Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013

Posted on February 23, 2016 by Maurice Preter MD

Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013

http://tinyurl.com/jqlst3n

Marcus A. Bachhuber, MD, MSHP, Sean Hennessy, PharmD, PhD, Chinazo O. Cunningham, MD, MS, and Joanna L. Starrels, MD, MS

Marcus A. Bachhuber, Chinazo O. Cunningham, and Joanna L. Starrels are with Division of General Internal Medicine, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY. Sean Hennessy is with Center for Clinical Epidemiology and Biostatistics and Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Correspondence should be sent to Marcus A. Bachhuber, MD, MSHP, 111 E 210 St, Bronx, NY 10467 (e-mail: ). Reprints can be ordered at http://www.ajph.org by clicking the “Reprints” link.

CONTRIBUTORS

All authors acquired, analyzed, or interpreted the data and critically revised the brief for important intellectual content. M. A. Bachhuber drafted the brief and had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. M. A. Bachhuber and S. Hennessy conceptualized and designed the study and performed statistical analysis. S. Hennessy, C. O. Cunningham, and J. L. Starrels supervised the study.

ABSTRACT

Objectives. To describe trends in benzodiazepine prescriptions and overdose mortality involving benzodiazepines among US adults.

Methods. We examined data from the Medical Expenditure Panel Survey and multiple-cause-of-death data from the Centers for Disease Control and Prevention.

Results. Between 1996 and 2013, the percentage of adults filling a benzodiazepine prescription increased from 4.1% (95% confidence interval [CI] = 3.8%, 4.5%) to 5.6% (95% CI = 5.2%, 6.1%), with an annual percent change of 2.5% (95% CI = 2.1%, 3.0%). The quantity of benzodiazepines filled increased from 1.1 (95% CI = 0.9, 1.2) to 3.6 (95% CI = 3.0, 4.2) kilogram lorazepam equivalents per 100 000 adults (annual percent change = 9.0%; 95% CI = 7.6%, 10.3%). The overdose death rate increased from 0.58 (95% CI = 0.55, 0.62) to 3.07 (95% CI = 2.99, 3.14) per 100 000 adults, with a plateau seen after 2010.

Conclusions. Benzodiazepine prescriptions and overdose mortality have increased considerably. Fatal overdoses involving benzodiazepines have plateaued overall; however, no evidence of decreases was found in any group. Interventions to reduce the use of benzodiazepines or improve their safety are needed. (Am J Public Health. Published online ahead of print February 18, 2016: e1–e3. doi:10.2105/AJPH.2016.303061)

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Magnesium intake decreases Type 2 diabetes Risk through the Improvement of Insulin Resistance and Inflammation

Posted on February 17, 2016 by Maurice Preter MD

Magnesium intake decreases Type 2 diabetes Risk through the Improvement of Insulin Resistance and Inflammation

http://tinyurl.com/zjbvklt

MEDLINE Abstract

Hata A ; Doi Y ; Ninomiya T ; Mukai N ; Hirakawa Y ; Hata J ; Ozawa M ; Uchida K ; Shirota T ; Kitazono T ; Kiyohara Y

AIMS: Early studies have shown that magnesium intake decreases the risk of Type 2 diabetes, but the results are still inconsistent. We prospectively examined the association between magnesium intake and incidence of Type 2 diabetes in a general Japanese population.

METHODS: A total of 1999 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed up prospectively for a mean of 15.6 years.

RESULTS: During the follow-up, 417 subjects developed Type 2 diabetes. The age- and sex-adjusted incidence of Type 2 diabetes significantly decreased with increasing magnesium intake quartile levels (? 148.5, 148.6-171.5, 171.6-195.5 and ? 195.6 mg/day, P for trend = 0.01). In multivariate analyses, after adjusting for comprehensive risk factors and other dietary factors, the hazard ratio of Type 2 diabetes was 0.67 (95% CI 0.49-0.92; P = 0.01) in the third quartile and 0.63 (95% CI 0.44-0.90; P = 0.01) in the highest quartile compared with the first quartile. In addition, the risk of Type 2 diabetes was 14% lower (P = 0.04) for a 1-sd increment of log-transformed magnesium intake in the multivariate-adjusted model. In stratified analysis, there were statistically significant interactions between magnesium intake and levels of homeostasis model assessment of insulin resistance, high sensitivity C-reactive protein or alcohol intake on the risk of Type 2 diabetes (all P < 0.05).

CONCLUSIONS: Our findings suggest that increased magnesium intake was a significant protective factor for the incidence of Type 2 diabetes in the general Japanese population, especially among subjects with insulin resistance, lowgrade inflammation and a drinking habit.

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Association of arterial stiffness with progression of subclinical brain and cognitive disease.

Posted on February 17, 2016 by Maurice Preter MD

Association of arterial stiffness with progression of subclinical brain and cognitive disease.

http://tinyurl.com/jcqsplz

Tsao CW1, Himali JJ2, Beiser AS2, Larson MG2, DeCarli C2, Vasan RS2, Mitchell GF2, Seshadri S2.

Author information

Abstract

OBJECTIVE:

We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing.

METHODS:

Framingham Offspring Cohort participants (n = 1,223, 61 ± 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 ± 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (ΔTrails B-A), and Similarities tests.

RESULTS:

Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and ΔTrails B-A association: SD unit change in outcome variable per SD change in tonometry variable [β] ± SE = 0.10 ± 0.04, p = 0.019; CPP and ΔSimilarities association: -0.08 ± 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([β ± SE] 0.07 ± 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume.

CONCLUSIONS:

In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.

© 2016 American Academy of Neurology.

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Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later

Posted on February 17, 2016 by Maurice Preter MD

Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later

http://tinyurl.com/zzlgg8k

Nicole L. Spartano, PhD, Jayandra J. Himali, PhD, Alexa S. Beiser, PhD, Gregory D. Lewis, MD, Charles DeCarli, MD, Ramachandran S. Vasan, MD and Sudha Seshadri, MD

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Correspondence to Dr. Spartano: spartano@bu.edu

Published online before print February 10, 2016doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002415Neurology 10.1212/WNL.0000000000002415

ABSTRACT

Objective: To determine whether poor cardiovascular (CV) fitness and exaggerated exercise blood pressure (BP) and heart rate (HR) were associated with worse brain morphology in later life.

Methods: Framingham Offspring participants (n = 1,094, 53.9% female) free from dementia and CV disease (CVD) underwent an exercise treadmill test at a mean age of 40 ± 9 years. A second treadmill test and MRI scans of the brain were administered 2 decades later at mean age of 58 ± 8 years.

Results: Poor CV fitness and greater diastolic BP and HR response to exercise at baseline were associated with a smaller total cerebral brain volume (TCBV) almost 2 decades later (all p < 0.05) in multivariable adjusted models; the effect of 1 SD lower fitness was equivalent to approximately 1 additional year of brain aging in individuals free of CVD. In participants with prehypertension or hypertension at baseline, exercise systolic BP was also associated with smaller TCBV (p < 0.05).

Conclusion: Our results suggest that lower CV fitness and exaggerated exercise BP and HR responses in middle-aged adults are associated with smaller brain volume nearly 2 decades later. Promotion of midlife CV fitness may be an important step towards ensuring healthy brain aging.

Received August 11, 2015.

Accepted in final form December 14, 2015.

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Association of Proton Pump Inhibitors With Risk of Dementia

Posted on February 17, 2016 by Maurice Preter MD

Association of Proton Pump Inhibitors With Risk of Dementia

A Pharmacoepidemiological Claims Data Analysis

http://tinyurl.com/zx9n3o8

Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1

 

 

JAMA Neurol. Published online February 15, 2016. doi:10.1001/jamaneurol.2015.4791

ABSTRACT

Importance  Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.

Objective  To examine the association between the use of PPIs and the risk of incident dementia in the elderly.

Design, Setting, and Participants  We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.

Exposures  Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Main Outcomes and Measures  The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.

Results  A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

Conclusions and Relevance  The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.

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