• Flu Season Has Started Early in the U.S.
• Does Muscle Strength During Adolescence Predict Longevity?
• Adverse CV Events with Metformin vs. Sulfonylureas
• Rising Incidence of Stroke Among Young Adults
• Response to Some Hypertension Treatments May Vary by BMI
• Pathway for Light Effects on Mood and Cognition
• Incomplete Recovery of the Gut Microbiome After Antibiotic Therapy in Infants
• Longer Treatment Offers No Advantage in Male UTIs; Routine Pre-Op Urine Cultures Useless
• ACOG Recommends Over-the-Counter Access to Oral Contraceptives
• Coating on Aspirin Might Reduce Its Cardioprotective Effects
• Aspirin to Prevent Recurrent Venous Thromboembolism, Revisited
• Benzodiazepines Associated with Increased Pneumonia Risks
• Alcohol Impairs Fear Extinction in Mice
• Not Sleeping Costs Money
• SSRIs and Intracerebral Bleeds: A Small Risk
MM: Yes, the flu season appears to be starting early but there is overwhelming evidence that the best way to prevent flu and colds is enhancement of the immune system and good hygiene. Good hygiene such as frequent hand washing with soap and sneezing into an elbow rather than into your hand or just into the air at large helps to prevent the spread of these viruses. Iimmune system enhancement helps to diminish the effects if the virus is contracted.
I encourage raising Vitamin D blood levels as one of the most cost effective and seemingly effective means of protecting oneself. If you are getting your blood tested for vitamin D, the test to ask for is the 25-(OH)-D test (aka 25-hydroxy-D). An optimal blood level range appears to be 60-80 ng/ml. Most adults who live in the midwest can achieve this level by taking 5000-10,000IU daily of vitamin D3. Vitamin D3 absorption appears to be enhanced by presenting it in a mixture of probiotics that seem to stabilize the gut tissue. Please ask the staff at Mark Drugs for more information or call to purchase your Vitamin D3 with Probiotics.
Flu Season Has Started Early in the U.S.
Flu season has gotten off to an early start in the U.S., with outpatient visits for influenza-like illness reaching the baseline level during the week of November 18–24. This is the earliest that influenza has reached that threshold since 2003–2004, according to the CDC.
Five states — Alabama, Louisiana, Mississippi, Tennessee, and Texas — reported high influenza activity, and widespread activity has been seen elsewhere.
Patients have tested positive for influenza A (H3N2 and 2009 H1N1) and influenza B viruses. The A viruses match what was included in this year's vaccine. Roughly 71% of the influenza B viruses were B/Wisconsin/1/2010-like, which was also included in the vaccine. The other 29% belonged to the B/Victoria line of viruses, not included in the vaccine.
So far, the circulating viruses have shown susceptibility to oseltamivir and zanamivir.
http://www.cdc.gov/flu/weekly/summary.htm
http://hosted.ap.org/dynamic/stories/U/US_MED_FLU_
SEASON?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT
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MM: Exercise and strength is beneficial at all stages of life. Recent studies have demonstrated that the elderly benefit by fewer falls, fewer broken bones and better cognition with increased muscle strength. It appears that starting early to play and establish fitness and muscle strength has long lasting effects. I always took it for granted when my parents told us to go out and play that it was so they could get a little personal time and space. Little did I realize how smart they really were.
BMJ 2012 Nov 20; 345:e7279
Does Muscle Strength During Adolescence Predict Longevity?
Male teens with low muscle strength had excess risk for premature death.
In adults, low muscle strength is associated with higher rates of all-cause and cardiovascular death, but whether the same is true for adolescents is unknown. In this prospective cohort study, Swedish investigators analyzed national data from mandatory conscription examinations in >1.1 million male adolescents (age range, 16–19) to determine the association between muscle strength and premature death (i.e., before age 55).
During a median follow-up of 24 years, >26,000 participants died. Adolescents in the lowest decile of muscle strength had the highest mortality. In analysis adjusted for multiple variables, high muscle strength (as measured with knee extension and handgrip) was associated with 20% to 35% lower risk for premature death from all causes, cardiovascular disease, or suicide. Muscle strength was not associated with premature death from cancer.
Comment: This large observational study suggests that low muscle strength during adolescence is a risk factor for premature death. However, whether strengthening programs aimed at adolescents with low muscle strength can lower premature mortality is unclear. Nonetheless, the authors' recommendation that such teens be encouraged to exercise is reasonable.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine December 6, 2012
Citation(s): Ortega FB et al. Muscular strength in male adolescents and premature death: Cohort study of one million participants. BMJ 2012 Nov 20; 345:e7279.
(http://dx.doi.org/10.1136/bmj.e7279)
http://www.ncbi.nlm.nih.gov/pubmed/23169869?dopt=Abstract
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MM: This study demonstrates that the act of simply lowering fasting blood glucose is not sufficient to have a lasting beneficial impact on health and wellness. Metformin increases the body's sensitivity to insulin thereby requiring less insulin to be present in order to lower blood sugar. Sulfonylureas increase production of insulin from the pancreas leading to lower blood sugar levels but a higher continual insulin presence that actually has a net effect of increasing insulin resistance and decreasing insulin sensitivity. There are bad effects of increasing insulin such as a thickening of blood vessel walls that lead to decreased elasticity and narrower channels for blood to pass through. This makes the heart work harder and can contribute to decreased wound healing, sight problems and erectile dysfunction to name a few. The bottom line is that we need to lower our blood sugars through diet and exercise first and medications as an adjunct. One of the best dietary ways to do this is by decreasing our carb load and eating foods with a lower glycemic index rating. The dietitians at Mark Drugs can help guide people in this area.
Ann Intern Med 2012 Nov 6; 157:601
Adverse CV Events with Metformin vs. Sulfonylureas
In an observational study, cardiovascular risk was significantly lower among patients taking metformin.
Few data are available on the effect of sulfonylureas and metformin on adverse cardiovascular (CV) outcomes among patients with type 2 diabetes. Using a Veterans Health Administration database, researchers identified 254,000 patients (primarily white men) who began metformin or sulfonylurea monotherapy between 2001 and 2008. Patients were followed until another antidiabetic agent was prescribed or a primary outcome (death or hospitalization for myocardial infarction or stroke) was reached. Patients with serious medical conditions (e.g., heart failure, HIV infection) or creatinine levels 
1.5 mg/dL were excluded.
Unadjusted rates of the primary outcome were 18.2 per 1000 person-years among sulfonylurea recipients and 10.4 per 1000 person-years among metformin recipients. After adjusting for potential confounders, 2.2 more adverse CV events or deaths per 1000 person-years occurred with sulfonylurea than with metformin. Results did not differ by type of sulfonylurea (glyburide or glipizide).
Comment: In this retrospective study, use of sulfonylureas as initial monotherapy for patients with type 2 diabetes was associated with higher risk for adverse CV events than was metformin. Whether the difference arose from excess CV risk with sulfonylureas, lower risk with metformin, or both is unclear. In addition, adjustment for confounding factors narrowed the difference in adverse outcomes substantially, raising concern that additional unmeasured confounders influenced these findings. Nevertheless, the results are consistent with metformin's current status as the initial agent of choice for type 2 diabetes.
— Jamaluddin Moloo, MD, MPH Published in Journal Watch General Medicine December 6, 2012
Citation(s): Roumie CL et al. Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: A cohort study. Ann Intern Med 2012 Nov 6; 157:601.
(http://annals.org/article.aspx?articleid=1389845)
http://www.ncbi.nlm.nih.gov/pubmed/23128859?dopt=Abstract
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MM: This disturbing trend seems to parallel our growing obesity and diabetes epidemics. Although the authors credit some of this rise to better testing, there has to be smoke before we notice a fire is burning and the rising incidence of stroke in young people is certainly smoke that we cannot and should not ignore.
Neurology 2012 Oct 23; 79:1781
Rising Incidence of Stroke Among Young Adults
The stroke incidence among adults aged 20 to 54 increased substantially during a 12-year period in a population-based study.
Hypothesizing that stroke in younger adults may be on the rise, researchers aimed to describe recent age-related temporal trends of stroke incidence. They identified ischemic and hemorrhagic stroke cases retrospectively through inpatient and outpatient records within a well-defined population base in Ohio and Kentucky. The investigators compared the annual incidence rates of stroke among young adults during a 12-year period, using both inpatient records and outpatient sampling to identify strokes.
The proportion of all strokes that occurred in adults aged 20 through 54 increased from 13% in the 1993–1994 period to 19% in 2005. In this age group, the incidence rate of stroke among blacks increased from 83 per 100,000 in 1993–1994 to 128 per 100,000 in 2005. Among whites in this age group, the incidence rate increased from 26 to 48 per 100,000. The authors conclude that the number of ischemic strokes diagnosed among young adults may be increasing. However, because they found that magnetic resonance imaging use also increased during this time, they speculate that the trend may be explained in part by recent improvements in diagnostic imaging.
Comment: Despite an overall decline in stroke incidence rates, hospital admissions for ischemic stroke among young adults in the U.S. are thought to be on the rise. This study suggests that in addition to hospital admissions, the overall incidence of stroke in young adults may be increasing. The strengths of the study were its well-defined population base and its consistent methodology spanning more than a decade. These findings support recent literature describing stroke trends among young adults in other populations (JW Neurol Feb 7 2012). However, the cause of the apparent rising incidence of stroke in the young is still not clear. Further efforts are critical to determine why stroke risk may be increasing, so that age-appropriate stroke prevention strategies can be implemented.
— Christine Fox, MD, MAS Dr. Fox is a Vascular Neurology Fellow, University of California, San Francisco.
Published in Journal Watch Neurology October 30, 2012
Citation(s): Kissela BM et al. Age at stroke: Temporal trends in stroke incidence in a large, biracial population. Neurology 2012 Oct 23; 79:1781.
http://www.ncbi.nlm.nih.gov/pubmed/23054237?dopt=Abstract
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Response to Some Hypertension Treatments May Vary by BMI
Hypertension treatment with the calcium-channel blocker amlodipine is effective in people of all BMI subgroups, whereas thiazide-based treatment is not as effective in normal-weight people, according to an industry-funded Lancet study.
In the ACCOMPLISH trial, some 11,000 patients with hypertension received benazepril and were randomized to add either hydrochlorothiazide or amlodipine.
After roughly 3 years' treatment, all BMI subgroups in the amlodipine group had roughly the same rate (5%) of the primary outcome — a composite of cardiovascular death, stroke, and MI. In contrast, in the hydrochlorothiazide group, obese patients had a lower rate of the primary outcome than did overweight or normal-weight patients (5%, 7%, and 9%, respectively).
The authors conclude: "Diuretic-based regimens seem to be a reasonable choice in obese patients in whom excess volume provides a rationale for this type of treatment ... An alternative therapeutic regimen that includes a calcium-channel blocker such as amlodipine, which works equally well across all BMI categories, provides an advantage with respect to clinical outcomes in patients who are not obese."
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61343-9/abstract
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MM: Here is more support for the use of Full Spectrum Light Therapy relative to Seasonal Affective Disorder (SAD). Many products claim to be Full Spectrum bulbs but are not. If the price is too good to be true, be wary but price alone does not guarantee that you are getting what you are paying for. True Full Spectrum Light bulbs are available at Mark Drugs.
Nature 2012 Nov 22; 491:594
Pathway for Light Effects on Mood and Cognition
In an animal study, change in light exposure increases corticosterone, depresses mood, and impairs learning via intrinsically photosensitive retinal ganglion cells.
Seasonal affective disorder is treated with light therapy, but the mechanism has been poorly understood. To investigate this issue, investigators altered the usual murine cycle of 12 hours of light and 12 hours of dark to a total of 7 hours. Mice with the shortened cycle had similar sleep amount and architecture as 24-hour cyclers.
Compared with 24-hour cyclers, 7-hour cyclers had higher corticosterone levels (the mouse equivalent of human cortisol) and had impaired performance on tests used to assess cognition and depression-like behaviors. Seven-hour cyclers had greater activity, as measured by cells with expressed early gene c-Fos, in hippocampal areas associated with memory ability and in limbic areas (amygdala and habenula). Localization of these effects to non–image-making intrinsically photosensitive retinal ganglion cells (ipRGCs), which express melanopsin, was shown by the lack of mood or cognitive effects in 7-hour cyclers that lacked ipRGCs. Chronic fluoxetine administration (3 weeks) and acute desipramine reversed the learning deficits and normalized corticosterone levels, but subchronic fluoxetine administration (4 days) did not. Anxiety-like behaviors did not differ between the 7- and 24-hour cyclers, demonstrating the specificity of aberrant light exposure to depression.
Comment: When sleep and circadian parameters are held constant, depressive and learning impairments can be directly attributed to intrinsically photosensitive retinal ganglion cells. This finding is useful for understanding how light therapy may work in humans with seasonal affective disorder. Patients and families may be relieved to learn that there is a direct physiological pathway because of some public skepticism about the value of light therapy.
— Barbara Geller, MD Published in Journal Watch Psychiatry December 3, 2012
Citation(s): LeGates TA et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 2012 Nov 22; 491:594.
http://www.ncbi.nlm.nih.gov/pubmed/23151476?dopt=Abstract
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MM: The evidence continues to grow supporting antibiotic use for life-threatening use only. The cavalier use of these drugs in the past has resulted in super bugs and inadequate performance of the antibiotics that we have available to us. Enhanced use of probiotics in conjunction with antibiotic use may be the answer but whether it will be sufficient to neutralize the potential down side of antibiotics continues to be a valid question. In any case, in my opinion probiotics must accompany all courses of antibiotics or it is otherwise irresponsible of the prescribing practitioner.
Antimicrob Agents Chemother 2012 Nov; 56:5811
Incomplete Recovery of the Gut Microbiome After Antibiotic Therapy in Infants
Antibiotic use in infants causes changes in the gut microbiome that persist for at least 8 weeks.
Systemic antibiotic therapy can alter the gut microbiome, especially during the first two years of life when the complex symbiosis between intestinal flora and an infant's initially sterile gut develops. The use of high-throughput polymerase-chain-reaction 16S ribosomal RNA sequencing now makes it possible to investigate quantitative changes in the various species of the gut microbiome.
Using this sequencing technique, researchers in Ireland analyzed the stools of 18 infants: 9 who had been treated within 48 hours after birth with parenteral ampicillin and gentamicin and 9 age-matched, untreated controls. Treated infants' stool samples were collected 4 and 8 weeks after cessation of antibiotic treatment.
Compared with controls, antibiotic-treated infants had stool samples that, at 4 weeks, showed significantly higher proportions of Enterobacteriaceae (55% vs. 37%) and Peptostreptococcaceae (23% vs. 2%), but significantly lower proportions of Actinobacteria, Bifidobacterium, and Lactobacillus. By 8 weeks, only the Enterobacteriaceae levels remained significantly higher in the treated infants, and the Actinobacteria, Bifidobacterium, and Lactobacillus levels recovered to levels similar to those in controls. Despite this recovery, the number of different Bifidobacterium species remained lower in the antibiotic-treated infants. Furthermore, it appeared that the longer the antibiotic treatment lasted, the less complete the microbiome's recovery was.
Comment: Antibiotic use induces major changes in the gut microbiome of infants, but we don't yet know what those changes mean. It's not clear what functions the various bacterial species have within the gut or what the long-term course is after antibiotic exposure. Future research might clarify how antibiotic-induced changes in the gut may influence childhood risks for allergy, autoimmune diseases, and even obesity (JW Infect Dis Sep 5 2012) — and, possibly, how such adverse outcomes could be avoided.
— Thomas Glück, MD Published in Journal Watch Infectious Diseases December 5, 2012
Citation(s): Fouhy F et al. High-throughput sequencing reveals the incomplete, short-term recovery of infant gut microbiota following parenteral antibiotic treatment with ampicillin and gentamicin. Antimicrob Agents Chemother 2012 Nov; 56:5811.
http://www.ncbi.nlm.nih.gov/pubmed/22948872?dopt=Abstract
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Longer Treatment Offers No Advantage in Male UTIs; Routine Pre-Op Urine Cultures Useless
Studies in veterans call into question two widespread practices: extended drug treatment for male urinary tract infection and preoperative use of urine cultures. Both studies appear in the Archives of Internal Medicine.
The first study followed outcomes in some 33,000 outpatients with urinary tract infections, two thirds of whom received treatment for longer than 7 days. Over 12-months' follow-up, longer therapy (more than 7 days) was not associated with a reduction in early or late recurrence. The risk for C. difficile infection was significantly higher with longer therapy.
Another study at a veterans medical center found that preoperative urinary cultures were ordered inconsistently and were associated with higher rates of surgical-site infection, diarrhea, and C. difficile. The presence of bacteriuria, however, was not associated with surgical-site infection.
A commentator recommends "a culture shift in antibiotic prescribing practices for men with bacteriuria from 'more is better' to 'less is more.'"
http://archinte.jamanetwork.com/article.aspx?articleid=1470563
http://archinte.jamanetwork.com/article.aspx?articleid=1470566
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Obstet Gynecol 2012 Dec; 120:1527
ACOG Recommends Over-the-Counter Access to Oral Contraceptives
Benefit of lowering incidence of unintended pregnancy outweighs potential risks.
The American College of Obstetricians and Gynecologists (ACOG), one of the nation's leading authorities on women's health, has endorsed over-the-counter (OTC) access to oral contraceptives (OCs). Having reviewed the relevant literature, the ACOG Committee on Gynecologic Practice recognizes that unintended pregnancies often result from gaps in contraceptive use. Better access (e.g., availability of multiple pill packs) has improved continuation rates.
The committee opinion also notes that women can effectively self-screen for potential contraindications to OC use. Although all medications carry some risk, the chance of serious adverse events attributable to OC use is no greater than that for many medications, such as acetaminophen, that are currently available OTC. Neither pelvic exams nor screening for cervical cancer or sexually transmitted diseases is required to safely use OCs, and OTC availability is unlikely to prompt women to skip preventive services. Therefore, the ACOG concludes that the benefits of OTC availability of OCs outweigh the potential risks.
Comment: Although most of the world's women currently can access oral contraceptives without prescriptions, it will probably be years before over-the-counter OCs will be available to U.S. women, because of the amount of documentation that must be submitted to the FDA to support such a change. Hopefully, the ACOG's endorsement will facilitate this process.
— Eleanor Bimla Schwarz, MD, MS Published in Journal Watch Women's Health December 6, 2012
Citation(s): Committee opinion No. 544: Over-the-counter access to oral contraceptives. Obstet Gynecol 2012 Dec; 120:1527.
(http://dx.doi.org/10.1097/01.AOG.0000423818.85283.bd)
http://www.ncbi.nlm.nih.gov/pubmed/23168791?dopt=Abstract
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MM: Although we have seen data in the past that has indicated a decreased platelet aggregating effect of enteric coated aspirin vs. plain aspirin, the debate continues. A good question would be, are the incidence of GI problems such as ulcer and upset stomach decreased by 50% since the possibility of decreased effectiveness is decreased by almost that same amount?
Coating on Aspirin Might Reduce Its Cardioprotective Effects
Enteric coating can affect aspirin's inhibition of platelet aggregation, according to a study in Circulation.
Researchers used three assays — platelet aggregation, serum thromboxane formation, and urinary excretion of a thromboxane metabolite — to test response to an oral dose of 325-mg immediate-release or enteric-coated aspirin in 400 healthy volunteers (median age, 26). The study was partly funded by Bayer HealthCare.
No participant showed resistance to the immediate-release formulation. Up to 49% showed resistance to enteric-coated aspirin, but most were not resistant upon retesting.
The authors conclude that "we failed to find a single case of true drug resistance" and that their findings show "inconsistent platelet inhibition" after ingestion of enteric-coated aspirin
http://circ.ahajournals.org/content/early/2012/12/04/CIRCULATIONAHA.112.117283.abstract
http://www.nytimes.com/2012/12/05/business/coating-on-buffered-aspirin-may-hide-its-heart-protective-effects.html?_r=0
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MM: Decreasing risk of a venous thromboembolism (VTE) by 1/3 is pretty significant. If this is truly the case, then aspirin use in this group is certainly mandated. I think the jury is still out when it comes to the preventive benefits, especially of a daily dose, of coated aspirin
N Engl J Med 2012 Nov 4
Aspirin to Prevent Recurrent Venous Thromboembolism, Revisited
Taken together, two trials suggest that aspirin is moderately effective.
In the recent Italian WARFASA trial, aspirin lowered the incidence of recurrent venous thromboembolism (VTE) after first unprovoked VTE events (JW Gen Med May 24 2012). Now, in an international study (ASPIRE), investigators have addressed the same issue in 822 adults who completed 3 to 12 months of standard anticoagulation therapy for unprovoked VTE (42% with pulmonary embolism, 57% with proximal deep venous thrombosis only). Patients then were randomized to receive either 100 mg of aspirin or placebo daily. During average follow-up of 3 years, the following outcomes were noted:
- In the intent-to-treat analysis, the annual rate of recurrent VTE (the primary outcome) was 6.5% in the placebo group and 4.8% in the aspirin group (P=0.09).
- The annual rate of a secondary outcome — a composite of VTE events, myocardial infarction, stroke, or cardiovascular death — was 8.0% in the placebo group and 5.2% in the aspirin group (P=0.01).
- Major bleeding occurred in six placebo recipients and eight aspirin recipients.
- All-cause mortality was 4% in both groups.
Comment: After completing initial courses of anticoagulation, patients with unprovoked VTE are at high risk for recurrence. Indefinite continuation of warfarin lowers that risk substantially but confers considerable ongoing bleeding risk. Aspirin offers a reasonable compromise for such patients. In ASPIRE, a reduction in the VTE endpoint with aspirin didn't quite reach statistical significance, but a combined venous–arterial endpoint did. Because the ASPIRE and WARFASA trials were nearly identical, the two research teams planned prospectively to pool their results. The pooled results appear in this report: Aspirin lowered risk for recurrent VTE by 32% (P=0.007) and lowered risk for combined vascular events (venous and arterial) by 34% (P=0.002) without significantly raising risk for major bleeding.
— Allan S. Brett, MD Published in Journal Watch General Medicine November 4, 2012
Citation(s): Brighton TA et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012 Nov 4; [e-pub ahead of print].
(http://dx.doi.org/10.1056/NEJMoa1210384)
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Benzodiazepines Associated with Increased Pneumonia Risks
Benzodiazepines as a class are associated with heightened risks for community-acquired pneumonia and pneumonia-related death, according to a case-control study in Thorax.
Researchers used a U.K. database to assemble a cohort of some 5000 cases of community-acquired pneumonia and 30,000 matched controls. Benzodiazepine exposure was associated with a higher risk for pneumonia (odds ratio, 1.54) as compared with no exposure. After a pneumonia diagnosis, benzodiazepine use — whether current, recent, or past — was also associated with higher mortality.
The authors speculate that the effect observed may be due to activation of GABA receptors on immune cells. That speculation was strengthened by finding an increased pneumonia risk with another — non-benzodiazepine — drug that also targets GABA receptors. The authors consider their findings "hypothesis-generating," but consistent with "movement away from benzodiazepine sedation" during intensive care.
http://thorax.bmj.com/content/early/2012/11/12/thoraxjnl-2012-202374
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Nat Neurosci 2012 Oct; 15:1359
Alcohol Impairs Fear Extinction in Mice
The research may explain why PTSD may be more persistent in drinkers.
Episodic heavy drinking is associated with auto accidents, domestic violence, and other situations that evoke traumatic memories and post-traumatic stress disorder (PTSD). Effective PTSD treatments rely on fear extinction, or replacement of neutral associations for traumatic ones, which relies on activation of the medial prefrontal cortex (mPFC) in all species. Because individuals with alcohol dependence have deficits in mPFC-mediated functions, these researchers used mice to investigate the effect of several weeks of intermittent exposure to inhaled alcohol (chronic intermittent ethanol; CIE) or vaporized air on the later acquisition and extinction of conditioned fear (a sound paired with foot shock).
CIE and control groups had similar anxiety levels before training, had the same degree of freezing during training (i.e., fear acquisition), and extinguished fear during an initial session of exposure to the sound without a shock. However, CIE animals had impaired retention of extinction on subsequent trials. CIE animals also had significant hypertrophy of dendrites in the prelimbic mPFC (but not other regions). CIE was associated with blunting of mPFC firing, lower mPFC expression of a subunit of the N-methyl-D-aspartate (NMDA) receptor, and decreased NMDA receptor signaling with exposure to the tone alone during late extinction and extinction retrieval. The same deficit of extinction retention in alcohol-naive mice was observed after infusion of an NMDA antagonist after extinction training.
Comment: These results indicate that chronic intermittent ethanol down-regulates N-methyl-D-aspartate receptors in the medial prefrontal cortex, with changes in dendritic morphology and interference with encoding of extinction in these neurons. As a result, chronic alcohol use may make fear extinction more difficult after traumatic experiences, and PTSD may be more persistent in drinkers. Whether abstinence can reverse these effects and make PTSD more treatable remains to be seen.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry November 9, 2012
Citation(s): Holmes A et al. Chronic alcohol remodels prefrontal neurons and disrupts NMDAR-mediated fear extinction encoding. Nat Neurosci 2012 Oct; 15:1359.
http://www.ncbi.nlm.nih.gov/pubmed/22941108?dopt=Abstract
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Arch Gen Psychiatry 2012 Oct 1; 69:1054
Not Sleeping Costs Money
Insomnia, independent of chronic conditions, is associated with workplace accidents and/or errors in an epidemiologically based study.
Insomnia, which is highly prevalent, is associated with cognitive and affective dysfunction. This manufacturer-funded, validated telephone survey of insured individuals who were demographically similar to the overall U.S. population addressed the impact of insomnia on work performance. Interviewers obtained information about type and consequences of insomnia; chronic illnesses including cardiovascular disorders, diabetes, musculoskeletal disorders, respiratory disease, digestive disorders, pain disorders, mental disorders, other sleep disorders, and climacteric symptoms; and costly workplace accidents and errors (
$500) in the previous 12 months.
Insomnia persisting at least 1 year was reported by 20% of the 4991 employed respondents, with a higher prevalence in those under age 65. The prevalence of costly accidents and errors was 1.1% and 3.4%, respectively, with some respondents reporting both. Insomnia was significantly associated with all but one of the 18 chronic conditions measured, with an odds ratio of 5.5 for major depression. After adjustment for comorbid chronic disorders, insomnia was significantly associated with costly accidents and/or errors (OR, 1.4). The authors estimated that 7.2% of workplace accidents and/or errors were associated with insomnia. In contrast, independent of insomnia, only neuropathic pain, sleep apnea, and emotional disorders other than depression were significantly associated with accidents and/or errors. The mean reported cost was $8102 for accidents, $26,188 for errors, and $22,645 for either. Mean costs had a large spread (highest reported costs: accidents, $100,000; errors, $1 million), and median costs were lower.
Comment: These results indicate that insomnia is costly as well as troublesome and is potentially dangerous regardless of age, sex, and education. Screening for insomnia in the workplace may be a cost-effective intervention.
— Steven Dubovsky, MD Published in Journal Watch Psychiatry November 19, 2012
Citation(s): Shahly V et al. The associations of insomnia with costly workplace accidents and errors: Results from the America Insomnia Survey. Arch Gen Psychiatry 2012 Oct 1; 69:1054.
http://www.ncbi.nlm.nih.gov/pubmed/23026955?dopt=Abstract
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MM: Statistics are a funny thing. A 42-51% increased risk seems significant to me but I guess the overall incidence is so low that the relative increase is insignificant. I think that it's important to be aware of this potential problem as more and more people are using this class of drug. Undoubtedly the number of users alone will increase the likelihood of many clinicianss seeing this endpoint at some time or another.
Neurology 2012 Oct 30; 79:1862
SSRIs and Intracerebral Bleeds: A Small Risk
Clinicians should remain aware of the possibility, but these medications are probably safe for almost all patients.
Depression both occurs frequently after stroke and increases the risk for stroke (JW Neurol Nov 1 2011), and so the use of selective serotonin reuptake inhibitors (SSRIs) is common in patients with stroke histories or at risk for stroke. Because SSRIs have been associated with gastrointestinal bleeding, there is concern that these medications might also increase risk for intracerebral bleeds.
These authors performed a meta-analysis of 16 observational studies that included an appropriate, non-SSRI control group (N=506,411 patients). A small but significant increase in intracerebral hemorrhages was seen with SSRI exposure (adjusted rate ratio, 1.42), and for intracranial hemorrhage (ARR, 1.51). Risk for subarachnoid hemorrhage did not increase. Risk with SSRIs plus oral anticoagulants (examined in 5 studies) was higher than with anticoagulants alone. Seven studies examined treatment duration; risk appeared to be limited to the first several months of treatment.
Comment: The authors estimate that the increased risk with SSRI treatment for additional intracerebral bleeding episodes would result in 1 additional intracerebral bleeding episode per 10,000 people treated for 1 year (or an increased rate from 24.6 to 34.6 per 100,000 person/years). The editorialists note that the studies may not have controlled for possibly confounding risk factors for both stroke and depression (e.g., diabetes, small vessel disease, alcoholism).
This small increase in risk should have negligible impact on most patients. The authors suggest that alternative therapies (non-SSRI antidepressants) might be appropriate for patients who are already at an increased risk for intracerebral bleeds — e.g., those on long-term anticoagulants or with severe alcohol abuse, previous intracranial bleeding, or cerebral amyloid angiopathy.
— Jonathan Silver, MD Published in Journal Watch Psychiatry November 5, 2012
Citation(s): Hackam DG and Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: A meta-analysis. Neurology 2012 Oct 30; 79:1862.
http://www.ncbi.nlm.nih.gov/pubmed/23077009?dopt=Abstract
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