Mind / Body Blog

More on Vitamin D deficiency in Hashimoto’s thyroiditis

The need for high dose steroid treatment or even IVIG seems to be called into question based on these results. One ounce of prevention?

1.    J Pediatr Endocrinol Metab. 2012;25(5-6):467-70.
Vitamin D status in children with Hashimoto thyroiditis.

Camurdan OM, Döğer E, Bideci A, Celik N, Cinaz P.
Department of Pediatric Endocrinology, School of Medicine, Gazi University, Ankara, Turkey. turkalpo@yahoo.com
Abstract

OBJECTIVE:

To investigate vitamin D status in children with Hashimoto thyroiditis.

SUBJECTS AND METHODS:

The study group consisted of 78 children recently diagnosed as Hashimoto thyroiditis and 74 subjects as the control group. Parameters of calcium metabolism, thyroid function tests, and 25-hydroxyvitamin D [25(OH)D] levels were measured.

RESULTS:

Vitamin D deficiency rate was significantly higher in the Hashimoto group compared with the control subjects (73.1% vs. 17.6%, p < 0.0001). In the Hashimoto group, mean 25(OH)D levels were significantly lower compared with the control group (31.2 +/- 11.5 versus 57.9 +/- 19.7 nmol/L, p < 0.001) and was inversely correlated with the anti-thyroid peroxidase (anti-TPO) levels (r = -0.30, p = 0.007).

CONCLUSION:

The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.

PMID: 22876540 [PubMed – indexed for MEDLINE]
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2.    Thyroid. 2011 Aug;21(8):891-6. doi: 10.1089/thy.2009.0200. Epub 2011 Jul 13.
Relative vitamin D insufficiency in Hashimoto’s thyroiditis.

Tamer G, Arik S, Tamer I, Coksert D.
Department of Endocrinology and Metabolism, Goztepe Education and Research Hospital, Istanbul, Turkey. hgtamer@yahoo.com
Abstract

BACKGROUND:

Vitamin D insufficiency, defined as serum levels of 25-hydroxyvitamin D [25(OH)D3] lower than 30 ng/mL, has been reported to be prevalent in several autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. The goal of the present study was to assess whether vitamin D insufficiency is also a feature of Hashimoto’s thyroiditis (HT).

METHODS:

We performed a prevalence case-control study that included 161 cases with HT and 162 healthy controls. Serum levels of 25(OH)D3, calcium, phosphorus, and parathyroid hormone were measured in all 323 subjects.

RESULTS:

The prevalence of vitamin D insufficiency in HT cases (148 of 161, 92%) was significantly higher than that observed in healthy controls (102 of 162, 63%, p < 0.0001). Among HT cases, the prevalence rate of vitamin D insufficiency showed a trend to be higher in patients with overt hypothyroidism (47 of 50, 94%) or subclinical hypothyroidism (44 of 45, 98%) than in those with euthyroidism (57 of 66, 86%), but the differences were not significant (p = 0.083).

CONCLUSION:

Vitamin D insufficiency is associated with HT. Further studies are needed to determine whether vitamin D insufficiency is a casual factor in the pathogenesis of HT or rather a consequence of the disease.

PMID: 21751884 [PubMed – indexed for MEDLINE]
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3.    Diabetologia. 2009 Dec;52(12):2542-50. doi: 10.1007/s00125-009-1554-x. Epub 2009 Oct 13.
Calcium, vitamin D and dairy intake in relation to type 2 diabetes risk in a Japanese cohort.

Kirii K, Mizoue T, Iso H, Takahashi Y, Kato M, Inoue M, Noda M, Tsugane S; Japan Public Health Center-based Prospective Study Group.
Collaborators: Tsugane S, Inoue M, Sobue T, Hanaoka T, Ogata J, Baba S, Mannami T, Okayama A, Kokubo Y, Miyakawa K, Saito F, Koizumi A, Sano Y, Hashimoto I, Ikuta T, Tanaba Y, Miyajima Y, Suzuki N, Nagasawa S, Furusugi Y, Nagai N, Sanada H, Hatayama Y, Kobayashi F, Uchino H, Shirai Y, Kondo T, Sasaki R, Watanabe Y, Miyagawa Y, Kobayashi Y, Kishimoto Y, Takara E, Fukuyama T, Kinjo M, Irei M, Sakiyama H, Imoto K, Yazawa H, Seo T, Seiko A, Ito F, Shoji F, Saito R, Murata A, Minato K, Motegi K, Fujieda T, Matsui K, Abe T, Katagiri M, Suzuki M, Doi M, Terao A, Ishikawa Y, Tagami T, Sueta H, Doi M, Urata M, Okamoto N, Ide F, Sakiyama H, Onga N, Takaesu H, Uehara M, Horii F, Asano I, Yamaguchi H, Aoki K, Maruyama S, Ichii M, Takano M, Tsubono Y, Suzuki K, Honda Y, Yamagishi K, Sakurai S, Tsuchiya N, Kabuto M, Yamaguchi M, Matsumura Y, Sasaki S, Watanabe S, Akabane M, Kadowaki T, Noda M, Mizoue T, Kawaguchi Y, Takashima Y, Yoshida M, Nakamura K, Matsushima S, Natsukawa S, Shimizu H, Sugimura H, Tominaga S, Iso H, Iida M, Ajiki W, Ioka A, Sato S, Maruyama E, Konishi M, Okada K, Saito I, Yasuda N, Kono S.

Department of Epidemiology and International Health, Research Institute, International Medical Center of Japan, Tokyo, Japan.

Abstract

AIMS/HYPOTHESIS:

Calcium and vitamin D have been implicated in the development of type 2 diabetes, but epidemiological evidence is limited. We examined prospectively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort.

METHODS:

Participants were 59,796 middle-aged and older men and women, who participated in the Japan Public Health Center-based Prospective Study and had no history of type 2 diabetes or other serious diseases. Dietary intake of calcium and vitamin D were estimated using a validated food frequency questionnaire. Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes.

RESULTS:

During a 5 year follow-up, 1,114 cases of type 2 diabetes were documented. Overall, calcium intake was not associated with a significantly lower risk of type 2 diabetes; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 (95% CI 0.71-1.22) in men and 0.76 (95% CI 0.56-1.03) in women. However, among participants with a higher vitamin D intake, calcium intake was inversely associated with diabetes risk; the odds ratio for the highest vs lowest intake categories was 0.62 (95% CI 0.41-0.94) in men and 0.59 (95% CI 0.38-0.91) in women. Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only.

CONCLUSIONS/INTERPRETATION:

Calcium and vitamin D may not be independently associated with type 2 diabetes risk. Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation.

PMID: 19823801 [PubMed – indexed for MEDLINE]
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4.    Int J Immunogenet. 2008 Apr;35(2):125-31. doi: 10.1111/j.1744-313X.2008.00748.x. Epub 2008 Feb 11.
Association of vitamin D receptor gene 3′-variants with Hashimoto’s thyroiditis in the Croatian population.

Stefanić M, Papić S, Suver M, Glavas-Obrovac L, Karner I.
Department of Nuclear Medicine, Radiation Protection and Pathophysiology, Clinical Hospital Osijek, Osijek, Croatia.

Abstract

Hashimoto’s thyroiditis (HT) is the most frequent autoimmune thyroid disease with strong genetic background. Vitamin D receptor (VDR) endocrine system affects immunosuppressive, regulatory and tolerogenic decisions required for induction and maintenance of peripheral immune tolerance. With respect to the biological function of the VDR and functionally plausible gene-expression data, we sought to test whether particular 3′-restriction fragment length polymorphisms (RFLP) and haplotypes previously directly or indirectly associated with VDR mRNA 3′-allelic imbalance phenotype and differences in total VDR mRNA expression are implicated in HT susceptibility. Thus, 145 Croatian HT patients and 145 age-, sex- and ethnically matched euthyroid controls were genotyped for VDR rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI) polymorphisms by polymerase chain reaction-RFLP method. Covariate-adjusted single-locus and haplotype-phenotype regression analyses were performed. Permutation corrections (P(c)) and Akaike Information Criteria were used for model comparisons. The best-fit [global P(c) = 7.2 x 10(-4)]BsmI-TaqI BT haplotype was found significantly more often in subjects without HT [12.2% vs. 3.7%; odds ratio (OR, 95% confidence intervals) = 0.28 (0.14-0.56), P(c) = 8 x 10(-4)], whereas the bT haplotype was significantly more frequent in individuals with HT [45.7% vs. 61.8%; OR = 1.91 (1.37-2.65), P(c) = 4 x 10(-4)]. Two extended BsmI-ApaI-TaqI RFLP haplotypes, the common baT [35.7 vs. 47.3%, OR = 1.63 (1.17-2.27), P(c) = 0.012] and rare BaT variants [6.5 vs. 1.2%, OR = 0.17 (0.06-0.55), P(c) = 1.2 x 10(-3)] were associated with HT, representing predisposing and protective haplotypes, respectively. In single-RFLP association analyses, only rs1544410 polymorphism was associated with HT phenotype (allelic P(c) = 0.0078) and appeared to function under the recessive model, with decreased risk of HT among the BB homozygotes [OR = 0.39 (0.21-0.7), P(c) = 0.0052] when compared to the reference b(+)-genotypes. These data suggest that common haplotypic variants within the VDR gene 3′-region previously linked to VDR mRNA expression and allelic imbalance could be associated with HT in the general population, and thus, may be involved in the pathogenesis of HT.

PMID: 18279374 [PubMed – indexed for MEDLINE]
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5.    J Clin Lab Anal. 2006;20(3):109-12.
Vitamin D receptor gene polymorphisms are associated with risk of Hashimoto’s thyroiditis in Chinese patients in Taiwan.

Lin WY, Wan L, Tsai CH, Chen RH, Lee CC, Tsai FJ.
Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Abstract

The etiology of the autoimmune thyroid, Hashimoto’s thyroiditis (HT) is not very clear. However, genetic susceptibility is thought to play a critical role. The vitamin D receptor (VDR)-related endocrine system has been demonstrated to be able to carry out modulation of the immune response. Here, we investigated whether single nucleotide polymorphisms (SNPs) of VDR are associated with HT patients. VDR SNP was detected by polymerase chain reaction (PCR)-based restriction analysis in 109 patients with HT and 90 normal controls. Significant differences were found in the genotype distribution of VDR SNP between Hashimoto’s thyroiditis patients and controls (P=0.0458). Allelic frequency of the VDR gene distinguished HT patients from controls (P=0.0089). The results revealed a significant difference between HT patients and normal controls in VDR SNP and a statistic correlation between VDR-FokI polymorphisms and HT formation. It could be concluded that patients who carry the C/C homozygote of the VDR-FokI gene polymorphism in exon 2 may have a higher risk of developing HT in Chinese patients in Taiwan.

(c) 2006 Wiley-Liss, Inc.

PMID: 16721822 [PubMed – indexed for MEDLINE]
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North Shore-Lenox Hill Hospital Neurology Grand Rounds on May 21, 2013 Topic: Panic, Separation Anxiety, Suffocation False Alarms and Endogenous Opioids: How panic research can inform clinical neurology.

I will be giving North Shore-Lenox Hill Hospital Neurology Grand Rounds on May 21, 2013 – all invited!

Topic:    Panic, Separation Anxiety, Suffocation False Alarms and Endogenous Opioids: How panic research can inform clinical neurology. 

Speaker:  Maurice Preter, MD

Date:          5/21/2013

Time:    8:30-9:30 AM                 

Location:  2nd Floor Achelis Conference Room

[PDF is here: North Shore flyer may 21]

Learning Objectives: Upon completion of this session, participants should be able to:

1) Understand research on panic and separation anxiety

2) Be able to apply the research findings on panic and separation anxiety to neurology practice.

Target Audience: Neurologists, Neurosurgeons, Neuropsychiatrists and Neuroradiologists

CME Accreditation:

North Shore-LIJ Health System is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

 Credit Designation

The North-Shore LIJ Health System designates this live activity for a maximum of 1 AMA PRA Category 1 credit ™.  Physicians should only claim credit commensurate with the extent of their participation in the activity.

Disclosure Policy:  North Shore-LIJ Health System adheres to the ACCME’s New Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by North Shore-LIJ for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations.

Planner and Speaker’s Disclosures: Dr. Preter has nothing to disclose.

Recognition of Program Support: An announcement of program support will be made to all attendees at the beginning of each Regularly Scheduled Session

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Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study : The Lancet Neurology

The Lancet Neurology, Volume 12, Issue 3, Pages 244 – 252, March 2013

Published Online: 23 January 2013

Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study

Prof Kimford J Meador MD a Corresponding AuthorEmail Address, Gus A Baker PhD b, Nancy Browning PhD c, Morris J Cohen EdD d, Rebecca L Bromley PhD e, Jill Clayton-Smith MD f, Laura A Kalayjian MD g, Andres Kanner MD h, Joyce D Liporace MD i, Page B Pennell MD j, Michael Privitera MD k, David W Loring PhD a, for the NEAD Study Group†

Summary

Background

Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age.

Methods

In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866.

Findings

We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94—101) than to carbamazepine (105, 102—108; p=0·0015), lamotrigine (108, 105—110; p=0·0003), or phenytoin (108, 104—112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=—0·56, p<0·0001), verbal ability (r=—0·40, p=0·0045), non-verbal ability (r=—0·42, p=0·0028), memory (r=—0·30, p=0·0434), and executive function (r=—0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ improved with age for infants exposed to any antiepileptic drug. Compared with a normative sample (173 [93%] of 187 children), right-handedness was less frequent in children in our study overall (185 [86%] of 215; p=0·0404) and in the lamotrigine (59 [83%] of 71; p=0·0287) and valproate (38 [79%] of 40; p=0·0089) groups. Verbal abilities were worse than non-verbal abilities in children in our study overall and in the lamotrigine and valproate groups. Mean IQs were higher in children exposed to periconceptional folate (108, 95% CI 106—111) than they were in unexposed children (101, 98—104; p=0·0009).

Interpretation

Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.

Funding

US National Institutes of Health, UK Epilepsy Research Foundation.

via Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study : The Lancet Neurology.

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Job creation (paying jobs, that is) anyone? Suicide Among Adults Aged 35–64 Years — United States, 1999–2010

Job creation (paying jobs, that is) anyone?

From the CDC:
Suicide Among Adults Aged 35–64 Years — United States, 1999–2010
.

Suicide Among Adults Aged 35–64 Years — United States, 1999–2010

Weekly

May 3, 2013 / 62(17);321-325

Suicide is an increasing public health concern. In 2009, the number of deaths from suicide surpassed the number of deaths from motor vehicle crashes in the United States (1). Traditionally, suicide prevention efforts have been focused mostly on youths and older adults, but recent evidence suggests that there have been substantial increases in suicide rates among middle-aged adults in the United States (2). To investigate trends in suicide rates among adults aged 35–64 years over the last decade, CDC analyzed National Vital Statistics System (NVSS) mortality data from 1999–2010. Trends in suicide rates were examined by sex, age group, race/ethnicity, state and region of residence, and mechanism of suicide. The results of this analysis indicated that the annual, age-adjusted suicide rate among persons aged 35–64 years increased 28.4%, from 13.7 per 100,000 population in 1999 to 17.6 in 2010. Among racial/ethnic populations, the greatest increases were observed among American Indian/Alaska Natives (AI/ANs) (65.2%, from 11.2 to 18.5) and whites (40.4%, from 15.9 to 22.3). By mechanism, the greatest increase was observed for use of suffocation (81.3%, from 2.3 to 4.1), followed by poisoning (24.4%, from 3.0 to 3.8) and firearms (14.4%, from 7.2 to 8.3). The findings underscore the need for suicide preventive measures directed toward middle-aged populations.

CDC used the Web-based Injury Statistics Query and Reporting System (3) to compile NVSS data on suicides reported during 1999–2010 among U.S. residents aged >10 years. Age group–specific annual suicide rates, as well as age-adjusted annual suicide rates calculated using the U.S. standard 2000 population, were based on bridged race population estimates from the U.S. Census Bureau. Trends in age-adjusted suicide rates from 1999, when signs of an increase began (4), through 2010, the latest data available, were analyzed for adults aged 35–64 years by sex and mechanism of suicide. The three most common suicide mechanisms were firearms (i.e., penetrating injury or gunshot wound from a weapon using a powder charge to fire a projectile), poisoning (predominantly drug overdose), and suffocation (predominantly hanging). These three mechanisms and an “all other” mechanism category were used for comparisons. Data also were analyzed by age group, race/ethnicity,* and U.S. Census region.

Percentage changes in observed suicide rates from 1999 to 2010 were calculated along with corresponding 95% confidence intervals, assuming a Poisson distribution. Tests of significance of trends in annual age-adjusted suicide rates for adults aged 35–64 years across the 12-year period were conducted using joinpoint regression (5), assuming a log-linear model. This report focuses on adults aged 35–64 years because percentage changes from 1999 to 2010 in the annual age-adjusted suicide rates for persons aged 10–34 years and ≥65 years were comparatively small and not statistically significant (a 7.0% increase from 9.2 in 1999 to 9.9 in 2010 [p = 0.06] and a 5.9% decrease from 15.8 in 1999 to 14.9 in 2010 [p = 0.09], respectively). Finally, data were analyzed by state, and percentage changes in age-adjusted suicide rates from 1999 to 2010 were calculated for all 50 states.

From 1999 to 2010, the age-adjusted suicide rate for adults aged 35–64 years in the United States increased significantly by 28.4%, from 13.7 per 100,000 population to 17.6 (p<0.001) (Table 1). The suicide rate for men aged 35–64 years increased 27.3%, from 21.5 to 27.3, and the rate for women increased 31.5%, from 6.2 to 8.1 (Table 2). Among men, the greatest increases were among those aged 50–54 years and 55–59 years, (49.4%, from 20.6 to 30.7, and 47.8%, from 20.3 to 30.0, respectively). Among women, suicide rates increased with age, and the largest percentage increase in suicide rate was observed among women aged 60–64 years (59.7%, from 4.4 to 7.0).

By racial/ethnic population, the greatest increases from 1999 to 2010 among men and women overall were observed among AI/ANs (65.2%, from 11.2 to 18.5) and whites (40.4%, from 15.9 to 22.3). Among AI/ANs, the suicide rate for women increased 81.4%, from 5.7 to 10.3; the rate for men increased 59.5%, from 17.0 to 27.2. Among whites, the rate for women increased 41.9%, from 7.4 to 10.5; the rate for men increased 39.6%, from 24.5 to 34.2.

Suicide rates from 1999 to 2010 increased significantly across all four geographic regions and in 39 states. In 2010, rates for adults aged 35–64 years were highest (19.5 per 100,000 population) in the West U.S. Census Region (Table 1). By suicide mechanism, age-adjusted rates increased for the three primary mechanisms for both men and women (Figure). Firearms and suffocation were the most common mechanisms for men (14.3 and 6.8 in 2010, respectively), whereas poisoning and firearms were the most common mechanisms for women (3.4 and 2.5 in 2010, respectively). By mechanism, the greatest increase was observed for use of suffocation (81.3%, from 2.3 to 4.1), followed by poisoning (24.4%, from 3.0 to 3.8) and firearms (14.4%, from 7.2 to 8.3) (Table 1). By sex, the increase for suffocation was 75.0% for men (from 3.9 to 6.8) and 115.0% for women (from 0.7 to 1.5) (Table 2). From 1999 to 2010, suicides by suffocation increased from 18% to 24% of all suicides for men and from 12% to 18% of all suicides for women.

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JAMA Internal Medicine | Perioperative Use of Selective Serotonin Reuptake Inhibitors and Risks for Adverse Outcomes of SurgeryPerioperative SSRI Use and Adverse Outcome Risk

Original Investigation | ONLINE FIRST

Perioperative Use of Selective Serotonin Reuptake Inhibitors and Risks for Adverse Outcomes of Surgery

Andrew D. Auerbach, MD, MPH; Eric Vittinghoff, PhD; Judith Maselli, MSPH; Penelope S. Pekow, PhD; John Q. Young, MD; Peter K. Lindenauer, MD, MS
JAMA Intern Med. 2013;():1-7. doi:10.1001/jamainternmed.2013.714.
Text Size: A A A
Published online April 29, 2013

Importance  Single-site studies have described an association between use of selective serotonin reuptake inhibitors (SSRIs) and adverse outcomes of surgery. Multicenter studies including a broad range of surgical procedures that explore rare outcomes, such as bleeding and mortality, and that account for indications for administration of SSRIs are needed.

Objective  To determine whether perioperative use of SSRIs is associated with adverse outcomes of surgery in a national sample of patients.

Design  Retrospective study of patients 18 years or older who underwent major surgery from January 1, 2006, through December 31, 2008, at 375 US hospitals. We used multivariable hierarchical models to estimate associations between SSRI use and our outcomes. Pharmacy data were used to determine whether a patient received an SSRI in the perioperative period.

Setting  Three hundred seventy-five US hospitals.

Participants  Five hundred thirty thousand four hundred sixteen patients 18 years or older.

Exposure  Perioperative use of SSRIs.

Main Outcomes and Measures  In-hospital mortality, length of stay, readmission at 30 days, bleeding events, transfusions, and incidence of ventricular arrhythmias.

Results  Patients receiving SSRIs were more likely to have obesity, chronic pulmonary disease, or hypothyroidism (P < .001 for each) and more likely to have depression (41.0% vs 6.2%, P < .001). After adjustment, patients receiving SSRIs had higher odds of in-hospital mortality (adjusted odds ratio, 1.20 [95% CI, 1.07-1.36]), bleeding (1.09 [1.04-1.15]), and readmission at 30 days (1.22 [1.18-1.26]). Similar results were observed in propensity-matched analyses, although the risk of inpatient mortality was attenuated among patients with depression. Sensitivity analyses suggest that, to invalidate our results, an unmeasured covariate would have to have higher prevalence and be more strongly associated with mortality than any covariate included in our models.

Conclusions and Relevance  Receiving SSRIs in the perioperative period is associated with a higher risk for adverse events. Determining whether patient factors or SSRIs themselves are responsible for elevated risks requires prospective study.

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