Metformin use after Cervical Cancer Diagnosis among Older Women with Diabetes may be Associated with a Significant Decrease in Mortality

Posted on March 16, 2016 by Maurice Preter MD

 

Metformin use after Cervical Cancer Diagnosis among Older Women with Diabetes may be Associated with a Significant Decrease in Mortality

http://tinyurl.com/jjrnofe

Kathy Han1,2,*,
Melania Pintilie3,
Lorraine L. Lipscombe4,55,
Iliana C. Lega4,
Michael F. Milosevic1,2, and
Anthony W. Fyles1,2

1Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
2Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.
3Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
4Women’s College Research Institute, Women’s College Hospital, Toronto, Ontario, Canada.
5Institute of Clinical Evaluative Studies, Toronto, Ontario, Canada.

↵*Corresponding Author:

Kathy Han, Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada. Phone: 141-6946-2919; Fax: 141-6946-6561; E-mail: Kathy.Han@rmp.uhn.on.ca
Note: M.F. Milosevic and A.W. Fyles contributed equally to this article.

Abstract

Background: To examine the association between metformin use and mortality in patients with diabetes and cervical cancer.

Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥ age 66 years diagnosed with cervical cancer between 1997 and 2010. The association between metformin exposure and cervical cancer–specific mortality was examined using Fine–Gray regression models, with noncancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models.

Results: Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer–specific deaths. The median follow-up was 5.8 years (interquartile range 4.2–9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer–specific mortality and overall mortality in a dose-dependent fashion [HR 0.79; 95% confidence interval (CI), 0.63–0.98; and HR 0.95; 95% CI, 0.90–0.996 per each additional 365 g of metformin use, respectively]. There was no significant association between cumulative use of other antidiabetic drugs and cervical cancer–specific mortality.

Conclusion: This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer–specific and overall mortality among older women with diabetes.

Impact: Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer. Cancer Epidemiol Biomarkers Prev; 25(3); 507–12. ©2015 AACR.

Received September 29, 2015.

Revision received December 18, 2015.

Accepted December 18, 2015.

©2015 American Association for Cancer Research.

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Higher Rates of Antidepressant Use Associated With Alzheimer’s Disease

Posted on March 16, 2016 by Maurice Preter MD

Higher Rates of Antidepressant Use Associated With Alzheimer’s Disease

http://tinyurl.com/j25ksu5

Puranen A1,2, Taipale H1,2,3, Koponen M1,2, Tanskanen A4,5,6, Tolppanen AM2,3, Tiihonen J4,6, Hartikainen S1,2.

1Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.
2School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
3Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, Kuopio, Finland.
4Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
5National Institute for Health and Welfare, Helsinki, Finland.
6Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.

Abstract

OBJECTIVES:

The study aimed to investigate the incidence of antidepressant use in persons with and without Alzheimer’s disease (AD) from 9 years before to 4 years after AD diagnosis and to examine the incidence of different antidepressant groups.

METHODS:

We used register-based data from the Medication use and Alzheimer’s disease cohort including all Finnish persons diagnosed with AD in 2005-2011 with their age-matched and gender-matched comparison persons without AD. In this study, 62,104 persons with AD and 62,104 comparison persons were included. Data on dispensed antidepressants during 1995-2012 were collected from the Prescription Register. A 1-year washout period was utilized to measure the rate of new antidepressant users every 6-month period starting from 9 years before and until 4 years after the AD diagnoses. The incidence rate between persons with and without AD was compared with Poisson regression.

RESULTS:

The incidence of antidepressant use in persons with AD was higher during the whole study period compared with that in persons without AD. The incidence rate was highest at 6 months after AD diagnosis (incidence rate ratio = 5.22, 95% confidence interval 4.77-5.72). Selective serotonin reuptake inhibitors were the most frequently initiated group (61.3% of initiations in persons with AD).

CONCLUSIONS:

The incidence of antidepressant use was higher in persons with AD than in comparison persons, and it was not explained by history of hospital-treated psychiatric disorders. Widespread use of antidepressants in persons with AD is concerning as their efficacy is controversial and their use is associated with adverse events.

Copyright © 2016 John Wiley & Sons, Ltd.

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Hostile attitudes and effortful coping in young adulthood predict cognition 25 years later

Posted on March 9, 2016 by Maurice Preter MD

 

Hostile attitudes and effortful coping in young adulthood predict cognition 25 years later

http://tinyurl.com/zg5xmrl

Emiliano Albanese, MD, PhD, Karen A. Matthews, PhD, Julia Zhang, MSc, David R. Jacobs Jr, PhD, Rachel A. Whitmer, PhD, Virginia G. Wadley, PhD, Kristine Yaffe, MD, Stephen Sidney, MD, PhD and Lenore J. Launer, PhD

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Correspondence to Dr. Launer: launerl@nia.nih.gov

Published online before print March 2, 2016doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002517Neurology 10.1212/WNL.0000000000002517

ABSTRACT

Objective: We studied the relation of early-life (mean age 25 years) and mid-life (mean age 50 years) cognitive function to early measures of hostile attitudes and effortful coping.

Methods: In 3,126 black and white men and women (born in 1955–1968) from the Coronary Artery Risk Development in Young Adults Study (CARDIA), we used linear regression to examine the association of hostile attitudes (Cook-Medley questionnaire) and effortful coping assessed at baseline (1985–1986) to cognitive ability measured in 1987 and to a composite cognitive Z score of tests of verbal memory, psychomotor speed, and executive function ascertained in midlife (2010–2011).

Results: Baseline hostility and effortful coping were prospectively associated with lower cognitive function 25 years later, controlling for age, sex, race, education, long-term exposure to depression, discrimination, negative life events, and baseline cognitive ability. Compared to the lowest quartile, those in the highest quartile of hostility performed 0.21 SD units lower (95% confidence interval [CI] −0.39, −0.02). Those in the highest quartile of effortful coping performed 0.30 SD units lower (95% CI −0.48, −0.12) compared to those in the lowest quartile. Further adjustment for cumulative exposure to cardiovascular risk factors attenuated the association with the cognitive composite Z score for hostility.

Conclusions: Worse cognition in midlife was independently associated with 2 psychological characteristics measured in young adulthood. This suggests that interventions that promote positive social interactions may have a role in reducing risk of late-age cognitive impairment.

  • Received June 14, 2015.
  • Accepted in final form December 14, 2015.
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Recognizing and preventing epilepsy-related mortality

Posted on February 23, 2016 by Maurice Preter MD

Recognizing and preventing epilepsy-related mortality

http://tinyurl.com/gp8oojy

Orrin Devinsky, MD, Tanya Spruill, PhD, David Thurman, MD, PhD and Daniel Friedman, MD, MSc

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Correspondence to Dr. Devinsky: od4@nyu.edu

Published online before print December 16, 2015doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002253Neurology February 23, 2016 vol. 86 no. 8 779-786

ABSTRACT

Epilepsy is associated with a high rate of premature mortality from direct and indirect effects of seizures, epilepsy, and antiseizure therapies. Sudden unexpected death in epilepsy (SUDEP) is the second leading neurologic cause of total lost potential life-years after stroke, yet SUDEP may account for less than half of all epilepsy-related deaths. Some epilepsy groups are especially vulnerable: individuals from low socioeconomic status groups and those with comorbid psychiatric illness die more often than controls. Despite clear evidence of an important public health problem, efforts to assess and prevent epilepsy related deaths remain inadequate. We discuss factors contributing to the underestimation of SUDEP and other epilepsy-related causes of death. We suggest the need for a systematic classification of deaths directly due to epilepsy (e.g., SUDEP, drowning), due to acute symptomatic seizures, and indirectly due to epilep(e.g., suicide, chronic effects of antiseizure medications). Accurately estimating the frequency of epilepsy-related mortality is essential to support the development and assessment of preventive interventions. We propose that educational interventions and public health campaigns targeting medication adherence, psychiatric comorbidity, and other modifiable risk factors may reduce epilepsy related mortality. Educational campaigns regarding sudden infant death syndrome and fires, which kill far fewer Americans than epilepsy, have been widely implemented. We have done too little to prevent epilepsy related deaths. Everyone with epilepsy and everyone who treats people with epilepsy need to know that controlling seizures will save lives.

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Cause of death and predictors of mortality in a community-based cohort of people with epilepsy

Posted on February 23, 2016 by Maurice Preter MD

Cause of death and predictors of mortality in a community-based cohort of people with epilepsy

http://tinyurl.com/hdbgazx

Mark R. Keezer, MDCM, MSc, FRCP(C), Gail S. Bell, MB, ChB, MD, Aidan Neligan, PhD, MRCP, Jan Novy, MD, PhD and Josemir W. Sander, MD, PhD, FRCP

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Correspondence to Dr. Sander: l.sander@ucl.ac.uk

Published online before print January 15, 2016doi:http:/​/​dx.​doi.​org/​10.​1212/​WNL.​0000000000002390Neurology February 23, 2016 vol. 86 no. 8 704-712

ABSTRACT

Objective: The risk of premature mortality is increased in people with epilepsy. The reasons for this and how it may relate to epilepsy etiology remain unclear.

Methods: The National General Practice Study of Epilepsy is a prospective, community-based cohort that includes 558 people with recurrent unprovoked seizures of whom 34% died during almost 25 years of follow-up. We assessed the underlying and immediate causes of death and their relationship to epilepsy etiology. Psychiatric and somatic comorbidities of epilepsy as predictors of mortality were scrutinized using adjusted Cox proportional hazards models.

Results: The 3 most common underlying causes of death were noncerebral neoplasm, cardiovascular, and cerebrovascular disease, accounting for 59% (111/189) of deaths, while epilepsy-related causes (e.g., sudden unexplained death in epilepsy) accounted for 3% (6/189) of deaths. In 23% (43/189) of individuals, the underlying cause of death was directly related to the epilepsy etiology; this was significantly more likely if death occurred within 2 years of the index seizure (percent ratio 4.28 [95% confidence interval 2.63–6.97]). Specific comorbidities independently associated with increased risk of mortality were neoplasms (primary cerebral and noncerebral neoplasm), certain neurologic diseases, and substance abuse.

Conclusions: Comorbid diseases are important causes of death, as well as predictors of premature mortality in epilepsy. There is an especially strong relationship between cause of death and epilepsy etiology in the first 2 years after the index seizure. Addressing these issues may help stem the tide of premature mortality in epilepsy.

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