Citations

Abstract Introduction Cognitive behavior therapy for insomnia (CBT-I), a first-line therapy for patients with chronic insomnia disorder (ChID), is underutilized due to reduced access to trained providers and other barriers. We developed an interactive care plan (ICP) combining individual aspects of CBT-I. This ICP, which integrates with the electronic health record (EHR), is designed to deliver personalized and scalable CBT-I to patients with ChID. We report data from initial implementation and evaluation of a ChID ICP deployed at a tertiary sleep medicine clinic. Methods The ICP was developed following patient and provider interviews and focus groups. Patients diagnosed with ChID were offered enrollment and engaged in the ICP through an app. The ICP has embedded logic that may escalate care or offer an exit from the program, depending upon the patient’s response to questions. Key variables ascertained from the patient included sleep efficiency (SE), sleep timing and the Insomnia Severity Index (ISI), and how satisfied they were with their progress (Likert scale). We also measured In Basket messaging related to use of the ICP. Results A total of 222 patients [57% female, age=56.4±15.9 years (average ±SD), 92.7% white] were enrolled in the initial 120 days of ICP implementation. Most referrals were initiated by physicians or advanced practitioners (77.9%). ISI at initiation was 15±5.18 and SE was 74.55±16.65%. Patients spent 35.9±26.25 days engaging with the ICP. The ISI score at 28 days was 12.89±4.98 and SE was 78.9±13.4% with both showing significant improvement from baseline (p=0.013; p=0.002; respectively). Self-rated satisfaction with progress did not significantly correlate with actual improvement in ISI or SE (p>0.05). The ICP generated 3.89±2.3 In Basket messages per patient. Conclusion Patients who actively engaged with the ICP showed significant improvements in insomnia severity and sleep efficiency. While a majority of the patients were neutral towards the ICP and only a small minority expressed dissatisfaction, these data indicate that the ICP will have clinical utility in busy sleep medicine practices with reduced access to behavioral sleep specialists. Support (If Any)

Aim. To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. Methods. A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). Results. From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD −7.1%; 95% CI [−16.0, 1.8]), LVEDV (MD −5.2%; 95% CI [−15.8, 5.4]), or LVEF (MD 0.68; 95% CI [−4.36, 5.73]) versus the non-image-guided approach. Conclusion. The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.

Abstract Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.

Introduction: To improve CRT outcomes, image-guided approaches targeting left ventricular (LV) lead placement at the segment of latest mechanical activation have been compared to non-image-guided approaches with mixed results. A meta-analysis was conducted to assess the association between an image-guided approach and CRT outcomes. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that compared any image-guided versus any non-image-guided approach for LV lead placement. Two independent reviewers screened titles and abstracts then reviewed full text of identified studies. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses were performed for NYHA class improvement and changes in LV end systolic volume, LV end diastolic volume, and LVEF using random effects models. Results: Of 5715 citations screened, 5 RCTs with a total of 818 patients met the inclusion criteria. Speckle tracking echocardiography (STE) was the primary imaging method in all studies, but 3 studies included CT, CMR, SPECT, and/or PET in addition to STE. The comparator arms were standard of care in 4 studies and an electrically guided approach in one. Mean age ranged from 66 to 72 years, 76% were male, and 53% had ischemic cardiomyopathy. Among 747 evaluable patients, concordant or adjacent LV lead was achieved in 348 of 386 (90%) in the image-guided arm and 291 of 361 (81%) in the control arm. At 6 months, the image-guided approach was statistically significantly associated with a NYHA class improvement, but no other statistically significant differences were found (Figure). Conclusion: An image-guided CRT approach was associated with significant Improvement in NYHA class but not in echocardiographic measures, possibly due to small sample size and high LV concordance with area of latest activation in both study arms - the latter of which merits further investigation.

Introduction: CRT outcomes with image-guided left ventricular (LV) lead placement within the LV segment of latest mechanical activation have been assessed in several randomized controlled trials (RCTs) with equivocal results, possibly due to variable achievement of concordant LV lead placement in the image-guided and comparator arms. We conducted meta-analyses to assess CRT outcomes associated with concordant LV lead placement. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that reported outcomes in those with LV lead placement at or adjacent to the site of latest mechanical activation (concordant) versus those with LV lead placement distant to the site of latest mechanical activation (discordant) as determined by any imaging method. Two independent reviewers screened titles and abstracts then reviewed full text for inclusion/exclusion. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses for death, death or HF hospitalization, and changes in LVESV and LVEF were performed using random effects models. Results: Among 5715 citations identified, 9 papers from 8 studies (including 4 RCTs) were selected that included 1004 patients with concordant LV lead placement and 380 with discordant LV lead placement. Mean patient age ranged from 66 to 68 years, 82% were male, and 64% had ischemic cardiomyopathy. Segment of latest activation was determined by speckle tracking echocardiography (STE) in 7 (88%) studies. Meta-analyses demonstrated statistically significant lower all-cause mortality or HF hospitalization and reduction in LVESV with a concordant LV lead (Figure). There were trends toward lower all-cause mortality and increased LVEF. Conclusion: A concordant LV lead, as determined primarily by STE, was associated with better CRT outcomes. Further study of feasible methods to achieve concordance in clinical practice is needed.

Introduction: CRT optimizations has the potential to improve the 30% non-response rate. Randomized trials (RCTs) comparing device and echo-guided CRT optimization have been overall small and results have been conflicting. Methods: We searched the EMBASE and MEDLINE databases from January 2008 through September 2020 for RCTs and prospective observational studies that randomized patients to either echo-guided or device-based CRT optimization. Included studies had to report on at least one of the following outcomes of interest: all-cause mortality, heart failure hospitalization (HFH), NYHA class improvement, mean EF at follow up, LVEDD, 6MWD, and QoL. A meta-analyses on the outcomes of interest was performed using random effects models. Results: We included seven RCTs representing a total of 2,730 patients. Of those, 1,113 patients were randomized to echo-guided optimization, and 1,617 were randomized to device-based optimization. The mean age of patients was 64.5 years, and they were predominantly men (60%). In the device-based optimization group, there was 93 deaths (5.7%) and 142 HFH (5.1%). In the echo-guided optimization group, there was 57 deaths (10.2%) and 112 HFH (12.4%). On random effects meta-analysis, the device-based optimization group had a lower rate of HFH compared with the echo-guided optimization group (OR 0.81, 95% CL 0.70-0.95, Figure). However, differences in the following outcomes between the two groups were not statistically significant: all-cause mortality, mean follow up EF, LVEDD, NYHA class improvement, 6MWD improvement range or QoL. Conclusions: This meta-analysis suggests that echo-guided optimization of CRT is equivalent to device-based optimization in relation to the clinical outcomes of death, EF, LVEDD, NYHA and 6MWD but suggests that device-related optimization could reduce HFH. The latter merits further investigation in relation to different device-base optimization algorithms.

Abstract Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. Highlights The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.

Abstract Background The yield of next-generation sequencing (NGS) added to a Sanger sequencing–based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) assay was evaluated in clinical practice for diagnosis of bacterial infection. Methods PCR targeting the V1 to V3 regions of the 16S rRNA gene was performed, with amplified DNA submitted to Sanger sequencing and/or NGS (Illumina MiSeq) or reported as negative, depending on the cycle threshold value. A total of 2146 normally sterile tissues or body fluids were tested between August 2020 and March 2021. Clinical sensitivity was assessed in 579 patients from whom clinical data were available. Results Compared with Sanger sequencing alone (400 positive tests), positivity increased by 87% by adding NGS (347 added positive tests). Clinical sensitivity of the assay that incorporated NGS was 53%, which was higher than culture (42%, P < .001), with an impact on clinical decision-making in 14% of infected cases. Clinical sensitivity in the subgroup that received antibiotics at sampling was 41% for culture and 63% for the sequencing assay (P < .001). Conclusions Adding NGS to Sanger sequencing of the PCR-amplified 16S rRNA gene substantially improved test positivity. In the patient population studied, the assay was more sensitive than culture, especially in patients who had received antibiotic therapy.