Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness. Design, Setting, and Participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023. Exposure: COVID-19 status (positive vs negative) at enrollment. Main Outcome and Measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms. Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]). Conclusions and Relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Transitioning to college: Testing cognitive bias modification for interpretations as an inoculation tool for social anxiety in college first-years.

BACKGROUND AND OBJECTIVES: Reducing social anxiety development among incoming college students may improve college adjustment and mental health outcomes. This study tested whether cognitive bias modification for interpretations (CBM-I) reduces social anxiety and increases adjustment during the transition to college, and whether changes in outcomes would be mediated by changes in interpretation biases. METHODS: Participants (N = 73) were randomly assigned to a 3-session weekly CBM-I condition or symptom tracking (ST) control condition. Multilevel models were used to estimate within-person trajectories from baseline to one week post-intervention and to test whether trajectories differed by condition. RESULTS: Those in the CBM-I condition (vs. ST) reported higher increases in social adjustment across time. There were not significant differences between conditions for changes in social anxiety, academic adjustment, and personal adjustment. CBM-I was indirectly linked to improvements in outcome variables via more adaptive interpretation biases. LIMITATIONS: CBM-I was administered in a laboratory setting, requiring more resources than some computerized interventions. CONCLUSIONS: Data tentatively support CBM-I for first-year students to increase social adjustment. Further, mediation findings provide support for targeting interpretation biases to improve social anxiety and adjustment outcomes. Yet, CBM-I did not outperform ST in improving social anxiety symptoms or other areas of college adjustment, and effect sizes were small, suggesting that more work is needed to amplify the potential of CBM-I as a therapeutic tool.

Cognitive behavioral therapy for anxiety and opioid use disorder: Development and pilot testing.

INTRODUCTION: Anxiety disorders are highly prevalent among people with opioid use disorder (OUD), and they have a negative impact on disorder course and treatment outcomes. The objective of this Stage 1 A/1B behavioral treatment development trial was to develop a novel cognitive-behavioral therapy (CBT) protocol for co-occurring anxiety disorders and OUD. METHODS: Following a period of iterative manual development involving patient interviews and feedback from content experts, we tested a 12-session individual CBT protocol in a small, open pilot trial (N = 5). This was followed by a small, randomized controlled trial (N = 32), comparing the new protocol to 12 sessions of manualized Individual Drug Counseling. All participants also received medication for OUD. RESULTS: Overall, support for feasibility and acceptability was strong, based on recruitment and retention rates and patient satisfaction ratings. Within-subjects results identified 11-point reductions in anxiety symptom severity (on a 0-56 point scale); these gains were sustained through 3 months of follow-up. However, these changes did not differ between randomized conditions. With respect to opioid outcomes, 85 % of participants were abstinent in the prior month at the end of treatment. Opioid use outcomes also did not differ by treatment condition. CONCLUSIONS: These results support the feasibility and acceptability of a CBT protocol for co-occurring anxiety and OUD. However, in this small pilot trial results do not show an initial benefit over an evidence-based psychosocial treatment targeted to OUD alone, in combination with medication for OUD.

Examining Alcohol-Related Blackouts and Drinking Motives Over Time Among College Women.

OBJECTIVE: Excessive alcohol consumption and its consequences among college women continues despite prevention efforts. One common consequence, alcohol-related blackouts (ARBs), are periods of alcohol-activated anterograde amnesia. The purpose of the current project is to extend the ARB and drinking motive literature by examining their relationship over time. METHOD: A sample of 424 women (88.9% White) completed online surveys assessing their ARBs and drinking motives weekly for 10 weeks. A series of hierarchical generalized linear models were estimated to examine the between-person and within-person effects of each drinking motive on repeated measures of experiencing a blackout across the time points. RESULTS: Women who report higher levels of drinking motives compared with others were more likely to report having blackout experiences. College women who reported higher levels of conformity motives did not have increased odds of experiencing a blackout. In weeks when they reported elevated levels of drinking motives, they were also more likely to experience an ARB. CONCLUSIONS: In general, college women who reported higher levels of social, coping, or enhancement motives experienced more blackouts than students who reported lower levels of these motives. Women who were underage were more likely to experience a blackout compared with women who were 21 or older. In a given week, 52.6% to 70.7% of the students consumed alcohol, and among women who drank in a given week, the prevalence of blackouts ranged from 8.5% to 14.6%. The results suggest that changes in motivational levels might provide a possible intervention point for ARBs risk.

Following social media influencers who share alcohol-related content is associated with college drinking.

INTRODUCTION: Frequent exposure to peer-shared alcohol-related content (ARC) on social media is associated with greater alcohol consumption and related consequences among undergraduates. Social media influencers also share ARC; yet, the effect of exposure to influencer-shared ARC on alcohol outcomes has not been examined. The current study examined whether following influencers who share ARC and the frequency of sharing were associated with alcohol outcomes, and associations between influencer type (e.g., actors) and alcohol outcomes. METHODS: Undergraduates (N = 528) from two universities in the United States completed an online survey assessing demographics, social media use, alcohol use and related consequences. They listed up to five influencers they followed and viewed the most content from. A series of linear regression models were conducted. RESULTS: Having a larger proportion of influencers sharing ARC was associated with greater quantity, frequency and peak drinks, but not consequences. Frequency of influencers sharing ARC was associated with greater quantity and peak drinks, but not frequency or consequences. Findings remained significant, even after controlling for peer ARC. Actor ARC, everyday person ARC and 'other' type influencer ARC were associated with several alcohol outcomes. DISCUSSION AND CONCLUSIONS: This study added to the literature by examining how following influencers who share ARC, and sharing frequency, were associated with drinking outcomes over and above exposure to peer ARC. It also examined whether ARC content from specific types of influencers was associated with alcohol outcomes. Findings highlight that the source of ARC is relevant when studying the effects of ARC exposure on college drinking.

Distressed Drinking: The Moderating Impact of Distress Tolerance on the Relation Between Anxiety Sensitivity, Panic Symptoms, and Alcohol Use and Problems.

OBJECTIVE: Undergraduate students are at particular risk for greater alcohol use, which is linked to anxiety disorders among a variety of other negative consequences. Understanding transdiagnostic factors underlying alcohol use problems and other disorders, such as anxiety and mood disorders, can help identify potential targets for intervention. METHOD: The present study (N = 208 undergraduates; 76.9% female) tested relations between self-reported anxiety sensitivity, panic symptoms, alcohol use and problems, and two different measures of distress tolerance. Specifically, the distress tolerance measures assessed (a) perceived ability to handle negative emotion states (emotional distress tolerance), measured via self-report, and (b) behavioral ability to tolerate discomforting physical sensations (physical distress tolerance), measured via a breath-holding duration task. RESULTS: Consistent with expectations, anxiety sensitivity was associated with greater panic symptoms, which in turn was associated with greater alcohol use problems, for individuals with low but not high levels of physical distress tolerance. Contrary to expectations, there was no evidence that panic symptoms explained the relation between anxiety sensitivity and alcohol use and problems at either low or high levels of emotional distress tolerance. CONCLUSIONS: Taken together, these results suggest that a possible target to decrease alcohol use problems is to increase capacity to withstand or engage with discomforting physiological and panic sensations (i.e., to cultivate greater physical distress tolerance).

Postacute Sequelae of SARS-CoV-2: Musculoskeletal Conditions and Pain.

Musculoskeletal and pain sequelae of COVID-19 are common in both the acute infection and patients experiencing longer term symptoms associated with recovery, known as postacute sequelae of COVID-19 (PASC). Patients with PASC may experience multiple manifestations of pain and other concurrent symptoms that complicate their experience of pain. In this review, the authors explore what is currently known about PASC-related pain and its pathophysiology as well as strategies for diagnosis and management.

Developing Digital Therapeutics for Chronic Pain in Primary Care: A Qualitative Human-Centered Design Study of Providers' Motivations and Challenges.

BACKGROUND: Digital therapeutics are growing as a solution to manage pain for patients; yet, they are underused in primary care where over half of the patients with chronic pain seek care. Little is known about how to successfully engage primary care providers in recommending digital therapeutics to their patients. Exploring provider motivations in chronic pain management would potentially help to improve their engagement and inform the development of digital therapeutics. OBJECTIVE: This study examined primary care providers' motivations for chronic pain management, including their strategies and challenges, to inform the future development of chronic pain-related digital therapeutics tailored to primary care settings. METHODS: We conducted qualitative semistructured interviews with health care providers recruited from 3 primary care clinics in Washington and 1 clinic in Colorado between July and October 2021. The sample (N=11) included 7 primary care physicians, 2 behavioral health providers, 1 physician assistant, and 1 nurse. Most providers worked in clinics affiliated with urban academic health systems. Guided by the human-centered design approach and Christensen's Job-to-be-Done framework, we asked providers their goals and priorities in chronic pain management, their experiences with challenges and strategies used to care for patients, and their perceptions of applying digital therapeutics in clinical practice. Transcripts were analyzed using a thematic analysis approach. RESULTS: We found that primary care providers were motivated but challenged to strengthen the patient-provider alliance, provide team-based care, track and monitor patients' progress, and address social determinants of health in chronic pain management. Specifically, providers desired additional resources to improve patient-centered communication, pain education and counseling, and goal setting with patients. Providers also requested greater accessibility to multidisciplinary care team consultations and nonpharmacological pain treatments. When managing chronic pain at the population level, providers need infrastructure and systems to systematically track and monitor patients' pain and provide wraparound health and social services for underserved patients. Recommendations on digital therapeutic features that might address provider challenges in achieving these motivations were discussed. CONCLUSIONS: Given the findings, to engage primary care providers, digital therapeutics for chronic pain management need to strengthen the patient-provider alliance, increase access to nonpharmacological treatment options, support population health tracking and management, and provide equitable reach. Leveraging digital therapeutics in a feasible, appropriate, and acceptable way to aid primary care providers in chronic pain management may require multimodal features that address provider motivations at an individual care and clinic or system level.

Why am I craving? The role of elaboration on ambiguous desire states.

Objective: We examined how attributions of broad ambiguous desire symptoms (eg, irritability) and elaborations on specific substances (ie, caffeine/food) influence subsequent self-reported cravings for these substances. Participants: 346 undergraduates were randomized to attribute their ambiguous desire symptoms to a lack of caffeine, food, or a vacation (active control), and then elaborate on the assigned stimulus. There was also a no-elaboration control group. Methods: Generalized Linear Models were used to test whether elaborating on one substance would increase cravings for that substance and decrease craving for the unelaborated substance relative to controls. Results: Participants who elaborated in terms of food reported increased food cravings, whereas participants who elaborated in terms of caffeine reported increased caffeine cravings. Conclusions: Findings suggest that food and caffeine cravings are malleable, and point to the importance of elaboration in polysubstance contexts. Food and caffeine elaborations may matter for heightening craving and determining the targets of craving.

Anxiety sensitivity and panic symptoms: the moderating influence of distress tolerance.

BACKGROUND AND OBJECTIVES: Anxiety sensitivity (AS) is the fear of consequences of anxiety-related sensations, and has been linked to the development of panic symptoms. Distress tolerance (DT) encompasses one's behavioral or self-perceived ability to handle aversive states. We examined whether higher DT buffers the relationship between AS and changes in panic symptoms across two timepoints, spaced ∼three weeks apart. DESIGN AND METHODS: At Time 1, 208 participants completed questionnaires and a physical DT task (breath-holding duration), a cognitive DT task (anagram persistence), and a self-report measure of DT (perceived DT). Panic symptoms were assessed at both timepoints. Structural equation modeling was used to evaluate two models in which AS and DT predicted changes in panic. RESULTS: Contrary to hypotheses, for those with longer breath-holding duration (higher physical DT), higher fears of physical anxiety-related sensations (higher physical AS) were associated with worse panic outcomes over time. CONCLUSIONS: Findings suggest that those with lower physical DT may have been less willing to engage with difficult tasks in the short-term. Although disengagement in the short-term may provide temporary relief, it is possible that averse psychopathological consequences stemming from rigid or habitual avoidance of distressing states may develop over longer periods of time.

Perspectives of COVID-19 vaccine-hesitant emergency department patients to inform messaging platforms to promote vaccine uptake.

OBJECTIVES: Efforts to promote COVID-19 vaccine acceptance must consider the critical role of the emergency department (ED) in providing health care to underserved patients. Focusing on patients who lacked primary care, we sought to elicit the perspectives of unvaccinated ED patients regarding COVID-19 vaccination concerns and potential approaches that might increase their vaccine acceptance. METHODS: We conducted this qualitative interview study from August to November 2021 at four urban EDs in San Francisco, California; Seattle, Washington; Durham, North Carolina; and Philadelphia, Pennsylvania. We included ED patients who were ≥18 years old, fluent in English or Spanish, had not received a COVID-19 vaccine, and did not have primary care physicians or clinics. We excluded patients who were unable to complete an interview, in police custody, under suspicion of active COVID-19 illness, or presented with a psychiatric chief complaint. We enrolled until we reached thematic saturation in relevant domains. We analyzed interview transcripts with a content analysis approach focused on identifying concerns about COVID-19 vaccines and ideas regarding the promotion of vaccine acceptance and potential trusted messengers. RESULTS: Of 65 patients enrolled, 28 (43%) identified as female, their median age was 36 years (interquartile range 29-49), and 12 (18%) interviews were conducted in Spanish. Primary concerns about COVID-19 vaccines included risk of complications, known and unknown side effects, and fear of contracting COVID-19 from vaccines. Trust played a major role for patients in deciding which sources to use for vaccine information and in engendering vaccine acceptance. Health care providers and family or friends were commonly cited as trusted messengers of information. CONCLUSIONS: We characterized concerns about COVID-19 vaccines, uncovered themes that may promote vaccine acceptance, and identified trusted messengers-primarily health care professionals. These data may inform the development of nuanced COVID-19 vaccine messaging platforms to address COVID-19 vaccine hesitancy among underserved ED populations.

Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection.

Introduction: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. Methods: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. Results: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). Discussion: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes.

The impact of a rapid home test on telehealth decision-making for influenza: a clinical vignette study.

BACKGROUND: Home testing for influenza has the potential to aid triage and management decisions for patients with influenza-like illness. As yet, little is known about the effect of the home influenza testing on clinical decision-making via telehealth. The goal of this study was to determine the clinicians' decision thresholds for influenza and whether the availability of a home influenza test affects clinical decisions. METHODS: We identified primary care physicians at 4 different sites in the US, largely via in-person continuing education meetings. Clinicians were asked for each vignette whether to treat empirically ("rule in"), ask the patient come to the clinic for further evaluation ("test"), or neither test nor treat ("rule out"). They were then given the results of a home influenza test, and were again asked to select from these three options. We measured the agreement of physician estimates of the likelihood of influenza with the probability based on a clinical prediction model. The test and treatment thresholds of influenza were determined based on mixed-effect logistic regressions. RESULTS: In total, 202 clinicians made 570 sets of clinical decisions. Agreement between estimated and actual probability of influenza was fair. The test and treatment thresholds were 24% (95% CI: 22% to 25%) and 63% (95% CI: 58% to 65%) before revealing the actual likelihood of influenza. After providing the results of a home flu test the thresholds were similar, 26% (95% CI: 24% to 29%) and 59% (95% CI: 56% to 62%). However, approximately half of clinicians changed their cliical management decision after being given the home influenza test result, largely by categorizing more patients in the "rule out" and "rule in" groups, and reducing the need for in-person evaluation from 41% of patients to only 20%. CONCLUSION: In the context of a telehealth visit for a patient with influenza-like illness, we identified a test threshold of approximately 25% and a treatment threshold of approximately 60%. Adding the home influenza test results reduced uncertainty and significantly decreased the need for in-person visits.

A pilot study of benzodiazepine cue-induced craving.

OBJECTIVES: The misuse of benzodiazepines is a growing concern due to increases in both access to these medications and their associated public health harms, most concerningly risk for overdose when combined with other substances. Although cue reactivity-the subjective and physiological response to cues or reminders of substance use-has been identified for most major classes of substances, it has yet to be studied with benzodiazepines. In this preliminary study, our objective was to assess whether images of benzodiazepines were associated with greater craving and anxiety than neutral images in adults who reported misuse of benzodiazepines. METHODS: We recruited a sample of 38 adults from a substance use disorder treatment setting and administered a standard cue reactivity task using pictorial images along with a battery of self-report measures. RESULTS: Results indicated significantly higher craving and anxiety in response to benzodiazepine relative to neutral cues, with cues eliciting a moderate to high level of craving, on average. Craving was associated with several risk factors for benzodiazepine misuse, including insomnia and distress intolerance. CONCLUSIONS: This preliminary study suggests that benzodiazepine cues can become conditioned to elicit craving responses and that the degree of cue reactivity is correlated with known risk factors for benzodiazepine misuse.

Diagnostic Accuracy of an At-Home, Rapid Self-test for Influenza: Prospective Comparative Accuracy Study.

BACKGROUND: Rapid diagnostic tests (RDTs) for influenza used by individuals at home could potentially expand access to testing and reduce the impact of influenza on health systems. Improving access to testing could lead to earlier diagnosis following symptom onset, allowing more rapid interventions for those who test positive, including behavioral changes to minimize spread. However, the accuracy of RDTs for influenza has not been determined in self-testing populations. OBJECTIVE: This study aims to assess the accuracy of an influenza RDT conducted at home by lay users with acute respiratory illness compared with that of a self-collected sample by the same individual mailed to a laboratory for reference testing. METHODS: We conducted a comparative accuracy study of an at-home influenza RDT (Ellume) in a convenience sample of individuals experiencing acute respiratory illness symptoms. Participants were enrolled in February and March 2020 from the Greater Seattle region in Washington, United States. Participants were mailed the influenza RDT and reference sample collection materials, which they completed and returned for quantitative reverse-transcription polymerase chain reaction influenza testing in a central laboratory. We explored the impact of age, influenza type, duration, and severity of symptoms on RDT accuracy and on cycle threshold for influenza virus and ribonuclease P, a marker of human DNA. RESULTS: A total of 605 participants completed all study steps and were included in our analysis, of whom 87 (14.4%) tested positive for influenza by quantitative reverse-transcription polymerase chain reaction (70/87, 80% for influenza A and 17/87, 20% for influenza B). The overall sensitivity and specificity of the RDT compared with the reference test were 61% (95% CI 50%-71%) and 95% (95% CI 93%-97%), respectively. Among individuals with symptom onset ≤72 hours, sensitivity was 63% (95% CI 48%-76%) and specificity was 94% (95% CI 91%-97%), whereas, for those with duration >72 hours, sensitivity and specificity were 58% (95% CI 41%-74%) and 96% (95% CI 93%-98%), respectively. Viral load on reference swabs was negatively correlated with symptom onset, and quantities of the endogenous marker gene ribonuclease P did not differ among reference standard positive and negative groups, age groups, or influenza subtypes. The RDT did not have higher sensitivity or specificity among those who reported more severe illnesses. CONCLUSIONS: The sensitivity and specificity of the self-test were comparable with those of influenza RDTs used in clinical settings. False-negative self-test results were more common when the test was used after 72 hours of symptom onset but were not related to inadequate swab collection or severity of illness. Therefore, the deployment of home tests may provide a valuable tool to support the management of influenza and other respiratory infections.

SwabExpress: An End-to-End Protocol for Extraction-Free COVID-19 Testing.

BACKGROUND: The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse-transcription PCR (RT-qPCR). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce. To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. METHODS: We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral inactivation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. RESULTS: After optimization, SwabExpress has a low limit of detection at 2-4 molecules/µL, 100% sensitivity, and 99.4% specificity when compared side by side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. CONCLUSION: SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

Evaluating Specimen Quality and Results from a Community-Wide, Home-Based Respiratory Surveillance Study.

While influenza and other respiratory pathogens cause significant morbidity and mortality, the community-based burden of these infections remains incompletely understood. The development of novel methods to detect respiratory infections is essential for mitigating epidemics and developing pandemic-preparedness infrastructure. From October 2019 to March 2020, we conducted a home-based cross-sectional study in the greater Seattle, WA, area, utilizing electronic consent and data collection instruments. Participants received nasal swab collection kits via rapid delivery within 24 hours of self-reporting respiratory symptoms. Samples were returned to the laboratory and were screened for 26 respiratory pathogens and a housekeeping gene. Participant data were recorded via online survey at the time of sample collection and 1 week later. Of the 4,572 consented participants, 4,359 (95.3%) received a home swab kit and 3,648 (83.7%) returned a nasal specimen for respiratory pathogen screening. The 3,638 testable samples had a mean RNase P relative cycle threshold (Crt ) value of 19.0 (SD, 3.4), and 1,232 (33.9%) samples had positive results for one or more pathogens, including 645 (17.7%) influenza-positive specimens. Among the testable samples, the median time between shipment of the home swab kit and completion of laboratory testing was 8.0 days (interquartile range [IQR], 7.0 to 14.0). A single adverse event occurred and did not cause long-term effects or require medical attention. Home-based surveillance using online participant enrollment and specimen self-collection is a safe and feasible method for community-level monitoring of influenza and other respiratory pathogens, which can readily be adapted for use during pandemics.

Sex differences in benzodiazepine misuse among adults with substance use disorders.

Women are more likely than men to be diagnosed with anxiety disorders and to be prescribed benzodiazepines. People with substance use disorders are at a heightened risk for the misuse of benzodiazepines, yet little is known about sex differences in the prevalence, correlates or patterns of benzodiazepine misuse in this population. The aim of this study was to characterize sex differences in benzodiazepine misuse in a sample of adults receiving substance use disorder treatment (N = 352). Almost half of the sample had been prescribed a benzodiazepine and more than 40% had misused a benzodiazepine. Women were more likely to have a lifetime prescription than men, but were not more likely to report misuse or regular misuse. Consistent with data for other substances, women were more likely to report misusing benzodiazepines to cope and reported greater anxiety sensitivity. The vast majority (97%) of participants reported co-use of benzodiazepines with other substances and 65% of women reporting misusing benzodiazepines via a non-oral route of administration (e.g., intranasal). Although benzodiazepine misuse prevalence was not substantively different between men and women, several sex differences in clinical characteristics and patterns of use were identified. Further research on the nature of sex differences in benzodiazepine misuse is needed to inform targeted treatment for both men and women with substance use disorders.

SwabExpress: An end-to-end protocol for extraction-free COVID-19 testing.

BACKGROUND: The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse transcription PCR (RT-qPCR) (1). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce (2). To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. METHODS: We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral activation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. RESULTS: After optimization, SwabExpress has a low limit of detection at 2-4 molecules/uL, 100% sensitivity, and 99.4% specificity when compared side-by-side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. CONCLUSION: SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.