Search

Background: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations., Methods: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them., Results: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use., Conclusions: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research., Limitations: Online data collection may have resulted in the underrepresentation of certain population groups., Competing Interests: Declaration of competing interest None pertaining to the current paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders., Methods: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions., Results: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome., Conclusions: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

Introduction: The current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak., Materials and Methods: The data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively., Statistical Analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables., Results: Clinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p < 0.0001). Suicidal tendencies were at least doubled in terms of RASS scores. Approximately one-third of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop clinical depression was associated with a history of Bipolar disorder (RR = 4.23)., Conclusions: The current study reported findings in health care professionals similar in magnitude and quality to those reported earlier in the general population although rates of clinical depression, suicidal tendencies, and adherence to conspiracy theories were much lower. However, the general model of factors interplay seems to be the same and this could be of practical utility since many of these factors are modifiable., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: During the COVID-19 pandemic various degrees of lockdown were applied by countries around the world. It is considered that such measures have an adverse effect on mental health but the relationship of measure intensity with the mental health effect has not been thoroughly studied. Here we report data from the larger COMET-G study pertaining to this question., Material and Methods: During the COVID-19 pandemic, data were gathered with an online questionnaire from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Anxiety was measured with the STAI, depression with the CES-D and suicidality with the RASS. Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively., Statistical Analysis: It included the calculation of Relative Risk (RR), Factorial ANOVA and Multiple backwards stepwise linear regression analysis RESULTS: Approximately two-thirds were currently living under significant restrictions due to lockdown. For both males and females the risk to develop clinical depression correlated significantly with each and every level of increasing lockdown degree (RR 1.72 and 1.90 respectively). The combined lockdown and psychiatric history increased RR to 6.88 The overall relationship of lockdown with severity of depression, though significant was small., Conclusions: The current study is the first which reports an almost linear relationship between lockdown degree and effect in mental health. Our findings, support previous suggestions concerning the need for a proactive targeted intervention to protect mental health more specifically in vulnerable groups., (Copyright © 2022. Published by Elsevier B.V.)

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular., Competing Interests: Declaration of Competing Interest Guy M. Goodwin is a NIHR Emeritus Senior Investigator, holds shares in P1vital and P1Vital products and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, P1Vital, Sage, Servier. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Michael Berk is supported by a NHMRC Senior Principal Research Fellowship (1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. Andreas Meyer-Lindenberg has received consultant fees from: Boehringer Ingelheim, Elsevier, Brainsway, Lundbeck Int. Neuroscience Foundation, Lundbeck A/S, The Wolfson Foundation, Bloomfield Holding Ltd, Shanghai Research Center for Brain Science, Thieme Verlag, Sage Therapeutics, v Behring Röntgen Stiftung, Fondation FondaMental, Janssen-Cilag GmbH, MedinCell, Brain Mind Institute, Agence Nationale de la Recherche, CISSN (Catania Internat. Summer School of Neuroscience), Daimler und Benz Stiftung, American Association for the Advancement of Science, Servier International. Additionally, he has received speaker fees from: Italian Society of Biological Psychiatry, Merz-Stiftung, Forum Werkstatt Karlsruhe, Lundbeck SAS France, BAG Psychiatrie Oberbayern, Klinik für Psychiatrie und Psychotherapie Ingolstadt, med Update GmbH, Society of Biological Psychiatry, Siemens Healthineers, Biotest AG -All unrelated to this work. Terence A. Ketter has been a consultant to Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, Abbvie, and Alkermes. Joseph Goldberg has been a consultant to BioXCel, Otsuka, Sage Pharmaceuticals, Sunovion, and WebMD, and served on the speaker boards for Allergan, Intracellular Therapies, and Sunovion. Rif S. El-Mallakh is on the speaker bureau of Alkermes, Eisai, Indivior, Intra-Cellular Therapeutics, Janssen, Lundbeck, Noven, Otsuka, Sunonvion, and Teva. Lakshmi N Yatham has been on speaker/advisory boards for, or has received research grants from Abbvie, Alkermes, Allergan, CANMAT, CIHR, DSP, Merck, and Sanofi Rasmus W. Licht has within the preceding three years served an advisory board of Janssen Cilag and Sagw, and received speaker honorarium from Astra-Zeneca, Jannsen-Cilag, Servier and Lundbeck Allan H. Young has been employed by King's College London; Honorary Consultant SLaM (NHS UK). Young has participated in paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS Allan H. Young's independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.Consultant to Johnson & Johnson and Livanova. Received honoraria for attending advisory boards and presenting talks at meetings organized by LivaNova. Prof. Alessandro Serretti is or has been consultant/speaker for: Abbott, Abbvie, Angelini, Astra Zeneca, Clinical Data, Bo- heringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier. Ayşegül Yildiz has nothing to declare. Jean Michel Azorin has received honoraria or research or educational conference grants from Lundbeck and Otsuka. Othman Sentissi has received advisory board honoraria or research or educational conference from Otsuka, Lilly, Lundbeck, Sandoz, Janssen and Sunovion on an institutional account for research and teaching. Prof. Gordon Parker has received lecture fees and board member honoraria from Otsuka, Servier and Lundbeck. Dr. David Bond has received consulting fees and/or research grants from Alkermes, Myriad Genetics, the National Institutes of Health, the University of Minnesota Department of Psychiatry and Behavioral Sciences, and the University of Minnesota Foundation. Prof. Giulio Perugi has received grant/research support from Eli Lilly & Co.; is on the speaker/advisory board of Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Eli Lilly & Co., Jannsen-Cilag, and Lundbeck; and has acted as consultant of AstraZeneca, Eli Lilly & Co., and Lundbeck. Prof. Eduard Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB- Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. Dina Popovic has served as a speaker and/or medical writer and/or consultant and/or has participated in advisory boards for Bristol-Myers Squibb, Dexel, Merck Sharp & Dohme, Janssen-Cilag, Lundbeck, Ferrer, and Forum Pharmaceuticals. None of the remaining authors have conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. and ECNP. All rights reserved.)

Introduction: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study., Material and Methods: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively., Statistical Analysis: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables., Results: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed., Conclusions: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them., Competing Interests: Conflict of Interest None pertaining to the current paper., (Copyright © 2021 Elsevier B.V. and ECNP. All rights reserved.)

Objectives: The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC)., Methods: Psychiatric symptoms, socio-demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD-RC) and without (BD-NRC) RC were compared., Results: Of 726 BD patients, 159 (21.9%) met DSM-5 criteria for RC. BD-RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007)., Conclusions: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Twin studies are among the most promising strategies for studying heritable disorders, including bipolar disorder (BD). The aim of the present study was to identify distinguishing genes between monozygotic (MZ) twins with different BD phenotype and compare them to their non-affected siblings. Whole-exome sequencing (WES) can identify rare and structural variants that could detect the polygenetic burden of complex disorders. WES was performed on a family composed of two MZ twins with BD, their unaffected brother and unaffected parents. The twins have a discordant response to lithium and distinct course of illness. Following WES, six genes of particular interest emerged: Neurofibromin type 1 (NF1), Biorientation of chromosomes in cell division 1 (BOD1), Golgi-associated gamma adaptin ear-containing ARF binding protein 3 (GGA3), Disrupted in schizophrenia 1 (DISC1), Neuromedin U receptor 2 (NMUR2), and Huntingtin interacting protein 1-related (HIP1R). Interestingly, many of these influence glutamatergic pathways and thus the findings may have therapeutical implications. These results may provide important insights to unveil genetic underpinnings of BD and the response to lithium., Competing Interests: Competing interest Prof. Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. Prof. Serretti is or has been consultant/speaker for: Abbott, Abbvie, Angelini, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier. Dr. Popovic has served as a speaker and/or medical writer or has participated in advisory boards for Bristol-Myers Squibb, Merck Sharp & Dohme, Janssen-Cilag, Ferrer, and Forum Pharmaceuticals., (Copyright © 2020. Published by Elsevier B.V.)

Recent success of established treatment has driven concerns about the ethics of using placebo-controlled trials in psychiatry. Active-controlled (superiority or non-inferiority) trials do not include a placebo-arm and thus avoid the associated ethical concerns but show disadvantages in other respects. The aim of this paper is to review the available literature and critically discuss the evidence regarding the use of placebo-controlled- versus active-controlled trials. A MEDLINE/PubMed and Google Scholar search was performed. Studies included focused on the deliberation on placebo-controlled- versus active-controlled trials. Twenty-six studies were included. The most cited benefits of placebo-controlled trials were greater scientific reliability of the results and no average impact on patients' health. Disadvantages were mainly related to withholding effective treatment and limited generalizability. The most frequent argument in favor of active-controlled trials is the lower chance of receiving ineffective medication during the trial. Downsides include larger sample sizes, higher costs and lower scientific reliability of results. Most authors agree that all trial designs are relevant to psychiatric research depending on study goals. Whatsoever, data does not support forgoing placebo-controlled trials. Expert consensus is warranted to permit drawing conclusions on the debate on the relevance of placebo-controlled trials., Competing Interests: Conflict of Interest All authors declare that they have no conflict of interests., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Bipolar disorder (BD) is a highly heritable and disabling mental illness, commonly associated with substance abuse, being alcohol abuse the most frequent. Comorbid BD and substance abuse disorders are often associated with high levels of health service utilization and destabilization of the course of illness resulting in poor treatment outcomes. Although recent genome-wide association studies have detected a number of risk genes for BD, the data is still sparse and inconclusive for those genes that may contribute to the increased risk of comorbid alcohol abuse (AA) in BD. The primary aim of the present study was to investigate the effects of 46 single-nucleotide polymorphisms (SNPs) within eight genes on different phenotypes of BD patients, such as comorbid alcohol abuse. We further assessed clinical variables associated with AA., Methods: One-hundred fifty-eight BD I and II patients were enrolled in a naturalistic cohort study. Genomic DNA of 92 patients was extracted from whole blood using standard procedures and 46 tag SNPs in eight genes of interest (ANK, CACNA1C, CACNB2, FKBP5, GRM7, ITIH3, SYNE1 and TCF4) were genotyped., Results: Seventy-one patients out of 158 (45%) satisfied diagnostic criteria for comorbid AA. Among 46 SNPs analyzed, the only SNP associated with comorbid AA was rs1034936 polymorphism in the CANCA1C gene. This polymorphism was also associated with lifetime cocaine abuse, manic switch and current atypical antipsychotics., Conclusions: Our findings suggest a role of rs1034936 CACNA1C gene variant in BD-AA group. Despite their preliminary nature, the present results may provide new insight on mechanisms underlying AA in BD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Several single-center studies have found raloxifene, an estrogen agonist, to be effective in ameliorating symptoms of schizophrenia in stable patients as augmentation of antipsychotics. This multicenter study assessed whether raloxifene plus antipsychotic treatment, in comparison to placebo plus antipsychotics, improves symptoms or cognition in severely ill decompensated schizophrenia patients., Methods: In this 16-week, double-blind, randomized, placebo-controlled study, 200 severely ill, decompensated postmenopausal women who met DSM-IV-TR criteria for schizophrenia or schizoaffective disorder were recruited from January 2011 to December 2012 and were randomized to receive either raloxifene 120 mg/d plus antipsychotics or placebo plus antipsychotics. The primary outcome measure was Positive and Negative Syndrome Scale (PANSS) total score at the end of the trial., Results: The placebo plus antipsychotics group experienced statistically significant improvement in PANSS total score (P < .001) compared to the raloxifene plus antipsychotics group, using mixed models for repeated measures, with results favoring placebo by 4.5 points (95% CI, 2.3-6.7). These results were clearly outside the 95% confidence interval. This negative effect was more pronounced in patients who had more frequent relapses and in those with baseline PANSS scores of 100 or higher. There were no differences between groups in Clinical Global Impression Scale-Severity scores or Composite Brief Assessment of Cognition in Schizophrenia scores at 16 weeks (P > .3). Baseline follicle-stimulating hormone and estradiol levels did not alter the drug-placebo differences., Conclusions: Individuals in the active treatment arm showed worse outcome than those in the placebo arm, most likely as a result of chance variation, but the results unequivocally show no benefit of antipsychotics plus raloxifene versus antipsychotics plus placebo in this large randomized, double-blind, placebo-controlled trial in postmenopausal women. These data do not support the use of raloxifene in severely decompensated schizophrenia patients until reliable research identifies what subgroup of patients or domain of outcome is benefited., Trial Registration: ClinicalTrials.gov identifier: NCT01280305., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Background: Since 2001, we have observed patients with a clinical picture consistent with West Nile virus (WNV) infection, which was defined as nonprimary infection (NPI) owing to the presence of highly elevated serum immunoglobulin G antibody titers with a high avidity index (≥ 55%), absent or low titers of serum and cerebrospinal fluid (CSF) immunoglobulin M, and occasionally positive results of WNV-specific real-time reverse-transcription polymerase chain reaction analysis of CSF and/or blood specimens., Methods: We investigated 124 patients with a diagnosis of primary WNV infection (PI) or NPI during 2005-2007 at Sheba Medical Center (Tel-Hashomer, Israel). Logistic regression was used to evaluate the association of variables with PI and NPI and with in-hospital mortality., Results: A total of 68 and 50 patients with PI and NPI, respectively were included; 6 patients had incomplete data. In multivariate models, NPI was significantly associated with underlying psychiatric disorders (adjusted odds ratio [aOR], 13.73; 95% confidence interval [CI], 2.28-82.56; P = .004), hospitalization during winter and spring (aOR, 8.82; 95% CI, 1.59-48.87; P = .013), and fever (aOR, 0.61; 95% CI, .39-.95; P = .031). In-hospital mortality was significantly associated with NPI (aOR, 3.86; 95% CI, 1.12-13.28; P = .032) and a higher Charlson comorbidity index (aOR, 1.37; 95% CI, 1.03-1.83; P = .032)., Conclusions: The possibility that NPI may be an emerging clinical entity with a high mortality rate must be considered seriously., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infections are emerging, but their clinical significance remains unclear. Our objective was to compare patients who had hVISA bacteremia with patients who had methicillin-resistant S. aureus (MRSA) bacteremia., Methods: A total of 27 case patients with hVISA bacteremia were compared with 223 control patients with MRSA bacteremia. Medical records of all patients were reviewed, and factors independently associated with infection-related mortality were assessed by logistic regression., Results: Patients with hVISA bacteremia were not significantly different from those with MRSA bacteremia with respect to age, comorbidities, duration of hospital stay, and infection-attributable mortality. However, the median duration of bacteremia among patients with hVISA was significantly longer than that among patients with MRSA (12 vs. 2 days; P = .005), and patients with hVISA had a greater prevalence of complications, such as endocarditis (18.5% vs. 3.6%; P = .007) and osteomyelitis (25.9% vs. 7.2%, respectively; P = .006). Rifampin resistance emerged more frequently among hVISA isolates than among MRSA isolates (44% vs. 5.9%; P < .001). Factors independently associated with infection-related mortality in all patients were age, Charlson comorbidity index, female sex, and being bedridden., Conclusions: hVISA bacteremia was significantly associated with prolonged bacteremia duration, greater rates of complications, and emergence of rifampin resistance, compared with MRSA bacteremia. However, no significant difference in mortality existed between patients with hVISA bacteremia and those with MRSA bacteremia.