Statin Therapy: Rethinking Benefits and Risks

A recent 30-page manuscript provides an exhaustive review of the evidence for the efficacy and safety of statin therapy.

The authors of this excellent review provide some context for the relative value of statins.

The note that putting 10000 individuals with a history of a vascular event on a statin drug for 5 years would prevent 1,000 subsequent events. This is an example of secondary prevention--preventing another adverse outcome in those already experiencing an adverse event.

But the statin drugs also appear very powerful in primary prevention-preventing a first event in those at high risk for vascular disease. They estimate putting 10,000 individuals at high risk for vascular events on statins would result in prevention of 500 vascular events over five years.

This review provides an up-to-date review of the safety of statins and generally supports the therapy as very low risk.

One proposed adverse event of statin therapy is concern about memory and cognition. However, the authors note that well-designed studies of statin therapy in older individuals find no evidence of adverse cognitive effects compared to placebo.

They argue that:

"..given the weight of evidence against adverse effects of statin therapy on memory or other adverse effects of cognition, it would now be appropriate for regulatory authorities to consider removal from the lists of potential adverse effects on the drug labels so that patients are not inappropriately deterred from using statin therapy." (emphasis mine).

The authors go on to emphasize the potential adverse public health consequences of misleading claims regarding the safety of the statin drug class.

This excellent review is likely to lead to further discussion about extending the indications for statin use in the general population.

This review also supports discussion between individuals and their physicans on the appropriateness of statin therapy as part of a disease prevention progra.

Readers with more interest in this topic can access the full free-text manuscript by clicking on the link in the citation below.

Follow me on Twitter by clicking HERE.

Photo of osprey in flight is from my photography files.

Collins R, Reith C, Emberson J et al.  (2016). Interpretation of the evidence for the efficacy and safety of statin therapy Lancet : http://dx.doi.org/10.1016/S0140-6736(16)31357-5

Obesity Surgery: VA Outcome Study

Weight loss (bariatric) surgery is likely to become increasingly important to address the obesity epidemic in the U.S. and other nations.

There are several types of surgical techniques used for bariatric surgery.

One of the most invasive is the Rous-en-Y gastric bypass (RYG) operation. This operation involves bisection of the small intestine and reattachment of the upper section to a position lower down the small intestine. This provides for a shorter distance for food to be absorbed.

Less invasive techniques using a sleeve (sleeve gastrectomy SB) or adjustable gastric banding (AGB) around the stomach are also common surgical approaches.

A recent large Veterans Administration bariatric surgery outcome study helps in understanding the long-term relative weight loss efficacy of three types of operations. This study compared outcomes between three types of operations (RYGB

The chart I have put together from data abstracted from the manuscript is above. The summary findings include the following key items:

• All three surgical interventions were superior to no operation controls
• All three surgical interventions maintained significant weight loss at five years
• Rous-en-Y (RYB) was superior to SG and AGB at one and five years.
• The study supports about a 30%/20%/10% five year weight reduction for the RYG/SG/AGB operations

I have included a schematic of the RYG procedure from the Wikipedia Commons file here. This schematic has the tranverse colon cut away to show the small intestine re-attachment site.

There are some significant limitations of this study. Surgical procedures were not randomized and study subjects differed on some clinical and demographic features at baseline. VA subjects are predominantly male and results may not be generalizable to women.

There was not a detailed report of risks and complications for each procedure.

Nevertheless, this is an important study that supports use of bariatric surgery as an option in the treatment of high-risk severely obese U.S. veterans.

Follow me on Twitter at WRY999

Chart above is an original chart produced by me from data abstracted from the manuscript.

Readers can access the manuscript abstract by clicking on the PMID link below

The Wikipedia Commons file was originally uploaded by Topnife at English Wikipedia - Transferred from en.wikipedia to Commons., Attribution, https://commons.wikimedia.org/w/index.php?curid=3153491

Maciejewski ML, Arterburn DE, Van Scoyoc L, Smith VA, Yancy WS Jr, Weidenbacher HJ, Livingston EH, & Olsen MK (2016). Bariatric Surgery and Long-term Durability of Weight Loss. JAMA surgery PMID: 27579793

"The Biggest Loser": Long-term Effects

Yesterday I posted a link to a New York Times article that posted a summary outcome in fourteen participants in TV's "The Biggest Loser" show.

The study found a trend towards post-show weight gain for 13/14 of the participants.

Four participants actually gained so much weight that after six years they weighed more than before participating in the show.

A key finding from the study was this weight gain could be explained by a metabolic response resulting in up to 800 calories less burned daily after weight loss.

I have previously posted notes from a lecture I attended by Dr. Kevin Hall who is mentioned in the NYT piece.

For me, the take home message is that long-term weight loss maintenance is extremely difficult. A better strategy might be to aim for consuming a healthy diet and achieving daily recommended exercise levels.

A link to the NYT article is here:

Notes on Dr. Hall's lecture at the Laureate Institute for Brain Research is here:

Follow me on Twitter: @WRY999

Graphic is an original screen shot from my Twitter feed.

Fothergill, E., Guo, J., Howard, L., Kerns, J., Knuth, N., Brychta, R., Chen, K., Skarulis, M., Walter, M., Walter, P., & Hall, K. (2016). Persistent metabolic adaptation 6 years after “The Biggest Loser” competition Obesity DOI: 10.1002/oby.21538

Delirium and Aortic Valve Surgery Outcome

Delirium is an acute confusional state that is common in elderly hospitalized patients.

I think of it light a sign of acute brain failure requiring aggressive attentional for detection and treatment of any reversible underlying causes.

Delirium in elderly hospitalized patients is a marker for poor outcome in a variety of medical and surgical subjects.

A recent study published by a Norwegian team found effects on outcome for delirium following surgical aortic valve replacement. The key findings from the study included:

• An lower rate of delirium for subjects receiving catheter valve replacement than surgical replacement
• Lower physical outcome scores at 6 months for those experiencing post-op delirium
• Longer term outcomes between those with delirium and those without delirium were not different

The study supports monitoring for delirium during the period after aortic valve surgery. Delirium may indicate a need for more intensive rehabilitation in the short-term recovery period.

The free full text manuscript can be accessed here.

Follow me on Twitter: @WRY999

Eide LS, Ranhoff AH, Fridlund B, Haaverstad R, Hufthammer KO, Kuiper KK, Nordrehaug JE, Norekvål TM, & Delirium in Octogenarians Undergoing Cardiac Surgery or Intervention-CARDELIR Investigators (2016). Delirium as a Predictor of Physical and Cognitive Function in Individuals Aged 80 and Older After Transcatheter Aortic Valve Implantation or Surgical Aortic Valve Replacement. Journal of the American Geriatrics Society PMID: 27106745

Predictors of Poor Outcome After Traumatic Brain Injury

The outcome following traumatic brain injury (TBI) is often unpredictable and variable.

Two individuals with similar types of TBI can have quite different outcomes ranging from total disability to functional employment.

Torun Finnanger and colleagues from Norway and Australia recently reported on a study that examined a number of predictor variables on self-reported outcome following TBI.

In this study, 67 adolescents and adults with moderate to severe TBI completed baseline assessments and were followed for a period of 2 to 5 years. 

The key outcome variables in this study was self-reported executive, behavioral and emotional impairment at the follow-up time point. TBI subjects were compared on a variety of variables with a control group without injury.

Early assessment variables that were examined for correlation with outcome after TBI included:

• Pre-trauma level of education
• Brain injury severity rating: Glasgow Coma Score
• Duration of post-traumatic amnesia
• Brain imaging: presence of imaging markers for brain traumatic axonal injury on brain MRI with inclusion of diffusion tensor imaging (DTI) data
• Neuropsychological assessment obtained three months after injury including: Motor function, information processing speed, attention, visual memory, verbal memory and executive function
• Presence of the symptoms of depression using Beck Depression Inventory 3 and 12 months after injury

The key findings from this longitudinal predictor study included:

• Self-reported impairment in executive function at 2-5 years follow up was linked to fewer years of education, early depression symptoms and traumatic axonal injury
• Injury at a younger age predicted increased aggression and conduct disorder behavioral problems
• Traumatic axonal injury and early depression symptoms predicted increased depression and anxiety symptoms at follow up.

The authors conclude their study supports inclusion of self-reported executive, emotional and behavioral assessments in the monitoring of TBI subjects.

Additionally, they note early MRI imaging assessment of axonal injury (in the first two weeks following TBI) and early assessment of depressive symptoms add information to standard neuropsychological assessment batteries.

They note accurately defining high-risk groups more poor outcome may allow targeting of more aggressive treatment strategies. 

"Furthermore, psychological and/or pharmaceutical interventions, with a focus on depressive symptomatology may be helpful in reducing the long-term problems experienced by persons sustaining a TBI.."

This study is filled with a ton of data. Readers with more interest in the study can find the free full-text manuscript by clicking on the PMID link in the citation below.

Follow the author on Twitter WRY999.

Image of brain white matter pathways is an iPad screen shot from the 3D Brain app from the authors files.

Finnanger TG, Olsen A, Skandsen T, Lydersen S, Vik A, Evensen KA, Catroppa C, Håberg AK, Andersson S, & Indredavik MS (2015). Life after Adolescent and Adult Moderate and Severe Traumatic Brain Injury: Self-Reported Executive, Emotional, and Behavioural Function 2-5 Years after Injury. Behavioural neurology, 2015 PMID: 26549936

Family Therapy for Adolescent Anorexia Nervosa

There is very limited research to guideline clinicians, patients and their family members in choosing the best treatments for anorexia nervosa and other eating disorders.  So when a well-designed and informative study is published it is noteworthy and important to review.   James Lock and colleagues summarized their findings from a randomized trial of family therapy versus individual therapy in a randomized controlled trial for adolescents with anorexia nervosa in the October 2010 issue of Archives of General Psychiatry.

This study found family-based therapy superior to individual-based therapy for these adolescents.  The elements of family therapy for anorexia in the study were outlined as:

• Phase one- “absolve the parents from the responsibility of causing the (eating) disorder” as well as being positive by complimenting positive elements of their parenting style and behavior—families were encouraged to work out a plan suited to their family for restoring the weight of the child
• Phase two-return responsibility for weight and eating to the adolescent using an age-appropriate method
• Phase three-establish a healthy adolescent-parent relationship pattern

This therapy was provided in twenty session lasting one hour per session over a one year period of time. 

Full remission of the eating disorder was accomplished in 49% of the family therapy group compared to only 22% of the individual therapy group.

So why was family therapy more effective in this adolescent population with anorexia nervosa?  The authors don’t discuss this issue much in the comment section of the manuscript.  They note that the family therapy method acts by “empowering parents to directly address behaviors maintaining weight loss in their children”.

This parent led approach may be specifically appropriate in anorexia nervosa, a disorder that appears more frequently in middle and upper class families (one of the few mental disorders showing this pattern).   It is noteworthy that the parents in this study had an average of 16 to 18 years of education and might be more effective than less well-educated parents in taking on a direct role taught by expert therapists in the management of anorexia related behaviors and interpersonal problems.

The family therapy method used in this study has been published in a book: Lock J, Le Grange D, Agras WS, Dare C. Treatment Manual for Anorexia Nervosa: A Family-Based Approach. New York, NY: Guilford Publications, Inc; 2001.   A link to this book on Amazon.com is here.


Baby duck in flowers courtesy of Yates Photography.


Lock J, Le Grange D, Agras WS, Moye A, Bryson SW, & Jo B (2010). Randomized clinical trial comparing family-based treatment with adolescent-focused individual therapy for adolescents with anorexia nervosa. Archives of general psychiatry, 67 (10), 1025-32 PMID: 20921118