• Early Vitamin D Status is Multiple Sclerosis Predicts Course
• The Evidence on Photoprotection and Vitamin D
• High (and Low?) Endogenous Estradiol Levels Linked to Increased Dementia
in Postmenopausal Women
• Fever Following Influenza and Pneumococcal Conjugate Vaccines
• Keep Eating Nuts While Pregnant
• Oral Immunotherapy Shows Promise in Children with Peanut Allergy
• Chinese Herbals Delay Progression to Type 2 Diabetes
• Exercise Reduces Sexual Side Effects of Antidepressants (SSRI's & SNRI's)
• Sexual Function on the Other Side of the Pond
• α-Blockers vs. α-Blockers plus Anticholinergics for Benign Prostatic Hyperplasia
• More Ambulatory Activity Improves Cardiovascular Health in Patients at High Risk
• HCV (Hepatitis C) Website Offers Expert advice, Guidelines on Treatment
MM: There continues to be arguments in the Healthcare Professional communities regarding the value of vitamin D. These arguments frequently make their way into the lay press and unfortunately serve only to confuse the general public more on this issue. Multiple studies have been published in the peer reviewed literature indicating a benefit of higher vitamin D levels in patients with auto-immune disorders and especially those with MS. This study should serve as a heads up to those with conditions along the MS spectrum such as Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FMS) to take a look at their vitamin D levels and supplement until they reach a blood level of 60-80ng/ml.
Early Vitamin D Status is Multiple Sclerosis Predicts Course
By Joe Elia
Higher vitamin D levels within a year after the early manifestations of multiple sclerosis are linked to better clinical outcomes, according to a JAMA Neurology article.
For 5 years, investigators followed over 400 patients suspected to be in the early stage of MS. Those with serum 25-hydroxyvitamin D levels of 50 nmol/L (20 ng/mL) or more during the first year, when compared with patients having lower values, showed less progression during the 5 years' observation. The higher-level patients had "a 4-times lower change in T2 lesion volume, a 2-fold lower rate of brain atrophy, and lower disability."
The authors note that their findings concur with earlier evidence although they don't offer a possible explanation for the effect. They say the results "suggest that identification and correction of vitamin D insufficiency has an important role in the early treatment of MS."
http://archneur.jamanetwork.com/article.aspx?articleid=1815002
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MM: The authors assess that there is a large portion of the population and especially healthcare professionals who are vitamin D insufficient/deficient, that the use of sunscreen and photo-protective clothing may magnify this situation more and that supplementation is likely the best approach to increasing overall levels. Unfortunately, they fail to recognize studies that have indicated that supplementation combined with moderate sun exposure tends to confer the greatest longitudinal benefits with the least risk of skin trauma due to prolonged sun exposure.
Photodermatol Photoimmunol Photomed 2014 Jan 9;
The Evidence on Photoprotection and Vitamin D
Less protection or more supplementation?
Vitamin D is a steroid hormone that is responsible for bone health. Its synthesis in the epidermis following ultraviolet B exposure has led to concern that sunscreens and other photoprotective measures may promote vitamin D deficiency. These authors reviewed the known evidence on this question.
They report high risk for vitamin D deficiency in patients with photosensitivity disorders (lupus, porphyria) or heavier pigmentation, breast-fed infants, people taking anticonvulsants and glucocorticosteroids, those who live farther from the equator or in areas with heavy pollution, and those with low sunlight exposure (elderly, home-bound, indoor workers). In the last class are medical resident, 26% of whom were vitamin D deficient in the fall, while 47% were deficient in the springtime.
Studies evaluating the effect of sunscreens on vitamin D levels have yielded conflicting results. Rigorous application of sunscreen does reduce serum vitamin D concentrations, but the lower amounts applied under “real life conditions” have no appreciable effects on vitamin D levels. On the other hand, individuals who avoid the sun, wear long-sleeved clothing and hats, and limit outdoor activities to sun-protected areas have lower vitamin D levels than those who do not. In Dutch studies of vitamin D-deficient non-Caucasians, vitamin D supplementation increased vitamin D levels better than 30 minutes of daily sun exposure between March and September.
Comment: Careful evaluation of vitamin D status, especially in those at high risk or who avoid the sun, is necessary to prevent the orthopedic consequences of vitamin D deficiency. Most studies showed that sunscreens used normally do not have a major effect on vitamin D production. Normalization of vitamin D status is difficult, if not impossible, to achieve by increasing sun exposure or limiting sunscreen use, especially in darkly pigmented people who live farther from the equator or in heavily polluted cities and in most people during the winter months. Thus, recommending that patients spend a few minutes in the sun or limit sunscreen use is unlikely to significantly raise vitamin D levels. Supplements are a much better way to achieve vitamin D sufficiency.
Citation(s): Kannan S and Lim HW.Photoprotection and Vitamin D: A review. Photodermatol Photoimmunol Photomed 2014 Jan 9; [e-pub ahead of print].
(http://dx.doi.org/10.1111/phpp.12096)
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MM: For many years I have said that, " it is not sufficient that women receive the right hormones but that they get the right hormones for them." This means that not only must they receive those hormones but that they also receive the proper amount to bring them into an optimal range. This includes not only supplementation when necessary but also for those with exceptionally high endogenous levels, the proper supplements to encourage proper metabolism and breakdown of those hormones. Mark Drugs can provide an in-depth assessment to determine what those products are that are needed to reach a state of optimal health. Please contact us to help assess and guide you towards your personal optimal healthy place.
High (and Low?) Endogenous Estradiol Levels Linked to Increased Dementia in Postmenopausal Women
By Amy Orciari Herman
High levels of endogenous estradiol are associated with increased risk for incident dementia among postmenopausal women, especially among those who have diabetes, a Neurology study finds.
Using data from a French prospective cohort, researchers identified some 130 postmenopausal women who developed dementia and 540 who remained dementia-free over a 4-year period. Endogenous estradiol was measured at baseline. None were using hormone therapy.
After multivariable adjustment, researchers found a J-shaped association between estradiol and dementia: Compared with women with moderate estradiol levels, those with the highest levels had a 2.4-fold risk for dementia, and those with the lowest levels had a 2.2-fold risk. In an analysis stratified according to diabetes status, diabetic women with high estradiol had a 14-fold increase in dementia risk.
The researchers attribute the increased risk at low estradiol levels to possible reverse causation. Regarding the link between high estradiol and dementia in diabetic women, they write: "It is plausible that higher endogenous [estradiol] together with diabetes promote a set of unfavorable vascular processes to increase risk of dementia in postmenopausal women."
http://www.neurology.org/content/early/2014/01/29/WNL.0000000000000107.abstract
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MM: Aside from the debate whether vaccinations are appropriate or not, I am not in favor of loading infants with multiple immunizations in a single visit. Although it is certainly more convenient to make only a single visit to the doctor's office, and I realize that moms' time is limited, I do not feel that it is worth the risk to the child.
JAMA Pediatr 2014 Jan 6
Fever Following Influenza and Pneumococcal Conjugate Vaccines
Text-message–based reporting detected higher rates of fever following simultaneous vaccine administration.
During the 2010-2011 influenza season, the CDC's Vaccine Safety Datalink project noted a slight increase in the risk for febrile seizures (~1 seizure per 2000-3000 children) in children who received the trivalent inactivated influenza vaccine (TIV) and pneumococcal conjugate vaccine (PCV13) simultaneously. Seizures were most common in children aged 6–23 months, and the slight increase in risk is noted in vaccine information sheets. To examine the incidence of fever following these vaccinations during the 2011–2012 influenza season (November–April) in the New York City area, investigators utilized text messaging to follow children aged 6–23 months who received both vaccines.
Families were instructed to take the child's temperature nightly for 7 nights and prompted to report the highest temperature via text message. Of 530 enrolled children, 212 received both TIV and PCV13 at the same visit. The rate of fever >38°C on days 0-1 was higher in children who received the two vaccines at the same visit than in children who received either vaccine alone (38% vs. 8%–10%; adjusted relative risk, 2.7). Risk for fever >39°C was higher when the two vaccines were administered together compared with when TIV was administered alone but not when PCV13 was administered alone. No differences were reported on days 2–7 postvaccination. Compliance with text message reporting was high and comparable to phone and paper reporting.
Comment: This study confirms a slight, and questionably clinically significant, increase in fever on the day of and day following simultaneous immunization with TIV-1 and PCV13 vaccines. The previously reported small increased risk for febrile seizure after simultaneous administration of these vaccines may be related to the increase in fever detected in this study by text messaging. Given the challenge of immunizing infants and children in a timely manner, the observation of increased risk for fever should not deter physicians from continuing to administer multiple vaccines to most children in a single visit.
Citation(s): Stockwell MS et al. Risk of fever after pediatric trivalent inactivated influenza vaccine and 13-valent pneumococcal conjugate vaccine. JAMA Pediatr 2014 Jan 6; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamapediatrics.2013.4469)
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MM: Food allergies and sensitivities seem to be increasing in our society. This approach may present a relatively non-invasive means to combat some of those sensitivities.
JAMA Pediatr 2013 Dec 23
Keep Eating Nuts While Pregnant
Children had substantially lower risk for nut allergies if their mothers ate nuts regularly around the time of pregnancy.
Even as the prevalence of childhood peanut and tree nut (P/TN) allergies rises, recent guidelines do not offer clear advice on whether introducing these allergens early in life or prenatally affects risk for such allergies (either positively or negatively). Researchers examined reported diet from women in the Nurses' Health Study II as well as later reports of food allergies in 8205 of their children. Dietary history determined P/TN intake within 1 year of pregnancy in 76% of mothers, and serial surveys showed that maternal P/TN consumption was generally stable regardless of pregnancy. Medical records were reviewed to confirm the children's allergy diagnoses and symptoms; 140 cases of P/TN allergy were identified.
Analysis adjusted for confounders showed that among the 98% of mothers who did not have P/TN allergies, those who consumed ≥5 servings of P/TN weekly during the peripregnancy period were substantially less likely than those who ate <1 serving monthly to have children with P/TN allergies (odds ratio, 0.31). Even 1 to 4 servings weekly significantly reduced this risk (OR, 0.56). Results were similar regardless of the children's age when first introduced to nuts.
Comment: This study supports the hypothesis that peripregnancy nut consumption by mothers induces tolerance rather than sensitization in their children, notably lowering risk for nut allergies. The study design minimizes the recall bias present in recent retrospective studies. Although the findings reflect the general population of white women, they go a long way toward confirming that eating nuts seems justified in pregnant and lactating women (who do not have nut allergies).
Citation(s): Frazier AL et al. Prospective study of peripregnancy consumption of peanuts or tree nuts by mothers and the risk of peanut or tree nut allergy in their offspring. JAMA Pediatr 2013 Dec 23; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamapediatrics.2013.4139)
Gupta R. To eat or not to eat: What foods are safe to consume during pregnancy? JAMA Pediatr 2013 Dec 23; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jamapediatrics.2013.4602)
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MM: More info on nuts and allergies.
Oral Immunotherapy Shows Promise in Children with Peanut Allergy
By Kelly Young
Oral immunotherapy in children with peanut allergy is associated with a high rate of desensitization, according to a phase II trial in the Lancet.
Roughly 100 children (aged 7 to 16 years) with peanut allergy were randomized to usual care (peanut avoidance) or 26 weeks of oral immunotherapy — daily doses of peanut flour that increased over time, up to a maintenance dose of 800 mg/day. After 26 weeks, 62% of patients in the treatment group were desensitized (i.e., no reaction during a blinded food challenge of 1400 mg). No patients in the control group were desensitized. Oral itching was the most common side effect, occurring after 6% of doses. Intramuscular adrenaline was administered twice.
A commentator writes that oral immunotherapy "is not ready for clinical use." He says that more research needs to be done on short- and long-term effects, mechanism of action, outcomes, and protocols. "This must be done without added pressure or heightened expectations to quickly produce a marketable therapy.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62301-6/abstract
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MM: For those people who are pre-disposed to a diabetic or pre-diabetic condition and who want to use an alternative approach, this Chinese Medicine herbal combination may be a valuable tool. at this point the studies look promising and we may see this product becoming available in the USA in the not too distant future.
Chinese Herbals Delay Progression to Type 2 Diabetes
By Amy Orciari Herman
A combination of Chinese herbal medicines can delay progression to diabetes in high-risk patients, according to a small study in the Journal of Clinical Endocrinology and Metabolism.
Some 400 patients in China with impaired glucose tolerance were randomized to receive Tianqi -- a capsule containing 10 Chinese herbal medicines -- or placebo for 12 months (5 capsules 3 times daily). All participants also received lifestyle education.
At the end of the study, significantly fewer Tianqi patients than placebo recipients had progressed to diabetes (18% vs. 29%). In addition, significantly more Tianqi recipients had achieved normal glucose tolerance (63% vs. 47%). Adverse events did not differ between groups.
The researchers say Tianqi offers similar benefits to metformin and may be better tolerated. Calling for larger clinical trials, they conclude: "Tianqi holds promising potential as an effective and practical means to prevent [type 2 diabetes]."
http://press.endocrine.org/doi/abs/10.1210/jc.2013-3276
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MM: Sexual side effects from antidepressants are quite common and frustrating for many people. These adverse reactions put strain on relationships and can destroy marriages that have already been taxed. Although vigorous exercise is not for everyone, this may be a tool that can be used in multiple dimensions. Couples can start by taking casual walks together. People tend to enjoy them more and have an opportunity to share, talk and get the benefit of some exercise that may lead to enhanced mood. reduced stress and overall improved relationships, sexual and otherwise. This is an alternative to vigorous exercise but still demaonstrtes many similar benefits but still retains the unfortunate time constraints that were identified in this study and that attributed to a significant portion of the drop-out rate.
Depress Anxiety 2013 Nov 1
Exercise Reduces Sexual Side Effects of Antidepressants (SSRI's & SNRI's)
Sexual functioning improved in women with regularly scheduled exercise and sexual activity
Adverse sexual effects are common in women taking antidepressants. Exercise can increase sexual arousal in healthy women, improve sexual function in depressed women not taking medication, and increase genital arousal in women taking antidepressants in a laboratory setting.
Now, investigators have conducted a randomized, crossover trial to assess whether exercise could alleviate sexual side effects from selective serotonin or norepinephrine reuptake inhibitors in 52 affected women (mean age, 32; 73% meeting DSM-IV-TR criteria for sexual dysfunction). After a 3-week interval for measuring baseline sexual activity (alone or with a partner), participants exercised vigorously for 30 minutes 3 times per week for 3 weeks and were assigned to engage in sex within 30 minutes of exercising or 6 hours or more after exercising. Participants then switched groups for another 3 weeks. A total of 42% dropped out of the study, mostly because of time constraints.
Exercise before sex increased sexual desire overall, and, in women with sexual dysfunction, it increased global sexual function. Improvement of sexual function with exercise at least 6 hours before sex was not statistically significant. Orgasm improved with scheduling of regular sexual activity. Sexual satisfaction was not significantly affected.
Comment: The authors hypothesized that exercise-induced stimulation of the sympathetic nervous system would increase sexual desire and arousal, especially if exercise occurred shortly before sexual activity. Of note, simply scheduling regular sexual activity improved orgasm, whereas scheduling exercise, especially just before sexual activity, increased desire. The high dropout rate suggests that these interventions are not for everyone. However, clinicians should consider prescribing regularly scheduled exercise and sexual activity for women with sexual side effects from antidepressants.
Citation(s): Lorenz TA and Meston CM.Exercise improves sexual function in women taking antidepressants: Results from a randomized crossover trial. Depress Anxiety 2013 Nov 1; [e-pub ahead of print].
(http://dx.doi.org/10.1002/da.22208)
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MM: This is a very comprehensive study that may relate to Americans as well as to Brits. As we have similar cultures, many of these findings may be useful.
Lancet 2013 Nov 30; 382:1817
Sexual Function on the Other Side of the Pond
A British population survey showed low sexual function was common in all age groups; correlates included depression, poor health, and postmenopausal status.
Healthy sexuality contributes to overall quality of life. Now, the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) provides a picture of sexual health, attitudes, and practices in England, Scotland, and Wales. A probability sample of 6777 women and 4913 men (age range, 16–74 years) with ≥1 sexual partner during the previous year completed the validated, computer-administered survey.
Scores were calculated from components such as sexual response (e.g., interest in and enjoyment of sex), relationship elements (e.g., agreement on sexual likes and dislikes), and appraisal of sex life (e.g., satisfaction, avoidance). Low sexual function was defined relative to the rest of the sample (i.e., scoring in the lowest quintile).The percentage of women with low sexual function changed with age (aged 16–24, 13%; aged 55–64, 27%; aged 65–74, 24%). Low function correlated strongly with current depression, poor general health, and postmenopausal status. Other factors included dissatisfaction with sexual relationship, lack of sexual competence (e.g., not using reliable contraception), and histories of coerced (“nonvolitional”) sex or diagnosis of sexually transmitted infection during the past 5 years. Women's most commonly reported sexual problems included lack of sexual interest (about one quarter of 16- to 24-year-olds and about one third of other age groups), difficulty reaching climax (16%), and vaginal dryness (13%).In another portion of Natsal-3, 19% of 8869 women reported having experienced nonvolitional sex attempts, about half of which had been completed. In most instances of completed nonvolitional sex, perpetrators were current or former intimate partners (41%), family members or friends (20% overall; 45% in teens aged 13–15 years), or known in some other way (21%). Some (42%) of these women told someone about the act, but only 13% reported it to police (more likely when the perpetrator was a stranger).
Comment: The entire body of Natsal-3 data is far more extensive than is summarized here. In sum, the information might not be practice-changing, but it does provide insight into sexual function in a culture not dissimilar to that in the U.S. As an editorialist observes, “positive sexual experience is good for us [and] negative sexual experience is bad for us,” a reminder that our patients' sexual well-being affects their health and vice versa.
Citation(s): Mitchell KR et al. Sexual function in Britain: Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Lancet 2013 Nov 30; 382:1817.
(http://dx.doi.org/10.1016/S0140-6736(13)62366-1)
Macdowall W et al. Lifetime prevalence, associated factors, and circumstances of non-volitional sex in women and men in Britain: Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Lancet 2013 Nov 30; 382:1845.
(http://dx.doi.org/10.1016/S0140-6736(13)62300-4)
Wellings K and Johnson AM. Framing sexual health research: Adopting a broader perspective. Lancet 2013 Nov 30; 382:1759.
(http://dx.doi.org/10.1016/S0140-6736(13)62378-8)
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MM: Combination therapy is frequently used in a number of different areas. It is often thought that if we use a 'shotgun' approach, then we can get better results than if we focus on a single therapy or treatment or approach. This is often accurate when it comes to herbal products but not always when we are using allopathic medicines. Most allopathic approaches to poly-pharmacy tend to increase a single drug to its maximum dose or until an appropriate response is obtained then add additional drugs and follow the same path until resolution of the problem is achieved. This study indicates that this approach for BPH may not be appropriate.
J Urol 2013 Dec; 190:2153
α-Blockers vs. α-Blockers plus Anticholinergics for Benign Prostatic Hyperplasia
A meta-analysis does not show a convincing advantage for combination therapy.
In patients with benign prostatic hyperplasia (BPH), α-blockers such as tamsulosin and doxazosin work primarily by relieving obstructive symptoms (e.g., incomplete emptying, weak stream). However, many BPH patients also have “storage symptoms” (e.g., frequency, urgency, nocturia) for which anticholinergic drugs such as oxybutynin and tolterodine might be helpful. Researchers conducted this meta-analysis of seven studies (3600 BPH patients) in which α-blocker monotherapy was compared with combination therapy (α-blocker plus anticholinergic agent).Combination therapy, compared with monotherapy, improved symptoms on a storage subscore of the widely used International Prostate Symptom Score (I-PSS); although the difference was statistically significant, it averaged only 0.7 points on the 15-point subscore. One concern about add-on anticholinergic therapy is a predisposition to acute urinary retention; this occurred significantly more often with combination therapy than with monotherapy (1.4% vs. 0.4%) during 12 weeks of treatment.
Comment: The authors suggest that their findings confirm the efficacy and safety of combined therapy — I disagree. First, they only reported outcomes on the storage subscale of I-PSS; I looked at the publications representing the three largest trials included in this analysis, and add-on anticholinergic therapy did not improve I-PSS total symptom scores (comprising both storage and obstructive symptoms) or quality-of-life scores in any of them. Second, even 1 additional case of acute urinary retention per 100 treated patients is concerning in a 3-month study; what might happen over 1 or 2 years? And, third, the authors don't discuss the nonurinary side effects of anticholinergic drugs in older people. Although combined therapy might be worthwhile for selected individuals, potential benefits do not outweigh potential harms, on average.
Citation(s): Filson CP et al. The efficacy and safety of combined therapy with α-blockers and anticholinergics for men with benign prostatic hyperplasia: A meta-analysis. J Urol 2013 Dec; 190:2153.
(http://dx.doi.org/10.1016/j.juro.2013.05.058)
http://www.ncbi.nlm.nih.gov/pubmed/23727412?access_num=
23727412&link_type=MED&dopt=Abstract
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MM: Nike coined the phrase, "Just Do IT!". These words are perfect to describe the cardiovascular benefits of moderate exercise and simply getting up and moving around. It's wonderful that these researchers could actually quantify the amount of benefit relative to the amount of movement and then convert this into real life terms.
This Lancet 2013 Dec 20
More Ambulatory Activity Improves Cardiovascular Health in Patients at High Risk
Every increment of 2000 steps daily lowered CV risk by 8%.
Higher levels of self-reported physical activity have been associated with lower risk for cardiovascular (CV) morbidity and mortality. But no studies have documented this association when physical activity is measured objectively. In a randomized pharmacotherapy trial (NAVIGATOR trial; NEJM JW Cardiol Mar 14 2010), 9306 patients (age, ≥50) who were at high risk for diabetes and CV disease used pedometers to record their ambulatory activity for 7 consecutive days at the start of the study and again after 1 year on a lifestyle modification program. Researchers now report on the association between ambulatory activity — at baseline and after 1 year — and risk for adverse CV events (CV-related mortality, nonfatal stroke, or myocardial infarction).
During average follow-up of 6 years, CV risk was 10% lower for every increment of 2000 steps daily in baseline activity, and was 8% lower for every increase of 2000 steps daily between the baseline and 1-year measurements. Similarly, every 2000 steps-per-day decrease was associated with an 8% increase in CV risk. These associations were statistically significant, independent of each other, and unaffected by age, sex, body-mass index, and other potential confounders.
Comment: Two thousand steps is roughly equivalent to 20 minutes of moderately paced walking. In the absence of data from randomized trials, this analysis strengthens the evidence that increasing physical activity improves cardiovascular health in people at high risk for adverse cardiovascular events.
Citation(s): Yates T et al. Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): A cohort analysis. Lancet 2013 Dec 20; [e-pub ahead of print].
(http://dx.doi.org/10.1016/S0140-6736(13)62061-9)
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MM: Hepatitis C is on the rise and more information must be made available to the public. This website collects and simplifies much of the data that is presently available but frequently difficult to readily access.
HCV (Hepatitis C) Website Offers Expert advice, Guidelines on Treatment
By Joe Elia
A website designed to help physicians treat the estimated 3 to 4 million Americans with hepatitis C infection has made its debut.
Clinicians from the sponsoring organizations — the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America, and the International Antiviral Society-USA — stress the ability of new direct-acting antivirals, such as simeprevir and sofosbuvir, to cure most patients. However, because there aren't enough specialists to treat all known cases, the hope is that more gastroenterologists and primary care clinicians will begin using these new regimens, given their improved tolerability.
A summary of the supporting evidence (and the quality of that evidence) follows each recommendation. The site does not address treatment costs.
http://hcvguidelines.org/
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