BMJ Open. 2012 Nov 19;2(6). pii: e001461. doi: 10.1136/bmjopen-2012-001461. Print 2012.
Monday, December 17, 2012
Saturday, November 24, 2012
Altering microRNA in colorectal cancer with histone deacetylase inhibitors
On 23rd November 2012
“Altering microRNA in colorectal cancer with histone deacetylase inhibitors”
“Altering microRNA in colorectal cancer with histone deacetylase inhibitors”
Low sodium diet significantly increases morbidity and mortality in systolic HF
Discussed on 9th November 2012
Heart. 2012 Aug 21. [Epub ahead of print]
Low sodium versus normal sodium diets in systolic heart failure: systematic review and meta-analysis.
Source
Ithaca, New York, USA.Abstract
CONTEXT:
A low sodium diet has been proposed to reduce the risk of heart failure (HF) hospitalisations and is currently advocated in consensus guidelines, yet some evidence suggests adverse neurohumoral activation for sodium restriction in the HF setting.OBJECTIVES:
To evaluate the effects of a restricted sodium diet in patients with systolic HF.DATA SOURCES:
A systematic review and meta-analysis of randomised trials OVID MEDLINE, PubMed, Excerpta Medica (Embase), the Cochrane Controlled Trials Register, Scopus, Web of Science and Google Scholar were searched up to April 2012.STUDY SELECTION:
Two independent reviewers selected studies for inclusion on the basis of a randomised controlled trial design that included adults with systolic HF receiving a restricted salt diet or control diet and reporting mortality (all-cause, sudden death or HF-related) and HF-related hospitalisations.DATA EXTRACTION AND ANALYSIS:
Descriptive and quantitative information was extracted from included studies. A random-effects model was used to compute pooled risk ratios (RR) for mortality and morbidity outcomes.RESULTS:
Six randomised trials comparing low sodium diets (1.8 g/day) with normal sodium diets (2.8 g/d) in 2747 patients with systolic HF were identified. Compared with a normal sodium diet, a low sodium diet significantly increased all cause mortality (RR 1.95, 95% CI 1.66 to 2.29), sudden death (RR 1.72, 95% CI 1.21 to 2.44), death due to HF (RR 2.23, 95% CI 1.77 to 2.81) and HF readmissions (RR 2.10, 95% CI 1.67 to 2.64).CONCLUSION:
Compared with a normal sodium diet, a low sodium diet significantly increases morbidity and mortality in systolic HF.Thursday, November 1, 2012
Fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease
Journal club on 2nd November 2012
BMJ. 2012 Oct 30;345:e6698. doi: 10.1136/bmj.e6698.
Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis.
Chowdhury R, Stevens S, Gorman D, Pan A, Warnakula S, Chowdhury S, Ward H, Johnson L, Crowe F, Hu FB, Franco OH.
Source
Department of Public Health and Primary Care, University of Cambridge, UK.Abstract
OBJECTIVE:
To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention.DESIGN:
Systematic review and meta-analysis.DATA SOURCES:
Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. ELIGIBILITY CRITERIA: Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible.RESULTS:
26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups.CONCLUSIONS:
Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.Wednesday, October 24, 2012
Angiotensin receptor blockers for heart failure
JC on 19th October 2012
Pubmed
Cochrane Database Syst Rev. 2012 Apr 18;4:CD003040.
Angiotensin receptor blockers for heart failure.
Source
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada. bsheran@ti.ubc.caAbstract
BACKGROUND:
Chronic heart failure (HF) is a prevalent world-wide. Angiotensin receptor blockers (ARBs) are widely prescribed for chronic HF although their role is controversial.OBJECTIVES:
To assess the benefit and harm of ARBs compared with ACE inhibitors (ACEIs) or placebo on mortality, morbidity and withdrawals due to adverse effects in patients with symptomatic HF and left ventricular systolic dysfunction or preserved systolic function.SEARCH METHODS:
Clinical trials were identified by searching CENTRAL, HTA, and DARE , (The Cochrane Library 2010 Issue 3), as well as MEDLINE (2002 to July 2010), and EMBASE (2002 to July 2010). Reference lists of retrieved articles and systematic reviews were checked for additional studies not identified by the electronic searches.SELECTION CRITERIA:
Double blind randomised controlled trials in men and women of all ages who have symptomatic (NYHA Class II to IV) HF and: 1) left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) ≤40%; or 2) preserved ejection fraction, defined as LVEF >40%.DATA COLLECTION AND ANALYSIS:
Two authors independently assessed risk of bias and extracted data from included studies.MAIN RESULTS:
Twenty two studies evaluated the effects of ARBs in 17,900 patients with a LVEF ≤40% (mean 2.2 years). ARBs did not reduce total mortality (RR 0.87 [95% CI 0.76, 1.00]) or total morbidity as measured by total hospitalisations (RR 0.94 [95% CI 0.88, 1.01]) compared with placebo.Total mortality (RR 1.05 [95% CI 0.91, 1.22]), total hospitalisations (RR 1.00 [95% CI 0.92, 1.08]), MI (RR 1.00 [95% CI 0.62, 1.63]), and stroke (RR 1.63 [0.77, 3.44]) did not differ between ARBs and ACEIs but withdrawals due to adverse effects were lower with ARBs (RR 0.63 [95% CI 0.52, 0.76]). Combinations of ARBs plus ACEIs increased the risk of withdrawals due to adverse effects (RR 1.34 [95% CI 1.19, 1.51]) but did not reduce total mortality or total hospital admissions versus ACEI alone.Two placebo-controlled studies evaluated ARBs in 7151 patients with a LVEF >40% (mean 3.7 years). ARBs did not reduce total mortality (RR 1.02 [95% CI 0.93, 1.12]) or total morbidity as measured by total hospitalisations (RR 1.00 [95% CI 0.97, 1.05]) compared with placebo. Withdrawals due to adverse effects were higher with ARBs versus placebo when all patients were pooled irrespective of LVEF (RR 1.06 [95% CI 1.01, 1.12]).AUTHORS' CONCLUSIONS:
In patients with symptomatic HF and systolic dysfunction or with preserved ejection fraction, ARBs compared to placebo or ACEIs do not reduce total mortality or morbidity. ARBs are better tolerated than ACEIs but do not appear to be as safe and well tolerated as placebo in terms of withdrawals due to adverse effects. Adding an ARB in combination with an ACEI does not reduce total mortality or total hospital admission but increases withdrawals due to adverse effects compared with ACEI alone.Pubmed
Thursday, October 18, 2012
Benzodiazepine use and risk of dementia
Journal club on 5th October 2012.
Pub
BMJ. 2012 Sep 27;345:e6231. doi: 10.1136/bmj.e6231.
Benzodiazepine use and risk of dementia: prospective population based study.
Source
Université Bordeaux Segalen, F-33000 Bordeaux, France.Abstract
OBJECTIVE:
To evaluate the association between use of benzodiazepines and incident dementia.DESIGN:
Prospective, population based study.SETTING:
PAQUID study, France.PARTICIPANTS:
1063 men and women (mean age 78.2 years) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up.MAIN OUTCOME MEASURES:
Incident dementia, confirmed by a neurologist.RESULTS:
During a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10 to 1.94). Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users.CONCLUSIONS:
In this prospective population based study, new use of benzodiazepines was associated with increased risk of dementia. The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study. Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population, indiscriminate widespread use should be cautioned against.Pub
Benzodiazepine use and risk of dementia: prospective population based study
This study demonstrates a clear association between the use of
benzodiazepines and a subsequent diagnosis of dementia but it does not
demonstrate causality.
Sleep disturbance is a common feature across many forms of neurodegenerative disease (1) and may precede a diagnosis of dementia by some years. A clear example of this is the strong association between a developing a REM sleep behavioural disorder (RBD) and alpha-synucleinopathies, including Dementia with Lewy bodies. The ten year risk of a significant neurodegenerative disease following ‘idiopathic’ RBD has been estimated at around 40% (2). Benzodiazepines remain a commonly used treatment for sleep disturbance and the introduction of benzodiazepines between years three and five of the study may indicate the onset of dementia pathology without the diagnosis being made until later.
Furthermore psychiatric symptoms and disorders other than depression (the only one considered in the analysis), including anxiety are common and may lead to the introduction of a benzodiazepine. These may therefore also herald the emergence of a neurodegenerative disorder or other dementia long before a formal diagnosis of dementia is made.
The authors admit that the indications for the introduction of a benzodiazepine may be prodromal symptoms of dementia but argue against this reverse causality confounding their results. They use a three year run-in time and exclude participants who have been exposed to benzodiazepines prior to or during this. This allows for adjustment for pre-existing factors already treated with benzodiazepines but not the emergence of new ones. The increase in association strength of new use of benzodiazepines and dementia diagnosis after about seven years of follow up does not differentiate between benzodiazepine use or any underlying symptomatic risk factors for dementia being treated. Similarly the lack of increase of association strength amongst cohorts of new benzodiazepines users at later stages of the study cannot be used to make inferences about the underlying causality. The small sample sizes and wide confidence intervals for hazard ratio for each subsequent cohort precludes significant comparisons of risk between them.
This paper raises an important issue but does not provide evidence of a causal link between benzodiazepines and dementia. It must be treated with caution, especially in view of the potential harm or anxiety induced by such reports or sudden changes in prescription practice.
BMJ
Sleep disturbance is a common feature across many forms of neurodegenerative disease (1) and may precede a diagnosis of dementia by some years. A clear example of this is the strong association between a developing a REM sleep behavioural disorder (RBD) and alpha-synucleinopathies, including Dementia with Lewy bodies. The ten year risk of a significant neurodegenerative disease following ‘idiopathic’ RBD has been estimated at around 40% (2). Benzodiazepines remain a commonly used treatment for sleep disturbance and the introduction of benzodiazepines between years three and five of the study may indicate the onset of dementia pathology without the diagnosis being made until later.
Furthermore psychiatric symptoms and disorders other than depression (the only one considered in the analysis), including anxiety are common and may lead to the introduction of a benzodiazepine. These may therefore also herald the emergence of a neurodegenerative disorder or other dementia long before a formal diagnosis of dementia is made.
The authors admit that the indications for the introduction of a benzodiazepine may be prodromal symptoms of dementia but argue against this reverse causality confounding their results. They use a three year run-in time and exclude participants who have been exposed to benzodiazepines prior to or during this. This allows for adjustment for pre-existing factors already treated with benzodiazepines but not the emergence of new ones. The increase in association strength of new use of benzodiazepines and dementia diagnosis after about seven years of follow up does not differentiate between benzodiazepine use or any underlying symptomatic risk factors for dementia being treated. Similarly the lack of increase of association strength amongst cohorts of new benzodiazepines users at later stages of the study cannot be used to make inferences about the underlying causality. The small sample sizes and wide confidence intervals for hazard ratio for each subsequent cohort precludes significant comparisons of risk between them.
This paper raises an important issue but does not provide evidence of a causal link between benzodiazepines and dementia. It must be treated with caution, especially in view of the potential harm or anxiety induced by such reports or sudden changes in prescription practice.
BMJ
Wednesday, September 19, 2012
Common medications for common cold
Diphenhydramine (benadryl) - antihistamine
Chlorpheniramine - antihistamine
Guaifenesin - expectorant. Works by thinning the mucus in the air passages to make it easier to cough up the mucus and clear the airways.
Dextromethorphan - antitussive. Works by decreasing activity in the part of the brain that causes coughing.
Pseudoephedrine - nasal decongestant. Works by causing narrowing of the blood vessels in the nasal passages.
Thursday, August 30, 2012
Duloxetine for kneee OA pain
JC: 31st August 2012
Age Ageing. 2012 Sep;41(5):646-52. Epub 2012 Jun 27.
Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial.
Source
Geriatric Unit, Internal Medicine Department, University of Alexandria, Alexandria, Egypt.Abstract
BACKGROUND:
pain is the leading symptom of osteoarthritis (OA) and is often chronic in nature, leading to significant morbidity and decreased quality of life. Duloxetine, a selective serotonin norepinephrine reuptake inhibitor has been demonstrated to have a centrally acting analgesic effect.OBJECTIVES:
the aim of the present study was to investigate the efficacy of duloxetine in reducing pain in older adults with knee OA.METHODS:
totally, 288 patients aged 65 years and above with primary knee OA were enrolled in this study. Patients were randomised 1:1. Totally, 144 received 60 mg/day of duloxetine HCL and 144 received placebo for 16 weeks. Outcome measures included pain reduction and improvement in physical functioning scores. Pain was assessed using the visual analogue pain scale (VAS; 0-100 mm). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to assess function.RESULTS:
two-hundred and seventy four of the 288 patients completed the study. There was a statistically significant reduction in pain and a significant improvement in WOMAC scores at 16 weeks in the duloxetine group versus the placebo group. No serious side effects were reported.CONCLUSIONS:
the findings of the present study provide evidence for the efficacy and tolerability of duloxetine in reducing pain and subsequently improving function in older adults with knee OA. Trial Registration: NCT01425827.-------------------------------------------------------------------------------------------------------------------------
During the discussion, there was some skepticism about the resources that a university in Alexandria will have access to.....
Thursday, August 23, 2012
Journal Club on 24th of August 2012
NEJM
Health Law, Ethics, and Human Rights
Ethical Considerations in Studying Drug Safety — The Institute of Medicine Report
August 22, 2012
(10.1056/NEJMhle1207160)
Thursday, August 16, 2012
Journal club on 17th August 2012
N Engl J Med. 2012 Aug 9;367(6):570-2.
Preclinical success against Alzheimer's disease with an old drug.
Source
Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, USA.- PMID:
- 22873540
- [PubMed - in process]
Saturday, August 11, 2012
Journal club on 10th August 2012
Am Heart J. 2012 Apr;163(4):720-8. Epub 2012 Mar 14.
Safety and effectiveness of antithrombotic strategies in older adult patients with atrial fibrillation and non-ST elevation myocardial infarction.
Fosbol EL, Wang TY, Li S, Piccini JP, Lopes RD, Shah B, Mills RM, Klaskala W, Alexander KP, Thomas L, Roe MT, Peterson ED.
Source
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27705, USA. emil.fosbol@duke.eduAbstract
BACKGROUND:
We aimed to study the comparative safety and effectiveness of various antithrombotic treatment strategies among older adults with non-ST elevation myocardial infarction (NSTEMI) and atrial fibrillation (AF).METHODS:
Using the CRUSADE registry linked to longitudinal Medicare claims data, we examined NSTEMI patients aged ≥ 65 years with a concomitant diagnosis of AF. Multivariable Cox analysis was used to compare risk of rehospitalization for bleeding and a major cardiac composite end point of death, readmission for myocardial infarction, or stroke, according to discharge antithrombotic strategy.RESULTS:
Among 7619 NSTEMI patients with AF, 29% were discharged on aspirin alone; 37%, on aspirin + clopidogrel; 7%, on warfarin alone; 17%, on aspirin + warfarin; and 10%, on warfarin + aspirin + clopidogrel. There was no difference in predicted stroke risk between groups. By 1 year, 12.2% of patients were rehospitalized for bleeding, and 33.1% had a major cardiac event. Relative to aspirin alone, antithrombotic intensification was associated with increased bleeding risk (aspirin + clopidogrel adjusted HR 1.22, 95% CI 1.03-1.46 and warfarin + aspirin HR 1.46, 95% CI 1.21-1.80). Patients treated with aspirin + clopidogrel + warfarin had the highest observed bleeding risk (HR 1.65, 95% CI 1.30-2.10). One-year risk of the major cardiac end point was similar between groups, although, relative to aspirin only, there was a trend toward lower risk for the warfarin + aspirin group (HR 0.88, 95% CI 0.78-1.00).CONCLUSIONS:
Older NSTEMI patients with AF are at high risk for subsequent bleeding and major cardiac events. Increased antithrombotic management was associated with increased bleeding risk. Further investigation is needed to clarify whether these risks are counterbalanced by reduced thromboembolic events in this population.Copyright © 2012 Mosby, Inc. All rights reserved.
http://www.ncbi.nlm.nih.gov/pubmed/22520540
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