Citations

AbstractTo examine the length of a hexanucleotide expansion in C9orf72, which represents the most frequent genetic cause of frontotemporal lobar degeneration and motor neuron disease, we employed a targeted amplification-free long-read sequencing technology: No-Amp sequencing. In our cross-sectional study, we assessed cerebellar tissue from 28 well-characterized C9orf72 expansion carriers. We obtained 3507 on-target circular consensus sequencing reads, of which 814 bridged the C9orf72 repeat expansion (23%). Importantly, we observed a significant correlation between expansion sizes obtained using No-Amp sequencing and Southern blotting (P = 5.0 × 10−4). Interestingly, we also detected a significant survival advantage for individuals with smaller expansions (P = 0.004). Additionally, we uncovered that smaller expansions were significantly associated with higher levels of C9orf72 transcripts containing intron 1b (P = 0.003), poly(GP) proteins (P = 1.3 × 10− 5), and poly(GA) proteins (P = 0.005). Thorough examination of the composition of the expansion revealed that its GC content was extremely high (median: 100%) and that it was mainly composed of GGGGCC repeats (median: 96%), suggesting that expanded C9orf72 repeats are quite pure. Taken together, our findings demonstrate that No-Amp sequencing is a powerful tool that enables the discovery of relevant clinicopathological associations, highlighting the important role played by the cerebellar size of the expanded repeat in C9orf72-linked diseases.

Background: News articles, commentaries, and opinion articles have suggested that ongoing social distancing measures coupled with economic challenges during COVID-19 may worsen stress, affective state, and substance use across the globe. We sought to advance our understanding of the differences between individuals who change their substance use patterns during a public health crisis and those who do not. Methods: Cross-sectional survey of young adults (18–25 years of age) assessing respondent characteristics and vaping, tobacco, alcohol, and/or marijuana use. We calculated prevalence estimates, prevalence changes, and prevalence ratios with associated 95% confidence intervals and looked for differences with the chi-square test. Results: Of the total sample, 53.2% ( n = 542/1018) young adults reported vaping or using tobacco, alcohol, and/or marijuana. Among the 542 respondents reporting use, 34.3% reported a change in their use patterns. Among respondents reporting changes in substance use patterns during the pandemic ( n = 186), 68.8% reported an increase in alcohol use, 44.0% reported a decrease in vaping product use, and 47.3% reported a decrease in tobacco product use due to COVID-19. Substance use changed significantly for respondents with increasing degree of loneliness (continuous loneliness score: prevalence ratio = 1.12, 95% confidence interval = 1.01–1.25), anxiety (prevalence ratio = 1.45, 95% confidence interval = 1.14–1.85), and depression (prevalence ratio = 1.44, 95% confidence interval = 1.13–1.82). Conclusion: Self-reported substance use among young adults was observed to change during a pandemic, and the degree of loneliness appears to impact these changes. Innovative strategies are needed to address loneliness, anxiety, depression, and substance use during global health crises that impact social contact.

Objective: We surveyed patients who visited multiple outpatient specialty practices to understand what summary content was most helpful with the goal of optimizing meaningful outpatient clinical visit summary content. Materials and Methods: We constructed a survey instrument to measure delivery, use, and contents of clinical visit summaries. We surveyed patients who visited with at least 2 different outpatient medical specialties to understand preferences. Results: Most patients in our sample valued the summary information they received, and retained it as healthcare documentation (84%) and/or quick reference in supporting self-care (70%). Patients most commonly reported that information on results of completed tests (91%) and treatment plan instructions (89%) were very helpful. Additionally, patients expressed the importance of online access to clinical visit summary information. Discussion: Most patients used the clinical visit summary as healthcare documentation, and valued online availability of their summary information. Patients most often reported that information on results of recently completed tests and specific instructions on treatment plan were very helpful. Patients who sought further information after their visit most often looked to a provider and/or online. Conclusions: Patients valued clinical visit summary accessibility and as a reference tool to summarize care and provide next steps. Optimal clinical visit summaries might collate and integrate assessments and recommendations from multiple specialties into coherent care plans for patients.

AbstractBackgroundDespite malnutrition being associated with increased mortality and morbidity, there continues to be great difficulty in defining criteria and implementing widespread screening. Tools used to diagnose decreased fat‐free mass (FFM [sarcopenia]) should be easy to use, relatively inexpensive, and safe. Bioelectrical impedance analysis (BIA) has the potential to meet these criteria, but reliability across body mass index (BMI) classes is a concern.MethodsA total of 176 healthy ambulatory participants (aged 18–65 years) were recruited equally (n = 44) in 4 BMI categories: (1) 18.5–24.9, (2) 25.0–29.9, (3) 30–34.9, and (4) ≥35.0. Participants were fasting overnight and had S‐MFBIA (InBody 770) measurements the next morning, with DXA being performed subsequently within 30 minutes.ResultsThe measurement (mean ± SD) for FFM with DXA was 52.8 ± 11.0, and BIA was 53.6 ± 11.0. Delta (S‐MFBIA vs DXA) was 0.8 ± 2.2 (5% limits of agreement −3.5 to +5.2), and concordance correlation coefficient (CCC) was 0.98 (95% CI, 0.97–0.98). The measurements (mean ± SD) for PBF with DXA was 37.5 ± 10.6% and S‐MFBIA was 36.6 ± 11.3%. Delta (S‐MFBIA vs DXA) was −0.9 ± 2.6 (5% limits of agreement 6.0 to +4.2), and CCC was 0.97 (95% CI, 0.96–0.98). The CCC according to the 4 BMI groups for FFM and PBF was between 0.96–0.98 and 0.90–0.94, respectively.ConclusionsFFM and PBF measured by S‐MFBIA had good agreement with DXA across all BMI categories measured in the current study of ambulatory participants.

Introduction: CBD is a major phytocannabinoid in hemp ( Cannabis sativa containing less than 0.3% THC). Hemp cigarettes are a combustible form of hemp consisting of dried and smokable flowers, which represent 2% of the overall CBD market, and the market is expected to grow. Combustion and pyrolysis of organic material are associated with the production of carbonyl compounds, which are known toxicants and are associated with adverse health outcomes. Concentrations of carbonyl compounds in mainstream hemp cigarette smoke are unknown. Materials and Methods: We analyzed and compared carbonyl concentrations in the mainstream smoke produced by a hemp cigarette (Brand B), a premium hemp cigarette (Brand A), Marlboro Red tobacco cigarette, and a research reference tobacco cigarette using high-performance liquid chromatography. We measured carbonyl concentrations in μg per puff and mg per cigarette. Carbonyls investigated were formaldehyde, acetaldehyde, acetone, acrolein, propionaldehyde, crotonaldehyde, 2-butanone, and butyraldehyde. Significance was determined using Tukey's test. Results: We observed that Brand B had significantly higher butyraldehyde than any cigarette. No significant differences were observed in crotonaldehyde concentration in the cigarettes. For the remaining carbonyls, Brand A had consistently lower concentrations in mainstream smoke than tobacco cigarettes. Hemp cigarettes emit carbonyls in a lower concentration in μg/puff than tobacco cigarettes, but the magnitude of significance generally decreases when normalized to mg/cigarette. Conclusions: Smoke from hemp cigarettes contains carbonyls at biologically significant concentrations. Opportunities may exist to reduce carbonyl production in these products, and identified potential risks must be considered when balancing the harms and benefits of hemp cigarettes when used for therapeutic purposes.

Background: Chronic illness is often comorbid with the psychological state of loneliness. Models of care for patients who experience chronic migraines may often lack an understanding of psychosocial influences of the illness. Addressing the effects of loneliness on the health behaviors of chronic migraine patients may further elucidate gaps in care that exist beyond the biomedical approach to migraine treatment. The primary aim of this study was to assess the relationship between loneliness and behavioral health decisions in chronic migraine patients, specifically patient ability to self-manage, and effectiveness of treatments. Methods: We conducted a cross-sectional survey among patients (n = 500) with migraine and assessed for the experience of loneliness by using the University of California, Los Angeles–Revised (UCLA-R) Three-item Loneliness Scale and the extent of migraine-related disability via the Migraine Disability Assessment (MIDAS). Furthermore, we evaluated patients for their ability to self-manage their migraines, and perceived effectiveness of treatment. Results: Nearly half of our population reported at least one measure of loneliness (230/500, 46.0%). Patients experiencing chronic migraine were statistically more likely to report feeling lonely when compared to patients with episodic migraines ( P < .001). Patients who report loneliness had lower odds of feeling ’very satisfied” with their ability to self-manage their migraine symptoms (aOR = 0.34, 95% CI 0.14-0.81) and had lower odds of feeling “very satisfied” with their ability to avoid conditions that cause their headache (aOR = 0.39, 95% CI 0.16-0.91). Conclusions: Loneliness has significant effects on the illness experience of patients with chronic migraines, including their ability to self-manage or be satisfied with their current state of care. Psychosocial models of care that address loneliness among patients with chronic migraine may help improve health outcomes and management.

INTRODUCTION: Chronic pelvic pain (CPP) affects up to 15% of women in the United States. The endocannabinoid system can be a pharmacological target for endometriosis-related pelvic pain, as cannabis receptors are highly expressed in the uterus and other non-reproductive tissues. We hypothesize that many patients with CPP use cannabis and report improvement in symptoms. METHODS: An anonymous, confidential, electronic survey was performed from March through August 2019. Patients aged 18 through 89 were included if they had a diagnosis of pelvic/perineal pain, dyspareunia, or endometriosis. Subjects were approached during outpatient appointments. Study approval was obtained from the Institutional Review Board. RESULTS: A total of 122 of 240 (50.8%) patients responded. Of these, 113 self-reported a diagnosis of CPP (92.6%). Twenty-six patients reported cannabis use (23%). Six (24%) used Cannabidiol (CBD), 3 (12%) used tetrahydrocannabinol (THC), and 15 (60%) used a combination of CBD and THC. Frequency of use varied, with the majority using at least once per week (n=18, 69.2%). Only 5 (19.2%) utilized a State Medical Cannabis Program to obtain a certification. Of users, 24 (92.3%) reported improvement in symptoms, including pain, cramping, muscle spasms, anxiety, depression, sleep disturbances, libido, and irritability. However, 21 (80.7%) reported side effects; the most common were dry mouth, sleepiness, and feeling “high.” CONCLUSION: Up to 23% of patients with CPP report use of cannabis as an adjunct to their prescribed therapy, and they use a variety of formulations and doses. Most report daily or weekly use. Although side effects are common, most users report improvement in symptoms.

Abstract Objective Financial impacts associated with a switch to a different electronic health record (EHR) have been documented. Less attention has been focused on the patient response to an EHR switch. The Mayo Clinic was involved in an EHR switch that occurred at 6 different locations and with 4 different “go-live” dates. We sought to understand the relationship between patient satisfaction and the transition to a new EHR. Materials and Methods We used patient satisfaction data collected by Press Ganey from July 2016 through December 2019. Our patient satisfaction measure was the percent of patients responding “very good” (top box) to survey questions. Twenty-four survey questions were summarized by Press Ganey into 6 patient satisfaction domains. Piecewise linear regression was used to model patient satisfaction before and after the EHR switch dates. Results Significant drops in patient satisfaction were associated with the EHR switch. Patient satisfaction with access (ease of getting clinic on phone, ease of scheduling appointments, etc.) was most affected (range of 6 sites absolute decline: -3.4% to -8.8%; all significant at 99% confidence interval). Satisfaction with providers was least affected (range of 6 sites absolute decline: -0.5% to -2.8%; 4 of 6 sites significant at 99% confidence interval). After 9-15 months, patient satisfaction with access climbed back to pre-EHR switch levels. Conclusions Patient satisfaction in several patient experience domains dropped significantly and stayed lower than pre–“go-live” for several months after a switch in EHR. Satisfaction with providers declined less than satisfaction with access.