Physiologic and anatomic determinants of hyoid motion during drug-induced sleep endoscopy.

PURPOSE: To examine factors accounting for differences in hyoid motion during obstructive breathing events amongst obstructive sleep apnea (OSA) patients. METHODS: This was a prospective cohort study from June 2022 to October 2022. Patients with OSA undergoing evaluation for PAP alternative therapies with drug-induced sleep endoscopy with positive airway pressure titration (DISE-PAP). All patients underwent DISE-PAP and concurrent hyoid-focused ultrasound. DISE-PAP enabled measurement of airway physiology (flow, respiratory effort) and airway collapsibility (pharyngeal opening pressure, PhOP). Hyoid-ultrasound enabled hyoid bone movement during obstructive breathing. Respiratory effort was measured using a retro-epiglottic pressure-sensitive catheter. Hyoid position was measured using a standardized, awake, CT protocol. Regression analyses adjusted for age, race, sex, and BMI were performed to associate indices of respiratory effort and CT data with hyoid motion. RESULTS: On average, the 26 patients in this cohort were older (63.9 ± 10.5 years), male (69%), overweight (29.6 ± 3.99 kg/m2), and with moderate-to-severe OSA (26.8 ± 10.4 events/hour). Greater respiratory effort was associated with increased hyoid motion (ß [95% CI] = 0.034 [0.016,0.052], standardized ß = 0.261,p = 0.0003). Higher hyoid position was associated with greater hyoid displacement (ß [95% CI] = -0.20 [-0.38,-0.01], Standardized ß = -0.57, p = 0.036). CONCLUSION: Our data demonstrate that greater respiratory effort, higher hyoid position, and higher airway collapsibility, but not airflow, are associated with greater hyoid motion during obstructive breathing in DISE. These findings suggest that downward hyoid movement represents a compensatory response to upper airway obstruction. Further studies should investigate the vectors of hyoid motion to better understand its role in sleep-related airway collapse.

Predictive modeling of initiation and delayed mental health contact for depression.

BACKGROUND: Depression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment. METHODS: We obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis. RESULTS: 108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586-0.602; machine learning F-measure = 0.46). CONCLUSIONS: Having VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.

Contrast-enhanced US Evaluation of Hepatocellular Carcinoma Response to Chemoembolization: A Prospective Multicenter Trial.

Background Contrast-enhanced (CE) US has been studied for use in the detection of residual viable hepatocellular carcinoma (HCC) after locoregional therapy, but multicenter data are lacking. Purpose To compare two-dimensional (2D) and three-dimensional (3D) CE US diagnostic performance with that of CE MRI or CT, the current clinical standard, in the detection of residual viable HCC after transarterial chemoembolization (TACE) in a prospective multicenter trial. Materials and Methods Participants aged at least 21 years with US-visible HCC scheduled for TACE were consecutively enrolled at one of three participating academic medical centers from May 2016 to March 2022. Each underwent baseline 2D and 3D CE US before TACE, 2D and 3D CE US 1-2 weeks and/or 4-6 weeks after TACE, and CE MRI or CT 4-6 weeks after TACE. CE US and CE MRI or CT were evaluated by three fellowship-trained radiologists for the presence or absence of viable tumors and were compared with reference standards of pathology (18%), angiography on re-treatment after identification of residual disease at 1-2-month follow-up imaging (31%), 4-8-month CE MRI or CT (42%), or short-term (approximately 1-2 months) CE MRI or CT if clinically decompensated and estimated viability was greater than 50% at imaging (9%). Diagnostic performance criteria, including sensitivity and specificity, were obtained for each modality and time point with generalized estimating equation analysis. Results A total of 132 participants were included (mean age, 64 years ± 7 [SD], 87 male). Sensitivity of 2D CE US 4-6 weeks after TACE was 91% (95% CI: 84, 95), which was higher than that of CE MRI or CT (68%; 95% CI: 58, 76; P < .001). Sensitivity of 3D CE US 4-6 weeks after TACE was 89% (95% CI: 81, 94), which was higher than that of CE MRI or CT (P < .001), with no evidence of a difference from 2D CE US (P = .22). CE MRI or CT had 85% (95% CI: 76, 91) specificity, higher than that of 4-6-week 2D and 3D CE US (70% [95% CI: 56, 80] and 67% [95% CI: 53, 78], respectively; P = .046 and P = .023, respectively). No evidence of differences in any diagnostic criteria were observed between 1-2-week and 4-6-week 2D CE US (P > .21). Conclusion The 2D and 3D CE US examinations 4-6 weeks after TACE revealed higher sensitivity in the detection of residual HCC than CE MRI or CT, albeit with lower specificity. Importantly, CE US performance was independent of follow-up time. Clinical trial registration no. NCT02764801 © RSNA, 2023 Supplemental material is available for this article.

Prognostic Role of Lymph Node Sampling in Adolescent and Young Adults With Fibrolamellar Carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is rare among adolescent and young adult (AYA) patients, and resection or transplant remains the only curative therapy. The role of lymph node (LN) sampling is not well-defined. The aim of this study was to describe practice patterns, as well as investigate the impact of LN sampling on survival outcomes in this population. MATERIALS AND METHODS: A retrospective cohort study using the 2004-2018 National Cancer Database (NCDB) was performed. Patients ≤21 y old with nonmetastatic HCC who underwent liver resection or transplant were evaluated. Clinical features of patients who underwent LN sampling were compared to those who did not, and univariable and multivariable logistic regression was performed to evaluate independent predictive factors of node positivity. Survival analysis was performed using Kaplan-Meier methods and Cox Proportional Hazard Survival Regression. RESULTS: A total of 262 AYA patients with HCC were identified, of whom 137 (52%) underwent LN sampling, 44 patients had positive nodes, 40 (95%) of them had tumors >5 cm; 87 (64%) of patients with sampled nodes had fibrolamellar carcinoma (FLC), which was an independent risk factor for predicting positive nodes (P = 0.001). There was no difference in overall survival between patients who underwent LN sampling and those who did not; however, 5-y overall survival for node-positive patients was 40% versus 79% for node-negative patients (P < 0.0001). CONCLUSIONS: In AYA patients with HCC, LN sampling was not associated with an independent survival benefit. However, FLC was an independent risk factor for LN positivity, suggesting a role for routine LN sampling in these patients.

Ultrasound Pressure Estimation for Diagnosing Portal Hypertension in Patients Undergoing Dialysis for Chronic Kidney Disease.

OBJECTIVES: Hepatic venous pressure gradient (HVPG) is considered the standard in quantifying portal hypertension, but can be unreliable in dialysis patients. A noninvasive ultrasound technique, subharmonic-aided pressure estimation (SHAPE), may be a valuable surrogate of these pressure estimates. This study compared SHAPE and HVPG with pathology findings for fibrosis in dialysis patients. METHODS: This was a subgroup study from an IRB-approved trial that included 20 patients on dialysis undergoing SHAPE examinations of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI), during infusion of Sonazoid (GE Healthcare, Oslo, Norway). SHAPE was compared to HVPG and pathology findings using the Ludwig-Batts scoring system for fibrosis. Logistic regression, ROC analysis, and t-tests were used to compare HVPG and SHAPE with pathological findings of fibrosis. RESULTS: Of 20 cases, 5 had HVPG values corresponding to subclinical and clinical portal hypertension (≥6 and ≥10 mmHg, respectively) while 15 had normal HVPG values (≤5 mmHg). SHAPE and HVPG correlated moderately (r = 0.45; P = .047). SHAPE showed a trend toward correlating with fibrosis (r = 0.42; P = .068), while HVPG did not (r = 0.18; P = .45). SHAPE could differentiate between mild (stage 0-1) and moderate to severe (stage 2-4) fibrosis (-10.4 ± 4.9 dB versus -5.4 ± 3.2 dB; P = .035), HVPG could not (3.0 ± 0.6 mmHg versus 4.8 ± 0.7 mmHg; P = .30). ROC curves showed a diagnostic accuracy for SHAPE of 80%, while HVPG reached 76%. CONCLUSION: Liver fibrosis staging in dialysis patients evaluated for portal hypertension appears to be more accurately predicted by SHAPE than by HVPG; albeit in a small sample size.

Diagnosing Portal Hypertension with Noninvasive Subharmonic Pressure Estimates from a US Contrast Agent.

Background The current standard for assessing the severity of portal hypertension is the invasive acquisition of hepatic venous pressure gradient (HVPG). A noninvasive US-based technique called subharmonic-aided pressure estimation (SHAPE) could reduce risk and enable routine acquisition of these pressure estimates. Purpose To compare quantitative SHAPE to HVPG measurements to diagnose portal hypertension in participants undergoing a transjugular liver biopsy. Materials and Methods This was a prospective cross-sectional trial conducted at two hospitals between April 2015 and March 2019 (ClinicalTrials.gov identifier, NCT02489045). This trial enrolled participants who were scheduled for transjugular liver biopsy. After standard-of-care transjugular liver biopsy and HVPG pressure measurements, participants received an infusion of a US contrast agent and saline. During infusion, SHAPE data were collected from a portal vein and a hepatic vein, and the difference was compared with HVPG measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity of SHAPE. Results A total of 125 participants (mean age ± standard deviation, 59 years ± 12; 80 men) with complete data were included. Participants at increased risk for variceal hemorrhage (HVPG ≥12 mm Hg) had a higher mean SHAPE gradient compared with participants with lower HVPGs (0.79 dB ± 2.53 vs -4.95 dB ± 3.44; P < .001), which is equivalent to a sensitivity of 90% (13 of 14; 95% CI: 88, 94) and a specificity of 80% (79 of 99; 95% CI: 76, 84). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the HVPG measurements (r = 0.68). Conclusion Subharmonic-aided pressure estimation is an accurate noninvasive technique for detecting clinically significant portal hypertension. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kiessling in this issue.

Hepatic Vein Contrast-Enhanced Ultrasound Subharmonic Imaging Signal as a Screening Test for Portal Hypertension.

BACKGROUND: Portal hypertension is the underlying cause of most complications associated with cirrhosis, with the hepatic venous pressure gradient (HVPG) used for diagnosis and disease progression. Subharmonic imaging (SHI) is a contrast-specific imaging technique receiving at half the transmit frequency resulting in better tissue suppression. AIMS: To determine whether the presence of optimized SHI signals inside the hepatic vein can be used as a screening test for portal hypertension. METHODS: This prospective trial had 131 patients undergoing SHI examination of portal and hepatic veins using a modified Logiq 9 scanner (GE, Waukesha, WI). Images acquired after infusion of the ultrasound contrast agent Sonazoid (GE Healthcare, Oslo, Norway) were assessed for the presence of optimized SHI signals in the hepatic vein and compared to the HVPG values obtained as standard of care. RESULTS: Of 131 cases, 64 had increased HVPG values corresponding to subclinical (n = 31) and clinical (n = 33) portal hypertension (> 5 and > 10 mmHg, respectively), and 67 had normal HVPG values (< 5 mmHg). Two readers performed independent, binary qualitative assessments of the acquired digital clips. Reader one (experienced radiologist) achieved for the subclinical subgroup sensitivity of 98%, specificity of 88%, and ROC area of 0.93 and for the clinical subgroup sensitivity of 100% and specificity of 61%, with an ROC area of 0.74. Reader two (less experienced radiologist) achieved for the subclinical subgroup sensitivity of 77%, specificity of 76%, and ROC area of 0.76 and for the clinical subgroup sensitivity of 88% and specificity of 63%, with an ROC area of 0.70. Readers agreement was of 83% with kappa value of 0.66. CONCLUSION: The presence of optimized SHI signals inside the hepatic vein can be a qualitative screening test for portal hypertension, which could reduce the need for invasive diagnostic procedures.

Antidepressant Augmentation: A Review of the Literature and a Review of the Pharmacoeconomic Considerations.

PURPOSE: Antidepressant augmentation strategies for treatment-resistant depression (TRD) are discussed here with an analysis of patient out-of-pocket costs for various medications. The choice of agent ranges from newer atypical antipsychotics (aripiprazole, brexpiprazole, quetiapine) to older agents including buspirone, liothyronine (T3), and lithium. We sought to better understand the differences among these agents to aid in clinical decision making. METHODS: We conducted a focused review of the support for each of the aforementioned agents in antidepressant augmentation. We then compared the approximate out-of-pocket cost for each medication during a typical augmentation trial using the typical prescription costs on ClinCalc.com derived from the Medical Expenditure Panel Survey. We calculated the cost to achieve response for one patient with TRD based on the number needed to treat (NNT). FINDINGS: We observed significant variance in cost to achieve response based on the NNT derived from our review of each of the medications. For example, the overall out-of-pocket cost for one patient to achieve response with aripiprazole (the costliest generic agent) could cover lithium prescriptions for 4 to 5 patients with TRD to achieve response. Although brexpiprazole was estimated separately because of its brand name cost, we estimated that 324 patients receiving lithium could achieve response for same cost of single patient receiving brexpiprazole. IMPLICATIONS: These findings suggest that among augmentation agents, there are differences in cost that may be highly important in clinical decision making. Other issues of medication monitoring may incur additional costs, and brand name medications offer significantly greater complexity and potential out-of-pocket costs to patients. The use of lithium as a first-line agent for TRD should be considered based on low cost, lowest NNT, and data in support of its efficacy.

Risk of Mortality in Immigrants with Multiple Sclerosis in Ontario, Canada.

INTRODUCTION: Little is known about how mortality in multiple sclerosis (MS) may differ based on sociodemographic factors, such as immigrant status. We compared mortality in immigrants versus long-term residents with MS in Ontario, Canada. METHODS: In this retrospective cohort study, we applied a validated algorithm to linked, population-based immigration and health administrative data to identify incident MS cases in Ontario between 1994 and 2014. We identified date of death, if it occurred. We used a Cox model adjusting for age, sex, income, and comorbidity, to compare survival in immigrants versus long-term residents. RESULTS: There were 23,603 incident MS cases of whom 1,410 (6.0%) were immigrants. After adjusting for covariates, risk of death was higher in immigrants in the first year after diagnosis (hazard ratio [HR] 1.66; 95% CI 1.05-2.63, p = 0.031). However, in years 1-5 (HR 0.63; 95% CI 0.40-0.98, p = 0.041) and 5-10 (HR 0.42; 95% CI 0.24-0.75, p = 0.003) after diagnosis, risk of death was lower in immigrants. Older age at onset and comorbidity were associated with higher mortality; female sex and higher socioeconomic status were associated with lower mortality. CONCLUSIONS: In this large population with universal access to health care, immigrants with MS had higher mortality compared to long-term residents in the first year after onset and lower mortality thereafter. Lower mortality in immigrants to Canada is well described and thought to be due to the healthy immigrant effect. Higher mortality in the first year after MS onset warrants further investigation as some early deaths may be preventable.

American Association for Geriatric Psychiatry-Strategic Thinking.

Never has there been a more pressing time for the American Association for Geriatric Psychiatry (AAGP) to articulate a unified strategy to meet the challenges of our aging world. To this end, this report summarizes an AAGP leadership meeting that reviewed the results from a recent membership survey and launched a strategic planning process on behalf of AAGP members and stakeholders. This meeting was the first step in drafting a blueprint for the future that may serve as our guide in the context of finite resources to meet the infinitely complex and growing need for education, research, public advocacy, and clinical practice support. The following report serves to invite our valued colleagues to provide feedback and actively participate in defining our mission. Among the outcomes of the planning session, the following aspirations were identified by the participants 1) assert the AAGP as the "go to" organization for all things related to geriatric mental health, 2) prioritize activities that enhance the inclusivity/diversity of membership, and 3) collaborate across disciplines focused on geriatric mental health. From this initial framework, the group developed four general themes to guide AAGP's strategic future: 1) collaboration, 2) advocacy, 3) inclusivity, 4) high purpose. Inclusivity was further defined as encompassing growth, return on investment, and workforce development. Higher purpose was further defined as encompassing engagement, purpose, branding, communication, and expertise. The AAGP affirmed its commitment to serving the needs of its members and widening its scope of impact in view of staggering demands for better access to geriatric mental healthcare.

Mortality and Associated Risk Factors in Community-Dwelling Persons With Early Dementia.

OBJECTIVE: Examine mortality and associations with baseline characteristics among Veterans with early dementia. METHODS: Participants included dyads of community-based Veterans with early dementia and their caregivers (N=143) enrolled in a previous longitudinal study. Department of Veterans Health Affairs' electronic records were used to retrospectively collect Veteran mortality outcomes, over a 6-year period. Measures included baseline: demographics, dementia-related factors, other comorbid conditions, functioning, and medication use. Associations with baseline characteristics and mortality were examined with bivariate analyses and a series of Cox proportional hazard models. RESULTS: Over 6 years of study follow-up, 53.1% of participants died. The mean time to death was 3.09 years, with a range of 54 days to 5.91 years. Female sex, better cognition, and higher scores on the Tinetti Gait and Balance scale were protective factors in the final multivariable model, adjusting for other characteristics. CONCLUSIONS: While newly diagnosed with early dementia, over half of our sample died in the 6-year follow-up period, with the average death occurring only 3 years after initial diagnosis. The finding of lower mortality associated with better performance on gait/balance testing indicates an important opportunity for focused interventions and early detection of gait and balance changes early during cognitive decline.

Comparison of T1Rho MRI, Glucose Metabolism, and Amyloid Burden Across the Cognitive Spectrum: A Pilot Study.

OBJECTIVE: The pathological cascades associated with the development of Alzheimer's disease (AD) have a common element: acidosis. T1rho MRI is a pH-sensitive measure, with higher values associated with greater neuropathological burden. The authors investigated the relationship between T1rho imaging and AD-associated pathologies as determined by available diagnostic imaging techniques. METHODS: Twenty-seven participants (men, N=13, women, N=14; ages 55-90) across the cognitive spectrum (healthy control subjects [HCs] with normal cognition, N=17; participants with mild cognitive impairment [MCI], N=7; participants with mild AD, N=3) underwent neuropsychological testing, MRI (T1-weighted and T1rho [spin-lattice relaxation time in the rotating frame]), and positron emission tomography imaging ([11C]Pittsburg compound B for amyloid burden [N=26] and [18F]fluorodeoxyglucose for cerebral glucose metabolism [N=12]). The relationships between global T1rho values and neuropsychological, demographic, and imaging measures were explored. RESULTS: Global mean and median T1rho were positively associated with age. After controlling for age, higher global T1rho was associated with poorer cognitive function, poorer memory function (immediate and delayed memory scores), higher amyloid burden, and more abnormal cerebral glucose metabolism. Regional T1rho values, when controlling for age, significantly differed between HCs and participants with MCI or AD in select frontal, cingulate, and parietal regions. CONCLUSIONS: Higher T1rho values were associated with greater cognitive impairment and pathological burden. T1rho, a biomarker that varies according to a feature common to each cascade rather than one that is unique to a particular pathology, has the potential to serve as a metric of neuropathology, theoretically providing a measure for assessing pathological status and for monitoring the neurodegeneration trajectory.

Multispectral photoacoustic imaging for the detection of subclinical melanoma.

BACKGROUND: Photoacoustic imaging (PAI) is a noninvasive technique for melanin detection within melanoma metastases. While ex vivo and early studies suggest promising clinical application, there are no standardized parameters for defining presence of melanoma metastases. METHODS: Following flank/hindlimb melanoma induction in BRaf-PTEN transgenic mice, bilateral inguinal lymph nodes (LN) were imaged in vivo at 4 to 8 weeks using PAI. Fourteen diagnostic parameters for in vivo detection of LN metastases were compared using the receiver operating characteristic and area-under-the-curve (AUC). Limits of detectability were assessed in ex vivo and in vitro phantom studies. RESULTS: Forty-nine LNs were imaged in 25 mice. Among metastatic LNs, tumor size ranged from scattered cells to 2.8 mm. The strongest predictor of LN metastasis was the ratio of peak 10% PA melanin signal in the LN compared with adjacent soft tissue (median 4.22 for positive LNs vs 1.07 for negative LNs, P < 0.0001). The AUC was 0.95 (95% CI, 0.90-1.00). In phantom studies, B16 tumor cells were detectable at a concentration of 10 to 25 cells/µL and at a tissue depth of 2.5-3 cm. CONCLUSIONS: We identified a simple, objective diagnostic parameter for identifying melanoma LN metastases in vivo. These findings may help inform the design of future clinical trials.

Assessment of Age-related Oxygenation Changes in Calf Skeletal Muscle by Photoacoustic Imaging: A Potential Tool for Peripheral Arterial Disease.

Peripheral artery disease is often asymptomatic, and various imaging and nonimaging techniques have been used for assessment and monitoring treatments. This study is designed to demonstrate the ability of photoacoustic imaging to noninvasively determine changes in tissue oxygenation that occur in mice's hind limb skeletal muscle as they age. Mice from two age cohorts were scanned bilaterally with a pulsed laser. The photoacoustic signal was unmixed to generate a parametric map of estimated oxygen saturation and then overlaid on grayscale ultrasound images. Tissue oxygenation measured in young and old mice was compared. Photoacoustic imaging visually and quantitatively showed the decrease in skeletal muscle oxygenation that occurs with age. Percent tissue oxygenation decreased from 30.2% to 3.5% (p < 0.05). This reduction corresponded to reduced fractional area of oxygenation, which decreased from 60.6% to 6.0% (p < 0.05). The change in oxygenation capacity of the still active vascular regions was insignificant (p > 0.05). Intrasubject, intra-, and interobserver comparisons showed low variability in measurements, exhibited by high regression and intraclass correlations exceeding 0.81 for all ages. The decrease in oxygenation detected by photoacoustic imaging paralleled the known oxygenation decrease observed in aging tissues, demonstrating that photoacoustic imaging can assess age-related changes in a mouse calf muscle. These intramuscular changes could potentially act as a strong diagnostic marker for peripheral artery disease. This study thus opens the doors for a novel, affordable, noninvasive method of evaluation free of radiation or exogenous material.

Serotonin Toxicity and Urinary Analgesics: A Case Report and Systematic Literature Review of Methylene Blue-Induced Serotonin Syndrome.

BACKGROUND: Serotonin syndrome (SS) is a potentially serious side effect of serotonergic drugs. Cases of SS have been reported from the administration of methylene blue (MB), an agent with monoamine oxidase inhibiting properties. To date, the reported cases of MB-induced SS have all been with MB given parenterally. We report a case induced by the initiation of a MB-containing oral agent. METHODS: A case of SS felt to be induced by the initiation of an MB-containing orally-administered urinary analgesic, started in a patient concurrently treated with multiple serotonergic drugs, is presented. A systematic literature review of MB-induced SS follows. The review consisted of searches in MEDLINE databases using the key terms "methylene blue" and "serotonin syndrome". The authors read all abstracts, and articles related to MB and serotonin toxicity; non-associated articles were discarded. Results are summarized. RESULTS: 23 manuscripts were identified, resulting in 50 unique cases of MB-induced SS. The majority of cases were related to peri-operative use of MB in parathyroidectomies or for the treatment of vasoplegic shock. All cases were associated with MB given parenterally. Concurrent treatment with serotonergic antidepressants was described in all 50 cases. Symptoms of SS ranged from mild to severe. One fatality was reported. CONCLUSIONS: Methylene blue can induce SS, felt to be secondary to MAOI properties. Although previous reports have exclusively been associated with MB given via parental administration, our case suggests that SS can be induced by oral administration of MB-containing agents.

Clinical repetitive transcranial magnetic stimulation for veterans with major depressive disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a relatively new treatment modality for patients with major depressive disorder (MDD). Numerous studies have demonstrated the efficacy of TMS for MDD in the general population. However, there is limited information regarding clinical outcomes among veterans receiving TMS for MDD. METHODS: The clinical outcome and characteristics of all veterans with MDD who were treated with TMS as outpatients at the James A. Haley Veterans' Hospital from October 2013 to December 2016 were assessed. RESULTS: Among 40 patients who received TMS, there was a significant improvement of depressive symptoms using the Quick Inventory of Depressive Symptomatology-Self-Report (45% response, 20% remission) and the Montgomery-Åsberg Depression Rating Scale (61.9% response, 42.9% remission). In addition to significant improvement in depressive symptoms, self-report of anxiety symptoms and function significantly improved. TMS was generally well tolerated, with only a small percentage of patients discontinuing treatment due to side effects. No seizures or persistent adverse effects were observed or reported. CONCLUSIONS: TMS is an effective and well-tolerated option for MDD in a veteran population with significant treatment resistance and multiple comorbidities.

Relapse risk after discontinuation of risperidone in Alzheimer's disease.

BACKGROUND: Among patients with Alzheimer's disease who have had a response to antipsychotic medication for psychosis or agitation-aggression, the risk of a recurrence of symptoms after discontinuation of the medication has not been established. METHODS: Patients with Alzheimer's disease and psychosis or agitation-aggression received open-label treatment with risperidone for 16 weeks. Those who had a response to risperidone therapy were then randomly assigned, in a double-blind fashion, to one of three regimens: continued risperidone therapy for 32 weeks (group 1), risperidone therapy for 16 weeks followed by placebo for 16 weeks (group 2), or placebo for 32 weeks (group 3). The primary outcome was the time to relapse of psychosis or agitation. RESULTS: A total of 180 patients received open-label risperidone (mean dose, 0.97 mg daily). The severity of psychosis and agitation were reduced, although there was a mild increase in extrapyramidal signs; 112 patients met the criteria for response to treatment, of whom 110 underwent randomization. In the first 16 weeks after randomization, the rate of relapse was higher in the group that received placebo than in the groups that received risperidone (60% [24 of 40 patients in group 3] vs. 33% [23 of 70 in groups 1 and 2]; P=0.004; hazard ratio with placebo, 1.94; 95% confidence interval [CI], 1.09 to 3.45; P=0.02). During the next 16 weeks, the rate of relapse was higher in the group that was switched from risperidone to placebo than in the group that continued to receive risperidone (48% [13 of 27 patients in group 2] vs. 15% [2 of 13 in group 1]; P=0.02; hazard ratio, 4.88; 95% CI, 1.08 to 21.98; P=0.02). The rates of adverse events and death after randomization did not differ significantly among the groups, although comparisons were based on small numbers of patients, especially during the final 16 weeks. CONCLUSIONS: In patients with Alzheimer's disease who had psychosis or agitation that had responded to risperidone therapy for 4 to 8 months, discontinuation of risperidone was associated with an increased risk of relapse. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00417482.).

Frontal hypometabolism in elderly breast cancer survivors determined by [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET): a pilot study.

PURPOSE: The term "chemobrain" is sometimes used to denote deficits in neuropsychological functioning that may occur as a result of cancer treatment. As breast cancer survivors now commonly reach late life, it is not known whether previous exposure to chemotherapy may affect long-term risk for cognitive impairment. To help address this concern, this study tested whether successfully surviving chemotherapy earlier in life was associated with later differences in brain metabolic function as an older adult compared to controls. This question was examined using positron emission tomography measures of brain glucose metabolism in elderly women cancer survivors. METHODS: Breast cancer survivors (N = 10), currently free of recurrent cancer and without a diagnosis of a cognitive disorder, were compared to matched healthy controls (N = 10). All subjects were imaged at rest with [(18)F]fluorodeoxyglucose. Images were analyzed semi-quantitatively using the Alzheimer's Discrimination Tool and a volume of interest-based approach derived from co-registered magnetic resonance imaging. RESULTS: Relative [(18)F]fluorodeoxyglucose uptake (normalized to global) was significantly lower in the survivors compared with control subjects in bilateral orbital frontal regions, consistent with differences between the groups in cognition and executive function (i.e., Trail Making Test, Part B and mini-mental state examination) and despite no significant differences with respect to age, education, intelligence, or working memory. None of the survivors and only one control manifested a global positron emission tomography score consistent with an Alzheimer's disease metabolic pattern. CONCLUSION: Breast cancer survivors treated with chemotherapy may manifest long-term changes in brain glucose metabolism indicative of subtle frontal hypometabolism, a finding consistent with results from neuropsychological testing and other imaging modalities.