mosca points out that "only a handful" of primary-prevention studies were available for analysis, and four of these trials enrolled patients at low risk for cardiovascular events, making it difficult to provide much clarity surrounding the controversy of statin use in women. In addition, the meta-analysis focused on the relative reduction in risk and does not provide data on the absolute benefit of treatment.
If treatment decisions regarding statins are driven by the annual mortality risk of the patient in primary prevention, the absolute risk of cardiovascular disease and corresponding proportional reduction in risk from statin therapy are needed to make "informed clinical choices."
"Only then we will know with less uncertainty whether what is good for the gander is also good for the goose," writes Mosca.
Thursday, February 02, 2012
vitamine D
From Journal of the American Geriatrics Society
Effect of Vitamin D Supplementation on Muscle Strength, Gait and Balance in Older Adults
A Systematic Review and Meta-analysis
Posted: 01/25/2012; J Am Geriatr Soc. 2011;59(12):2291-2300. © 2011 Blackwell Publishing
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Abstract and Introduction
Abstract
Objectives: To systematically review and quantitatively synthesize the effect of vitamin D supplementation on muscle strength, gait, and balance in older adults.
Design: Systematic review and meta-analysis.
Setting: MEDLINE, EMBASE, Cochrane Library, bibliographies of selected articles, and previous systematic reviews were searched between January 1980 and November 2010 for eligible articles.
Participants: Older adults (≥60) participating in randomized controlled trials of the effect of supplemental vitamin D without an exercise intervention on muscle strength, gait, and balance.
Measurements: Data were independently extracted, and study quality was evaluated. Meta-analysis using a fixed-effects model was performed and the I 2 statistic was used to assess heterogeneity.
Results: Of 714 potentially relevant articles, 13 met the inclusion criteria. In the pooled analysis, vitamin D supplementation yielded a standardized mean difference of −0.20 (95% confidence interval (CI) = −0.39 to −0.01, P = .04, I 2 = 0%) for reduced postural sway, −0.19 (95% CI = −0.35 to −0.02, P = .03, I 2 = 0%) for decreased time to complete the Timed Up and Go Test, and 0.05 (95% CI = −0.11 to 0.20, P = .04, I 2 = 0%) for lower extremity strength gain. Regarding dosing frequency regimen, only one study demonstrated a beneficial effect on balance with a single large dose. All studies with daily doses of 800 IU or more demonstrated beneficial effects on balance and muscle strength.
Conclusion: Supplemental vitamin D with daily doses of 800 to 1,000 IU consistently demonstrated beneficial effects on strength and balance. An effect on gait was not demonstrated, although further evaluation is recommended.
Introduction
Vitamin D deficiency has recently gained much attention because of its association with cardiovascular disease, cancer, falls, fractures, and mortality.[1–3] Older adults are especially at risk of developing vitamin D deficiency because of low sunshine exposure, less skin capacity to synthesize vitamin D, poorer absorption of vitamin D with less activation in the kidneys and peripheral tissues, and fewer or lower expression of vitamin D receptors in peripheral tissues.[4–7]
In older adults, vitamin D deficiency has been associated with important determinants of disability, including poor physical performance, low muscular strength, cognitive impairment, falls, and fractures.[8–15] Falls and fractures are also strongly associated with muscle weakness and gait and balance deficits.[16] Because muscle weakness is a feature of the clinical syndrome of vitamin D deficiency, it has been postulated that vitamin D deficiency may precipitate and potentiate muscle weakness and functional decline in older people.[17]
During the last decade, it has been demonstrated that vitamin D supplementation reduces fall risk in older adults when doses of 700 to 1,000 IU per day are used.[18,19] This beneficial effect on fall reduction in isolation from exercise prescription seems to occur through action on neuromuscular function.[17,18] Vitamin D receptors (VDRs) are present in several tissues throughout the body, including bone, muscle, and brain,[20,21] and their expression and activity decline with aging.[20] Serum levels of vitamin D decline significantly with aging, and this has been associated with reduced VDR activation and reduced muscle cell function.[21] This low expression and activity has been well documented in muscle, which affects the response of myocytes to vitamin D.[21]
Additionally, VDRs have been located in the human cortex and hippocampus and at a cellular level are present in neurons and glial cells.[20] Vitamin D deficiency in older people has been associated with impairments in the central nervous system, including cognitive decline and balance problems,[22] and in the peripheral nervous system, including reduction of nerve conduction velocity.[23] It has been suggested that vitamin D affects neuromuscular control and coordination[24] and may act as a neurosteroid hormone.[25]
Based on these age-associated changes, there is a compelling rationale to believe that there is a beneficial effect of vitamin D supplementation on neuromuscular function in older adults, particularly when high doses are used.[17] A recent review of vitamin D in adult health and disease supported fall risk reduction but did not comment on physical function effects.[26]
Previous systematic reviews on the effect of vitamin D supplementation on muscle function reported insufficient evidence to support the therapeutic use of vitamin D alone.[8,27] The use of vitamin D in combination with calcium supplementation was noted to have some supporting evidence, although more-definitive work was recommended.[27] A potential explanation for these inconclusive findings could be related to variation in important research elements, such as heterogeneity in study quality, and variability in assessment methods of physical performance. Most importantly, and in light of the recent meta-analysis findings on fall risk, an important factor to consider is the dose and treatment regimen of vitamin D evaluated in each study.[18]
As was hypothesized in a previous review in 2005,[17] higher doses of vitamin D, at least 800 IU daily, may be necessary to improve muscle strength- and physical performance-related outcomes in older adults. Therefore, the objective of this systematic review was to assess the efficacy of vitamin D supplementation, including variations in dose and treatment regimen, on muscle strength, balance, and gait in older adults.
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gout jicht diuretics diuretica
From British Medical Journal
Antihypertensive Drugs and Risk of Incident Gout Among Patients With Hypertension
Population Based Case-Control Study
Posted: 01/20/2012; BMJ © 2012 BMJ Publishing Group
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- Abstract and Introduction
Abstract
Objective To determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension.
Design Nested case-control study.
Setting UK general practice database, 2000-7.
Participants All incident cases of gout (n=24,768) among adults aged 20-79 and a random sample of 50,000 matched controls.
Main outcome measure Relative risk of incident gout associated with use of antihypertensive drugs.
Results After adjusting for age, sex, body mass index, visits to the general practitioner, alcohol intake, and pertinent drugs and comorbidities, the multivariate relative risks of incident gout associated with current use of antihypertensive drugs among those with hypertension (n=29,138) were 0.87 (95% confidence interval 0.82 to 0.93) for calcium channel blockers, 0.81 (0.70 to 0.94) for losartan, 2.36 (2.21 to 2.52) for diuretics, 1.48 (1.40 to 1.57) for β blockers, 1.24 (1.17 to 1.32) for angiotensin converting enzyme inhibitors, and 1.29 (1.16 to 1.43) for non-losartan angiotensin II receptor blockers. Similar results were obtained among those without hypertension. The multivariate relative risks for the duration of use of calcium channel blockers among those with hypertension were 1.02 for less than one year, 0.88 for 1-1.9 years, and 0.75 for two or more years and for use of losartan they were 0.98, 0.87, and 0.71, respectively (both P<0.05 for trend).
Conclusions Compatible with their urate lowering properties, calcium channel blockers and losartan are associated with a lower risk of incident gout among people with hypertension. By contrast, diuretics, β blockers, angiotensin converting enzyme inhibitors, and non-losartan angiotensin II receptor blockers are associated with an increased risk of gout.
Introduction
Hypertension is one of the most common comorbidities of gout. According to the latest estimates from the US National Health and Nutrition Examination Survey (2007-8), 74% of patients with gout have hypertension,[1] which corresponds to 6.1 million adults in the United States alone. This substantial burden of comorbidity possibly stems from copathogenesis of the two conditions or renal changes in hypertension leading to decreased urate excretion. Studies have shown that the presence of hypertension is independently associated with the risk of incident gout[2] through reduced renal blood flow with increased renal and systemic vascular resistance and decreased renal excretion of urate.[3-6]
Certain antihypertensive drugs also increase the levels of serum uric acid and thus may contribute to the risk of gout. For example, in addition to the well known entities of diuretic induced hyperuricaemia and gout,[3,7,8] the use of β blockers has been shown to increase levels of serum uric acid in short-term trials.[8,9] However, calcium channel blockers and losartan have been found to lower serum uric acid levels,[10-16] carrying the potential to lower the risk of gout. To date, however, no study has investigated the relation between various antihypertensive agents and the risk of gout. To address these issues, we analysed a cohort of 24,768 people with newly diagnosed gout and 50,000 matched controls from the health improvement network database.
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gout jicht diuretics diuretica
Gout and Diuretics in Hypertensive Patients
Diuretic use raised risk for gout by several percentage points.
Observational data have suggested that gout is associated independently with both hypertension and diuretic use. In a prospective study, researchers determined incidence of diuretic-associated gout in nearly 6000 hypertensive patients with no histories of gout at baseline.
During 9 years of follow-up, 37% of patients received diuretics. Incidence of gout was 5.5% among diuretic users (5.0% among thiazide users and 7.0% among loop-diuretic users) and 2.9% among patients who did not use diuretics. After adjustment for potentially confounding variables (except serum uric acid), use of thiazides and loop diuretics were both significantly associated with incident gout (hazard ratios, 1.4 and 2.3, respectively). Compared with serum uric acid levels in nonusers of diuretics, levels rose by a mean of 0.65 mg/dL among those who began taking thiazides and 0.96 mg/dL among those who began taking loop diuretics. The association between diuretics and gout was no longer significant after additional adjustment for serum uric acid; this finding is consistent with the assumption that diuretic-induced increases in serum uric acid mediate the association between diuretic use and gout.
Comment: According to these results, diuretic use raises risk for gout by several percentage points in hypertensive patients. Increased risk for gout is among the potential adverse effects of thiazides that clinicians should consider when choosing first-line antihypertensive drugs.
Published in Journal Watch General Medicine January 26, 2012
