scholarly journals Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Mikael Landén ◽  
Henrik Larsson ◽  
Paul Lichtenstein ◽  
Johan Westin ◽  
Jie Song
Keyword(s):  
Bipolar Disorder ◽  
Cox Regression ◽  
Psychiatric Symptoms ◽  
Respiratory Infections ◽  
Lithium Treatment ◽  
Mood Stabilizer ◽  
Patient Register ◽  
Real World Evidence ◽  
Swedish Patient

Abstract Background In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment. Conclusions This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.

scholarly journals Respiratory infection during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

2020 ◽  
Author(s):  
Mikael Landén ◽  
Paul Lichtenstein ◽  
Henrik Larsson ◽  
Jie Song
Keyword(s):  
Bipolar Disorder ◽  
Cox Regression ◽  
Psychiatric Symptoms ◽  
Respiratory Infections ◽  
Lithium Treatment ◽  
Mood Stabilizer ◽  
Patient Register ◽  
Real World Evidence ◽  
Swedish Patient

AbstractObjectiveIn vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium’s effect on psychiatric symptoms, we also studied the effect of the most common alternative to lithium to prevent mood episodes in bipolar disorder, valproate.MethodWe followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005–2013. We applied a with-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods.ResultsDuring follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61–0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06–1.73) compared with periods off treatment.ConclusionsThis study provides real-world evidence that lithium protects against respiratory infections and suggests that the repurposing potential of lithium for antiviral effects is worthy of investigation.

Alternative treatment options for lithium-induced nephrogenic diabetes insipidus

2016 ◽  
Vol 33 (S1) ◽  
pp. S392-S392 ◽  
Author(s):  
S. López-Romeo ◽  
G. Ledesma-Iparraguirre
Keyword(s):  
Bipolar Disorder ◽  
Case Report ◽  
Diabetes Insipidus ◽  
Alternative Treatment ◽  
Nephrogenic Diabetes Insipidus ◽  
Lithium Treatment ◽  
Treatment Options ◽  
Mood Stabilizer ◽  
Manic Episode ◽  
Forced Diuresis

IntroductionLithium is currently a drug of choice for treating persons with bipolar disorder and is widely used in this population. Approximately, 30% of patients taking lithium experience at least one episode of lithium toxicity. Treatment of acute toxicity involves correction of electrolyte abnormalities, volume repletion followed by forced diuresis, and dialysis in severe cases. A case report is described and it is reviewed some alternative treatment options before considering withdrawal of lithium treatment in lithium-induced nephrogenic diabetes insipidus.Case reportA 58-year-old woman diagnosed of hypertension and bipolar disorder for 20 years. At first, she was controlled with valproic acid until she suffered a manic episode which required a mood stabilizer switch. She started a treatment with lithium 1200 mg/day and olanzapine to 10 mg/day and was completely recovered. After a year of stabilization, olanzapine was retired and she maintained stabilized with lithium 1000 mg/day during last 17 years. During last 8 months, she suffered polydipsia and polyuria (4 L/day). She was diagnosed of nephrogenic diabetes insipidus. Some measures like liquid restriction, lithium monodose and low sodium diet were carried out, obtaining a partial response. Taking into account, she was stabilised with lithium for many years, it was decided to introduce hydrochlorothiazide 25 mg/day, clinical and analytical resolution of nephrogenic diabetes insipidus was obtained. A year later, she maintains psychopathological stabilization, without any lithium secondary effects.ConclusionSome treatment options for lithium-induced nephrogenic diabetes insipidus could be introducing thiazides, amiloride, indomethacin, desmopressin or carbamazepine, instead of withdrawal lithium.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Studying cellular functions in bipolar disorder: Are there specific predictors of lithium response?

2019 ◽  
Author(s):  
Pradip Paul ◽  
Shruti Iyer ◽  
Ravi Kumar Nadella ◽  
Rashmitha Nayak ◽  
Anirudh S. Chellappa ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Lithium Treatment ◽  
Healthy Population ◽  
Outpatient Services ◽  
Mitochondrial Potential ◽  
Lithium Response ◽  
Cellular Phenotypes

ABSTRACTBackgroundLithiumis the first-line mood stabilizer for the treatment of bipolar disorder (BD). In order to interrogate cellular phenotypes related to disease and lithium treatment response, this study used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs) from BD patients who are well characterized for clinical lithium response.MethodsBDpatientsdiagnosed according to the DSM-IV criteria; were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Clinical lithium response was assessed using the “Alda scale” and “NIMH Retrospective Life chart method”. The controls were ethnically matched healthy subjects with no family history of neuropsychiatric illness. NPCs from two BD patients from the same family who clearly differed in their clinical response to lithium were chosen, and compared with healthy population controls. Whole transcriptome sequencing (RNA-Seq) and analysis were performed, with and withoutin vitrolithium (1mM for 7 days). In addition, mitochondrial membrane potential (MMP), cell viability and cell proliferation parameters were examined. Experiments were also performed in 25 LCLs from BD patients (16 lithium responders and 9 lithium non-responders), and 12 healthy control LCLs, to evaluate them in a system amenable to clinical translation.ResultsRNA-Sequencingand analysis did not reveal differences in NPCs onin vitrolithium treatment. MMP was lower in BD, both in NPCs and LCLs; reversal within vitrolithium happened only in LCLs and was unrelated to lithium response. Cell proliferation was higher in BD compared to controls, and there was no change on lithium addition. Cell viability assays indicated greater cell death in BD; which could only be rescued in LCLs of clinical lithium responders. The latter finding was associated with enhancedBCL2andGSK3Bexpression within vitrolithium.DiscussionOverall, our study findings indicate that there are cellular phenotypes related to the disease (mitochondrial potential, cell proliferation) in NPCs and LCLs. We also observed clinical lithium response related phenotypes (cell viability,BCL2/ GSK3Bexpression) in LCLs. The next step would be to evaluate a larger set of PBMCs from clinical lithium response groups of BD to derive cellular phenotypes related to direct clinical application.

scholarly journals Circular RNA circCCNT2 is upregulated in the anterior cingulate cortex of individuals with bipolar disorder

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rixing Lin ◽  
Juan Pablo Lopez ◽  
Cristiana Cruceanu ◽  
Caroline Pierotti ◽  
Laura M. Fiori ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Anterior Cingulate Cortex ◽  
Rna Sequencing ◽  
Lithium Treatment ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Circular Rnas ◽  
Sequencing Analysis ◽  
The Brain

AbstractGene expression dysregulation in the brain has been associated with bipolar disorder, but little is known about the role of non-coding RNAs. Circular RNAs are a novel class of long noncoding RNAs that have recently been shown to be important in brain development and function. However, their potential role in psychiatric disorders, including bipolar disorder, has not been well investigated. In this study, we profiled circular RNAs in the brain tissue of individuals with bipolar disorder. Total RNA sequencing was initially performed in samples from the anterior cingulate cortex of a cohort comprised of individuals with bipolar disorder (N = 13) and neurotypical controls (N = 13) and circular RNAs were identified and analyzed using “circtools”. Significant circular RNAs were validated by RT-qPCR and replicated in the anterior cingulate cortex in an independent cohort (24 bipolar disorder cases and 27 controls). In addition, we conducted in vitro studies using B-lymphoblastoid cells collected from bipolar cases (N = 19) and healthy controls (N = 12) to investigate how circular RNAs respond following lithium treatment. In the discovery RNA sequencing analysis, 26 circular RNAs were significantly differentially expressed between bipolar disorder cases and controls (FDR < 0.1). Of these, circCCNT2 was RT-qPCR validated showing significant upregulation in bipolar disorder (p = 0.03). This upregulation in bipolar disorder was replicated in an independent post-mortem human anterior cingulate cortex cohort and in B-lymphoblastoid cell culture. Furthermore, circCCNT2 expression was reduced in response to lithium treatment in vitro. Together, our study is the first to associate circCCNT2 to bipolar disorder and lithium treatment.

scholarly journals COVID-19 outcomes among hospitalized men with or without exposure to alpha-1-adrenergic receptor blocking agents

2021 ◽  
Author(s):  
Shilong Li ◽  
Tomi Jun ◽  
Zichen Wang ◽  
Yu-Han Kao ◽  
Emilio Schadt ◽  
...  
Keyword(s):  
New York ◽  
Hospital Mortality ◽  
Adrenergic Receptor ◽  
Cox Regression ◽  
Respiratory Infections ◽  
Age Groups ◽  
Medical Response ◽  
Real World Evidence ◽  
Level Data ◽  
Α1 Blocker

Importance: Alpha-1-adrenergic receptor antagonists (α1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as α1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between α1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: α1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to α1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to α1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of α1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient α1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient α1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of α1-blockers in COVID-19 are warranted.

Predictive Model for Live Birth at 12 Months After Starting In-Vitro Fertilization Treatment

MedPharmRes ◽  
2018 ◽  
Vol 2 (2) ◽  
pp. 5-20
Author(s):  
Vu Ho ◽  
Toan Pham ◽  
Tuong Ho ◽  
Lan Vuong
Keyword(s):  
In Vitro Fertilization ◽  
Live Birth ◽  
Cox Regression ◽  
Financial Burden ◽  
Oocyte Retrieval ◽  
Operating Characteristics ◽  
Vitro Fertilization ◽  
Cox Regression Analysis ◽  
Significant Difference

IVF carries a considerable physical, emotional and financial burden. Therefore, it would be useful to be able to predict the likelihood of success for each couple. The aim of this retrospective cohort study was to develop a prediction model to estimate the probability of a live birth at 12 months after one completed IVF cycle (all fresh and frozen embryo transfers from the same oocyte retrieval). We analyzed data collected from 2600 women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at a single center in Vietnam between April 2014 and December 2015. All patients received gonadotropin-releasing hormone (GnRH) antagonist stimulation, followed by fresh and/or frozen embryo transfer (FET) on Day 3. Using Cox regression analysis, five predictive factors were identified: female age, total dose of recombinant follicle stimulating hormone used, type of trigger, fresh or FET during the first transfer, and number of subsequent FET after the first transfer. The area under the receiver operating characteristics curve for the final model was 0.63 (95% confidence interval [CI] 0.60‒0.65) and 0.60 (95% CI 0.57‒0.63) for the validation cohort. There was no significant difference between the predicted and observed probabilities of live birth (Hosmer-Lemeshow test, p > 0.05). The model developed had similar discrimination to existing models and could be implemented in clinical practice.

Considering a Potential Role of Linalool as a Mood Stabilizer for Bipolar Disorder

2020 ◽  
Vol 26 (40) ◽  
pp. 5128-5133
Author(s):  
Kate Levenberg ◽  
Wade Edris ◽  
Martha Levine ◽  
Daniel R. George
Keyword(s):  
Bipolar Disorder ◽  
Treatment Options ◽  
Mood Stabilizer ◽  
Well Being ◽  
Epidemiologic Studies ◽  
Treatment Regimens ◽  
Bipolar Spectrum Disorders ◽  
Short And Long Term

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

scholarly journals EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1410
Author(s):  
Anna Buchholz ◽  
Aurelia Vattai ◽  
Sophie Fürst ◽  
Theresa Vilsmaier ◽  
Christina Kuhn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Vulvar Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Common Finding ◽  
Cancer Tissue ◽  
Vulvar Carcinoma ◽  
Tissue Samples

New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

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