• Coconut Oil Touted as Alzheimer's Remedy
• Obesity Worsens the Flu in Mice and Men
• What's the Best Approach for Managing Neck Pain?
• Obstructive Sleep Apnea and Cardiovascular Mortality
• Vitamin D and UVB Radiation: How Much Is Necessary?
• PPIs Associated with Increased Risk for C. difficile-Associated Diarrhea
• When Should Bone-Density Tests Be Repeated?
• Smoking Increases the Risk for Acute Pancreatitis
• Smoking Is Associated with Increased Risk for Nonmelanoma Skin Cancer
• Can Carotid Ultrasound Screening Motivate Smokers to Quit?
• Prostate Cancer Screening: Still No Mortality Benefit
• ACP Issues Guidelines for Oral Treatment of Type 2 Diabetes
• Is Maggot Therapy Beneficial for Venous Ulcers?
• Study Shows that FDA Drug Warnings are Often Ineffective
• Improvement in Visual Function with Stem-Cell Therapy in Progressive MS
• Neuromyelitis Optica Treatment with Targeted Molecular Therapy
• A Common Y-Chromosome Variant May Explain Increased CVD Risk in Men
• Bread, Poultry Account for Large Part of America's Sodium Consumption
• Do Vasomotor Symptoms Influence Mood — Or Vice Versa?
• How Well Are We Treating Depression?
MM: This is a video news article that lasts about 5 minutes but seems quite well done. It brings out some interesting misinformation regarding coconut oil.
Coconut Oil Touted as Alzheimer's Remedy
Researchers say the ketones found in coconut oil have slowed the progression of Alzheimer's disease in some people and may actually prevent it.
YouTube Video from CBN News:
http://www.cbn.com/media/player/index.aspx?s=/mp4/LJO190v1_WS
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MM: There are many benefits to keeping a leaner physique other that vanity that seem to be coming to the fore. Immune system stability may be one of the most important. We know about cardiovascular risk, sleep apnea and a host of others. The challenge is not just losing weight that we are saddled with but the infinitely more difficult task of keeping it off. Please contact the satff at Mark Drugs for more information on how to develop some of the very successful techniques that we have available to help.
J Infect Dis 2012 Jan 15; 205:244
Obesity Worsens the Flu in Mice and Men
Further, in obese mice, preventive measures often fail.
Obesity often complicates medical care, but seldom has it proven as clear-cut a health risk as during the 2009 H1N1 influenza pandemic, when it was one of the most significant identified risk factors for complications and death. Two animal studies now confirm this observation.
In one study, both lean and obese mice received three doses of influenza vaccine and were then challenged with H1N1 influenza virus. Almost 90% of the lean mice survived, but all the obese mice died within 2 weeks, with lung pathology characteristic of severe influenza. Vaccination induced significantly lower antibody titers in obese mice than in lean mice, and the serum of the obese mice had significantly less neutralizing activity against the virus.
In another study, obese mice had mortality rates of 80% to 100% after inoculation with H1N1 or another type of influenza virus, whereas lean control mice had a 20% mortality rate. Pulmonary viral titers were similar in lean and obese mice, but in the obese mice, lavage fluid had significantly more inflammatory cells of all types, and on pathology, even obese survivors had a striking reduction in repair of denuded bronchiolar epithelium. Prophylactic oseltamivir, administered before viral challenge at a dose analogous to human dosing, attenuated mortality somewhat among the obese animals, but it took a dose five times higher to protect them all from flu challenge.
Comment: These studies provide clear evidence that the patterns observed in 2009 were no coincidence. As an editorialist observes, the biology is still being unraveled, but the failure of both vaccination and chemoprophylaxis in obese mice suggests that new strategies for both may be needed for obese humans.
— Abigail Zuger, MD Published in Journal Watch General Medicine February 7, 2012
Citation(s):Kim Y-H et al. Diet-induced obesity dramatically reduces the efficacy of a 2009 pandemic H1N1 vaccine in a mouse model. J Infect Dis 2012 Jan 15; 205:244.
(http://dx.doi.org/10.1093/infdis/jir731)
http://www.ncbi.nlm.nih.gov/pubmed/22147801?dopt=Abstract
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MM: In this study a literal hands on approach seems to be best. The value of human touch may be the greatest and most effective soothing tool we have. From a mother’s caress to a massage therapist’s skilled approach, it may not be the actual technique that is used but rather simple human contact that shows the greatest benefit. Mark Drugs has an outstanding Massage Therapist in-house at our Roselle Location. Please visit our website: www.MarkDrugs.com for more information or to schedule an appointment with Bodycare by Lisa.
Ann Intern Med 2012 Jan 3; 156:1.
What's the Best Approach for Managing Neck Pain?
Spinal manipulation led to greater pain reduction than medication but was comparable to home exercise.
Little research is available to guide treatment decisions for patients with neck pain. In this trial, researchers randomized 272 patients with neck pain of 2 to 12 weeks' duration and a pain score 
3 on a 10-point scale to receive one of three interventions: spinal manipulation (including both high-velocity joint thrust manipulation and low-velocity joint oscillation) performed by chiropractors, medication (nonsteroidal anti-inflammatory agents, acetaminophen, muscle relaxants, or narcotics) prescribed by physicians, or home exercise after instruction by physical therapists.
At baseline, the mean pain score was about 5 in all groups. At the end of the 12-week intervention, the mean reduction in pain score for the spinal manipulation group (3.8 points) was similar to the reduction for the home exercise group (3.3 points) — but significantly greater than that for the medication group (2.8 points).
Comment: In this study of acute and subacute neck pain, spinal manipulation and home exercise each proved marginally more efficacious than medication alone. In practice, a combination of these interventions, chosen in conjunction with the patient, could prove to be the ideal approach.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine February 9, 2012
Citation(s):Bronfort G et al. Spinal manipulation, medication, or home exercise with advice for acute and subacute neck pain: A randomized trial. Ann Intern Med 2012 Jan 3; 156:1. (http://www.annals.org/content/156/1_Part_1/1.full)
http://www.ncbi.nlm.nih.gov/pubmed/22213489?dopt=Abstract
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Ann Intern Med 2012 Jan 17; 156:115
Obstructive Sleep Apnea and Cardiovascular Mortality
Untreated OSA is associated with excess risk for cardiovascular death.
Prevalence of obstructive sleep apnea (OSA) has risen as a consequence of the obesity epidemic; OSA now affects 2% to 3% of middle-aged women and even larger numbers of men. The benefits of continuous positive airway pressure (CPAP) treatment have been well established for men with OSA (JW Gen Med Apr 22 2005), but less so among women.
In a prospective cohort study of 1116 women who were referred to two Spanish sleep centers, investigators showed that untreated OSA was associated with significantly elevated rates of cardiovascular (CV) mortality during a median follow-up of 72 months. In models adjusted for age, body-mass index, hypertension, diabetes mellitus, and previous CV events, women with untreated severe OSA were more than three times as likely to die of CV disease as women without OSA. In contrast, those with severe OSA who received CPAP treatment were no more likely than women without OSA to die of CV disease. Adherence to CPAP was independently associated with lower mortality risk.
Comment: Study participants who adhered to continuous positive airway pressure likely differed in other aspects of cardiovascular health compared with those who did not adhere. In addition, bias could have been introduced as a result of the participants' selective referral for sleep studies. The authors do not present models adjusted for a number of variables that affect CV mortality (e.g., current smoking, aspirin use). Given other evidence (JW Gen Med Oct 22 2009), both aggressive weight loss and CPAP treatment should be recommended for women and men with obstructive sleep apnea.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health February 9, 2012
Citation(s):Campos-Rodriguez F et al. Cardiovascular mortality in women with obstructive sleep apnea with or without continuous positive airway pressure treatment: A cohort study. Ann Intern Med 2012 Jan 17; 156:115.
http://www.ncbi.nlm.nih.gov/pubmed/22250142?dopt=Abstract
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Br J Dermatol 2011 Oct 20
Vitamin D and UVB Radiation: How Much Is Necessary?
For individuals unable to benefit from supplements, ultraviolet B exposure every 2 weeks may be an alternative.
Adequate vitamin D levels are necessary for bone health and might prevent a variety of other diseases. Many individuals are able to maintain adequate circulating concentrations of this important molecule during the summer, when ambient ultraviolet B (UVB) from sunlight is greatest. However, during winter months, when terrestrial UVB is at its nadir, levels can drop precipitously, particularly in regions far from the equator. For most, vitamin D deficiency can be addressed by the administration of supplements. However, physician-monitored UVB treatments have been advocated as an alternative therapeutic approach (see JW Dermatol May 7 2010).
Investigators in Denmark assessed how much artificial UVB is necessary to maintain summertime vitamin D concentrations. Every 1, 2, or 4 weeks during a 16-week period between October and February, 55 subjects received one standard erythemal dose (equivalent to 10 minutes of summer noonday sun exposure) to about 88% of total body area from a broadband UVB light source; a control group received no UVB.
UVB administered every 2 weeks was sufficient to maintain summertime vitamin D levels. Smaller changes were observed in those with higher concentrations at baseline and in older subjects, and greater changes were seen in those with higher body mass index and total body surface area.
Comment: For individuals resistant to or unable to take supplements, ultraviolet B exposure every 2 weeks may be an alternative method for maintaining summertime levels of vitamin D in winter. Narrowband UVB might be a better choice than the broadband UVB used in this study, because it may have fewer long-term adverse effects. It is important to emphasize that tanning beds do not emit the appropriate wavelengths and have been linked to melanoma and nonmelanoma skin cancers. Increasing UV exposure is not necessarily healthier; higher baseline vitamin D levels correlated with smaller increases in vitamin D concentrations.
— Craig A. Elmets, MD Published in Journal Watch Dermatology January 13, 2012
Citation(s): Bogh MKB et al. A small suberythemal UVB dose every second week is sufficient to maintain summer vitamin D levels: A randomized controlled trial. Br J Dermatol 2011 Oct 20; [e-pub ahead of print]. (http://dx.doi.org/10.1111/j.1365-2133.2011.10697.x).
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PPIs Associated with Increased Risk for C. difficile-Associated Diarrhea
Patients who use proton-pump inhibitors may face increased risk for developing Clostridium difficile-associated diarrhea, the FDA warned on Wednesday. The agency is also reviewing the same risk for patients on histamine H2 receptor blockers.
The warning follows an FDA review of 28 observational studies. In 23 of the studies, patients who were exposed to PPIs had a higher risk for C. difficile infection or disease, compared with those who were not.
Clinicians are advised to give patients the lowest dose of PPI therapy for the shortest duration possible. Patients should be counseled to seek treatment right away if they experience abdominal pain, diarrhea that does not improve, and fever while using PPIs.
A complete list of affected prescription and OTC products is available in the FDA drug safety communication.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts
/ucm290838.htm
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N Engl J Med 2012 Jan 19; 366:225
When Should Bone-Density Tests Be Repeated?
A 15-year interval is reasonable in older women if baseline BMD is normal or only mildly osteopenic.
For many conditions, screening is conducted at arbitrary intervals — and bone-mineral density (BMD) testing is no exception. In a prospective study, researchers sought to determine reasonable intervals for BMD screening. They identified 5000 women (age, 
67) without osteoporosis at baseline BMD testing and followed them for up to 15 years. Baseline BMD levels were classified as normal (femoral neck or total-hip T scores, –1.00 or higher) or as indicative of mild osteopenia (T-score range, –1.01 to –1.49), moderate osteopenia (range, –1.50 to –1.99), or advanced osteopenia (range, –2.00 to –2.49).
The interval during which at least 10% of women developed osteoporosis (T score –2.5 or lower) was longer than 15 years for those whose baseline BMDs were normal or only mildly osteopenic and was 5 years for those with baseline moderate osteopenia and 1 year for those with baseline advanced osteopenia. These estimates changed very little after adjustment for age, body-mass index, and several other relevant variables. The estimated time for 2% of women to experience hip or vertebral fractures was at least 15 years for those with normal BMD or mild osteopenia and 5 years for those with moderate-to-advanced osteopenia.
Comment: This analysis challenges the practice of repeating bone-mineral density tests routinely every few years. Very few older women with normal BMD developed osteoporosis within 15 years after a normal test result. For women whose baseline BMDs fell within the lower portion of the osteopenic range, screening intervals required to avoid missing the development of osteoporosis were progressively shorter. Future updates of screening guidelines should incorporate these findings. However, keep in mind that factors other than BMD affect fracture risk, and that this study did not address who might benefit from treatment.
— Allan S. Brett, MD Published in Journal Watch General Medicine January 24, 2012
Citation(s):Gourlay ML et al. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med 2012 Jan 19; 366:225.
(http://dx.doi.org/10.1056/NEJMoa1107142)
http://www.ncbi.nlm.nih.gov/pubmed/22256806?dopt=Abstract
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Gut 2012 Feb; 61:262
Smoking Increases the Risk for Acute Pancreatitis
Risk for nongallstone-related acute pancreatitis is higher for smokers and increases further with alcohol use.
Acute pancreatitis, which is increasing in the U.S. and many other countries, is usually caused by alcohol or gallstones. Alcohol can cause an episode of acute pancreatitis but usually leads to chronic pancreatitis, typically after multiple acute episodes. Recent data from several countries have shown that smoking is an equally potent cause of chronic pancreatitis (JW Gastroenterol Aug 14 2009) and that the combination of alcohol and smoking is particularly toxic.
Now, investigators have explored the association between cigarette smoking and acute pancreatitis in a prospective, population-based cohort study involving 84,667 individuals in Sweden. Information on smoking history, including duration and frequency (calculated into pack-years) was collected via questionnaire from participants, and acute pancreatitis was identified using a comprehensive, national inpatient register.
During a median follow-up of 12 years, 541 patients had a first episode of acute pancreatitis, with 44% attributed to gallstones and 56% to other causes. Smoking was an independent risk factor for nongallstone-related pancreatitis. The risk was highest among current smokers with 
20 pack-years of smoking compared with never-smokers (relative risk, 2.29; 95% confidence interval, 1.63–3.22). Duration of smoking was a better predictor of increased risk than smoking intensity. Smoking had no effect on the risk for gallstone-related pancreatitis. Alcohol use had an additive effect on the risk for nongallstone-related acute pancreatitis among smokers. Among those who consumed 
400 g monthly (approximately 1 drink daily), current smokers with 
20 pack-years of smoking had a fourfold higher risk than never-smokers. Elevated risk for nongallstone-related pancreatitis in former smokers persisted 20 years after smoking cessation in those who drank 
400 g monthly but only 10 years in those who drank less.
Comment: This study provides the first detailed analysis of the role of smoking in acute pancreatitis. Smoking increases the risk for nongallstone-related pancreatitis but not for gallstone-related pancreatitis. As demonstrated in previous studies of chronic pancreatitis, the increased risks associated with smoking and alcohol are additive. Equal efforts should be expended to help our patients with both acute and chronic pancreatitis to stop smoking as well as drinking.
— Chris E. Forsmark, MD Published in Journal Watch Gastroenterology February 10, 2012
Citation(s):Sadr-Azodi O et al. Cigarette smoking, smoking cessation and acute pancreatitis: A prospective population-based study. Gut 2012 Feb; 61:262.
http://www.ncbi.nlm.nih.gov/pubmed/21836026?dopt=Abstract
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Cancer Causes Control 2011 Nov 19;
Smoking Is Associated with Increased Risk for Nonmelanoma Skin Cancer
Smoking is associated with risk for squamous cell carcinoma in both men and women, but especially among women.
Previous studies examining the association between smoking and nonmelanoma skin cancer (NMSC) have produced mixed results. Investigators conducted a case-control study comparing patients who had basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with a control group of individuals attending a skin cancer detection screening. The analysis controlled for variations in skin, eye, and hair color; alcohol consumption; history of blistering sunburn; occupational sun exposure; and tanning ability. The control population was examined for skin cancer and those with skin cancer were eliminated.
A history of ever smoking was associated with SCC but not with BCC. A dose-dependent curve associated greater risk for SCC with more cigarettes smoked per day and with higher number of pack-years of smoking. Analyzed by sex, the data showed a greater SCC risk in women than in men (relative risk, 3.00 for women, 1.97 for men). Whether persons who quit smoking lowered their risk for NMSC was not ascertained.
Comment: Limitations to this study include recall bias, but this is a powerful piece of work in a clinical setting. One of the study's major strengths is that investigators examined the control population, thereby eliminating a confounding factor should controls have otherwise undetected nonmelanoma skin cancer. Bottom line: Smoking is associated with risk for squamous cell carcinoma in both men and women, but especially among women. Thus, we have yet another reason to encourage smoking cessation.
— Jeffrey P. Callen, MD Published in Journal Watch Dermatology February 10, 2012
Citation(s):Rollison DE et al. Case–control study of smoking and non-melanoma skin cancer. Cancer Causes Control 2011 Nov 19; [e-pub ahead of print].
(http://dx.doi.org/10.1007/s10552-011-9872-y)
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Arch Intern Med 2012 Jan 23
Can Carotid Ultrasound Screening Motivate Smokers to Quit?
In a randomized trial, screening was ineffective.
One possible role of cardiovascular (CV) screening tests is to motivate people with abnormal results to make lifestyle changes. To see whether this strategy works, Swiss researchers randomized 536 heavy smokers (age range, 40–70) to receive carotid ultrasound screening or no screening. Those with carotid plaques (58% of screened patients) received photographs of the plaques along with detailed explanations. Patients in both groups received intensive smoking cessation counseling.
Smoking abstinence rates at 1 year (confirmed by measurement of exhaled carbon monoxide and serum cotinine levels) were about 20% in both groups. Moreover, 12-month changes in CV risk factors such as lipid levels and blood pressure were similar in the two groups. Within the screening group, smoking cessation outcomes in patients with plaques did not differ significantly from outcomes in those without plaques.
Comment: Carotid ultrasound screening failed to motivate patients to quit smoking, over and above smoking cessation counseling. These findings — added to the evidence that patients with asymptomatic carotid stenosis who receive contemporary preventive medical therapies are unlikely to benefit from carotid revascularization (JW Gen Med Sep 15 2011) — suggest that carotid screening is not appropriate. An editorialist argues that, to motivate patients, improving patient–physician communication and relationships is a more-promising approach than ordering tests.
— Allan S. Brett, MD Published in Journal Watch General Medicine February 7, 2012
Citation(s):Rodondi N et al. Impact of carotid plaque screening on smoking cessation and other cardiovascular risk factors: A randomized controlled trial. Arch Intern Med 2012 Jan 23; [e-pub ahead of print]. (http://dx.doi.org./10.1001/archinternmed.2011.1326)
O'Malley PG. On motivating patients: A picture, even if worth a thousand words, is not enough. Arch Intern Med 2012 Jan 23; [e-pub ahead of print].
(http://dx.doi.org./10.1001/archinternmed.2011.1948)
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J Natl Cancer Inst 2012 Jan 18; 104:125
Prostate Cancer Screening: Still No Mortality Benefit
Results after 13 years of follow-up in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial confirmed earlier findings.
Prior results from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial showed no mortality benefit of prostate cancer screening after 7 to 10 years of follow-up (N Engl J Med 2009; 360:1310). The trial involved 76,685 men (age range, 55–74) who were randomized to screening or usual care (controls). Participants in the screening arm were offered annual prostate-specific antigen (PSA) tests for 6 years and digital rectal exams (DREs) for 4 years. A positive test was defined as a PSA value >4 ng/mL or a suspicious DRE.
Now, results after 13 years of follow-up are as follows:
- Prostate cancer was diagnosed in 4250 (11.1%) of 38,340 participants in the screening arm and 3815 (9.9%) of 38,345 controls.
- High-grade prostate cancer (Gleason score 8–10) was diagnosed in a similar number of patients in the screening and control arms (401 and 454, respectively).
- A similar number of deaths occurred in the screening and control groups (158 and 145).
- Cumulative mortality rates from prostate cancer were similar in the screening and control arms (3.7 and 3.4 per 10,000 person-years).
- The difference in number of deaths from causes other than the prostate, lung, or colorectal cancers was of borderline significance in the screening and control arms (5783 vs. 5982; relative risk, 0.96; 95% confidence interval, 0.93–1.00).
- RRs for prostate cancer–specific mortality were similar in both arms among subgroups defined by age, pretrial PSA testing, or comorbidities.
Comment: This follow-up of the original PLCO Cancer Screening Trial continues to demonstrate that no mortality benefit is achieved from prostate cancer screening. These results also support both a recently published meta-analysis of all randomized screening trials for prostate cancer, which failed to demonstrate a significant effect of screening on prostate cancer specific or overall mortality (JW Oncol Hematol Sep 9 2008), as well as a recent U.S. Preventive Services Task Force recommendation against prostate cancer screening (JW Gen Med Aug 26 2008). Although subsets of individuals (e.g., blacks and those with family histories of prostate cancer) likely should be considered appropriate candidates for screening, the era of routine PSA-based screening might finally and appropriately be coming to an end.
— Robert Dreicer, MD, MS, FACP Published in Journal Watch Oncology and Hematology
February 7, 2012
Citation(s):Andriole GL et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality results after 13 years of follow-up. J Natl Cancer Inst 2012 Jan 18; 104:125.
http://www.ncbi.nlm.nih.gov/pubmed/22228146?dopt=Abstract
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ACP Issues Guidelines for Oral Treatment of Type 2 Diabetes
The American College of Physicians has updated its evidence-based guidelines for oral treatment of type 2 diabetes. The recommendations, - a 19 page report - published in the Annals of Internal Medicine, include the following:
- When diet, exercise, and weight loss fail to improve hyperglycemia in patients with diabetes, clinicians should add oral drug therapy.
- Metformin is the drug of choice for initial monotherapy unless contraindicated.
- If metformin and lifestyle modifications fail to control hyperglycemia, a second oral agent should be added. No combination therapy is recommended over another, but some studies indicate that metformin plus another agent generally has better efficacy than other monotherapies or combination therapies.
http://www.annals.org/content/156/3/218.full.pdf+html
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Arch Dermatol 2011 Dec 19
Is Maggot Therapy Beneficial for Venous Ulcers?
Maggot therapy produced more-rapid debridement of venous ulcers with necrosis or slough, but with no apparent benefit for healing.
Since antiquity, many observers have noted that wounds infested with maggots were clean and healed well, but the first known intentional therapeutic use of these fly larvae was by a Civil War surgeon, who felt that such treatment saved many lives. This therapy became popular only after William Baer, an American orthopedic surgeon, having noted the benefits of maggot infestation in wounded World War I soldiers, employed it in patients with osteomyelitis in 1928. With the advent of antibiotics, however, larval therapy nearly disappeared. It has been revived lately because of its apparent value in wound debridement, disinfection, and stimulation of healing, but only recently has its efficacy been investigated in randomized trials.
This multicenter French study involved 105 patients whose nonhealing, lower-limb venous ulcers had substantial slough in the wound. The patients were randomized to maggot debridement twice weekly or to surgical debridement thrice weekly. They were blindfolded during treatment to prevent them from knowing which treatment they received. The major outcome was the percentage of slough in the ulcers, and secondary outcomes included wound healing, pain, bacterial cultures, and duration of wound care. There were no significant differences in any of these outcomes at days 15 and 30, but slough was significantly reduced at day 8 in the maggot group.
Comment: A previous randomized trial of maggot therapy for venous ulcers with necrosis or slough in the wounds also showed more-rapid debridement, but again without a difference in healing time or bacterial load. These new findings demonstrate no significant benefit for larval therapy and challenge the belief that slough removal in venous ulcers promotes wound healing and reduces the bacterial load ("bioburden"). It apparently does neither.
— Jan V. Hirschmann, MD Published in Journal Watch Dermatology February 10, 2012
Citation(s):Opletalová K et al. Maggot therapy for wound debridement: A randomized multicenter trial. Arch Dermatol 2011 Dec 19; [e-pub ahead of print].
(http://dx.doi.org/10.1001/archdermatol.2011.1895)
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Study Shows that FDA Drug Warnings are Often Ineffective
A 20-year review finds that the FDA's communications to physicians and patients about the newly discovered dangers of approved medications often miss the mark. Researchers examined cases from the 1990 to 2010 time period in which the FDA added warnings to labels, issued public health advisories, or wrote letters to physicians and other prescribers to inform them of unanticipated drug risks. However, these actions often did not achieve their aim or resulted in unintended consequences, said the review published online in January in the journal Medical Care.
http://www.ama-assn.org/amednews/2012/01/30/prsb0130.htm
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Lancet Neurol 2012 Feb; 11:150
Improvement in Visual Function with Stem-Cell Therapy in Progressive MS
A small, open-label, proof-of-concept study suggests clinical and electrophysiological benefits.
Multipotent mesenchymal stromal cells have potential for use in treating multiple sclerosis (MS) because they can differentiate into mesodermal cell derivatives. The cells are thought to take residence within the central nervous system (CNS) and to provide neuroprotective and reparative benefits. Researchers conducted this phase IIa, open-label, proof-of-concept study of autologous mesenchymal stem cell therapy in 10 patients with secondary-progressive MS and involvement of the visual pathways. The researchers obtained mesenchymal stromal cells directly from the patients through bone marrow aspiration, expanded them in laboratory cultures, and infused them as a single dose. Patients were not permitted any other disease-modifying treatments during the study. The primary objective was to assess feasibility and safety. Secondary objectives included numerous clinical, electrophysiological, and structural outcomes, such as visual acuity, contrast sensitivity, color vision, visual-evoked potentials (VEPs), and findings on perimetry, optic nerve magnetic resonance imaging, and optical coherence tomography.
Comparing the monthly rate of change during at least 6 months after treatment with the rate of change during at least 12 months before treatment, investigators observed improvements in visual acuity (a difference of –0.02 logMAR), 5% contrast sensitivity (–0.04 logMAR difference), VEP latency (–1.33 millisecond difference), VEP amplitude (0.259 μV difference), and optic nerve area (0.126 mm2 difference). The infusions were well tolerated; adverse events included a spontaneously resolving rash, a self-limiting upper-respiratory tract infection, and a treated urinary tract infection, in one patient each.
Comment: In this commendable proof-of-concept study, non-immunoablative autologous mesenchymal stem cell transplants showed promise. The treatment appears reasonably straightforward and well tolerated. In contrast to other autologous stem cell transplants (JW Neurol Mar 21 2011), the present technique requires no immunoablation or immunosuppression. However, additional studies are needed before patients embark on this treatment outside of a proper clinical study. Clinicians need to be aware that opportunistic clinics around the world offer bone marrow infusions at steep prices, with cash payment required up front.
Inherent study limitations include its being single-center, open-label, nonblinded, and small. Pathologic confirmation that the stem cells ultimately resided within the CNS was not possible. The large number of endpoints assessed in so few patients may have resulted in a type I error. Visual benefits of logMAR –0.02 (visual acuity) and –0.04 (5% contrast sensitivity) translate to improvements of only 1 or 2 letters, respectively. The authors acknowledge most of these limitations, and interested patients should be informed of these details.
— Robert T. Naismith, MD Published in Journal Watch Neurology February 7, 2012
Citation(s):Connick P et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: An open-label phase 2a proof-of-concept study. Lancet Neurol 2012 Feb; 11:150.
http://www.ncbi.nlm.nih.gov/pubmed/22236384?dopt=Abstract
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Ann Neurol 2012 Jan 23
Neuromyelitis Optica Treatment with Targeted Molecular Therapy
A proof-of-concept study establishes the effectiveness of therapy with a monoclonal antibody specific to aquaporin-4 in animal models.
Neuromyelitis optica (NMO) is a distinct autoimmune disease, typically characterized by aquaporin-4 (AQP4) antibodies, which are associated with complement-mediated attack against astrocytes. The disease may result in devastating visual loss and spinal cord injury. It is currently treated with generalized immunosuppression.
In the present study, investigators developed a modified antibody against AQP4, which they engineered to not fix complement and to compete with the pathogenic AQP4 antibodies (which do fix complement). They engineered the inactive antibody by introducing point mutations designed to make the antibody deficient in initiating complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. (The institutions of two of the study authors have applied for a patent covering the investigational antibody.)
The investigators demonstrated that the therapeutic antibody prevented cell killing by NMO immunoglobulin G (IgG) when incubated with complement in a live-cell assay. They also cultured ex vivo mouse spinal cord slices and incubated these with complement and purified IgG obtained from patients with NMO. When treated with the mutant antibody, the spinal slices had reduced NMO lesion severity, with less loss of AQP4, glial fibrillary protein, and myelin. Similarly, introduction of the mutant antibody into an in vivo mouse model of NMO reduced myelin loss and lesion severity scores.
Comment: Although many diseases are associated with autoantibodies, very few involve a single, putatively directly pathogenic antibody. This remarkable report provides proof-of-concept evidence that some diseases may be directly modified by targeting nothing more than the aberrant antibody. In other words, broad-spectrum immunosuppression, whether against T cells or B cells, may not be necessary if the initiating step of the disease can be circumvented by flooding the system with nonpathogenic antibody.
This novel antibody has not been tested in humans and will need proper clinical study. Whether all aspects of NMO are caused by the AQP4 antibody alone is also subject to debate. For example, some individuals with NMO are negative for this antibody. Nonetheless, with our increasing understanding about the molecular basis of many diseases, specific target-based therapies have great future potential.
— Robert T. Naismith, MD Published in Journal Watch Neurology February 7, 2012
Citation(s): Tradtrantip L et al. Anti–aquaporin-4 monoclonal antibody blocker therapy for neuromyelitis optica. Ann Neurol 2012 Jan 23; [e-pub ahead of print].
(http://dx.doi.org/10.1002/ana.22657)
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A Common Y-Chromosome Variant May Explain Increased CVD Risk in Men
Common European variants of the Y chromosome seem linked to inflammatory responses — and thus to cardiovascular risk — according to research published in the Lancet.
Investigators examined Y chromosomes in two groups of subjects. In the first group, chromosomal markers were compared between men with confirmed coronary disease and healthy controls. They found a common variant called haplogroup I to be significantly more common in men with coronary disease.
The second group included men at high risk for coronary disease. Those who suffered a coronary event were compared with those who did not. Again, haplogroup I was significantly more common among those suffering an event. In addition, traditional coronary risk factors did not differ between cases and controls.
The authors conclude that the presence of haplogroup I increased coronary risk by 50%.
An analysis of macrophage RNA transcripts showed differences related to inflammatory response, which seemed exaggerated in those with haplogroup I.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61453-0/fulltext
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Bread, Poultry Account for Large Part of America's Sodium Consumption
More than 40% of sodium consumed in the U.S. comes from 10 food categories, with bread and poultry among the top 5, according to an MMWR report.
CDC researchers examined data on some 7200 U.S. individuals aged 2 years and older who completed 24-hour dietary recalls as part of the 2007–2008 National Health and Nutrition Examination Survey. Overall, the mean daily sodium consumption (excluding table salt) was 3266 mg, well above recommendations to keep intake below 2300 mg.
The top 10 food categories contributing to sodium consumption were, in descending order: bread and rolls, cold cuts, pizza, poultry, soups, sandwiches, cheese, pasta mixed dishes, meat mixed dishes, and savory snacks. Two thirds of sodium came from foods purchased at stores; the rest came from restaurants, cafeterias, and other sources.
MMWR's editors suggest that clinicians advise most patients to read labels and choose lower-sodium foods.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm61e0207a1.htm
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Menopause 2011 Dec; 18:1270
Do Vasomotor Symptoms Influence Mood — Or Vice Versa?
Vasomotor symptoms were related to next-day negative affect.
Vasomotor symptoms are experienced by more than three quarters of women during the menopausal transition. The Daily Hormone Study (a subset of the Study of Women's Health Across the Nation) was conducted to evaluate presence of vasomotor symptoms (VMS) and their relation to mood. A total of 625 women (age range at entry, 42–52) completed this 3-year study. Participants maintained daily diaries of mood and physical symptoms during the previous 24-hour period for one menstrual cycle or 50 days, whichever was shorter.
In all, 52% of participants reported ever experiencing VMS during the study period; of these, only 6% reported daily VMS. Occurrence of VMS was significantly associated with negative mood within each 24-hour period, but the relation was unidirectional: VMS were associated with next-day negative affect, but negative mood was not associated with next-day VMS. Difficulty sleeping because of night sweats also contributed significantly to next-day negative mood. No relation was found between positive affect and likelihood of VMS or vice versa.
Comment: These results are consistent with previous longer-duration data indicating that vasomotor symptoms have negative effects on mood. As an editorialist notes, the findings also call attention to the role of hormone therapy for effectively treating bothersome VMS and, by extension, their negative effects on mood.
— Anne A. Moore, WHNP/ANP-BC, FAANP Published in Journal Watch Women's Health January 19, 2012
Citation(s):Gibson CJ et al. Negative affect and vasomotor symptoms in the Study of Women's Health Across the Nation Daily Hormone Study. Menopause 2011 Dec; 18:1270
http://www.ncbi.nlm.nih.gov/pubmed/21900850?dopt=Abstract
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Arch Gen Psychiatry 2011 Dec; 68:1218
How Well Are We Treating Depression?
Despite a broader range of antidepressants and psychotherapies and more generic medications, this analysis of Medicaid data shows that the treatment of depression has not become cheaper and better.
To determine trends in depression treatment, these researchers reviewed Florida Medicaid records of 56,805 adults diagnosed with depression in 1996–2006.
After adjustments for inflation and clinical factors such as comorbidity, the cost of mental health care per patient increased by 29% from 1996 to 2006, even though spending for inpatient mental health treatment decreased by 42% (because the hospitalization rate decreased from 9.1% to 5.1%) and spending on outpatient visits increased only 21%. Spending on antidepressants increased by 22%, while the cost of antianxiety drugs decreased, probably because almost all of these medications became generic. Fewer patients received psychotherapy (decrease from 57% to 38%). Prescriptions for antipsychotic drugs increased substantially; the increase of their costs by 949% accounted for most of the increased cost of pharmacotherapy and therefore of mental health care overall.
In proxy measures of quality of acute treatment, more patients in 2006 than in 1996 received antidepressants (75% vs. 65%) and received minimally adequate pharmacotherapy (68% vs. 59%), and fewer received psychotherapy (27% vs. 43%; 10%–14% receiving 
4 sessions). Follow-up visits for pharmacotherapy and posthospitalization decreased.
Comment: Increased spending on depression treatments in this study (largely attributable to antipsychotic prescriptions, especially quetiapine and risperidone) did not result in better care. Although more patients got adequate doses of antidepressants, fewer were followed regularly or received evidence-based psychotherapy for depression. The increased use of antipsychotics, which was probably a function of both the approval of aripiprazole and quetiapine for refractory depression and vigorous industry marketing, is worth careful consideration: No evidence exists for the superiority of this augmentation strategy, and adverse effects can be substantial. Without following patients adequately, it seems impossible to know whether recent approaches to pharmacotherapy are effective, let alone cost-effective.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry January 13, 2012
Citation(s):Fullerton CA et al. Ten-year trends in quality of care and spending for depression: 1996 through 2005. Arch Gen Psychiatry 2011 Dec; 68:1218.
http://www.ncbi.nlm.nih.gov/pubmed/22147841?dopt=Abstract
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