Psychiatric disorders during pregnancy in asymptomatic and mildly symptomatic SARS-CoV-2 positive women: Prevalence and effect on outcome.

The effect of psychiatric comorbidity on pregnancy outcome among SARS-CoV-2 positive women with asymptomatic and mildly symptomatic infections remains largely unknown. We reviewed the electronic medical records of all pregnant women who received care at Mayo Health System and tested positive for SARS-CoV-2 (RT-PCR) from March 2020 through October 2021. Among 789 patients, 34.2% (n = 270) had psychiatric comorbidity. Of those with psychiatric comrobidity, 62.2% (n = 168) had depression prior to pregnancy, and 5.2% (n = 14) reported new-onset depression during pregnancy. Before pregnancy, 65.6% (n = 177) had anxiety, and 4.4% (n = 12) developed anxiety during pregnancy Thirteen percent of SARS-CoV-2 positive pregnant women (n = 108) received psychotropic medication during pregnancy. In addition, 6.7% (n = 18) and 10.7% (n = 29) of pregnant women with psychiatric comorbidity had documented nicotine, cannabis and/ or illicit substance use during and prior to pregnancy, respectively. We depicted a significantly higher risk for cesarean delivery [35.6% vs. 24.9%) in asymptomatic and mildly symptomatic SARS-CoV-2 positive pregnant women with psychiatric comorbidity. In conclusion, the prevalence rates of depression, anxiety, and prescribed antidepressant medications during pregnancy among asymptomatic and mildly symptomatic SARS-CoV-2 infected women were substantially higher than average, which negatively impacted pregnancy and neonatal outcomes.

Psychosocial considerations in the combined bariatric surgery and organ transplantation population: a review of the overlapping pathologies and outcomes.

PURPOSE OF REVIEW: This review highlights the salient data of the psychosocial concerns that influence outcomes of bariatric surgery and organ transplantation. RECENT FINDINGS: Bariatric surgery has emerged as an important intervention with data supporting substantial and sustained weight loss, enhanced quality of life, remission of obesity-related medical comorbidities, and improved long-term patient and graft survival in transplant patients. Depression, suicide, anxiety, posttraumatic stress disorder, alcohol use, adherence, and psychopharmacology considerations can influence outcomes of both these surgeries. SUMMARY: Obesity is increasingly prevalent among patients pursuing transplantation surgery, and it is often a factor in why a patient needs a transplant. However, obesity can be a barrier to receiving a transplant, with many centers implementing BMI criteria for surgery. Furthermore, obesity and obesity-related comorbidities after transplant can cause poor outcomes. In this context, many transplant centers have created programs that incorporate interventions (such as bariatric surgery) that target obesity in transplant candidates. A presurgery psychosocial assessment is an integral (and required) part of the process towards receiving a bariatric surgery and/or a transplantation surgery. When conducting a dual (bariatric and transplantation surgery) psychosocial assessment, it is prudent to understand the overlap and differentiation of specific psychosocial components that influence outcomes in these procedures.

Challenges in the Treatment of Restless Legs Syndrome: A Case Report.

Treatment resistant restless legs syndrome (RLS) in the setting of psychiatric comorbidities can be difficult to manage. Our patient is a 69-year-old Caucasian gentleman with bipolar disorder type I, unspecified anxiety disorder, obstructive sleep apnea (OSA), and treatment-refractory RLS. At initial presentation, the patient's prescribed medication regimen included fluoxetine 40 mg daily, gabapentin 800 mg in the morning and 3200 mg at bedtime, pramipexole 0.375 mg daily, lamotrigine 200 mg daily, trazodone 200 mg at bedtime, and temazepam 15 to 30 mg as needed for insomnia and RLS. Over the course of nearly 4 years, treatment interventions for this patient's RLS included: cognitive behavioral therapy for insomnia, discontinuation of exacerbating medications, switching dopamine agonists, use of pregabalin and iron supplement. This report demonstrates a challenging case of RLS in the setting of psychiatric comorbidities, development of augmentation, and polypharmacy.

Substance use disorders: diagnosis and management for hospitalists.

Substance use disorder is a significant health concern. Hospitalists manage patient with various forms of substance use disorder on a daily basis. In this review, we have tried to synthesize evidence together to give a brief, yet succinct, review of commonly encounters disorders; alcohol intoxication and withdrawal, opioid intoxication and withdrawal, cocaine intoxication and methamphetamine intoxication. We describe clinical features, diagnosis and management, which would serve as a great resource for hospitalist when managing these complicated patients.

Evidence-Based Pharmacotherapies for Alcohol Use Disorder: Clinical Pearls.

Pathologic alcohol use affects more than 2 billion people and accounts for nearly 6% of all deaths worldwide. There are three medications approved for the treatment of alcohol use disorder by the US Food and Drug Administration (FDA): disulfiram, naltrexone (oral and long-acting injectable), and acamprosate. Of growing interest is the use of anticonvulsants for the treatment of alcohol use disorder, although currently none are FDA approved for this indication. Baclofen, a γ-aminobutyric acid B receptor agonist used for spasticity and pain, received temporary approval for alcohol use disorder in France. Despite effective pharmacotherapies, less than 9% of patients who undergo any form of alcohol use disorder treatment receive pharmacotherapies. Current evidence does not support the use of pharmacogenetic testing for treatment individualization. The objective of this review is to provide knowledge on practice parameters for evidenced-based pharmacologic treatment approaches in patients with alcohol use disorder.

Wernicke Encephalopathy-Clinical Pearls.

Wernicke encephalopathy (WE) was first described by Carl Wernicke in 1881. WE is caused by thiamine deficiency. Alcoholism is the most common etiologic factor associated with WE in the United States, but it can occur in any patient with a nutritional deficiency state such as hyperemesis gravidarum, intestinal obstruction, and malignancy. WE is a clinical diagnosis. The common findings include mental status changes, ocular dysfunction, and a gait apraxia, present in only 10% of cases. Only a few cases of WE are diagnosed before death. Approximately 80% of patients with untreated WE have development of Korsakoff syndrome, which is characterized by memory impairment associated with confabulation. The initial clinical diagnosis of WE is critical, keeping in mind that the classic triad of symptoms is often absent. Recognition of nutritional deficiency and any portion of the classic triad should prompt treatment. Additionally, hypothermia, hypotension, and coma should raise clinical suspicion for the disease. Primary treatment includes timely administration of thiamine, for which the route and dosage remain controversial. Clinical judgment should be exercised in diagnosis and treatment (dosage, frequency, route of administration and duration) in all cases of WE. Overdiagnosis and overtreatment may be preferred to prevent prolonged or persistent neurocognitive impairments given the excellent safety profile of thiamine. Further prospective research is warranted to better understand the disease biology, risk factors, and treatment recommendations.

Comparison of treatment options for depression in heart failure: A network meta-analysis.

BACKGROUND: Depression independently predicts poor outcomes in heart failure (HF) patients, including increased mortality, morbidity and 30-day re-hospitalization. In this network meta-analysis, we compared different interventions designed to treat depression in HF. MATERIALS AND METHODS: Electronic searches were conducted using Ovid MEDLINE, EMBASE, CINAHL, Web of Science, and PsycINFO up to November 2016. Included randomized clinical trials (RCTs) compared interventions (Exercise therapy (ET), cognitive behavioral therapy (CBT) or antidepressant (AD) medications) for depression in heart failure patients. The primary outcome was change in depressive symptoms based on validated measures of depression. Network meta-analysis based on random effects model estimating standardized mean difference (SMD) with 95% confidence interval (CI), compared the effects of the 3 classes of interventions with respect to usual care or placebo control conditions. RESULTS: A total of 21 RCTs (including 4563 HF patients) reporting the effects of treating depression in HF patients were included in the analysis. In comparison to placebo or usual standard of care, ET (SMD -0.38; 95% CI -0.54 to -0.22) and CBT (SMD -0.29; 95% CI -0.58 to -0.01) were associated with reduction in depressive symptoms whereas AD (SMD -0.16; 95% CI -0.44 to 0.11) was less effective. CONCLUSIONS: This meta-analysis is suggestive of therapeutic benefit of ET and CBT in comparison to usual standard of care in treating depression in HF patients. However, comparison among the three interventions was not conclusive. Future randomized clinical trials are warranted to compare the therapeutic effects of ET, CBT and AD in such patients.

Sleep Disturbances and Behavioral Disturbances in Children and Adolescents.

Sleep deprivation and sleep disorders are commonly seen in children and adolescents. They are often undiagnosed and undertreated. A balance of circadian rhythm and homeostatic drive determine sleep quality, quantity, and timing, which changes across the developmental years. Environmental and lifestyle factors can affect sleep quality and quantity and lead to sleep deprivation. A comprehensive assessment of sleep disorders includes parental report, children's self-report, and school functioning. Diagnostic tools are used in diagnosing and treating sleep disorders.

Universal precautions to reduce stimulant misuse in treating adult ADHD.

In the United States, stimulants remain the approved pharmacotherapy of choice for adults with attention-deficit/hyperactivity disorder (ADHD). Many patients respond to these drugs, but stimulants also have a significant potential for misuse. This article suggests the "universal precautions" approach to reducing these risks while promoting appropriate medication use.

Late-Onset Bipolar Disorder: A Case Report.

Treating refractory late-onset bipolar disorder has not been sufficiently presented in the literature. In this case report, we present a 54-year-old male with late-onset bipolar disorder, who did notimprove despite multiple medication and dosage changes. This case outlines the challenges in treatment of these patients as well as identifies areas of further study regarding late-onset bipolar disorder management.

Cost-effectiveness analysis of a risk-adapted algorithm of plerixafor use for autologous peripheral blood stem cell mobilization.

Historically, up to 30% of patients were unable to collect adequate numbers of peripheral blood stem cells (PBSCs) for autologous stem cell transplantation (ASCT). Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has shown superior results in mobilizing peripheral blood (PB) CD34+ cells in comparison to G-CSF alone, but its high cost limits general use. We developed and evaluated risk-adapted algorithms for optimal utilization of plerixafor. In plerixafor-1, PBSC mobilization was commenced with G-CSF alone, and if PB CD34 on day 4 or day 5 was <10/µL, plerixafor was administered in the evening, and apheresis commenced the next day. In addition, if on any day, the daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Subsequently, the algorithm was revised (plerixafor-2) with lower thresholds. If day-4 PB CD34 <10/µL for single or <20/µL for multiple transplantations, or day-1 yield was <1.5 × 10(6) CD34/kg, or any subsequent daily yield was <0.5 × 10(6) CD34/kg, plerixafor was added. Three time periods were analyzed for results and associated costs: January to December 2008 (baseline cohort; 319 mobilization attempts in 278 patients); February to November 2009 (plerixafor-1; 221 mobilization attempts in 216 patients); and December 2009 to June 2010 (plerixafor-2; 100 mobilization attempts in 98 patients). Plerixafor-2 shows a significant improvement in PB CD34 collection, increased number of patients reaching minimum and optimal goals, fewer days of apheresis, and fewer days of mobilization/collection, albeit at increased costs. In conclusion, although the earlier identification of ineffective PBSC mobilization and initiation of plerixafor (plerixafor-2) increases the per-patient costs of PBSC mobilization, failure rates, days of apheresis, and total days of mobilization/collection are lower.

Early versus delayed autologous transplantation after immunomodulatory agents-based induction therapy in patients with newly diagnosed multiple myeloma.

BACKGROUND: Early versus delayed autologous stem cell transplantation (SCT) results in comparable overall survival in patients with multiple myeloma (MM) who receive alkylator-based therapies. It is not clear whether this paradigm holds true in the context of new therapies, such as immunomodulatory drugs (IMiDs). METHODS: The authors studied 290 patients with untreated MM who received IMiD-based initial therapy, including 123 patients who received thalidomide-dexamethasone (TD) and 167 patients who received lenalidomide-dexamethasone (LD) induction before SCT. Patients who underwent a stem cell harvest attempt were considered transplantation-eligible and were included. SCT within 12 months of diagnosis and within 2 months of harvest were considered early SCT (n = 173; 60%). SCT >12 months after diagnosis was considered delayed SCT (n = 112; 40%). RESULTS: In the delayed SCT group, 42 patients had undergone SCT at the time of the current report, and the median estimated time to SCT was 5.3 months and 44.5 months in the early SCT and delayed SCT groups, respectively. The 4-year overall survival rate from diagnosis was 73% in both groups (P = .3) and was comparable in those who received TD (68% vs 64%, respectively) and those who received LD (82% vs 86%, respectively) as initial therapy. The time to progression after SCT was similar between the early and delayed SCT groups (20 months vs 16 months; P value nonsignificant). CONCLUSIONS: The current results indicated that, in transplantation-eligible patients who receive IMiDs as initial therapy followed by early stem cell mobilization, delayed SCT results in similar overall survival compared with early SCT. It is noteworthy that an excellent 4-year survival rate of >80% was observed among transplantation-eligible patients who received initial therapy with LD regardless of the timing of transplantation.

Changes in serum-free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis.

Current response criteria for light-chain amyloidosis (AL) relegate FLC response to a subsidiary status relative to serum M-protein response. Given that light chains form the substrate for amyloid fibril formation, we hypothesized that changes in FLC might better predict outcome compared to changes in intact immunoglobulin levels. Two patient cohorts were studied, 347 patients who underwent an autologous stem-cell transplant (SCT) and 96 patients treated with melphalan/dexamethasone. We identified the lowest value following therapy for intact serum M-protein and the difference between involved and uninvolved FLC (FLC-diff). We first examined the relative contribution of M-protein and FLC-diff on the overall survival (OS), and found that FLC reduction, rather than M-protein reduction, significantly impacted OS. The median OS was not reached among those with a 50% decrease in FLC-diff compared to 20 months for the remainder. On regression analysis, a 90% reduction in FLC-diff following SCT best predicted being alive at 3 or 5 years. The median OS among those with a 90% decrease was not reached compared to 37.4 months for the rest P < 0.001. The current study supports the notion that FLC response is a more useful measure of hematological response than M-protein response. It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL.

Evidence for cytogenetic and fluorescence in situ hybridization risk stratification of newly diagnosed multiple myeloma in the era of novel therapie.

Overall survival (OS) has improved with increasing use of novel agents in multiple myeloma (MM). However, the disease course remains highly variable, and the heterogeneity largely reflects different genetic abnormalities. We studied the impact of the Mayo risk-stratification model of MM on patient outcome in the era of novel therapies, evaluating each individual component of the model-fluorescence in situ hybridization (FISH), conventional cytogenetics (CG), and the plasma cell labeling index-that segregates patients into high- and standard-risk categories. This report consists of 290 patients with newly diagnosed MM, predominantly treated with novel agents, who were risk-stratified at diagnosis and were followed up for OS. Of these patients, 81% had received primarily thalidomide (n=50), lenalidomide (n=199), or bortezomib (n=79) as frontline or salvage therapies. Our retrospective analysis validates the currently proposed Mayo risk-stratification model (median OS, 37 months vs not reached for high- and standard-risk patients, respectively; P=.003). Although the FISH or CG test identifies a high-risk cohort with hazard ratios of 2.1 (P=.006) and 2.5 (P=.006), respectively, the plasma cell labeling index cutoff of 3% fails to independently prognosticate patient risk (hazard ratio, 1.4; P=.41). In those stratified as standard-risk by one of the 2 tests (FISH or CG), the other test appears to be of additional prognostic significance. This study validates the high-risk features defined by FISH and CG in the Mayo risk-stratification model for patients with MM predominantly treated with novel therapies based on immunomodulatory agents.

Impact of dexamethasone responsiveness on long term outcome in patients with newly diagnosed multiple myeloma.

Dexamethasone (Dex), alone or in combination, is commonly used for treating multiple myeloma. Dex as single agent for initial therapy of myeloma results in overall response rates of 50-60%. It is unclear whether steroid responsiveness reflects any biological characteristic that impacts long-term outcome. We studied a cohort of 182 patients with newly diagnosed myeloma seen between March 1998 and June 2007, initially treated with single-agent Dex for at least 4 weeks. The median age at diagnosis was 63 years (range, 39-81) and the median estimated survival was 55 months. At a median duration of therapy of 15 weeks, 91 (50%) patients had a partial response or better, 80 (44%) had less than partial response and the remaining (6%) patients were not evaluable. The median overall survival from diagnosis for the responders was 75 months compared to 71 months for remaining patients, P = 0.6.There was no correlation between baseline disease characteristics and Dex responsiveness. While overall survival was longer for the 130 (70%) patients who proceeded to an autologous stem cell transplant, no correlation was found between survival and Dex responsiveness among either group. Among this cohort of patients with myeloma, failure to respond to single agent steroid did not have an adverse impact on eventual outcome.

Dopamine regulates phosphorylation of VEGF receptor 2 by engaging Src-homology-2-domain-containing protein tyrosine phosphatase 2.

Vascular endothelial growth factor (VEGF)-induced receptor phosphorylation is the crucial step for initiating downstream signaling pathways that lead to angiogenesis or related pathophysiological outcomes. Our previous studies have shown that the neurotransmitter dopamine could inhibit VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), endothelial cell proliferation, migration, microvascular permeability, and thus, angiogenesis. In this study, we address the mechanism by which VEGFR-2 phosphorylation is regulated by dopamine. Here, we demonstrate that D2 dopamine receptor (D2DR) colocalizes with VEGFR-2 at the cell surface. Dopamine pretreatment increases the translocation and colocalization of Src-homology-2-domain-containing protein tyrosine phosphatase (SHP-2) with D2DR at the cell surface. Dopamine administration leads to increased VEGF-induced phosphorylation of SHP-2 and this increased phosphorylation parallels the increased phosphatase activity of SHP-2. Active SHP-2 then dephosphorylates VEGFR-2 at Y951, Y996 and Y1059, but not Y1175. We also observe that SHP-2 knockdown impairs the dopamine-regulated inhibition of VEGF-induced phosphorylation of VEGFR-2 and, subsequently, Src phosphorylation and migration. Our data establish a novel role for SHP-2 phosphatase in the dopamine-mediated regulation of VEGFR-2 phosphorylation.