jueves, 27 de diciembre de 2012

New Diabetes Guidelines Ease Systolic Blood Pressure Target

New clinical practice guidelines from the American Diabetes Association (ADA) include recommendations for a less stringent systolic blood pressure target and greater individualization with regard to the frequency of blood glucose self-monitoring.
The ADA's Clinical Practice Recommendations 2013 is published as a supplement to the January issue of Diabetes Care. Revised on an annual basis, the document includes the association's major position statement along with additional position statements on a range of diabetes management–related topics.

Completo aquí: http://www.medscape.com/viewarticle/776543?src=wnl_edit_medp_imed&spon=18

miércoles, 26 de diciembre de 2012

Keloids: What works against bulging scars?


Scars do not always disappear by themselves over months. On the contrary: if excessive formation of connective tissue occurs, medical attention is required. Colleagues to begin with create a goal for the therapy. Do patients feel disfigured, or do they suffer more from pain, itching and restricted movement? If after a maximum of six treatments, that is six months, a clear success has not arrived, it's time for a change of direction.

Fateful cut

The final fate of a scar begins its story directly after the injury: inflammatory processes primarily take off in order to remove necrotic cells and, where needed, also to remove germs. In the granulation phase, fibroblasts and keratinocytes are responsible for new tissue at the wound edge and extracellular matrix components are formed. In addition, new blood vessels grow. Here matrix metalloproteases and messengers play an important role. With the epithelialisation process, the wound closes on the outside, while down inside the business goes on, that is to say remodeling: using Transforming Growth Factor β1 (TGF-β1), fibroblasts convert to myofibroblasts. This creature should not be allowed to get off the leash, otherwise hypertrophic scars arise. The swelling at this point is limited to the area on the original wound. Connective tissue tumours, that is keloids, travel far beyond these boundaries. Genetic influences and environmental factors come into question as triggers, scientists have not yet fully understood the mechanisms. Since Europeans of darker skin types are at greater risk for keloids, genotype surely plays a role.

Side effect with benefits

In order to intervene against excessive connective tissue, certain recognised side effects of glucocorticoids help. They inhibit the division of fibroblasts. Also fewer glycosaminoglycans are synthesised, something which normally contributes to the strength of the tissue. According to the guideline 50 to 100 percent of all patients respond to an injection of triamcinolone acetonide (TAC), with nine to 50 per cent, however, there are subsequent recurrences. Externally, it makes no sense to use the drug. Dermatologists achieve the best results by a combination of several methods, for instance glucocorticoid plus cryosurgery.

Hot and cold

The power of iquid nitrogen lies within: unwanted cells die from cold; depending on the extent of the scar tissue several treatments are required. After that blisters form. In various sources of literature one can read about good success rates of over 60 percent, whereas keloids are much more demanding. In contrast to removing heat from cells, laser ablation makes use of high amounts of energy. Here too tissue perishes. Both methods are not recommended as postoperative prophylactic measures.

Scars pushed away

Keeping prevention in mind, pressure treatment is worth using where treating large scars – with quite good success rates; sufferers should carry good reserves of patience with them. If the patient him or herself or those in his or her family show signs of having the respective risk factor, immediate postoperative compression garments or suits with a pressure of 20 to 30 mmHg should be adapted for use. A treatment period of six to 24 months is to be expected. Via the effects of force, cells will have poorer blood circulation and metabolic processes slow down.

Scientists have also proven that collagens matures faster. Especially with keloids, which are often found on the ear cups, the method brings excellent results. Dermatologists at the University Hospital Mannheim for this reason developed compression rails. After surgical resection of keloids they first injected TAC. Patients received their individual rails to take home. The apparatus only has to be worn at night and is easily operated via magnets – which is good for dealing with compliance matters. After 16 months, the result were clear to be seen aesthetically speaking, and a follow-up after 24 months was likewise gratifying. There were no recurrences.

Wound refreshed

When there is hypertrophic scar under tension, surgeons are required. Using Z or W-plasty, they relieve the tissue. At the molecular level, scientists suspect that mechanical forces stimulate cells to synthesise more connective tissue. If delayed wound healing is hidden behind keloids or hypertrophic scars, the excision is off to a good start. And not least significantly, fresh wounds provide the opportunity to strike using immediate postoperative prophylactic measures against excessive scar tissue. Nonetheless, the authors of the guideline point out that there exist few studies of high methodological quality which allow one to quantify the success of treatment. In particular follow-up periods of assessment were quite short. Also, at times no distinction was made between keloids and hypertrophic scars.

Something known from tumour therapy

It's not always so that surgery is needed straight away. Cytostatic 5-fluorouracil (5-FU) is also effective against the proliferation of fibroblasts. Pregnancy or pre-existing diseases of the haematopoietic system should be excluded as possibilities. Otherwise, patients must be cautious to spread drug-containing creams only on their lesions. 5-FU introduced under the skin in a double blind study reduced the tissue more effective than TAC. 5-FU is however not suitable as a postoperative prophylaxis. Irradiation also prevents the event of recurrance. In publications, values between eight and thirty Gray can be found, which prevents abnormal tissue growth among 79 to 92 percent of patients. The guideline sets a slightly lower value, up to twelve Gray, distributed over as many as ten treatments. With keloids this strategy is recommended, even though not as first option. Hypertrophic scars should however not be irradiated.

The New and The Old Well-Known

In pharmacies in particular, many customers ask for silicone gels. These lead to occlusion effects, including near saturation of the stratum corneum. In any case, authors of a Cochrane Meta-analysis found only very weak evidence of a possible benefit. They asserted that several studies were of poor quality and not without bias. Apart from that, the new guideline mentions for the first time onion extracts with allantoin heparin. Quercetin, a flavonoid from onions, inhibits the proliferation of in-vitro fibroblasts, while allantoin acts keratolytically. Heparin seems in turn to impair the polymerisation of collagen. What's more cells also produce less growth factor, on account of this excessive collagen formation does not occur. In animal experiments, wounds healed faster and scarring decreased. In older, methodologically weaker studies pure onion extract in a comparison made with vaseline showed no benefit. However, a combination made with TAC in comparison to pure corticoid led to significantly better results.

viernes, 7 de diciembre de 2012

Diagnóstico y tratamiento de la faringitis por Streptococcus grupo A

La guía actualiza las recomendaciones de 2002 de la Infectious Diseases Society of America destinadas a los profesionales de la salud que atienden pacientes adultos y pediátricos con faringitis SGA.
Dres. Shulman ST, Bisno AL, Clegg HW, Gerber MA, Kaplan EL, Lee G, Martin JM, Van Beneden C.
Clin Infect Dis. 2012 Sep 9.

Eating Before Lipid Test OK

It may not be necessary to fast before a routine cholesterol check, a large community-based population study suggested.
Overall, the mean cholesterol subclass levels varied by less than 2% for total cholesterol and high density lipoprotein (HDL) cholesterol, by less than 10% for calculated low density lipoprotein (LDL) cholesterol, and by less than 20% for triglycerides, reported Christopher Naugler, MSc, MD, of the University of Calgary in Alberta, and colleagues.
"This finding suggests that fasting for routine lipid level determinations is largely unnecessary," they said in the Nov. 12 Archives of Internal Medicine

Fuente: http://www.medpagetoday.com/Cardiology/Dyslipidemia/35909?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&xid=NL_DHE_2012-11-13&eun=g419731d0r&userid=419731&email=drvictorcastaneda@gmail.com&mu_id=5519153

viernes, 30 de noviembre de 2012

HDL Cholesterol: Why Higher Levels No Longer Equal Lower Risk

A large genetic analysis reported in the May 17, 2012, issue of the Lancet1showed no association between naturally high levels of HDL cholesterol (HDL-C) and a reduced risk of heart disease, raising even more questions about available HDL-raising strategies and the pharmaceutical research and development programs focused on bringing new agents to market.

The results are the third data set in the past several years to cast doubt on the widely held HDL-C hypothesis: HDL protects against atherosclerosis. The AIM-HIGH study2 was stopped early when there was no clinical benefit seen from the addition of niacin to statin therapy in patients with established cardiovascular disease, despite significant improvement in levels of HDL-C.3 More recently, a Phase 3 clinical trial of the cholesteryl ester transfer protein inhibitor dalcetrapib (dal-OUTCOMES)4 also was stopped for lack of efficacy.5

• Do the disappointing results of the genetic analysis constitute a third strike and effectively “bench” HDL-raising as a means to help reduce cardiovascular risk?
• What important questions do these studies raise about the cardioprotective mechanisms of HDL-C?
• What should primary care physicians tell patients who ask about current HDL-raising strategies?
• Should those strategies be modified while scientists re-think the HDL hypothesis and re-focus investigation?

To answer these questions and put the issue into clinical perspective for primary care physicians, here are Drs Christopher Cannon and Payal Kohli. Dr Cannon, a senior investigator with the TIMI Study Group, is Editor-in-Chief of Cardiosource Science and Quality. He is also Professor of Medicine at Harvard Medical School and Associate Physician in the Cardiovascular Division of Brigham and Womens’ Hospital in Boston. Dr Kohli graduated from Harvard Medical School, completed her internal medicine training in Boston, and is currently a fellow in cardiovascular medicine at the University of California San Francisco.

Take-Home Points 1. The results of the genetic study challenge a number of established views about HDL-C: first is the concept that raising plasma HDL-C levels should translate into reduction in risk of MI and, second is the belief that HDL-C is an appropriate surrogate measure for risk of MI in intervention trials.
2. The genetic data do not place into question the value of using low HDL-C levels as a marker of risk for MI. Continue to check HDL-C levels, and for now, management of patients with low values should reinforce lifestyle change (eg, improved diet, regular exercise, weight loss, smoking cessation when relevant) and focus on meeting LDL-C targets.
3. Research is still ongoing for new drugs that raise HDL-C levels.

Fuente: http://www.consultantlive.com/cardiovascular-diseases/content/article/10162/2085045

jueves, 8 de noviembre de 2012

Long-Acting Insulins Win FDA Panel Support

SILVER SPRING, Md. -- An FDA advisory committee voted 8-4 Thursday in favor of approval of a new ultra-long-acting insulin for type 1 and type 2 diabetes.
But the Endocrinologic and Metabolic Drugs Advisory Committee also voted unanimously (12-0) in support of a cardiovascular outcomes trial for the product's two formulations, insulin degludec (Tresiba) and insulin degludec/aspart, (Ryzodeg), due to a potential signal in a meta-analysis of major trials conducted thus far.
The majority of panelists who voted in favor of approving the drug said such a trial could be done post marketing.
"I think this agent has advantages over what's currently available," said panelist Ellen Seely, MD, of Harvard University in Boston. "Both insulin glargine (Lantus) and insulin detemir (Levemir) were supposed to be 24-hour insulins but fell short of that. We've spent a long time searching for an insulin that would last 24 hours."
Thomas Weber, MD, of Duke University Medical Center, said he was impressed by the pharmacokinetics and that a true ability to dose just once a day, at any time, would help improve adherence among patients.
Yet some panelists said that the benefits of the drug were not overwhelming and expressed strong concerns over cardiovascular risks that may not outweigh any advantages.
Brendan Everett, MD, MPH, a cardiologist at Brigham & Women's Hospital in Boston, voted against approval, noting that diabetics already have a substantial burden of heart disease tied to high morbidity and mortality.
He cited current "experience with other anti-diabetic medications that have adverse cardiovascular risk profile but are widely used. As a result, we've put patients at risk for adverse outcomes."
"I don't know that what we've seen [in terms of a cardiovascular signal] is real," he added, "but I have enough concerns about it that I would want to know the answer before a large number of patients with diabetes take this medication."
Erica Brittain, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., who also cast a "No" vote, said she doesn't "feel comfortable exposing millions of patients to a drug when there is this much concern about the cardiovascular risks."
Robert Smith, MD, of Brown University in East Providence, R.I., and Marvin Konstam, MD, of Tufts Medical Center in Boston, cast the other dissenting votes.
In a separate vote on whether a cardiovascular outcomes trial is necessary, Brittain said her "Yes" vote was the "easiest vote I've had since I've been on this committee."
William Hiatt, MD, of the University of Colorado in Aurora, said he voted in favor of such a trial because the mechanism linking the insulin to heart problems "is completely unclear."
"Understanding what might be at play may be important in addition to simply counting events," Hiatt said.
Panelists' interpretations as to whether the insulin was associated with a lower risk of hypoglycemia compared with other insulins were varied. Many felt the risk of hypoglycemia was comparable to other therapies, though some believed there was indeed a signal for reduced hypoglycemic events with both versions of insulin degludec.
In its review of 16 trials, FDA found a suggestion of an excess risk of cardiovascular events with degludec compared with other insulins. The agency has continued to delay a decision on the company's new drug application, submitted last September.
The FDA was initially supposed to deliver its decision in October. The agency isn't obligated to follow the advice of its advisory committees, but often does.
European regulators gave the product a thumbs up last month.

Fuente: http://www.medpagetoday.com/Washington-Watch/FDAGeneral/35854?utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news

jueves, 1 de noviembre de 2012

Is Total Testosterone Measurement an Accurate Method of Predicting Hypogonadism in Men ?

Total testosterone measurement to predict male hypogonadism
Clinical question
How accurate is the measurement of total testosterone for predicting hypogonadism in men?
Bottom line
A total testosterone level of 280 ng/dL or higher is fairly accurate in ruling out hypogonadism in men, with a false negative rate of only 2.1%. A low total testosterone level (< 280 ng/dL) is only moderately useful in predicting hypogonadism (false positive rate = nearly 62%). (LOE = 1b)
Anawalt BD, Hotaling JM, Walsh TJ, Matsumoto AM. Performance of total testosterone measurement to predict free testosterone for the biochemical evaluation of male hypogonadism. J Urol 2012;187(4):1369-1373. [PubMed® abstract]
Study design: Cohort (retrospective)

Funding source: Foundation

Setting: Outpatient (specialty)

Male hypogonadism affects an estimated 5% to 10% of men older than 30 years. The measurement of free testosterone level, considered the reference standard for the biochemical diagnosis of hypogonadism (< 34 pg/mL), is costly and time consuming and so it's not often used in clinical practice. These investigators reviewed the medical records of all 3672 men, aged 20 years to 90 years, who were evaluated for possible hypogonadism at a Veterans Administration health system from 1997 through 2007. All patients were tested for total testosterone (TT), sex hormone-binding globulin (SHBG), albumin, and calculated free testosterone (cFT). Approximately one third of the men had diabetes mellitus and nearly half were obese (BMI > 30 kg/m2). One individual abstracted and recorded all data. The prevalence of low cFT was 15.2%. The sensitivity of TT (lower limit of normal = 280 ng/dL) to identify a low cFT was 91% and the specificity was 73.7%. The positive predictive value (the likelihood that a positive result, meaning abnormally low TT, is truly positive) was 38.3% (false positive rate = nearly 62%). The negative predictive value (the likelihood that a negative result, meaning a TT > 280 ng/dL, is truly negative) was 97.9% (false negative rate = 2.1%). The positive likelihood ratio for hypogonadism, defined as a low cFT, was greater than 10 (which is considered moderately to strongly clinically useful) only when the TT level was less than 200 ng/dL. The negative likelihood ratio of a TT level 280 ng/dL or greater was 0.12, which is considered moderately useful. A more useful clinical decision rule which will calculate posttest prevalence for individual levels of TT will be available later this summer in Essential Evidence Plus.
David Slawson, MD
Vice Chair, Department of Family Medicine
University of Virginia
Charlottesville, VA

Probiotics protect against diarrhoea associated with antibiotics

JAMA 2012;307:1959-69 [PubMed® abstract]

More evidence that probiotics can help prevent diarrhoea associated with antibiotics has emerged from a meta-analysis of randomised trials. The authors found 82 trials after a systematic search but only 63 reported how many people took the probiotics, how many took the control treatment, and how many developed diarrhoea. Across these 63 trials, probiotics were associated with a 42% reduction in the risk of diarrhoea (relative risk 0.58, 95% CI 0.50 to 0.68; number needed to treat 13, 10.3 to 19.1).
Most trials tested probiotic preparations containing lactobacilli, alone or in mixed cultures. The effect looked consistent in multiple different analyses, including two confined to high quality trials and another that looked specifically at adults taking antibiotics for Helicobacter pylori infections (the most commonly reported indication). The authors are confident their results are as robust as they can be given the generally poor quality of the evidence base.
Most trials were underpowered and badly reported. It is still hard to know the precise mix of micro-organisms that is likely to work best and the characteristics of patients most likely to benefit. Details of the antibiotics being taken were missing from many trials, as were reliable assessments of side effects. Still, we have enough encouraging evidence to justify further research to fine tune these results, say the authors. Diarrhoea associated with antibiotics is common and can be life threatening.

2012 ACC/AHA Unstable Angina and NSTEMI Guideline Update: 10 Points to Remember

Title: 2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Date Posted: July 16, 2012
Authors: Jneid H, Anderson JL, Wright RS, et al.
Citation: J Am Coll Cardiol 2012;Jul 16:[Link to free full-text JACC article PDF]
The following are 10 points to remember about this guideline update:
  1. Aspirin should be administered to unstable angina (UA)/non–ST-segment elevation myocardial infarction (NSTEMI) patients as soon as possible after hospital presentation and continued indefinitely in patients who tolerate it.
  2. A loading dose of P2Y12 receptor inhibitor therapy is recommended for UA/NSTEMI patients for whom percutaneous coronary intervention (PCI) is planned.
  3. Prasugrel should not be administered routinely to patients with UA/NSTEMI before angiography, such as in an emergency department, or used in patients with UA/NSTEMI who have not undergone PCI.
  4. Physicians and patients should be cautioned against early discontinuation of P2Y12 receptor inhibitors for elective noncardiac procedures.
  5. In patients taking a P2Y12 receptor inhibitor in whom coronary artery bypass grafting (CABG) is planned and can be delayed, it is recommended that the drug be discontinued to allow for dissipation of the antiplatelet effect. The period of withdrawal should be at least 5 days in patients receiving clopidogrel or ticagrelor and at least 7 days in patients receiving prasugrel unless the need for revascularization and/or the net benefit of the P2Y12 receptor inhibitor therapy outweighs the potential risks of excess bleeding.
  6. An early invasive strategy (i.e., diagnostic angiography with intent to perform revascularization) is indicated in UA/NSTEMI patients who have refractory angina or hemodynamic or electrical instability (without serious comorbidities or contraindications to such procedures).
  7. For UA/NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, heart failure, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed.
  8. Use of warfarin in conjunction with aspirin and/or P2Y12 receptor inhibitor therapy is associated with an increased risk of bleeding, and patients and clinicians should watch for bleeding, especially gastrointestinal, and seek medical evaluation for evidence of bleeding.
  9. Creatinine clearance should be estimated in UA/NSTEMI patients and the doses of renally cleared medications should be adjusted according to the pharmacokinetic data for specific medications.
  10. The development of regional systems of UA/NSTEMI care is a matter of utmost importance. This includes encouraging the participation of key stakeholders in collaborative efforts to evaluate care using standardized performance and quality-improvement measures, such as those endorsed by the American College of Cardiology and the American Heart Association for UA/NSTEMI.
Debabrata Mukherjee, M.D., F.A.C.C. (Disclosure)

jueves, 11 de octubre de 2012

Aceite de oliva y prevención de Diabetes

El aceite de oliva es el ingrediente principal de la dieta mediterránea y una reciente investigación demuestra que aporta beneficios tanto para los huesos como para el páncreas. Una investigación reciente publicada en la revista Journal of Clinical Endocrinology and Metabolism indica que el aceite de oliva ayuda a preservar la estructura ósea de las personas y al mismo tiempo permite que el páncreas siga produciendo insulina, con lo cual se previene la aparición de la diabetes.
Estudios anteriores habían demostrado que la dieta mediterránea ayuda a reducir la osteoporosis, considerando que la población de los países en los que se adopta la dieta mediterránea presenta huesos más saludables. Pero los estudios realizados hasta ahora solo identificaban la dieta mediterránea como un factor favorable para las personas, pero no se había identificado a los ingredientes que brindan beneficios para la salud.
El estudio ‘Efectos de la dieta mediterránea en la prevención primaria de la enfermedad cardiovascular’ (PREDIMED) se inició en el año 2003 y tenía como objetivo identificar los ingredientes que podrían ayudar a prevenir enfermedades cardiovasculares. En el proceso de análisis de los resultados obtenidos se han identificado ingredientes que ofrecen distintos beneficios para la salud de las personas.
Para realizar el estudio se analizó la evolución de 7.400 pacientes a quienes se les dividió en tres grandes grupos que consumiría una dieta mediterránea, pero con tres variantes: un grupo añadiría una dosis adicional de aceite de oliva, otro grupo frutos secos y el tercer grupo se alimentaría con una dieta baja en grasas.
Se hizo un seguimiento de dos años a pacientes con diabetes tipo 2, con hipertensión o con antecedentes familiares de enfermedad cardiovascular prematura. Los pacientes que utilizaron la dieta con aceite de oliva incrementaron de 20 a 30 ml diarios en sus alimentos.
Se identificó que los pacientes que recibieron una dosis adicional de aceite de oliva presentaban un incremento en la concentración total de osteocalcina y otros marcadores de formación ósea. Además los pacientes que tomaron las otras dietas no reportaron beneficios similares y el nivel de calcio disminuyó en los otros dos grupos, mientras que las personas que tomaron el aceite de oliva mantuvieron sin alteración sus niveles de calcio en la sangre.
El director de este estudio, el doctor José Manuel Fernández-Real, del departamento de Diabetes, Endocrinología y Nutrición del Hospital Dr. Josep Trueta de Gerona, indica que este es el primer estudio en el que se demuestra que el aceite de oliva preserva el hueso.
Los investigadores señalan que el próximo paso será efectuar un estudio en el que se aplique un método similar a personas sanas, sin antecedentes cardiovasculares, para identificar si se obtienen resultados similares y a la vez medir la densidad del hueso.

jueves, 20 de septiembre de 2012

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.
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.

sábado, 8 de septiembre de 2012

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

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]
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
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

(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 infectionS boulardii, ranging from 4×109 to 2×10100.47 (95% CI 0.35 to 0.63)
Avadhani 2010 (unclear)8 RCTs, 1220 adults, inpatients3 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 doses0.56 (95% CI 0.44 to 0.71)
McFarland 2006 (1977-2005)25 RCTs, 2810 children and adults, inpatients and outpatients including H pylori treatment6 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 outpatientsSingle agent lactobacillus, ranging from 2×10[9] to 4×1010Combined 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 outpatientsSingle (5 L rhamnosus) and mixed, ranging from 1×710 to 1×10100.48 (95% C1 0.35 to 0.65)
Szajewska 2006 (1966-December 2005)6 RCTs, 766 children, inpatients and outpatients2 RCTs lactobacillus GG, one S boulardii, 3 mixed, dose range unclear0.44 (95% CI 0.25 to 0.77)
Johnston 2007 (inception to August 2006)9 RCTs, 1946 children, inpatients and outpatients6 single, 3 mixed containing (alone or in combination) Lactobacillus spp, Bifidobacterium spp, Streptococcus spp, S boulardii, ranging from 8.25×106 to 4×1010Per-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 1080.50 (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

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
  • 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
  • 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.
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.

sábado, 1 de septiembre de 2012

Kidney Stones Predict Chronic Trouble, ESRD

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.

viernes, 17 de agosto de 2012

Simultaneous Control of Diabetes Mellitus, Hypertension, and Hyperlipidemia in 2 Health Systems

  1. John F. Steiner, MD, MPH

+ Author Affiliations: From the Institute for Health Research, Kaiser Permanente Colorado, Denver (E.B.S., E.A.B., J.F.S.); Department of Medicine, University of Colorado Denver (E.B.S.); Denver Health, Denver, CO (R.H., E.P.H.); Colorado Health Outcomes Program, University of Colorado Denver (B.L.B.); and Department of Family Medicine, University of Colorado Denver (E.A.B.).                          Correspondence to Emily B. Schroeder, MD, PhD, Institute for Health Research, Kaiser Permanente Colorado, PO Box 378066, Denver, CO 80237-8066. E-mail emily.x.schroeder@kp.org


Background—Many individuals with diabetes mellitus, hypertension, and hyperlipidemia have difficulty achieving control of all 3 conditions. We assessed the incidence and duration of simultaneous control of hyperglycemia, blood pressure, and low-density lipoprotein cholesterol in patients from 2 health care systems in Colorado.
Methods and Results—We performed a retrospective cohort study of adults at Denver Health and Kaiser Permanente Colorado with diabetes mellitus, hypertension, and hyperlipidemia from 2000 through 2008. Over a median of 4.0 and 4.4 years, 16% and 30% of individuals at Denver Health and Kaiser Permanente achieved the primary outcome (simultaneous control with a glycosylated hemoglobin (HbA1c) <7 .0=".0" and="and" ba="ba" blood="blood" cholesterol="cholesterol" dl="dl" goals="goals" hg="hg" less="less" lipoprotein="lipoprotein" low-density="low-density" mg="mg" mm="mm" pressure="pressure" respectively.="respectively." strict="strict" sub="sub" with="with">1c
<8 .0=".0" 44="44" 70="70" achieved="achieved" achieving="achieving" adherence="adherence" age="age" and="and" as="as" at="at" blood="blood" but="but" cardiovascular="cardiovascular" characteristics="characteristics" cholesterol="cholesterol" comorbidities="comorbidities" conditions="conditions" control.="control." control="control" denver="denver" disease="disease" dl="dl" ethnicity="ethnicity" health="health" hg="hg" in="in" increased.="increased." increased="increased" increasing="increasing" individuals="individuals" kaiser="kaiser" less="less" likely="likely" lipoprotein="lipoprotein" low-density="low-density" medication="medication" mg="mg" mm="mm" models.="models." more="more" multivariable="multivariable" not="not" of="of" or="or" other="other" p="p" permanente="permanente" predictive="predictive" presence="presence" pressure="pressure" severity="severity" significantly="significantly" simultaneous="simultaneous" sociodemographic="sociodemographic" strongly="strongly" the="the" underlying="underlying" was="was" were="were" white="white">
Conclusions—Simultaneous control of diabetes mellitus, hypertension, and hyperlipidemia was uncommon and generally transient. Less stringent goals had a relatively large effect on the proportion achieving simultaneous control. Individuals who simultaneously achieve multiple treatment goals may provide insight into self-care strategies for individuals with comorbid health conditions.

Aplica también para el salario médico !!!