An exploration into the relationship between insomnia and repetitive negative thinking among cancer survivors.

OBJECTIVE: Insomnia and repetitive negative thinking (RNT) are both prevalent among cancer survivors, yet little work has investigated their interrelationship. To explore the hypothesis that RNT and insomnia are related, we conducted secondary analyses on data from a pilot clinical trial of cognitive behavioral therapy for insomnia (CBT-I) for cancer survivors. METHODS: This study analyzed survey data from 40 cancer survivors with insomnia who participated in a pilot randomized trial of CBT-I. Correlations and linear regression models were used to determine associations between aspects of RNT and related constructs (fear of cancer recurrence [FCR], cancer-specific rumination, worry, and intolerance of uncertainty) and sleep (insomnia and sleep quality), while accounting for psychiatric symptoms such as anxiety and depression. Treatment-related change in RNT was examined using a series of linear mixed models. RESULTS: Evidence for an association between RNT and insomnia among cancer survivors emerged. Higher levels of FCR and cancer-related rumination were correlated with more severe insomnia symptoms and worse sleep quality. Notably, FCR levels predicted insomnia, even after controlling for anxiety and depression. Results identified potential benefits and limitations of CBT-I in addressing RNT that should be examined more thoroughly in future research. CONCLUSIONS: RNT is a potential target to consider in insomnia treatment for cancer survivors.

The Survivorship Sleep Program (SSP): A synchronous, virtual cognitive behavioral therapy for insomnia pilot program among cancer survivors.

BACKGROUND: For cancer survivors, insomnia is prevalent, distressing, and persists for years if unmanaged. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment yet can be difficult to access and may require modification to address survivorship-specific barriers to sleep. In this 2-phase study, the authors adapted and assessed the feasibility, acceptability, and preliminary effects of synchronous, virtual CBT-I adapted for cancer survivors (the Survivorship Sleep Program [SSP]). METHODS: From April to August 2020, cancer survivors with insomnia (N = 10) were interviewed to refine SSP content and delivery. From October 2020 to March 2021, 40 survivors were recruited for a randomized controlled trial comparing 4 weekly SSP sessions with enhanced usual care (EUC) (CBT-I referral plus a sleep hygiene handout). Feasibility and acceptability were assessed by enrollment, retention, attendance, fidelity, survey ratings, and exit interviews. Insomnia severity (secondary outcome), sleep quality, sleep diaries, and fatigue were assessed at baseline, postintervention, and at 1-month follow-up using linear mixed models. RESULTS: The SSP included targeted content and clinician-led, virtual delivery to enhance patient centeredness and access. Benchmarks were met for enrollment (56% enrolled/eligible), retention (SSP, 90%; EUC, 95%), attendance (100%), and fidelity (95%). Compared with EUC, the SSP resulted in large, clinically significant improvements in insomnia severity (Cohen d = 1.19) that were sustained at 1-month follow-up (Cohen d = 1.27). Improvements were observed for all other sleep metrics except sleep diary total sleep time and fatigue. CONCLUSIONS: Synchronous, virtually delivered CBT-I targeted to cancer survivors is feasible, acceptable, and seems to be efficacious for reducing insomnia severity. Further testing in larger and more diverse samples is warranted.

Including Distal Motor Function within the NIHSS: Correlation with Motor Arm Function and IV rt-PA Treatment Response.

OBJECTIVES: The Distal Motor Function (DMF) sub-score of the NIH Stroke Scale (NIHSS) was measured in the NINDS rt-PA Stroke Trials but is currently not included in the NIHSS. The correlation of DMF with the NIHSS Motor Arm Function (MAF) sub-score, the effect of IV tPA treatment on DMF, and whether adding DMF changes the utility of the NIHSS have not been analyzed. MATERIALS AND METHODS: MAF and DMF sub-scores were retrieved from the original NINDS rt-PA Stroke Trials for both sides of the body at baseline, 2 hours, 24 hours, 7-10 days, and 3 months after IV tPA treatment. MAF and DMF scores were correlated using Spearman correlation. Clustering of DMF and MAF scores was determined using a Bentler Comparative Fit Index (CFI) to estimate variation in NIHSS when adding DMF. The effect of IV tPA on DMF and MAF was assessed using a linear model comparing changes in scores from baseline to 3 months. RESULTS: MAF and DMF were highly correlated (p < 0.0001) across all time points for both dichotomous and continuous data on both sides. Intravenous tPA accounted for 21% of the change in DMF (p < 0.014, R2 = 0.0157, N = 423) and 39% of the change in MAF (p < 0.093, R2 = 0.0125, N = 547) from 0 to 3 months. On adding DMF to NIHSS, CFI decreased from 0.98 to 0.80 and DMF clustered with MAF, indicating that addition of DMF is unlikely to produce any discrepancy to NIHSS. CONCLUSIONS: Including DMF to the NIHSS does not appear to be of additional value. After IV tPA treatment, proximal and distal motor function in upper extremity strongly correlate over time but greater improvement in MAF is noted. Further research is needed on the role of IV tPA on minor strokes with deficits of DMF.

Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone.

BACKGROUND: The IRIS trial (Insulin Resistance Intervention After Stroke) demonstrated that pioglitazone reduced the risk for both cardiovascular events and diabetes mellitus in insulin-resistant patients. However, concern remains that pioglitazone may increase the risk for heart failure (HF) in susceptible individuals. METHODS: In IRIS, patients with insulin resistance but without diabetes mellitus were randomized to pioglitazone or placebo (1:1) within 180 days of an ischemic stroke or transient ischemic attack and followed for ≤5 years. To identify patients at higher HF risk with pioglitazone, we performed a secondary analysis of IRIS participants without HF history at entry. HF episodes were adjudicated by an external review, and treatment effects were analyzed using time-to-event methods. A baseline HF risk score was constructed from a Cox model estimated using stepwise selection. Baseline patient features (individually and summarized in risk score) and postrandomization events were examined as possible modifiers of the effect of pioglitazone. Net cardiovascular benefit was estimated for the composite of stroke, myocardial infarction, and hospitalized HF. RESULTS: Among 3851 patients, the mean age was 63 years, and 65% were male. The 5-year HF risk did not differ by treatment (4.1% pioglitazone, 4.2% placebo). Risk for hospitalized HF was low and not significantly greater in pioglitazone compared with placebo groups (2.9% versus 2.3%, P=0.36). Older age, atrial fibrillation, hypertension, obesity, edema, high C-reactive protein, and smoking were risk factors for HF. However, the effect of pioglitazone did not differ across levels of baseline HF risk (hazard ratio [95% CI] for pioglitazone versus placebo for patients at low, moderate, and high risk: 1.03 [0.61-1.73], 1.10 [0.56-2.15], and 1.08 [0.58-2.01]; interaction P value=0.98). HF risk was increased in patients with versus those without incident myocardial infarction in both groups (pioglitazone: 31.4% versus 2.7%; placebo: 25.7% versus 2.4%; P<0.0001). Edema, dyspnea, and weight gain in the trial did not predict HF hospitalization but led to more study drug dose reduction with a lower mean dose of pioglitazone versus placebo (29±17 mg versus 33±15 mg, P<0.0001). Pioglitazone reduced the composite outcome of stroke, myocardial infarction, or hospitalized HF (hazard ratio, 0.78; P=0.007). CONCLUSIONS: In IRIS, with surveillance and dose adjustments, pioglitazone did not increase the risk of HF and conferred net cardiovascular benefit in patients with insulin resistance and cerebrovascular disease. The risk of HF with pioglitazone was not modified by baseline HF risk. The IRIS experience may be instructive for maximizing the net benefit of this therapy. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00091949.

Achievement of Guideline-Recommended Weight Loss Among Patients With Ischemic Stroke and Obesity.

Background and Purpose- The proportion of patients with acute ischemic stroke or transient ischemic attack (TIA) and obesity who successfully achieve goals for weight reduction recommended by major professional organizations is unknown. Methods- We examined the experience of participants in the placebo group of the IRIS trial (Insulin Resistance Intervention after Stroke) with a body mass index ≥30 kg/m2 at entry. Patients were of age ≥40 years, with a qualifying stroke or TIA within 180 days of randomization and documented insulin resistance without diabetes mellitus. Weights at baseline and at years 1 and 2 after entry were analyzed to determine the proportion of patients achieving a 5% weight loss and achievement of body mass index <27 kg/m2. Results- Of 1937 subjects assigned to placebo, 855 (44%) had obesity at entry. Median age of these 855 subjects was 60 years (interquartile range, 53-68), 41% were women, and median time from stroke/TIA to trial entry was 79 days. Among 788 subjects in the trial at 1 year, 166 (21%) had lost at least 5% of their starting weight and 12 (2%) had achieved a body mass index <27 kg/m2. One hundred nine (14%) participants gained at least 5% of their baseline weight at 1 year. Among 744 subjects in the trial at 2 years, 185 (25%) had lost at least 5% of their baseline weight and 23 (3%) had achieved a body mass index <27 kg/m2. One hundred forty (19%) participants gained at least 5% of their starting weight at 2 years. Conclusions- Only one quarter of obese patients with a recent ischemic stroke or TIA lost a clinically significant amount of weight after their vascular event. Many patients gained weight. Enhancing weight loss after ischemic stroke or TIA may help improve functional outcome and reduce risk for future vascular events, but clinical trials are needed to test and confirm these potential benefits.

Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus.

BACKGROUND: Insulin resistance is highly prevalent among patients with atherosclerosis and is associated with an increased risk for myocardial infarction (MI) and stroke. The IRIS trial (Insulin Resistance Intervention after Stroke) demonstrated that pioglitazone decreased the composite risk for fatal or nonfatal stroke and MI in patients with insulin resistance without diabetes mellitus, after a recent ischemic stroke or transient ischemic attack. The type and severity of cardiac events in this population and the impact of pioglitazone on these events have not been described. METHODS: We performed a secondary analysis of the effects of pioglitazone, in comparison with placebo, on acute coronary syndromes (MI and unstable angina) among IRIS participants. All potential acute coronary syndrome episodes were adjudicated in a blinded fashion by an independent clinical events committee. RESULTS: The study cohort was composed of 3876 IRIS participants, mean age 63 years, 65% male, 89% white race, and 12% with a history of coronary artery disease. Over a median follow-up of 4.8 years, there were 225 acute coronary syndrome events, including 141 MIs and 84 episodes of unstable angina. The MIs included 28 (19%) with ST-segment elevation. The majority of MIs were type 1 (94, 65%), followed by type 2 (45, 32%). Serum troponin was 10× to 100× upper limit of normal in 49 (35%) and >100× upper limit of normal in 39 (28%). Pioglitazone reduced the risk of acute coronary syndrome (hazard ratio, 0.71; 95% confidence interval, 0.54-0.94; P=0.02). Pioglitazone also reduced the risk of type 1 MI (hazard ratio, 0.62; 95% confidence interval, 0.40-0.96; log-rank P=0.03), but not type 2 MI (hazard ratio, 1.05; 95% confidence interval, 0.58-1.91; P=0.87). Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100× upper limit of normal (hazard ratio, 0.44; 95% confidence interval, 0.22-0.87; P=0.02), but not smaller MIs. CONCLUSIONS: Among patients with insulin resistance without diabetes mellitus, pioglitazone reduced the risk for acute coronary syndromes after a recent cerebrovascular event. Pioglitazone appeared to have its most prominent effect in preventing spontaneous type 1 MIs. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00091949.

Treatment-related changes in insomnia, anticipatory pleasure, and depression symptoms: A proof-of-concept study with cancer survivors.

OBJECTIVE/BACKGROUND: Cancer survivors have elevated rates of insomnia and depression. Insomnia increases risk for depression onset, and the Integrated Sleep and Reward (ISR) Model suggests that impairments in reward responding (e.g., ability to anticipate and/or experience pleasure) plays a central role in this relationship. Cognitive behavioral therapy for insomnia (CBT-I) is efficacious for treating chronic insomnia and reducing depression in cancer survivor populations. The effects of CBT-I on anticipatory and consummatory pleasure are theoretically and clinically meaningful, yet remain unexamined. PATIENTS/METHODS: This secondary analysis of a pilot RCT (N = 40 cancer survivors with insomnia) explicated changes in anticipatory and consummatory pleasure and depression symptoms following a 4-session, synchronous, virtual CBT-I program versus enhanced usual care (referral to a behavioral sleep medicine clinic + sleep hygiene handout). Linear mixed models examined changes in anticipatory and consummatory pleasure and depression symptoms as predictors of changes in insomnia severity from baseline to post-intervention and 1-month follow-up. RESULTS: CBT-I buffered against deterioration in anticipatory pleasure but not consummatory pleasure or depression symptoms. Across conditions, increased anticipatory pleasure was associated with insomnia reduction through 1-month follow-up, even after adjusting for changes in depression symptoms. CONCLUSION: CBT-I may improve reward processing deficits in cancer survivors with insomnia. Findings provide support for the ISR Model and implicate pleasure as an important target for insomnia and depression.

A web-based interactive database system for a transcranial Doppler ultrasound laboratory.

BACKGROUND: Variations in transcranial Doppler (TCD) examination performance techniques and interpretive paradigms between individual laboratories are a common challenge in the practice of TCD. Demand for rapid access to patient ultrasound examination data and report for use in intensive care settings has necessitated a more flexible approach to data management. Both of these issues may benefit from a computerized approach. METHODS: We describe the application of a World Wide Web-based database system for use in an ultrasound laboratory. Results. Databasing information while generating a TCD report is efficient. Web accessibility allows rapid and flexible communication of time-sensitive report information and interpretation for more expeditious clinical decision making. CONCLUSIONS: Web-based applications can extend the reach and efficiency of traditionally structured medical laboratories.

Poststroke depression incidence and risk factors: an integrative literature review.

Depression is a frequent complication of stroke, but few nurse researchers have studied poststroke depression (PSD). We reviewed all published research (January 1980-March 2005) that examined the incidence of and risk factors for depression among stroke survivors during the first 3 months after stroke. Many of the 49 studies reviewed were complicated by methodological limitations, including differing definitions of stroke and depression, the use of screening instruments to diagnose depression, selection bias, assessment at different time intervals poststroke, exclusion of patients with physical or cognitive impairments, and failure to control for associated variables. The incidence of PSD ranged from 5% to 63%. A history of depression, increased stroke severity, and poststroke cognitive or physical impairment were found to be risk factors for PSD.

Ondansetron-related hemorrhagic posterior reversible encephalopathy syndrome (PRES) following gastric bypass.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome formally recognized in 1996, which describes specific changes noted on neuroimaging thought to be related to impaired cerebral blood flow autoregulation and endothelial dysfunction. We report a case of PRES in the setting of increased ingestion of ondansetron; complicated by hemorrhagic transformation and refractory intracranial hypertension. We hypothesize an association of 5-HT3 antagonism and PRES. FINDINGS: This is a case study report; with review of previously published literature through PubMed search. We describe the case of a 25 year old man following bariatric surgery who increased his ingestion of ondansetron, taking up to 40 tablets/day due to excessive nausea and vomiting. The patient was hospitalized for progressively more severe headache of 1 week's duration. Computed tomography (CT) revealed bilateral cerebral edema in the parietal and occipital lobes in the setting of elevated blood pressure (BP). Three days into his admission, following improvement in his BP with oral anti-hypertensive but continued use of the ondansetron, the patient developed near complete blindness. CT head imaging revealed progression of the posterior cerebral edema and intraparenchymal hemorrhage. He was admitted to our ICU and despite supportive treatment, his neurological examination worsened while CT head imaging findings remained stable. Invasive multimodality monitoring revealed elevated intracranial pressure. The patient was aggressively treated and after a prolonged hospitalization and rehabilitation course, made a significant recovery. CONCLUSION: This case highlights a very rare potential neurological complication of ondansetron, a commonly used medication. We hypothesize an underlying association between PRES and 5-HT3 antagonism, via the latter's potential role in endothelial dysfunction. Prompt recognition and treatment of PRES is essential, in order to prevent secondary cerebral injury and the associated potentially grave consequences.

Multiple sclerosis presenting as ataxic hemiparesis.

Multiple sclerosis (MS) can present with many clinical pictures, but only rarely as a lacunar syndrome. The following case presentation is of multiple sclerosis with initial presentation as ataxic hemiparesis (AH), indistinguishable from the vascular syndrome. This case serves to illustrate that even classic lacunar syndromes can actually be the initial manifestation of multiple sclerosis and that other etiologies besides ischemic stroke need to remain in the differential diagnosis until a definitive has been concluded.

Do DSM-5 eating disorder criteria overpathologize normative eating patterns among individuals with obesity?

BACKGROUND: DSM-5 revisions have been criticized in the popular press for overpathologizing normative eating patterns-particularly among individuals with obesity. To evaluate the evidence for this and other DSM-5 critiques, we compared the point prevalence and interrater reliability of DSM-IV versus DSM-5 eating disorders (EDs) among adults seeking weight-loss treatment. METHOD: Clinicians (n = 2) assigned DSM-IV and DSM-5 ED diagnoses to 100 participants via routine clinical interview. Research assessors (n = 3) independently conferred ED diagnoses via Structured Clinical Interview for DSM-IV and a DSM-5 checklist. RESULTS: Research assessors diagnosed a similar proportion of participants with EDs under DSM-IV (29%) versus DSM-5 (32%). DSM-5 research diagnoses included binge eating disorder (9%), bulimia nervosa (2%), subthreshold binge eating disorder (5%), subthreshold bulimia nervosa (2%), purging disorder (1%), night eating syndrome (6%), and other (7%). Interrater reliability between clinicians and research assessors was "substantial" for both DSM-IV (κ = 0.64, 84% agreement) and DSM-5 (κ = 0.63, 83% agreement). CONCLUSION: DSM-5 ED criteria can be reliably applied in an obesity treatment setting and appear to yield an overall ED point prevalence comparable to DSM-IV.

Screening for DSM-5 Other Specified Feeding or Eating Disorder in a Weight-Loss Treatment-Seeking Obese Sample.

OBJECTIVE: To evaluate the effectiveness of specific self-report questionnaires in detecting DSM-5 eating disorders identified via structured clinical interview in a weight-loss treatment-seeking obese sample, to improve eating disorder recognition in general clinical settings. METHOD: Individuals were recruited over a 3-month period (November 2, 2011, to January 10, 2012) when initially presenting to a hospital-based weight-management center in the northeastern United States, which offers evaluation and treatment for outpatients who are overweight or obese. Participants (N = 100) completed the Structured Clinical Interview for DSM-IV eating disorder module, a DSM-5 feeding and eating disorders interview, and a battery of self-report questionnaires. RESULTS: Self-reports and interviews agreed substantially in the identification of bulimia nervosa (DSM-IV and DSM-5: tau-b = 0.71, P < .001) and binge-eating disorder (DSM-IV and DSM-5: tau-b = 0.60, P < .001), modestly for subthreshold binge-eating disorder (tau-b = 0.44, P < .001), and poorly for other subthreshold conditions (night-eating syndrome: tau-b = -0.04, P = .72, r = 0.06 [DSM-5]). DISCUSSION: Current self-report assessments are likely to identify full syndrome DSM-5 eating disorders in treatment-seeking obese samples, but unlikely to detect DSM-5 other specified feeding or eating disorders. We propose specific content changes that might enhance clinical utility as suggestions for future evaluation.

Submandibular TCD approach detects post-bulb ICA stenosis in children with sickle cell anemia.

BACKGROUND: Transcranial Doppler (TCD) ultrasound is a procedure commonly used to screen individuals with the major hemoglobin S diseases, Hb SS and Hb S-beta(0), for significant stenoses in the circle of Willis. Flow velocities above 200 cm/s have been shown to identify patients at elevated risk for cerebral infarction. Among TCD's limitations is the inability to insonate the distal extracranial, petrous, and cavernous internal carotid artery (ICA) through the standard transtemporal approach. METHODS: We extended the submandibular approach to include infra-siphon portions of the ICA. RESULTS: Using the extended submandibular approach to evaluate these portions of the ICA, we identified stenotic lesions in 4 patients with Hb SS disease out of a population of 131 children with Hb SS. Three of the 4 patients had no history of overt stroke or stroke-like symptoms. Neuroimaging confirmed the stenotic lesions, and also revealed watershed infarction as well as discrete areas of silent infarction. All 4 children had neuropsychological impairment. CONCLUSIONS: The submandibular approach, when added to a standard transcranial Doppler examination, may increase the sensitivity of this technique to identify important potential sources of cerebral infarction.

Centenarian stroke treated with tissue-type plasminogen activator.

BACKGROUND: Elderly patients with acute ischemic stroke often do worse than younger counterparts independent of thrombolytic therapy. Further, tissue-type plasminogen activator, (t-PA) is frequently withheld from the very old. This may be the result of comorbid conditions prohibiting its use or possibly the fear of causing more harm than good. We present a case of a 100-year-old woman who was treated with t-PA for acute ischemic stroke with rapid resolution of symptoms. CASE DESCRIPTION: A 100-year-old woman presented to the emergency department with slurred speech, right hemiparesis and right hemisensory loss. Computed tomography revealed neither hemorrhage nor early ischemic changes. Intravenous t-PA was administered at 0.9 mg/kg 3 min prior to the 3-hour limit. She improved rapidly (NIHSS from 12 on admission to 4 at 1 month) and was discharged to the care of her family after 4 hospital days. CONCLUSION: Intravenous thrombolysis may be beneficial in the very elderly and should be considered in any eligible elderly patients with acute ischemic stroke, with a risk/benefit analysis individualized to each case.