• The use of Probiotics before Liver Transplantation to reduce Infection Rates
• Dextromethorphan-Quinidine associated with improved agitation in Alzheimer's
• Mediterranean Diet + Extra EVOO linked to reduced Breast Cancer Risk
• Over 10% of U.S. Adults have Diabetes
• Link between Smoking and Diabetes Risk Detailed
• Variability in Serum Testosterone after Application of Testosterone Gel
• Reanalysis: Paroxetine Ineffective and Harmful for treating Depression in Adolescents
• Sticking it to Alopecia.
• High Fish Consumption linked to Decreased Depression Risk, with some Caveats
• Vitamin D Deficiency a Risk Factor for MRSA Infection?
MM: We have stood by the premise that probiotics strengthen the immune system, decrease inflammation and assist the healing process as they stabilize the body. This is pertinent when surgery is to be performed or in the course of normal living. It is always nice to see that mainstream medicine is catching up with and even embracing integrative or alternative approaches to health but we still have a long way to go.
Clin Gastroenterol Hepatol 2015 Sep; 13:1567
The Use of Probiotics before Liver Transplantation to reduce Infection Rates
In a meta-analysis, probiotic use was associated with lower infection rates, shorter antibiotic courses, and shorter hospital and intensive care unit stays but not lower mortality.
Infections are common after liver transplantation due to posttransplant immunosuppressant use, as well as the surgery itself, and can lead to significant morbidity and mortality. Probiotics may prevent bacterial translocation from the gastrointestinal tract and thus reduce infection risk.
Now, researchers have performed a systematic review and meta-analysis to evaluate the effects of pretransplant probiotic use on infection rate, intensive care unit (ICU) stay, hospital stay, and 30-day mortality. They searched PubMed and EMBASE for relevant controlled trials published before April 2015. Four trials (3 of them randomized) totaling 246 participants — 123 taking probiotics and 123 controls — met inclusion criteria and were included in the study. In these trials, the intervention groups received enteral nutrition and fiber plus probiotics, whereas the control groups received enteral nutrition and fiber only.
Overall, the infection rate was lower in the probiotic groups (7% vs. 35%, relative risk, 0.21; 95% confidence interval, 0.11–0.41). Probiotics were associated with lower rates of urinary tract infection (2% vs. 16%; RR, 0.14; 95% CI, 0.04–0.47) and intra-abdominal infection (2% vs. 11%; RR, 0.27; 95% CI, 0.09–0.78). In addition, the probiotic groups had a shorter duration of antibiotic use, as well as shorter hospital and ICU stays (P<0.001 for all). However, mortality was similar between groups (RR, 0.97; 95% CI, 0.21–4.47).
COMMENT: Although the use of probiotics before or at the time of liver transplantation did not affect mortality, this meta-analysis demonstrates benefit in reducing infection rates, duration of antibiotic use, and lengths of ICU and hospital stay. Lactobacillus species were the main component of all the probiotics used, but the other components differed among the trials, so a specific brand, combination, or dosage cannot be recommended. Larger randomized, controlled trials are warranted to further evaluate probiotic use in this setting.
CITATION(S): Sawas T et al. Patients receiving prebiotics and probiotics before liver transplantation develop fewer infections than controls: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2015 Sep; 13:1567.
(http://dx.doi.org/10.1016/j.cgh.2015.05.027)
http://www.ncbi.nlm.nih.gov/pubmed/26044318?access_num=26044318&link_
type=MED&dopt=Abstract
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MM: Dextromethorphan (DM) was used for many decades as a cough suppressant until the FDA deemed that it was of limited or no value for that purpose. We have used it in compounding to potentiate the effects of narcotic analgesics such as morphine to decrease the overall dose and frequency needed by chronic pain or hospice patients. It is nice to see that more uses are coming to light for this historically safe chemical that has few potential side effects and very little risk of dependency or abuse.
Dextromethorphan-Quinidine associated with improved agitation in Alzheimer's
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
A combination of dextromethorphan and quinidine is associated with reduced agitation among patients who likely have Alzheimer disease, according to an industry-funded, phase II study in JAMA. Dextromethorphan affects receptors that modulate glutamate, serotonin, norepinephrine, and possibly other neurotransmitters.
Roughly 200 patients with probable Alzheimer's and moderate to severe agitation were randomized to placebo or escalating doses of dextromethorphan-quinidine, currently approved for pseudobulbar affect. Clinically meaningful reductions in agitation scores were seen after 5 weeks of treatment. At that point, placebo recipients were re-randomized to combination treatment or placebo for another 5 weeks.
After 10 weeks, 45% of those who received only combination treatment had a moderate or marked clinical improvement in agitation, compared with 21% of patients who took only placebo. Treatment did not appear to affect cognitive impairment, sedation, or major QTc prolongation.
Editorialists call the results "encouraging" but say the underlying mechanism is unclear given that "agitation is a broad syndrome."
http://jama.jamanetwork.com/article.aspx?articleid=2442936
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MM: We've all heard about the effects of the Mediterranean diet and its heart healthy characteristics but this new evidence indicates that this food mixture may have a significant effect on the immune system. That is not a big surprise as there is every likelihood that the diet diminishes systemic inflammation and inflammation is certainly a critical factor that effects the immune system and every aspect of health from the cardiovascular system to the immune system to the neurological system and the brain.
Mediterranean Diet + Extra EVOO linked to reduced Breast Cancer Risk
By Amy Orciari Herman, Edited by André Sofair, MD, MPH
A Mediterranean diet — particularly one high in extra-virgin olive oil (EVOO) — is associated with reduced risk for invasive breast cancer, according to a secondary analysis from the PREDIMED study published in JAMA Internal Medicine.
Over 4100 older Spanish women at high cardiovascular risk and without a history of breast cancer were randomized to a Mediterranean diet supplemented with either EVOO (1 L/week for the women and their families) or nuts (30 g/day) or to a control diet (dietary advice).
During a median 4.8 years' follow-up, 35 incident breast cancers occurred. After multivariable adjustment, women assigned to a Mediterranean diet plus EVOO showed a significant, 68% lower risk for breast cancer relative to controls. Those assigned to the diet plus nuts showed a 41% risk reduction relative to controls, but this was not statistically significant.
Dr. Andrew Kaunitz, editor-in-chief of NEJM Journal Watch Women's Health, offered his take: "That all participants were white and at elevated baseline risk for cardiovascular disease, and that breast cancer was not the primary outcome, represent study limitations. However, given the recognized cardiovascular benefits of a Mediterranean diet, it would now appear reasonable to also recommend this strategy for the possible prevention of breast cancer while awaiting future studies that focus on this outcome."
http://archinte.jamanetwork.com/article.aspx?articleid=2434738
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MM: These results are not surprising but they are troubling. With the increasing rate of obesity in western civilizations, it is not surprising to see a concomitant increase in diabetes, heart disease, auto-immune conditions and a host of other maladies that correspond to these conditions. Ignoring the problem will not make it go away, nor will developing new drugs to address the symptoms. We need to identify and address the underlying conditions that are pre-disposing us to this chronic ill health. This may be our diets, GMO's, lack of physical activity or our lifestyles in general. These changes are never easy but they will ultimately be necessary. It is unfortunate that when new approaches are presented or old approaches - such as the HCG Metabolic Syndrome Protocol - are presented, they are frequently met with considerable resistance if not outright hostility.
Over 10% of U.S. Adults have Diabetes
By Amy Orciari Herman, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
Over 1 in 10 U.S. adults had diabetes in 2011–2012, a JAMA study finds.
Researchers examined cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 through 2012. More than 26,000 U.S. adults were included. Among the findings for 2011–2012:
- The unadjusted prevalence of total diabetes was 12% to 14%, depending on the definition used (e.g., hemoglobin A1c of 6.5% or greater, fasting plasma glucose of 126 mg/dL or greater); about one third of cases were undiagnosed.
- Some 38% of all adults had prediabetes.
- The age-standardized diabetes prevalence was higher among Blacks, Hispanics, and Asians (over 20%) than among whites (11%).
From 1988 to 2012, diabetes prevalence increased, largely owing to a rise in diagnosed cases.
Undiagnosed diabetes dropped over the study period, which editorialists call "encouraging." However, they note that even in 2011–2012, over half of diabetic Asians were undiagnosed — lending support to recent, stricter screening recommendations for this ethnic group.
http://jama.jamanetwork.com/article.aspx?articleid=2434682
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MM: Smoking has been demonized by the current healthcare community. It may rightly be the case but the rise of "vaping" may not be any better for a person than inhaling glowing carcinogens. This is a more socially acceptable method of polluting the body relative to "second hand smoke" but it still has the risk of introducing chemicals into the body.
Link between Smoking and Diabetes Risk Detailed
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
Smoking — whether current, former, or passive — is associated with increased risk for type 2 diabetes, according to a meta-analysis in the Lancet Diabetes & Endocrinology.
Researchers examined data from nearly 90 studies reporting on smoking behaviors and incident type 2 diabetes; almost 6 million participants and 300,000 diabetes cases were included. Among the significant findings:
- Current smokers had a 37% increased risk for diabetes, relative to nonsmokers.
- Former smokers had a 14% increased risk, compared with those who'd never smoked.
- Among individuals who'd never smoked, those exposed to secondhand smoke had a 22% increased diabetes risk relative to unexposed participants.
- People who quit smoking had a 54% increased diabetes risk in the first 5 years after quitting, compared with those who'd never smoked; this risk increase declined to 11% by 10 years.
The researchers conclude that if the association between smoking and diabetes is causal, then an estimated 11.7% of type 2 diabetes cases among men and 2.4% among women can be attributed to active smoking.
http://www.thelancet.com/journals/landia/article/PIIS2213-8587(15)00316-2/abstract
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MM: This article inadvertently demonstrates what compounding pharmacists have been telling mzainstream medicine for years. Blood serum testing of transdermal hormones is an inaccurate method of testing. It wastes time and money and produces flawed results. The drug companies that produce the testosterone creams or estrogen patches endorse blood testing because it is the accepted means of examining the body. Unfortunately, when a hormone is presented to the body through the skin it does not reside in the blood for an extended period of time. It distributes into the fat and organs, otherwise known as "the tissues". This can easily and reliably be measured by saliva or urine, not blood. Once again, it is unfortunate that the insurance industry will typically not pay for urine or saliva testing. This is not due to their lack of reliability. This is due to there being the opportunity to simply refuse payment based on a weak lobby to have them pay for these tests and a lack of kickbacks disguised as rebates from laboratories. Ignorance and greed have once again topped appropriate and economical healthcare.
J Clin Endocrinol Metab 2015 Sep; 100:3280
Variability in Serum Testosterone after Application of Testosterone Gel
Within-person levels vary substantially on different days and within a 24-hour period.
Serum testosterone levels should be monitored periodically in patients who apply topical testosterone. To learn more about variability in testosterone measurements taken on different days or at different times of day, U.S. researchers studied 47 men (age, ≥65) with low testosterone levels (<275 ng/dL) who received either testosterone gel or placebo gel for 4 months*.
Testosterone levels were measured at three visits. At the first two visits, gel was applied at 8:00 a.m., and blood was drawn at 10:00 a.m. The third “visit” was admission to a clinical research unit, where eight blood levels were obtained during a 24-hour period (including 2 hours after 8:00 a.m. application of gel). The following results were noted:
- Among testosterone recipients, within-person variability across the three 10:00 a.m. testosterone levels was considerable; in most men, highest and lowest 10:00 a.m. levels differed by several hundred ng/dL.
- During the 24-hour sampling, the average testosterone level in the testosterone group was 453 ng/dL. However, in only one third of participants were all eight serum levels within the published reference range of 300 to 1000 ng/dL, and some participants had huge swings in serum testosterone throughout the day.
- Placebo recipients had much less variability than testosterone recipients in serum testosterone levels, reflecting endogenous testosterone secretion. Their 10:00 a.m. levels were mostly between 150 and 250 ng/dL across the 3 days of sampling, and 24-hour variability was modest.
COMMENT: This study demonstrates large within-person variation in serum testosterone levels after gel application. The authors conclude that dose adjustment based on a single measurement can misrepresent a patient's average serum level, but the optimal number of measurements remains unclear.
*This analysis is an interim substudy from the ongoing NIH-sponsored Testosterone Trial, in which 800 U.S. men (age, ≥65) have been randomized to receive testosterone gel or placebo. Enrollment criteria include at least one morning testosterone level <275 ng/dL and one or more symptoms that allegedly are associated with low testosterone in aging males (e.g., decreased sexual function, decreased vitality). Primary outcomes will include measures of physical, cognitive, and sexual function, as well as bone density and coronary plaque. Principal results have not yet been reported.
CITATION(S): Swerdloff RS et al. Serum testosterone (T) level variability in T gel-treated older hypogonadal men: Treatment monitoring implications. J Clin Endocrinol Metab 2015 Sep; 100:3280.
(http://dx.doi.org/10.1210/JC.2015-1542)
http://www.ncbi.nlm.nih.gov/pubmed/26120790?access_num=
26120790&link_type=MED&dopt=Abstract
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MM: I feel that it is important that patients and their families are aware that not every medication is appropriate for every group of people and that there are different stages of brain development at different ages where this is extremely pertinent. Although these antidepressants are extremely affordable, they may not be appropriate for teenagers requiring this class of drug.
Reanalysis: Paroxetine Ineffective and Harmful for Treating Depression in Adolescents
By Kelly Young, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
The antidepressants paroxetine and imipramine are ineffective — and even harmful — for treating major depression in adolescents, according to a reanalysis of study data published in The BMJ.
In 2001, researchers published results of the industry-funded Study 329. Briefly, nearly 300 adolescents with major depression were randomized to paroxetine, imipramine, or placebo plus supportive psychotherapy for 8 weeks. The researchers reported that paroxetine was a safe and effective treatment.
As part of the Restoring Invisible and Abandoned Trials (RIAT) initiative, another set of researchers combed through unpublished Study 329 data and found many flaws. For instance, the significant outcomes reported in Study 329 were not part of the original protocol, investigators changed the secondary outcomes partway through the trial, and they reported adverse events only when they affected 5% of patients or more.
The RIAT group found that at the end of treatment, there were no significant differences between either drug and placebo in any of the primary or secondary efficacy outcomes. In addition, the number of paroxetine users with suicidal or self-injurious behaviors increased from 5 in the original analysis to 11 in the RIAT analysis. There was also an increase in cardiovascular adverse events with imipramine.
In an accompanying feature, a BMJ editor writes that the reanalysis "has reignited calls for retraction of the original study, putting additional pressure on academic and professional institutions to publicly address the many allegations of wrongdoing."
http://www.bmj.com/content/351/bmj.h4320?utm_source=WhatCountsEmail&utm_
medium=Physician%27s%20First%20Watch+PFW%20with%20VALID%20Emails
+PFW%20with%20VALID%20Emails&utm_campaign=PFW%20150918%20LIVE
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MM: One of the most frequent questions that I get are related to hair loss. It is ironic that I am asked this question as I am follically challenged myself. I am interested in seeing if this treatment will be successful and also, at what point is a lost cause.
J Am Acad Dermatol 2015 Aug; 73:338
Sticking It to Alopecia
What is the lowest effective dose?
Injections of triamcinolone acetonide (TMC) predictably induce hair regrowth in alopecia areata. What is the lowest effective dose? High doses can produce atrophic “dents” in the scalp and limit the area that can be safely injected without too much systemic absorption. Low doses may be ineffective.
In a small pilot study, investigators injected placebo or one of three concentrations of TMC (2.5, 5, or 10 mg/mL) into randomly assigned quadrants of four patients with untreated patch-type alopecia areata. Each quadrant received six evenly spaced injections of 0.1 mL TMC in normal saline or placebo, with reinjections every 6 weeks for 7.5 months using a 3-mL syringe and 30-gauge needle. Hair density was assessed visually and quantified with use of an imaging device.
Significantly greater hair growth was observed in all four patients at all TMC-injected sites compared with placebo. No difference was observed between TMC-treated sites. Five injections caused reversible atrophy — four associated with 10 mg/mL concentrations and one with 2.5 mg/mL. Reports of injection pain were similar across concentrations.
COMMENT: This small informative study indicated that injections of TMC 2.5 mg/mL were sufficient to induce hair regrowth in patches of alopecia areata similar to higher concentrations. The study was small. Some hair growth did occur in placebo-treated sites. Some questions remain. Did higher concentrations allow hair to persist or persist longer than low concentrations? Did diffusion or systemic absorption affect results? Are there relationships to extent of disease, location of disease, type of alopecia areata, and alopecia duration before treatment? How far apart can injections be spaced? Are results in eyebrows and beard different? We need a bigger study to know, but meanwhile, I would use TMC 2.5 mg/mL as my usual starting dose. The lower dose might minimize systemic absorption and allow larger areas to be safely injected.
Of intralesional triamcinolone acetonide in alopecia areata: An intrasubject pilot study. J Am Acad Dermatol 2015 Aug; 73:338.
(http://dx.doi.org/10.1016/j.jaad.2015.04.049)
http://www.ncbi.nlm.nih.gov/pubmed/26183987?access_num=26183987&link_
type=MED&dopt=Abstract
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MM: I have to wonder if the benefits of a predominantly fish diet are limited to the aspects listed in this article or if it goes even further than this that there are benefits from limiting other aspects of our diets. It has been proposed that beef and other red meat as well as processed grains may increase systemic inflammation and that a diet that is heavily burdened by these foods may not be the healthiest choice. Humans are by definition omnivores as our digestive tracts can accommodate a wide range of foods and obtain nourishment from them. This being stated, it is not necessarily appropriate that we eat large amounts of everything that we can. Some discretion may be appropriate no matter how good it tastes.
High Fish Consumption Linked to Decreased Depression Risk, with Some Caveats
By Amy Orciari Herman, Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS
High intake of fish is associated with lower risk for depression — at least among Europeans — according to a meta-analysis in the Journal of Epidemiology and Community Health.
Researchers reviewed 26 observational studies comprising some 150,000 participants (mostly adults). After multivariable adjustment, those who consumed the most fish had a 17% lower relative risk for depression than those who consumed the least. Subgroup analyses showed similar, significant risk reductions in men and in women. However, in analyses according to study location, the reduction in depression risk was significant only in European countries.
The authors note that the precise biological mechanisms underlying the observed association are unknown. They note that omega-3s in fish may affect serotonergic and dopaminergic neurotransmission, and "high-quality protein, vitamins and minerals may have a protective effect on depression."
http://jech.bmj.com/content/early/2015/08/21/jech-2015-206278
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MM: I have had a surprisingly large number of MRSA cases over the years that have resolved rapidly when administering high doses of vitamin D3. I typically recommend 1000IU/pound of body weight for these patients. The duration varies from 1-2 months at this dose then they are maintained at 5000-10,000 units daily for up to 6 months to prevent recurrence to the MRSA. I have seen recurrence when the D3 at this dose is eliminated before 6 months. A potential criticism of this approach is that blood levels will exceed the accepted range of 30-100ng/ml but in my experience it is a rarity to see toxicity issues until blood levels reach or exceed 400ng/ml.
Vitamin D Deficiency a Risk Factor for MRSA Infection?
In a retrospective study involving Veterans Affairs patients in Atlanta, incidence of methicillin-resistant Staphylococcus aureus infections was nearly doubled among those with vitamin D deficiency
Vitamin D's importance for bone health is well established. Recently, its roles in immunologic, neurologic, cardiovascular, and respiratory functions have been described. Several reports have suggested associations between vitamin D deficiency (VDD) and greater illness severity, poorer outcomes, and higher mortality risk.
Using data on serum 25-hydroxy vitamin D (25(OH)D) levels of patients treated at the Atlanta Veterans Affairs Medical Center between January 2007 and August 2010, Thomason and colleagues explored the potential association between VDD and methicillin-resistant Staphylococcus aureus (MRSA) infections. Of 6405 patients with at least one 25(OH)D determination during the study period (mean age, 64.2; 89% men, 50% black; 15% HIV-infected), 41% were 25(OH)D deficient (<20 ng/mL). VDD was significantly associated with younger age, HIV infection, measurement during winter, female sex, body-mass index (BMI), and black race.
In all, 401 of the patients experienced MRSA infections between October 2005 and December 2010 (range, 1–5 episodes; 70% with only 1). The infections occurred between 1360 days before and 1669 days after 25(OH)D measurement (median, 77 days after measurement). Skin and soft tissue were the most common infection sites (58%). In multivariate analysis, MRSA infection was significantly associated with male sex, lower BMI, HIV infection, and VDD. Patients with VDD were twice as likely as those with normal 25(OH)D levels to experience a MRSA infection (odds ratio, 1.94; 95% confidence interval, 1.5–2.5).
Comment: We can reasonably assume that these findings apply not only to MRSA, but also to S. aureus in general — and possibly to other pathogens. They confirm the results of other observational studies suggesting an association between VDD and infection. However, as a recent report by Amrein and colleagues (Intensive Care Med 2015 Jul 4; [e-pub]) emphasizes, prospective studies are lacking, and whether VDD represents a modifiable factor for reducing susceptibility to infections or just indicates bad health remains uncertain.
Citation(s):Thomason J et al. Association between vitamin D deficiency and methicillin-resistant Staphylococcus aureus infection. Infection 2015 Jul 4; [e-pub]. (http://dx.doi.org/10.1007/s15010-015-0815-5)
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