La insulina detiene la aterosclerosis en los diabéticos

Medcenter Medical News

Un estudio ha demostrado que la insulina glargina, un fármaco que se utiliza para controlar la glucemia en los diabéticos, puede limitar efectivamente la aparición de aterosclerosis.

La investigación fue realizada para explorar las potenciales ventajas de la insulina glargina, una insulina de acción prolongada ―y de los ácidos grasos omega-3―. La profesora Eva Lonn de la McMasterUniversity, Ontario, Canadá, y sus colaboradores explican que se desconoce el efecto de estos dos compuestos sobre la aterosclerosis en las personas con diabetes de tipo 2.

Incorporaron a 12.537 pacientes provenientes de siete países, con una edad promedio de 63 años. Todos tenían diabetes de tipo 2 o prediabetes. La mayoría estaba recibiendo medicamentos para reducir su riesgo de aterosclerosis, por lo general estatinas, inhibidores de la ACE o betabloqueantes; todos recibieron insulina glargina, ácidos grasos omega-3 o placebo durante casi cinco años.

En contraste con los ácidos grasos omega-3 y el placebo, sólo la glargina redujo en grado importante las glucemias. También disminuyó el avance de la aterosclerosis en 12 zonas de las arterias carótidas.

La profesora Lonn dijo: «Nuestro estudio demuestra que en personas con alto riesgo que tienen enfermedad cardiovascular establecida o con factores de riesgo cardiovascular más diabetes de tipo 2 o prediabetes, la insulina glargina retrasa moderadamente el avance de la ateroesclerosis».

«Estos hallazgos respaldan la inocuidad cardiovascular de esta intervención e indican que el tratamiento con insulina glargina a más largo plazo podría evitar complicaciones cardiovasculares».

Sin embargo, añadió que todavía no está claro si la insulina glargina podía llevar a una reducción de los episodios cardiovasculares.

Pese a la falta de respaldo para los ácidos grasos omega-3 que se identificó en este estudio, la profesora Lonn señala que el consumir más pescado, puede tener otras ventajas en la salud. El estudio fue presentado el lunes (27 de agosto) en el Congreso de 2012 de la EuropeanSociety of Cardiology en Munich, Alemania.

 

Bibliografía

GRACE: Effects of Insulin Glargin and of Polyunsaturated Fatty Acids on Carotid Intima Media Thickness in High-Risk Diabetes. Presentado por Lonn, E., el 27 de agosto de 2012 en el congreso de la Sociedad Europea de Cardiología que tuvo lugar del 25 al 29 de agosto de 2012 en Munich, Alemania.

http://www.outcomes-umassmed.org/grace/study.aspx

Independencia !

Los antiinflamatorios no esteroideos no son los únicos responsables de las úlceras gastroduodenales

http://reserch.medcenter.com/content.html?returnCode=Y29uZmlnPTI1MTQ4JmNvZEVtYWlsPTQ4ODI0JmJvdG9uPTEyOTIzMCZlbnZpb25ybz00ODgyNCZ2aXJhbD0w&utm_source=Icommarketing&utm_medium=Email&utm_content=Vimovo_3_esp&utm_campaign=Icommarketing - Vimovo - envio_3_vimovo

Bibliografía

Yeomans N. The ulcer sleuths: The search for the cause of peptic ulcers. J Gastroenterol Hepatol. 26 (2011) Suppl. 1; 35–41.

Does taking probiotics routinely with antibiotics prevent antibiotic associated diarrhoea?

BMJ 2012;344:e682
[Link to free full-text BMJ article PDF | BMJ extract | PubMed® abstract]
Practice
Uncertainties Page

Christopher C Butler, professor of primary care medicine,
Donna Duncan, senior project manager,
Kerenza Hood, professor of statistics
Correspondence to: C C Butler butlercc@cf.ac.uk
[EXCERPTS]

Probiotics are thought to combat antibiotic associated diarrhoea through restoring resistance to colonisation by pathogenic bacteria after the normal colonic microflora have been damaged by antibiotics, by breaking down non-absorbable compounds into absorbable products, by interfering with pathogenic toxins, and by enhancing immunity.

What is the evidence of uncertainty?
The commonest outcome measure was diarrhoea, defined as three loose stools in a 24 hour or 48 hour period. The type of probiotic tested, study populations, and effect sizes varied widely between studies, with both statistically significant and non-significant findings for the primary outcome and widely differing rates of antibiotic associated diarrhoea. Many of the trials identified in the systematic reviews were of poor quality.

Systematic reviews of randomised placebo controlled trials (RCTs) and subsequent individual trials of probiotics to prevent antibiotic associated diarrhoea

 

Reference (search date)	Number of studies and/or total number of participants, care setting	Intervention: organism in probiotic and daily dose (colony forming units)	Outcome (risk ratio) for antibiotic associated diarrhoea
Systemic reviews
McFarland 2010 (1976-2009)	10 RCTs, 1858 adults, 4 trials in hospitalised patients, 1 outpatient, 3 in patients receiving antibiotic treatment for H pylori infection	S boulardii, ranging from 4×109 to 2×1010	0.47 (95% CI 0.35 to 0.63)
Avadhani 2010 (unclear)	8 RCTs, 1220 adults, inpatients	3 trials of S boulardii, 1 of L rhamnosus, 4 of mixed strains that included L casei, L acidophilus, L bulgaricus, S thermophilus, B bifidum, and L rhamnosus, range of doses	0.56 (95% CI 0.44 to 0.71)
McFarland 2006 (1977-2005)	25 RCTs, 2810 children and adults, inpatients and outpatients including H pylori treatment	6 trials S boulardii, 6 trials L rhamnosus, 6 other single strains, and 7 mixed strains, ranging from 1×107 to 1×1011(mean dose 3×109)	Combined 0.43 (95% CI 0.31 to 0.58); S boulardii 0.37 (95% CI 0.26 to 0.52); L rhamnosus 0.31 (95% CI 0.13 to 0.72)
Kale-Pradham 2010 (inception -May 2008)	10 RCTs, 1862 children and adults, inpatients and outpatients	Single agent lactobacillus, ranging from 2×10[9] to 4×1010	Combined 0.35 (95% CI 0.19 to 0.67); adults 0.24 (95% CI 0.08 to 0.75); children 0.44 (95% CI 0.18 to 1.08)
Sazawal 2006 (inception -February 2006)	19 RCTs, children and adults, inpatients and outpatients	Single (5 L rhamnosus) and mixed, ranging from 1×710 to 1×1010	0.48 (95% C1 0.35 to 0.65)
Szajewska 2006 (1966-December 2005)	6 RCTs, 766 children, inpatients and outpatients	2 RCTs lactobacillus GG, one S boulardii, 3 mixed, dose range unclear	0.44 (95% CI 0.25 to 0.77)
Johnston 2007 (inception to August 2006)	9 RCTs, 1946 children, inpatients and outpatients	6 single, 3 mixed containing (alone or in combination) Lactobacillus spp, Bifidobacterium spp, Streptococcus spp, S boulardii, ranging from 8.25×106 to 4×1010	Per-protocol analysis 0.49 (95% CI 0.32 to 0.74); intention to treat analysis 0.90 (95% CI 0.50 to 1.63); 5 studies of higher dose (5 to 40 × 109day) 0.35 (95% CI 0.25 to 47); 3 studies of low dose (<5 sup="sup">9

day) 0.89 (95% CI 0.53, 1.48) Randomised controlled trials published after search dates of systematic reviews Gao 2010255 adults, inpatients,
744 of 1120 (66.5%) eligible participants were not recruitedCombination of L acidophilus and L casei in low (5× 10⁹) or high (10×10⁹) doseHigh dose 0.34 (95% CI 0.20 to 0.60)
Low dose 0.64 (95% CI 0.42 to 0.97); 15.5% low dose, 28.2% high dose intervention, and 44.1% placebo treated patients developed diarrhoea Lonnermark 2010239 adults, inpatients and outpatients in a university hospital infectious diseases clinicL plantarum, 1×10¹⁰1.25 (95% CI 0.40 to 3.92); 7.5% intervention and 6.0% treated placebo patients developed diarrhoea Song 2010214 adults, inpatients, 10 tertiary hospitals treated for a range of respiratory tract infections (mostly pneumonia)L rhamnosus and L acidophilus, 2×10⁹0.54 (95% CI 0.17 to 1.74); 3.9% intervention and 7.2% placebo treated patients developed diarrhoea Psaradellis 2010437 adults, treated for a minimum of 12 hours in a hospital ward or emergency room in 8 centresL acidophilus and L casei, 5×10¹⁰0.74 (95% CI 0.53 to 1.02); 21.8% intervention and 29.4% placebo treated patients developed diarrhoea Merenstein 2009

Szymanski 2008

78 children aged 5 months to 16 years with respiratory tract infections, inpatients and outpatients

B longum, L rhamnosus, and L plantarum, twice daily at 108

0.50 (95% CI 0.06 to 3.50); 2.5% intervention and 5.3% placebo treated children developed diarrhoea

Is ongoing research likely to provide relevant evidence?
Six placebo controlled trials are in progress examining the effect of probiotics in preventing antibiotic associated diarrhoea in hospitalised patients. These studies will provide information on probiotics to prevent antibiotic associated diarrhoea in a wider range of hospitalised patients and may be large enough to provide information on which subgroups of patients are at greatest risk and are most likely to benefit.
There is an absence or insufficiency of high quality evidence to support routine use of probiotics to prevent antibiotic associated diarrhoea in all people, regardless of age, comorbidity, and care setting. For example, few trials have been done in primary care, and we found none from intermediate and social care settings. We found no pragmatic, open implementation studies.
What should we do in the light of uncertainty?
Good evidence exists to support using probiotics with S boulardii and Lactococcus rhamnosus GG (ATCC 53103) to prevent antibiotic associated diarrhoea, with emerging evidence for certain mixed strains that include L casei or L acidophilus. Probiotics also seem to be more effective at higher doses. However, because insufficient evidence exists to support routinely using probiotics for this purpose, and because of the low incidence and generally mild severity of antibiotic associated diarrhoea in otherwise healthy people, we recommend against routine use of probiotics in all people taking antibiotics to prevent antibiotic associated diarrhoea. Nevertheless, probiotics are cheap and safe, so routine use with antibiotics is justified in frail patients in hospital and possibly in children. Those who have previously had antibiotic associated diarrhoea should be offered probiotics when they are treated with antibiotics, regardless of setting, but probiotics should be avoided in people who are seriously immunocompromised. As probiotics seem more effective at higher doses, doses of at least 50 billion colony forming units should be used; probiotics should be taken for the duration of antibiotic treatment and continued for a week thereafter.
Evidence about the effectiveness of many strains is absent or insufficient. Head to head studies of probiotic strains are needed, as well as more studies to identify groups of patients at greatest risk and most likely to benefit, especially in the community and in intermediate care.
[Link to free BMJ article PDF for full text, images, and references]
© 2012 BMJ Publishing Group Ltd125 children with upper respiratory tract infections aged 1-5, in primary careKefir fermented milk from grains containing Lactococcus lactis, Lactococcus plantarum, Lactococcus rhamnosus, Lactococcus casei, Lactococcus lactis subspecies diacetylactis, Leuconostoc cremoris, Bifidobacterium longum, Bifidobacterium breve, Lactobacillus acidophilus, and Saccharomyces florentinus; doses of organisms not given0.82 (95% CI, 0.54 to
























 

Diagnosis and management of Raynaud’s phenomenon

Information sourced from BMJ:

BMJ 2012;344:e289
[Link to free BMJ article PDF for full text, images, and references | BMJ extract | PubMed® abstract]
Clinical Review

Diagnosis and management of Raynaud’s phenomenon

Beth Goundry, Laura Bell, Matthew Langtree, et al
[EXCERPTS]

Fig 1 Raynaud’s phenomenon showing typical colour changes

Fig 2 Severe Raynaud’s phenomenon showing colour changes and digital ulceration

Box 1 Conditions associated with secondary Raynaud’s phenomenon
Rheumatological

• Systemic sclerosis (90% of patients with this condition have Raynaud’s phenomenon)
• Mixed connective tissue disease (85%)
• Systemic lupus erythematosus (40%)
• Dermatomyositis or polymyositis (25%)
• Rheumatoid arthritis (10%)
• Sjögren’s syndrome
• Vasculitis

Haematological

• Polycythaemia ruba vera
• Leukaemia
• Thrombocytosis
• Cold agglutinin disease (Mycoplasma infections)
• Paraproteinaemias
• Protein C deficiency, protein S deficiency, antithrombin III deficiency
• Presence of the factor V Leiden mutation
• Hepatitis B and C (associated with cryoglobulinaemia)

Occlusive arterial disease

• External neurovascular compression, carpal tunnel syndrome, and thoracic outlet syndrome
• Thrombosis
• Thromboangiitis obliterans
• Embolisation
• Arteriosclerosis
• Buerger’s disease

Fig 3 Digital ulcer in severe Raynaud’s phenomenon

How is Raynaud’s phenomenon treated?
The first step in managing Raynaud’s phenomenon in primary care is lifestyle modification. Such advice can be given to patients while awaiting investigations and referral to secondary care if an underlying cause is suspected. Most people with primary Raynaud’s phenomenon respond well to lifestyle measures and need no further treatment. Patients with secondary Raynaud’s phenomenon require treatment of the underlying disorder, which entails referral to secondary care.
Non-drug based treatments
Conservative approaches to treatment aim to reduce exposure to triggers, such as cold and emotional stress.
Advise the patient to try to keep warm, perhaps by using hand and feet warmers, which are commercially available. The frequency and severity of attacks can be reduced by avoiding dramatic changes in environmental temperature and taking steps to reduce occupational cold exposure. Vasodilation can be increased during attacks by rotating the arms in a windmill pattern, placing the hands under warm water or in a warm body fold such as the axilla, and performing the swing-arm manoeuvre (raising both arms above the shoulders and forcefully swinging them across the body to generate a force that promotes blood flow distally to the fingers). Another simple tip is to avoid carrying bags by the handles, which impairs circulation to the fingers. There is little objective evidence to suggest that any nutritional supplement benefits patients with the condition. Minimising stress through general relaxation techniques may be of benefit. Biofeedback has been a popular treatment, but a recent Cochrane review found it to be no more effective than sham biofeedback. Support groups can provide helpful tips and guidance on self management. A prospective study showed that smoking cessation may help to reduce the severity but not occurrence of the condition.
Ginkgo biloba has been investigated over the past 10 years. A double blind placebo controlled trial found a 56% reduction in the frequency of attacks in established Raynaud’s phenomenon (compared with a 27% reduction in the placebo group). Another randomised multicentre flexible dose open trial found a 31% reduction compared with 50.1% for nifedipine, suggesting that Ginkgo may not be as effective as nifedipine. However, given that Ginko had no adverse effects and was well tolerated, further research may be worthwhile.
Drug treatments
Several randomised controlled trials are under way that may lead to an increase in the number of treatments for Raynaud’s phenomenon. However, to date, no guidelines have been published on the medical treatment of Raynaud’s phenomenon. We discuss drugs that are currently used off-label in the treatment of this condition and which the clinician may consider using on a case by case basis, taking care to balance evidence on efficacy versus toxicity. It is also important to review prescription drugs that aggravate symptoms.
Vasodilators
Calcium channel blockers—Non-cardioselective dihydropyridine calcium channel blockers are most widely used in the treatment of Raynaud’s phenomenon. Nifedipine promotes relaxation of vascular smooth muscle cells and leads to vasodilatation. A meta-analysis of randomised controlled trials found that nifedipine (10-20 mg three times daily) reduced the number of attacks by 2.8-5.0 a week and reduced their severity by 33%. However, effects may be short lived, and longer acting calcium channel blockers or amlodipine and diltiazem may be needed. Unfortunately, patients commonly report troubling adverse effects such as hypotension, flushing, headache, and tachycardia, so alternative treatments have been researched.
Topical nitrates—A randomised controlled study of 33 patients found that topical glyceryltrinitrate applied to the dorsum of the finger resulted in digital vasodilatation with fewer systemic side effects than with oral nitrates. Two large recent randomised controlled trials of MQX-503, a new formulation of nitroglycerin, applied to the affected finger found that it reduces the severity of Raynaud’s phenomenon, but not the duration or frequency of attacks. Evidence on topical nitrates is limited, but the results of current trials may provide more robust evidence of efficacy.

Prostaglandins—Prostaglandins have vasodilatory and antiproliferative effects, and they inhibit platelet aggregation. Their side effects are similar to those of calcium channel blockers. The European League Against Rheumatism recommends prostaglandins when calcium channel blockers have failed. Most published studies have focused on the use of intravenous iloprost. A randomised open label single centre study and a 2009 Cochrane review found that iloprost reduces the frequency and severity of attacks. A randomised study found cyclic use to be beneficial in terms of patient adherence and quality of life. However, two randomised controlled trials found that iloprost was only slightly better than nifedipine, and because iloprost is more expensive, the European League Against Rheumatism has advised that nifedipine should remain the first line drug for patients with Raynaud’s phenomenon. A double blind multicentre placebo controlled study and randomised double blind study found that orally administered prostaglandins are less effective than intravenous ones, although higher doses may confer benefit. Research is currently ongoing into the use of treprostinil, an oral prostaglandin analogue.

Phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, and vardenafil)—Phosphodiesterase type 5 breaks down cGMP in endothelial cells. Inhibition of this enzyme increases the amount of cGMP available to promote vascular smooth muscle relaxation and blood flow. A randomised double blind placebo controlled fixed dose crossover study and two case series found a decrease in the frequency and severity of attacks in patients treated with oral sildenafil but not tadalafil compared with placebo. These inhibitors also have a favourable effect on the Raynaud’s condition score and ulcer healing. The benefits of these orally delivered and well tolerated drugs suggest that they may be an effective treatment for patients with severe and disabling Raynaud’s phenomenon, although further studies are needed.
Antioxidants—N-acetylcysteine acts as a vasodilator via modulation of the vasodilator adrenomedullin. A recent observational study found that it decreases the frequency and severity of attacks. The number of digital ulcers and ulcer healing also improved.
Inhibitors of vasoconstriction
Angiotensin receptor antagonists—A randomised controlled trial suggested that losartan reduces the frequency and severity of attacks to a greater extent than nifedipine. The European League Against Rheumatism recommends its use, but this is an informal recommendation because of the lack of sufficient evidence.
Angiotensin converting enzyme inhibitors—These drugs are no longer recommended since a randomised double blind placebo controlled trial found that they do not reduce digital ulcers or the frequency or severity of attacks.
α1 adrenoceptor blockers—Limited low level evidence from a randomised double blind placebo controlled crossover study of 24 patients suggests that prazosin may reduce the frequency but not the severity of attacks compared with placebo. However, prazosin is rarely used in the treatment of Raynaud’s phenomenon because its potential adverse effects outweigh any benefit.
Endothelin receptor antagonists (bosentan)—Endothelin is a potent vasoconstrictor of vascular smooth muscle cells. Among its other actions, bosentan exerts a consistent effect on vasculature. The Randomized Placebo-controlled Investigation of Digital Ulcers in Scleroderma (RAPIDS-1 and 2) trials have shown that the number of new digital ulcers in patients with secondary Raynaud’s phenomenon decreased significantly when treated with bosentan. The European League Against Rheumatism recommends its use when symptoms are refractory to treatment with calcium channel blockers and prostaglandins.
Serotonin reuptake inhibitors—The exact role of serotonin reuptake inhibitors in the treatment of Raynaud’s phenomenon is not yet clear. These agents block the uptake of serotonin, which is a vasoconstrictor. A pilot study of 53 patients showed that fluoxetine reduces the severity and frequency of attacks compared with nifedipine in primary Raynaud’s phenomenon. Its effect in secondary Raynaud’s phenomenon was less pronounced. A Cochrane review of a small number of studies concluded that another serotonin reuptake inhibitor, ketanserin, was not beneficial in the treatment of Raynaud’s phenomenon. This agent may have a role in patients who cannot tolerate other drugs because of hypotension, but more research is needed.
Botulinum toxin A—Botulinum toxin A blocks vasoconstriction and, although there are no blinded placebo trials to date, preliminary reports have suggested that it can improve symptoms, decrease frequency of attacks, and improve healing of digital ulcers.

Kidney Stones Predict Chronic Trouble, ESRD

By Todd Neale, Senior Staff Writer, MedPage Today

Published: August 31, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that in this large registry cohort study, even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD.
• Point out however that the increases were small in absolute terms.

Having a kidney stone may portend poor renal function, including end-stage renal disease, researchers found.
Individuals who had at least one kidney stone event were significantly more likely to develop end-stage renal disease through 11 years of follow-up (HR 2.16, 95% CI 1.79 to 2.62), according to Marcello Tonelli, MD, of the University of Alberta in Edmonton, and colleagues.
Kidney stones also were associated with greater risks of developing stage 3b to 5 chronic kidney disease (HR 1.74, 95% CI 1.61 to 1.88) and a doubling of serum creatinine (HR 1.94, 95% CI 1.56 to 2.43) through 4 years of follow-up, the researchers reported online in BMJ.
They noted, however, that the absolute risks remained low, even among the individuals with kidney stones.
"Further research should be aimed at determining the mechanisms explaining this association and assessing the optimal way to prevent kidney stones in the general population, especially young women," who appeared to have greater risks compared with other groups, they wrote.
Tonelli and colleagues examined claims and facility utilization data from Alberta, where residents are covered by a universal healthcare system. The analysis included 3,089,194 adults who did not have end-stage renal disease or a history of pyelonephritis at baseline in April 1997; 63% had outpatient serum creatinine measurements in their records.
The main outcomes were the development of end-stage renal disease, new-onset stage 3b to 5 chronic kidney disease (an estimated glomerular filtration rate less than 45 mL/min/1.73 m²), and a sustained doubling of serum creatinine.
Overall, 0.8% of patients (23,706) had at least one kidney stone during follow-up, 0.2% (5,333) developed end-stage renal disease, 4% (68,525) developed stage 3b to 5 chronic kidney disease, and 0.3% (6,581) had a sustained doubling of serum creatinine.
After adjustment for age, sex, Aboriginal status, receipt of social assistance, rural residence, comorbidities, and prior nephrolithiasis, having at least one kidney stone was associated with developing end-stage renal disease.
And after further adjustment for baseline kidney function, kidney stones were associated with development of chronic kidney disease and a doubling of serum creatinine.
The risks appeared to be greater in women versus men -- possibly because of anatomical differences -- and in patients younger than 50 -- possibly because of the competing risk of death in older individuals, the researchers noted.
Even so, absolute risks of adverse renal outcomes remained low. The unadjusted rate of end-stage renal disease, for example, was 2.48 per million person-days in people with at least one stone during follow-up and 0.52 per million person-days in people who did not develop stones.
There are multiple possible mechanisms linking kidney stones to declines in renal function, according to the authors.
"The association between calcium kidney stones and progressive loss of kidney function may be the direct result of progressive calcification within the renal interstitium, and specifically at the tubular basement membrane and around the ducts of Bellini," they wrote. "Extension of such calcification into the tubular lumen might cause more renal damage, with potential for progressive scarring, chronic kidney disease, and ultimately end-stage renal disease."
"Alternatively," they continued, "crystallization within the tubular lumen itself may cause damage to the tubular epithelium, and/or obstruction leading to progressive scarring."
Other possible explanations include the loss of kidney function following multiple episodes of urinary tract obstruction or from the surgical or percutaneous treatment of stones.
Tonelli and colleagues acknowledged that the results may not apply to individuals who do not seek medical care for a stone episode.
Other limitations included the possibility of misclassification of the number of stone episodes, the inability to look at the composition of the stones, the possibility of residual confounding, and the lack of genetic information.

Primary source: BMJ
Source reference:
Alexander R, et al "Kidney stones and kidney function loss: a cohort study" BMJ 2012; DOI: 10.1136/bmj.e5287.

The study was supported by a team grant to the Interdisciplinary Chronic Disease Collaboration from the Alberta Heritage Foundation for Medical Research (AHFMR), by the Kidney Foundation of Canada, and by the University Hospital Foundation. Tonelli is supported by an AHFMR Population Health Scholar award and a Government of Canada Research Chair in the optimal care of people with chronic kidney disease. His co-authors reported support from a Clinician-Scientist award from the Canadian Institutes of Health Research, KRESCENT New Investigator awards, an Alberta Innovates Health Solutions Clinical Investigator Award, a Canadian Child Health Clinician Scientist Program Career Development award, and a grant from the NIH.
The authors reported that they had no conflicts of interest.