• Intranasal Oxytocin Looks Promising for Migraine
• Kovacaine Mist Nasal Spray as Dental Anesthetic
• Cyclosporine in Allergic Conjunctivitis
• Very Few Patients with Penicillin Allergy Histories Are Truly Allergic
• Gut Bacteria Predict Type 2 Diabetes
• Prognostic Importance of White Coat Hypertension: Two out of Three?
• Living Longer in the U.S., but Not Healthier
• More Evidence for Link Between Omega-3 Fatty Acids and Prostate Cancer
• Air Pollution's Health Effects
• The Growing Burden of Dementia in China
• Bariatric Surgery to Treat Diabetes in Nonmorbidly Obese Patients
• Some ARBs May Outperform Others in Lowering CV Risk in Diabetes
• FDA Approves First Non-hormonal Treatment for Menopausal Hot Flashes
• Music Therapy in the ICU — Another Way to Lower Sedation Use
• Prepartum Blood Test Predicts Postpartum Depression
• Is IVF Linked to Autism and Mental Retardation?
• Can 4-aminopyridine Improve Visual Function in MS Patients
MM: Migraines are one of the most poorly treated conditions that are life tormenting that we have to deal with. Intranasal treatments are quick and typically uncomplicated. Another compounded nasal preparation that has been found useful for migraine is intranasal Lidocaine 4%. It is inexpensive and may be worth trying before progressing to some of the other options.
Intranasal Oxytocin Looks Promising for Migraine
Results of a small study of oxytocin administered intranasally indicate that it may be helpful in the management of chronic migraine. The single-dose, placebo-controlled, double-blind study found the oxytocin to be safe and highly effective.
http://www.medscape.com/viewarticle/807277
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MM: Any time that we can avoid a needle is a good time in my book. Once again, a unique delivery system such as a nasal mist may present a good option for consumers.
Kovacaine Mist Nasal Spray as Dental Anesthetic
Oral anesthetic injections in the dentist's chair could soon become a thing of the past. In clinical tests, Kovacaine Mist Nasal Spray was found to be as effective as standard anesthetics in four out of five patients. About 75% of U.S. adults reportedly experience some degree of dental fear.
http://www.nydailynews.com/life-style/health/nasal-spray-replace-needles-dentist-chair-article-1.1391253
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Cyclosporine in Allergic Conjunctivitis
Topical cyclosporine in the treatment of symptoms of allergic conjunctivitis may help patients reduce their dependency on steroids. Affecting an estimated 20% to 30% of the world's population, allergic conjunctivitis' symptoms include tearing, itching, discharge, and photophobia. Primary treatment has included topical corticosteroids, but prolonged use can result in elevated intraocular pressure with subsequent glaucoma, cataract, and increased susceptibility to microbial infection, leading to associated visual morbidity. Although cyclosporin may not replace corticosteroids, it may be considered when a steroid-sparing agent is needed.
http://www.medscape.com/viewarticle/807500
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MM: Over the years we have been told that penicillin allergies are extremely common and life threatening. I find it interesting that this may only be a myth . What other medical myths have we bought into?
J Allergy Clin Immunol Prac 2013 May; 1:258
Very Few Patients with Penicillin Allergy Histories Are Truly Allergic
Penicillin allergy testing can safely exclude IgE-mediated penicillin allergy
Almost 8% of the U.S. population claims to be allergic to penicillin, but only a small proportion of these patients are truly allergic. Penicillin skin testing is the only way to identify IgE-mediated allergy (an immediate hypersensitivity reaction mediated by preformed IgE bound to the surface of mast cells and basophils). Penicilloyl-poly-lysine (Pre-Pen), the major determinant of penicillin allergy, has been available commercially since 2009, but clinicians rarely order skin testing. Some physicians are concerned that Pre-Pen testing is inadequate without also testing for minor determinants (penicilloate and penilloate), which are not readily available.From 2010 to 2012, 500 patients with histories of penicillin allergy (based on diagnoses recorded in their records) were skin tested in a California allergy department using penicilloyl-poly-lysine and fresh penicillin G. Negative tests were followed by 1-hour observed oral challenges with amoxicillin. Four patients reacted to one of the two skin-test agents, and another four exhibited positive objective symptoms after oral challenges. None of these reactions was life threatening or required epinephrine
Comment: In this study, fewer than 1 in 50 patients with penicillin allergy histories were truly allergic. We should stop accepting penicillin allergy history as a reason for lifelong avoidance. All drug reactions should be documented carefully. Patients with severe delayed reactions such as Stevens Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), or hemolytic anemia should never be challenged or tested; those with mild delayed reactions probably can undergo oral challenges. For those with potential IgE-mediated reactions (i.e., hives, edema, or other symptoms of anaphylaxis occurring within 1–2 hours), penicillin testing followed by oral challenge is safe and effective. Penicillin is the only antibiotic for which such testing is available.
Citation(s): Macy E and Ngor EW. Safely diagnosing clinically significant penicillin allergy using only penicilloyl-poly-lysine, penicillin, and oral amoxicillin. J Allergy Clin Immunol Prac 2013 May; 1:258.
(http://dx.doi.org/10.1016/j.jaip.2013.02.002)
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MM: Several studies have indicated that probiotic supplementation may be beneficial to diabetic patients. Here is more support for the use of probiotics in these patients. Current estimates are that there may be as many as 70 million plus adults in the USA who are diabetic or pre-diabetic. If the simple use of probiotics could help these patients, it's possible that the medical costs and associated public costs of diabetes could be greatly reduced.
Nature 2013 Jun 6; 498:99
Gut Bacteria Predict Type 2 Diabetes
Specific microbiome signatures were associated with current diabetes, impaired glucose tolerance, and normal glucose tolerance.
Development of type 2 diabetes mellitus is affected by environmental factors (lifestyle) as well as by genes. With the sequencing of the human genome, we expected to quickly identify the genes that render a person vulnerable to developing type 2 diabetes. However, although several of the approximately 22,000 human genes have been linked to diabetes, they aren't very powerful predictors of who will get the disease. Traditional environmental risk factors for type 2 diabetes (i.e., diet, exercise, and weight) are better predictors than known genes but still are only modestly prognostic. A new study suggests that a more powerful predictor of type 2 diabetes than either human genes or traditional risk factors is a new factor that is both environmental and genetic: the bacteria that live in our gut and their 5 million genes. Researchers evaluated the gut microbiomes of a population-based sample of 145 70-year-old Scandinavian women with or without type 2 diabetes. The gut microbiome “signature” could discriminate between the groups, and it also predicted which women with impaired glucose tolerance would develop diabetes. Similar signatures were used to distinguish participants with type 2 diabetes from those with normal glucose tolerance in a Chinese cohort
Comment: The gut microbiome has been associated with obesity, cardiovascular disease, and, now, type 2 diabetes. Association is not causality, but someday we might prevent and treat these diseases by manipulating gut flora. Who would have predicted that, even 20 years ago
Citation(s): Karlsson FH et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature 2013 Jun 6; 498:99.
(http://dx.doi.org/10.1038/nature12198)
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MM: I've always wondered if the fact that my BP goes up in the doctor's office was just me or if others had the same experience. And, if so, what is the clinical or therapy affected significance of that white coat hypertension. I am relieved to know that I may not be at increased risk but I have to wonder how many other people are taking unnecessary medication for blood pressure?
Hypertension 2013 Jul; 62:168
Prognostic Importance of White Coat Hypertension: Two out of Three?
In a long-term, population-based study, mortality risk was significantly elevated only in patients with hypertension on one of two out-of-office measures
Although white-coat hypertension (elevated blood pressure [BP] on office measurement with normal BP on out-of-office measurement) has been known for many years, its importance and role in management decisions remain unclear. In the PAMELA study, 2051 residents of a town in northern Italy underwent three different BP measurements: in an office, self-administered at home, and 24-hour ambulatory monitoring. Participants were characterized as having normotension (all 3 measures normal), sustained hypertension (all 3 measures elevated), or white-coat hypertension (elevated office measure and ≥1 normal out-of-office measures). The white-coat–hypertension group was subdivided into participants with normal values on both out-of-office measures (true white-coat hypertension) and those with an elevated value on one measure (partial white-coat hypertension).During an average of 16 years of follow-up, rates of cardiovascular and all-cause mortality increased progressively and significantly from normotension to white-coat hypertension to sustained hypertension. Compared with normotensive participants, rates of cardiovascular and all-cause mortality were significantly increased in participants with sustained hypertension and those with partial white-coat hypertension, but not in those with true white-coat hypertension. Results were similar after excluding participants receiving antihypertensive treatment. In 750 patients without sustained hypertension at baseline who underwent repeat measurements at 10 years, the rate of sustained hypertension increased progressively and significantly from normotension to true white-coat hypertension to partial white-coat hypertension.
Comment: In this study, the mortality risk associated with true white-coat hypertension was similar to that associated with normal blood pressure, whereas the risk associated with partial white-coat hypertension was comparable to that associated with sustained hypertension. These findings suggest that three forms of BP measurement (1 in-office, 2 out-of-office) are better than two for risk assessment in patients with white-coat hypertension
Citation(s): Mancia G et al. Long-term prognostic value of white coat hypertension: An insight from diagnostic use of both ambulatory and home blood pressure measurements. Hypertension 2013 Jul; 62:168.
http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.00690
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MM: Quality, not quantity is extremely important. We spend 12 times as much in healthcare on our elderly as other similar economic status countries yet the quality of life provided for our elderly is no better and in many cases much worse than that of other countries. We need to look at long term health and lifestyle earlier in our lives that will affect the status of our health when we are older. Diabetes and Metabolic Syndrome are key factors that tend to affect quality of life. Weight reduction and control along with both aerobic and weight resistant exercise are perhaps the greatest factors that can contribute to improving these conditions and improving the Quality of life in both the short and long term. Dietary modification and elimination of high fructose corn syrup (HFCS) from our diets will further facilitate this task
Living Longer in the U.S., but Not Healthier
By Kelly Young
Life expectancy in the U.S. has increased 3 years (from 75 to 78) over the past two decades, but Americans are more often living with disability.
Health improvements have not kept up with those in other developed nations, according to a report in JAMA. Researchers used data from the Global Burden of Disease 2010 Study of 34 countries to look at U.S. health. In 2010, the U.S. slipped to sixth-best in terms of years lived with disability. Morbidity and chronic disability represent roughly half of the country's health burden. The main risk factors related to disabilities included tobacco, overweight, hypertension, diabetes, inactivity, and alcohol. Poor diet contributed to a quarter of all deaths. An editorialist writes: "The landmark report ... demonstrates in stark, quantitative terms that the U.S. dilemma in health care remains strikingly unaltered" from the 1970s
http://jama.jamanetwork.com/article.aspx?articleid=1710486
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MM: I received several calls on this study this week and it is a confusing issue as Omega-3 Fatty Acids have repeatedly been shown to be beneficial to many health conditions. I would not stop taking my fish oil just yet. I think that we will discover that there are several confounding factors that will appear as we look longer and harder at this subject. The other thing to remember is that prostate cancer is typically a very slow developing condition and that the majority of older men have some level of this condition irrespective of whether that are consuming omega-3 fatty acids or not.
More Evidence for Link Between Omega-3 Fatty Acids and Prostate Cancer
By Amy Orciari
A new study confirms a previously reported association between high serum concentrations of omega-3 fatty acids and increased prostate cancer risk, researchers report in the Journal of the National Cancer Institute.In an analysis nested within a cancer prevention trial, some 800 men with prostate cancer were matched by age and race to a subcohort of 1400 men.
Compared with men in the lowest quartile of serum long-chain omega-3 fatty acid concentration, those in the highest quartile had a significant, 40% increased risk for low-grade prostate cancer or total prostate cancer; the risk for high-grade disease was increased by 70%, a finding of borderline statistical significance. The authors say their study, when considered alongside previous research, "strongly suggests" that long-chain omega-3 polyunsaturated fatty acids "do play a role in enhancing prostate tumorigenesis." They conclude that recommendations to increase omega-3 consumption "should consider its potential risks.
http://jnci.oxfordjournals.org/content/early/2013/07/09/jnci.djt174.abstract
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Air Pollution's Health Effects
By Kelly Young
Three studies published this week highlight the dangers that air pollution poses to human health.
The first, a Lancet Oncology meta-analysis of 17 cohort studies across Europe, found that people who lived in areas with elevated levels of particulate matter in the air were at increased risk for lung cancer over 13 years' follow-up. The association was strongest for adenocarcinomas.
Second, a meta-analysis of 35 international studies in the Lancet found that higher exposures to carbon monoxide, sulfur dioxide, nitrogen dioxide, and particulate matter were associated with increased risk for heart failure hospitalization or death. The authors estimate that reducing the average particulate matter concentration in the U.S. by 3.9 micrograms per cubic meter could avert roughly 8000 heart failure hospitalizations annually.
And finally, a study in PNAS found that in northern China, where coal is provided free for fuel burners, particulate concentrations are 55% higher than in the south. At the same time, life expectancies are 5.5 years shorter in the north, largely because of higher cardiorespiratory mortality.
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70279-1/abstract
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60898-3/abstract
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MM: Dementia and AD is a growing concern worldwide. The mere fact that China has such a large population lends it and world numbers to much greater risk than other countries when there is a statistically relevant trend.
Lancet 2013 Jun 8; 381:2016
The Growing Burden of Dementia in China
Previous global analyses likely underestimated the prevalence of dementia in East Asia.
As the life expectancy in population-dense, low-income nations such as China and India continues to improve the incidence and prevalence of dementia and other illnesses associated with aging are also likely to increase, creating new socioeconomic hardships. Previous estimates of the incidence of dementia in China were based on an incomplete review using only 25 studies in the Chinese literature published from 1980 to 2004, with supplemental information from publically available databases. The present systematic review included 89 studies published between 1990 and 2010 in Chinese or English, identified via PubMed, China National Knowledge Infrastructure, and Wanfang (a medical database). Most of the studies had >1000 participants, and 95% of the dementia cases were defined by well-established criteria. Of the 75 cross-sectional studies included, 68% involved a multidisciplinary assessment by neurologists and psychiatrists.
Using demographic data from the United Nations to compare to the data from more than 340,000 participants in these studies, the authors estimated that 9.19 million people in China had dementia in 2010, and 5.69 million had Alzheimer disease. The estimated prevalence correlated positively with advancing age, as would be predicted from other populations. However, the estimated prevalence of all dementias in participants aged 95 to 99 years was unexpectedly high, increasing from 42.1% in 1990 to 60.5% in 2010.
COMMENT: As observed in an accompanying editorial, this work is commendable for obtaining broader culturally relevant epidemiological data that improve our understanding of the global impact of dementia. The potential financial repercussions of previous underestimates of disease prevalence are sobering, and the apparent escalation in incidence warrants further study in other populations.
CITATION(S):Chan KY et al. Epidemiology of Alzheimer's disease and other forms of dementia in China, 1990–2010: A systematic review and analysis. Lancet 2013 Jun 8; 381:2016.
(http://dx.doi.org/10.1016/S0140-6736(13)60221-4)
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MM: I am not a big fan of lap-banding or stomach stapling as a first line treatment .I feel that the HCG metabolic Syndrome and Weight Loss Program is a much better option for these patients and is certainly more economically feasible.
JAMA 2013 Jun 5; 309:2240
Bariatric Surgery to Treat Diabetes in Nonmorbidly Obese Patients
Surgery offers better short-term metabolic outcomes than medical management, but cost, postoperative complications, and lack of long-term follow-up data support caution.
Because gastric bypass and other forms of bariatric surgery lower risk for diabetes and cardiovascular-related mortality in morbidly obese patients, attention now has focused on nonmorbidly obese patients with diabetes. Results of a recent randomized trial and a systematic review suggest potential benefits, but many uncertainties remain.In a trial conducted in the U.S. and China, 120 adults (mean age, 49; mean body-mass index, 35 kg/m2) with uncontrolled diabetes were randomized to Roux-en-Y gastric bypass surgery or intensive medical management consisting of 30 diet and exercise counseling sessions during 12 months. Surgery patients received usual lifestyle-modification counseling and postoperative eating guidance. Most enrollees also were taking medications for hypertension and hyperlipidemia. At 12 months, 11 medical-management patients and 28 surgical patients had achieved the composite outcome of glycosylated hemoglobin (HbA1c) <7.0%, LDL cholesterol level <100 mg/dL, and systolic blood pressure <130 mm Hg. The medical-management group attained a mean weight loss of 8%, compared with 26% in the surgical group. Among surgical patients, 10 had serious early or late postoperative complications (e.g., anastomotic leak, stricture, small bowel obstruction). Other adverse events were similar in the two groups.In a systematic review, three randomized clinical trials of surgery versus medical management in 290 nonmorbidly obese patients with diabetes or metabolic syndrome favored various bariatric surgery procedures for weight loss and glycemic control after 1 to 2 years of follow-up. Bariatric surgery also was favored over intensive medical management in observational studies. No follow-up data beyond 5 years were available in any surgical study, whereas medical-management studies showed benefits after 10 or more years of follow-up. Surgery-related mortality ranged from 0.3% to 1.0%, and almost all surgical studies were from single centers.
Comment : Comparing surgical and medical approaches to achieve weight loss and glycemic control and to lower cardiovascular risk in nonmorbidly obese patients is still in an early and uncertain phase. Short-term improvement in metabolic complications of obesity favors surgery, but the incidence of surgical complications is not trivial. Long-term follow-up data (for ≥10 years) are needed to understand the consequences of surgically altering intestinal function and nutrient absorption and to guide decision making. For many primary care physicians, recommending major surgery for clinical entities that traditionally have been treated medically is unsettling.
Citation(s): Ikramuddin S et al. Roux-en-Y gastric bypass vs intensive medical management for the control of type 2 diabetes, hypertension, and hyperlipidemia: The Diabetes Surgery Study randomized clinical trial. JAMA 2013 Jun 5; 309:2240.
(http://dx.doi.org/10.1001/jama.2013.5835)
http://www.ncbi.nlm.nih.gov/pubmed/23736733?access_num=23736733&link_type=
MED&dopt=Abstract
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Some ARBs May Outperform Others in Lowering CV Risk in Diabetes
By Kelly Young
The angiotensin-receptor blockers telmisartan and valsartan might help prevent major cardiovascular events better than other ARBs in patients with diabetes, according to a CMAJ study.Using Canadian databases, researchers identified 54,000 older adults with diabetes who were first-time users of ARBs. After multivariable adjustment, both telmisartan and valsartan were associated with about a 15% reduction in risk for hospital admission for acute myocardial infarction, heart failure, or stroke, compared with irbesartan. The risk was not significantly reduced for candesartan or losartan.
The authors conclude that "a class effect may not be assumed when using angiotensin-receptor blockers for the prevention of diabetes-related macrovascular complications or heart failure, and that telmisartan and valsartan may be the preferred drugs for this indication." Meanwhile, a commentator concludes, "without appropriately designed randomized controlled trials, there is scant evidence to support preferring one drug in this class over another for patients with type 2 diabetes.
http://www.cmaj.ca/content/early/2013/07/08/cmaj.121771.full.pdf+html
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MM: It is important to realize that paroxetine is NOT without side effects. It is notorious for diminishing and eliminating sex drive in women of all ages and this is already a primary concern of many menopausal and peri-menopausal women and paroxetine develops a very high dependency situation that makes it extremely difficult to withdraw the drug at a later date.
FDA Approves First Non-hormonal Treatment for Menopausal Hot Flashes
The FDA has approved Noven Therapeutics LLC's drug to treat hot flashes associated with menopause—a surprise decision, as an advisory committee to the regulator had voted against its approval. The drug, Brisdelle, is the first approved, non-hormonal treatment for hot flashes, the FDA said in a statement. The generic name for Brisdelle is "paroxetine" and another brand name product, "Paxil." In March, advisers to the FDA voted against Brisdelle, concluding that it did not show enough benefits to offset the risks.
http://www.reuters.com/article/2013/06/28/noven-fda-menopausedrug-idUSL3N0F43NU20130628
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JAMA 2013 Jun 12; 309:2335
Music Therapy in the ICU — Another Way to Lower Sedation Use
Awake intensive care unit patients who received music therapy were less anxious than those who did not.
Music therapy improves well-being in hospice patients, distracts patients during endoscopy, and helps treat depression in elders. Could it also decrease anxiety in critically ill patients?
Investigators randomized 373 awake and interactive intensive care unit (ICU) patients to one of three groups: patient-directed music through noise-cancelling headphones (with a visit by a music therapist to find preferred music and twice-daily prompts to listen to music); patient-initiated noise-cancelling headphone use only; or usual care. Anxiety was assessed daily with a 100-point visual-analog scale (VAS; range, 0 = “not anxious at all” to 100 = “most anxious ever”), and sedation doses and frequency were analyzed post hoc.
During a mean follow-up of 6 days, daily VAS scores of patients who received patient-directed music were significantly lower (by a mean of 19 points) than those of patients who received usual care; the headphones-alone group scored nonsignificantly lower (by a mean of 8 points) than the usual-care group. Sedation use was somewhat lower in the music-treated group
Comment: As editorialists note, this trial has several limitations, including lack of a standardized sedation protocol and use of an unvalidated anxiety-assessment tool. Despite this, the results suggest that an inexpensive intervention like patient-directed music in the ICU could help limit use of sedating medications and all the complications associated with them.
Citation(s): Chlan LL et al. Effects of patient-directed music intervention on anxiety and sedative exposure in critically ill patients receiving mechanical ventilatory support: A randomized clinical trial. JAMA 2013 Jun 12; 309:2335.
(http://dx.doi.org/10.1001/jama.2013.5670)
http://www.ncbi.nlm.nih.gov/pubmed/23689789?access_num=23689789&link_
type=MED&dopt=Abstract
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Mol Psychiatry 2013 May 21
Prepartum Blood Test Predicts Postpartum Depression
The extent of estrogen-induced DNA methylation in the blood cells of pregnant women with mood-disorder histories is associated with postpartum depression
Postpartum depression is thought to be triggered by sudden decreases in estrogen after delivery, although estrogen levels do not predict risk. In this elegantly designed study, researchers defined genomic regions of estrogen-mediated epigenetic change in murine hippocampus and then examined similar regions in blood-cell DNA in 93 pregnant women at risk for mood disorders because of their histories. Three authors have interests in a related patent application.
Two subgroups were drawn from this population — 32 women who were not depressed prepartum, of whom 11 developed postpartum depression, and 19 women who were depressed while pregnant, of whom 12 remained depressed postpartum. In both subgroups, women developing depression had larger methylation changes in these estrogen-sensitive genomic regions. Two biomarker genes in these areas predicted depression with an accuracy of 87% in antenatally euthymic women. After information on blood type counts (markers of inflammation) was incorporated, accuracy was 96% in all women with blood data. Pathway analysis suggested that these genes were involved in hippocampal synaptic plasticity.
Comment These findings suggest that women at risk for postpartum depression have enhanced prepartum sensitivity to estrogen-induced DNA methylation related to hippocampal plasticity. The sudden decreases in estrogen at delivery may impair hippocampal function by producing “atrophic” changes similar to those thought to underlie garden-variety major depression. Results from this small study must be replicated in larger samples. Still, it exemplifies the value of translational studies that use animal research for identifying key neurobiological areas to explore in humans.
Citation(s): Guintivano J et al. Antenatal prediction of postpartum depression with blood DNA methylation biomarkers. Mol Psychiatry 2013 May 21; [e-pub ahead of print].
(http://dx.doi.org/10.1038/mp.2013.6)
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JAMA 2013 Jul 3; 310:75
Is IVF Linked to Autism and Mental Retardation?
Compared with spontaneous conception, in vitro fertilization was associated with slightly higher risk for mental retardation
Although more than 5 million infants have been born worldwide as a result of in vitro fertilization (IVF), information about their neural development is limited. Swedish investigators used national health registers to evaluate risks for autistic disorder and mental retardation after spontaneous conception or IVF in a population-based, prospective cohort study of the >2.5 million offspring born in Sweden from 1982 through 2007. All offspring were followed through 2009; about 1.2% (almost 31,000) were conceived with IVF
Of 6959 children with autistic disorder, 103 (1.5%) were born following IVF. Of 15,830 with mental retardation, 180 (1.1%) were born after IVF. Risk for autistic disorder was not significantly increased after IVF (relative risk, 1.14; 95% confidence interval, 0.94–1.39), but risk for mental retardation was significantly increased (RR, 1.18; 95% CI, 1.01–1.36). In analysis limited to singletons, this excess risk was not statistically significant, suggesting an association with multiple births and preterm births. IVF with intracytoplasmic sperm injection (ICSI) was associated with higher risk for autistic disorder and mental retardation compared with IVF without ICSI; use of surgically extracted sperm for ICSI was also associated with excess risk for both disorders, although among singletons, this risk was no longer statistically significant
Comment: Couples undergoing in vitro fertilization should be reassured that absolute risks for autism spectrum disorders and mental retardation in their offspring are small indeed. The increased risk associated with intracytoplasmic sperm injection is of concern because it makes biological sense that sperm abnormalities might preclude spontaneous conception in couples with male-factor infertility; however, the low incidence of these neurologic disorders necessitates confirmation of the present findings. In addition, the extent to which the excess risk might arise from IVF, or from infertility itself, is not yet clear. An editorialist notes the importance of continually monitoring IVF infants and children for neurodevelopmental impairment to help understand and eliminate even modest risks
Citation(s): Sandin S et al. Autism and mental retardation among offspring born after in vitro fertilization. JAMA 2013 Jul 3; 310:75.
(http://dx.doi.org/10.1001/jama.2013.7222)
Cedars MI. In vitro fertilization and risk of autistic disorder and mental retardation. JAMA 2013 Jul 3; 310:42.
(http://dx.doi.org/10.1001/jama.2013.7223)
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Neurology 2013 May 14; 80:1862
Can 4-aminopyridine Improve Visual Function in MS Patients
Preliminary data showing a benefit in some patients with multiple sclerosis should prompt further investigations of this medication.
The purpose of this study was to assess if 4-aminopyridine (4-AP), a potassium-channel blocker that improves nerve conduction along demyelinated axons, improves visual acuity or other measures of visual function in multiple sclerosis (MS) patients with optic neuropathy. (An extended-release formulation is FDA-approved to improve walking in MS.) Enrolled patients had retinal nerve fiber layer thickness (RNFL) of ≤80 µm in one or both eyes or had a >10-µm difference between their eyes. They underwent baseline high-contrast and low-contrast (2.5% and 1.25%) visual acuity testing, optical coherence tomography, and visual evoked potentials (measuring P100 latency). Twenty two patients were randomized to compounded 4-AP (titrated over 5 weeks to a final dose of 10 mg three times daily) or placebo. Participants crossed over to the opposite treatment for weeks 6 to 10. Visual-function testing was performed at weeks 5 and 10.
Only 14 participants were included in the final analysis (2 withdrew, and 6 were excluded for relapse or nonadherence). The primary outcome (≥5-letter improvement on the 2.5% low-contrast chart) did not differ significantly between treatments. When all 28 eyes were assessed, the P100 latency improved by –1.20 milliseconds on 4-AP and increased by 1.57 milliseconds on placebo, a significant difference; the differences were more pronounced in eyes with RNFL thickness of 60 to 70 µm (–1.88 vs. +2.57 msec).
Comment Standard multiple sclerosis therapies reduce the risk for new disease activity, but interventions that improve quality of life through reduction of symptoms are needed. Treatment with 4-aminopyridine appears to improve some physiologic measures of vision. Whether the results were clinically meaningful is unclear, and the lack of an intent-to-treat analysis may bias the results. Still, larger studies of 4-AP's utility in MS are warranted
Citation(s): Horton L et al. Effect of 4-aminopyridine on vision in multiple sclerosis patients with optic neuropathy. Neurology 2013 May 14; 80:1862.
(http://dx.doi.org/10.1212/WNL.0b013e3182929fd5)
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