How accurate is the human olfactory system in detecting peanuts?

KEY POINTS: This is the first study to quantify the accuracy, sensitivity, and specificity of the human olfactory system in detecting peanuts in common food items. With more competing sensory input, the human olfactory sensitivity to peanuts decreases; this is especially evident when peanuts are mixed in sauces. Metrics established in this study can be used to develop standards for determining the clinical utility of allergen detecting devices that are currently under development.

Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.

BACKGROUND: Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care. METHODS: We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices. DISCUSSION: This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019137282.

"When I think about my future, I just see darkness": How youth exiting homelessness navigate the hazy, liminal space between socioeconomic exclusion and inclusion.

OBJECTIVES: The overarching objective of this mixed methods longitudinal study was to understand whether and how rent subsidies and mentorship influenced socioeconomic inclusion outcomes for youth exiting homelessness. The focus of this paper is on the qualitative objectives, which evolved from a primary focus on exploring how study mentorship was working as a facilitator of socioeconomic inclusion to focusing on how participants navigated the hazy, liminal space between socioeconomic exclusion and inclusion. METHODS: This was a convergent mixed methods study scaffolded by community-based participatory action axiology. The quantitative component is reported elsewhere and involved a 2-year pilot randomized controlled trial where 24 participants received rent subsidies and 13 were randomly assigned a study mentor; proxy indicators of socioeconomic inclusion were measured every 6 months for 2.5 years. Qualitative objectives were explored using a qualitative descriptive design and theoretically framed using critical social theory. The lead author interviewed 12 participants every 6 months for 2.5 years. Qualitative interviews were analyzed using reflexive thematic analysis with an emphasis on critical interpretation. RESULTS: Navigating the liminal space between socioeconomic exclusion and inclusion was complex and non-linear, and the way youth navigated that journey was more strongly associated with factors like informal mentorship (naturally occurring "coach-like" mentorship) and identity capital (sense of purpose, control, self-efficacy, and self-esteem), rather than whether or not they were assigned a formal study mentor. CONCLUSION: A holistic approach integrating coaching and attention to identity capital alongside economic supports may be key to helping youth exiting homelessness achieve socioeconomic inclusion.

RéSUMé: OBJECTIFS: L'objectif primordial de cette étude longitudinale à méthodes mixtes était de comprendre si et comment les suppléments au loyer et le mentorat influencent les résultats sur le plan de l'inclusion socioéconomique pour les jeunes qui sortent du sans-abrisme. Notre article porte sur des objectifs qualitatifs; à l'origine, il visait principalement à explorer l'efficacité du mentorat des études comme moyen de faciliter l'inclusion socioéconomique, puis il a évolué en s'attachant à la manière dont les participantes et les participants trouvaient leurs repères dans l'espace liminaire flou entre l'exclusion et l'inclusion socioéconomique. MéTHODE: Cette étude à méthodes mixtes convergentes est échafaudée sur l'axiologie de l'action participative communautaire. L'élément quantitatif, qui fait l'objet d'un autre article, a impliqué un essai pilote comparatif randomisé de deux ans où 24 participantes et participants ont reçu des suppléments au loyer, et 13 ont été jumelés de façon aléatoire à un tuteur ou une tutrice scolaire; des indicateurs approximatifs de l'inclusion socioéconomique ont été mesurés tous les six mois pendant deux ans et demi. Les objectifs qualitatifs ont été explorés à l'aide d'un protocole descriptif qualitatif et encadrés théoriquement par la théorie sociale critique. L'autrice principale a interviewé 12 participantes et participants tous les six mois pendant deux ans et demi. Les entretiens qualitatifs ont été analysés en employant l'analyse thématique réflexive et en mettant l'accent sur l'interprétation critique. RéSULTATS: L'exploration de l'espace liminaire entre l'exclusion et l'inclusion socioéconomique était complexe et non linéaire, et le parcours des jeunes était davantage associé à des facteurs comme le mentorat informel (le mentorat naturel semblable à celui d'un entraîneur ou d'une entraîneuse) et le capital identitaire (le sentiment d'avoir un but, le contrôle, l'auto-efficacité et l'estime de soi) qu'au fait d'avoir ou non été jumelés à un tuteur ou une tutrice dans leurs études. CONCLUSION: Une démarche holistique intégrant l'encadrement et l'attention au capital identitaire, en plus des mesures de soutien économique, pourrait être essentielle pour aider les jeunes qui sortent du sans-abrisme à s'intégrer sur le plan socioéconomique.

Long-term efficacy and safety of erenumab in patients with chronic migraine and acute medication overuse: A subgroup analysis.

OBJECTIVE: Assess the long-term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse. BACKGROUND: Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies. METHODS: This 52-week open-label extension study followed a 12-week double-blind placebo-controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once-monthly erenumab 70 mg or 140 mg. Patients were stratified by region and medication overuse status. Patients received erenumab 70 mg or 140 mg throughout or switched from erenumab 70 to 140 mg (based on protocol amendment to augment safety data at higher dose). Efficacy was assessed in patients with and without medication overuse at parent study baseline. RESULTS: Of 609 patients enrolled in the extension study, 252/609 (41.4%) met the criteria for medication overuse at parent study baseline. At Week 52, the mean change in monthly migraine days from parent study baseline was -9.3 (95% confidence interval: -10.4, -8.1 days) in the medication overuse subgroup versus -9.3 (-10.1, -8.5 days) in the non-medication overuse subgroup (combined erenumab doses); proportion of patients achieving ≥50% reduction in monthly migraine days at Week 52 was 55.9% (90/161; 48.2%, 63.3%) versus 61.3% (136/222; 54.7%, 67.4%), respectively. Among baseline users of acute migraine-specific medication, the mean change in monthly migraine-specific medication days at Week 52 was -7.4 (-8.3, -6.4 days) in the medication overuse subgroup versus -5.4 (-6.1, -4.7 days) in the non-medication overuse subgroup. Most patients (197/298; 66.1%) in the medication overuse subgroup transitioned to non-overuse status by Week 52. Erenumab 140 mg was associated with numerically greater efficacy than erenumab 70 mg across all endpoints. No new safety signals were identified. CONCLUSION: Long-term erenumab treatment demonstrated sustained efficacy and safety in patients with chronic migraine with and without acute medication overuse.

Effect of cone-beam computed tomography metal artefact reduction on incomplete subtle vertical root fractures.

Purpose: This study compared the accuracy of detection of incomplete vertical root fractures (VRFs) in filled and unfilled teeth on cone-beam computed tomography images with and without a metal artefact reduction (MAR) algorithm. Materials and Methods: Forty single-rooted maxillary premolars were selected and, after endodontic instrumentation, were categorized as unfilled teeth without fractures, filled teeth without fractures, unfilled teeth with fractures, or filled teeth with fractures. Each VRF was artificially created and confirmed by operative microscopy. The teeth were randomly arranged, and images were acquired with and without the MAR algorithm. The images were evaluated with OnDemand software (Cybermed Inc., Seoul, Korea). After training, 2 blinded observers each assessed the images for the presence and absence of VRFs 2 times separated by a 1-week interval. P-values<0.05 were considered to indicate significance. Results: Of the 4 protocols, unfilled teeth analysed with the MAR algorithm had the highest accuracy of incomplete VRF diagnosis (0.65), while unfilled teeth reviewed without MAR were associated with the least accurate diagnosis (0.55). With MAR, an unfilled tooth with an incomplete VRF was 4 times more likely to be identified as having an incomplete VRF than an unfilled tooth without this condition, while without MAR, an unfilled tooth with an incomplete VRF was 2.28 times more likely to be identified as having an incomplete VRF than an unfilled tooth without this condition. Conclusion: The use of the MAR algorithm increased the diagnostic accuracy in the detection of incomplete VRF on images of unfilled teeth.

Endothelium dysfunction in hind limb arteries of male Zucker Diabetic-Sprague Dawley rats.

Endothelium dysfunction produces peripheral vascular disease comorbidities in type 2 diabetes, including hypertension, and critical limb ischemia. In this study we aimed to test endothelial dysfunction, the vasodilator effects of a proteinase-activated receptor 2 (PAR2) agonist (2fLIGRLO), and thromboxane A2 synthase inhibitor (ozagrel) on PAR2 vasodilation in hind limb arteries ex vivo, using Zucker Diabetic-Sprague Dawley (ZDSD) rats, a model of type 2 diabetes. Male Sprague Dawley rats (SD) and ZDSD were fed a high-fat content 'Western diet' from 16 to 20 weeks of age (wks) then fed a standard laboratory diet. We identified diabetic ZDSD rats by two consecutive blood glucose measurements > 12.5 mM, based on weekly monitoring. We used acetylcholine, 2fLIGRLO, and nitroprusside with wire-myograph methods to compare relaxations of femoral, and saphenous arteries from diabetic ZDSD (21-23 wks) to age-matched normoglycemic SD. All arteries showed evidence of endothelium dysfunction using acetylcholine (reduced maximum relaxations, reduced sensitivity), and higher sensitivities to 2fLIGRLO, and nitroprusside in ZDSD vs SD. Ozagrel treatment of ZDSD distal segments, and end-branches of saphenous arteries decreased their sensitivities to 2fLIGRLO. We tested aortas for altered expression of endothelium-specific gene targets using PCR array and qPCR. PAR2, and placental growth factor gene transcripts were 1.5, and 4-times higher in ZDSD than SD aortas. Hind limb arteries of ZDSD exhibit endothelium dysfunction having less GPCR agonist induced vasodilation by endothelial NO-release. Different expression of several endothelial genes in ZDSD vs SD aortas, including PAR2, suggests altered inflammatory, and angiogenesis signaling pathways in the endothelium of ZDSD.

Effect of Portable Rent Subsidies and Mentorship on Socioeconomic Inclusion for Young People Exiting Homelessness: A Community-Based Pilot Randomized Clinical Trial.

Importance: There have been no published randomized clinical trials with a primary outcome of socioeconomic inclusion for young people who have experienced homelessness. Objective: To explore whether young people exiting homelessness who received rent subsidies and adult mentorship experienced more socioeconomic inclusion relative to young people who received only rent subsidies. Design, Setting, and Participants: This was a convergent mixed-methods, unblinded, 2-group, parallel randomized clinical trial with 1:1 allocation embedded within a community-based framework in 3 cities in Ontario, Canada. Participants were enrolled between March 1 and September 30, 2019, and were followed up through March 31, 2022. Interventions: Participants (n = 24) were randomly assigned adult mentors (n = 13) who had been recruited and screened by community partner agencies. All participants received portable rent subsidies (subsidy not tied to a specific location) for 2 years. Main Outcomes and Measures: Primary quantitative outcomes were self-reported measures of community integration (psychological and physical) and self-esteem-proxy indicators of socioeconomic inclusion. Community integration was measured with the Community Integration Scale, with a score range of 1 to 7 for the physical component and 4 to 20 for the psychological component; higher scores indicate higher integration. Self-esteem was measured with the Rosenberg Self-Esteem Scale, with a score range of 0 to 30; higher scores indicate greater self-esteem. Secondary quantitative outcomes included social connectedness, hopelessness, and academic and vocational participation. All analyses followed the intention-to-treat principle. Results: A total of 24 youths (12 women [50.0%]; mean [SD] age, 21.8 [2.2] years [range, 18-26 years]; race and ethnicity: 10 White [41.7%], 8 Black [33.3%], 2 Asian [8.3%], 2 Indigenous [8.3%], and 2 different choice [8.3%]) transitioned out of homelessness and into market-rent housing. All youths in the group that received mentorship and in the group that did not receive mentorship had stable or nonsignificant improvements in all study outcomes at the primary end point of 18 months compared with baseline (mean [SD] Community Integration Scale psychological score: mentorship group, 11.3 [2.6] at baseline and 11.2 [3.9] at 18 months; no-mentorship group, 10.8 [4.1] at baseline and 13.2 [2.9] at 18 months; mean [SD] Rosenberg Self-Esteem Scale score: mentorship group, 16.0 [4.6] at baseline and 18.1 [5.2] at 18 months; no-mentorship group, 16.3 [6.1] at baseline and 19.6 [5.7] at 18 months). However, there were no significant differences between the 2 groups in the Community Integration Scale psychological score (adjusted mean difference, -2.0; 95% CI, -5.0 to 1.0; P = .18) and Rosenberg Self-Esteem Scale score (adjusted mean difference, -1.4; 95% CI, -5.0 to 2.3; P = .44) 18 months after randomization. Ancillary analysis suggested that youths with informal mentors (mentors outside the study) at baseline felt more psychologically integrated at 18 months relative to those with no informal mentors at baseline (adjusted mean difference, 3.6; 95% CI, 0.4-6.8; P = .03). Conclusions and Relevance: In this randomized clinical trial, COVID-19 pandemic-related restrictions made it challenging for mentors and mentees to connect, which may have affected the findings. Steady socioeconomic outcomes-potentially attributable to portable rent subsidies-are noteworthy, given the socioeconomic inequities this population has faced during the COVID-19 pandemic. The possible benefit of informal mentorship warrants further investigation. This small pilot study was designed with the intention of generating data and hypotheses for a full-scale study; findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT03779204.

Characterization of Endothelium-Dependent Relaxation in the Saphenous Artery and Its Caudal Branches in Young and Old Adult Sprague Dawley Rats.

Ageing is associated with reduced endothelium-derived nitric oxide (NO) production in the femoral artery of Sprague Dawley (SD) rats. In the current study, we examined endothelium-dependent relaxation (EDR) in the saphenous artery and its caudal branches. We used acetylcholine and the Proteinase-Activated receptor-2 (PAR2)-specific agonist (2fLIGRLO) with nitroarginine methylester (L-NAME) to assess EDR in two groups of male SD rats (age in weeks: young, 10-12; old, 27-29). Acetylcholine and 2fLIGRLO were potent NO-dependent relaxant agents in all arteries. For all arteries, EDR by acetylcholine decreased significantly in old compared to young SD rats. Interestingly, PAR2-induced EDR of proximal saphenous artery segments and caudal branches decreased significantly in old compared to young, but did not differ for the in-between middle and distal ends of the saphenous artery. L-NAME treatment increased subsequent contractions of proximal and middle segments of saphenous arteries by phenylephrine and U46619 in young, but not in old, SD rats. We conclude the SD saphenous artery and caudal branches exhibit regional characteristics that differ in response to specific EDR agonists, endothelial NO synthase inhibitor, and changes to endothelium function with increased age, which are, in part, attributed to decreased sensitivity of vascular smooth muscle to the gaseous transmitter NO.

"We were building the plane as we were flying it, and we somehow made it to the other end": syringe service program staff experiences and well-being during the COVID-19 pandemic.

BACKGROUND: Syringe service programs (SSPs) provide essential harm reduction and prevention services for people who inject drugs in the USA, where SSP coverage is expanding. During the COVID-19 pandemic, US SSPs underwent unprecedented shifts in operational procedures (e.g., closures of physical sites, staff redeployment into pandemic response efforts). Given the critical role of US SSP workers in the pandemic, we sought to explore the occupational experiences and well-being of SSP staff to inform future emergency response efforts. METHODS: From July-October 2020, we conducted semi-structured interviews with staff members of four SSPs in diverse regions of Massachusetts. Trained interviewers administered qualitative interviews virtually. Interviews were coded in NVivo v12 and thematic analysis identified common occupational experiences and related impacts on staff well-being in the context of the COVID-19 pandemic. RESULTS: Among 18 participants, 12 (67%) had client-facing roles such as harm reduction specialists and six (33%) worked in program management or leadership. We found that staff were frequently anxious about SARS-CoV-2 transmission, which contributed to staff turnover. SSPs rapidly adapted and expanded their services to meet increasing client needs during the pandemic (e.g., food distribution, COVID-19 testing), leading to staff overexertion. Simultaneously, public health measures such as physical distancing led to staff concerns about reduced social connections with clients and coworkers. Through these challenges, SSPs worked to protect staff well-being by implementing flexible and tangible COVID-19-related policies (e.g., paid sick leave), mental health resources, and frequent communication regarding pandemic-related operational changes. CONCLUSION: SSPs in the USA adapted to the COVID-19 pandemic out of necessity, resulting in operational changes that threatened staff well-being. Despite the protective factors revealed in some narratives, our findings suggest that during prolonged, complex public health emergencies, SSPs may benefit from enhanced occupational supports to prevent burnout and promote wellness for this essential public health workforce.

Long-term efficacy and safety of erenumab in patients with chronic migraine in whom prior preventive treatments had failed: A subgroup analysis.

OBJECTIVE: To assess the long-term efficacy and safety of erenumab in the subgroup of patients with chronic migraine (CM) in whom prior preventive treatments had failed (TF) (≥1, ≥2, and ≥3 TF medication categories) and never failed (preventive naïve or prior preventive treatments had not failed), using the data from a 52-week, open-label treatment period (OLTP) of the parent study. BACKGROUND: Erenumab is a fully human monoclonal antibody that selectively binds to and inhibits the canonical calcitonin gene-related peptide receptor. There are limited long-term data evaluating the efficacy and safety of erenumab in patients with CM in whom prior preventive treatments had failed. METHODS: Patients who had completed the 12-week double-blind treatment period (DBTP) in the parent study were eligible to participate in the 52-week OLTP, during which they received erenumab every 4 weeks. The TF subgroups (≥1, ≥2, and ≥3 TF medication categories) were not mutually exclusive; patients in whom prior preventive treatments from ≥3 medication categories had failed were also counted in the ≥2 and ≥1 medication categories. Endpoints included monthly migraine days (MMD), monthly acute migraine-specific medication days (MSMD), achievement of ≥50%, ≥75%, and 100% reduction from baseline in MMD, and exposure-adjusted patient incidence rates of adverse events (AEs; per 100 patient-years). RESULTS: Erenumab treatment provided sustained mean reductions in MMD and MSMD relative to the parent study baseline throughout the 52 weeks of the OLTP across all TF subgroups. At Week 52, the mean MMD change was -8.6 (SD 6.6) (baseline: 18.4 [SD 4.5] days) in the ≥1 TF subgroup. A post hoc completer analysis (52 weeks [OLTP] erenumab) showed that compared with erenumab 70 mg, the 140 mg dose was associated with numerically greater reductions in the mean MMD (Week 40: -8.6 and -7.2 days; Week 52: -9.7 and -7.9 days [≥1 TF subgroup]) and a higher proportion of patients achieved ≥50%, ≥75%, and 100% response thresholds across all subgroups at Weeks 40 and 52. Overall the exposure-adjusted patient incidence rates of AEs did not increase during the OLTP versus the DBTP (≥1 TF subgroup: 141.9/100 versus 317.9/100 patient-years), and no new safety signals occurred. CONCLUSION: The long-term treatment with erenumab was well tolerated and showed sustained efficacy in patients with CM in whom prior preventive treatments had failed, with numerically greater treatment effects for 140 mg versus 70 mg.

Zucker Diabetic-Sprague Dawley (ZDSD) rat: Type 2 diabetes translational research model.

NEW FINDINGS: What is the topic of this review? The Zucker Diabetic-Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design. What advances does it highlight? Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co-morbidities. ABSTRACT: Type 2 diabetes (T2D) is a prevalent disease and a significant concern for global population health. For persons with T2D, clinical treatments target not only the characteristics of hyperglycaemia and insulin resistance, but also co-morbidities, such as obesity, cardiovascular and renal disease, neuropathies and skeletal bone conditions. The Zucker Diabetic-Sprague Dawley (ZDSD) rat is a rodent model developed for experimental studies of T2D. We reviewed the scientific literature to highlight the characteristics of T2D development and the associated phenotypes, such as metabolic syndrome, cardiovascular complications and bone and skeletal pathologies in ZDSD rats. We found that ZDSD phenotype characteristics are independent of leptin receptor signalling. The ZDSD rat develops prediabetes, then progresses to overt diabetes that is accelerated by introduction of a timed high-fat diet. In male ZDSD rats, glycated haemoglobin (HbA1c) increases at a constant rate from 7 to >30 weeks of age. Diabetic ZDSD rats are moderately hypertensive compared with other rat strains. Diabetes in ZDSD rats leads to endothelial dysfunction in specific vasculatures, impaired wound healing, decreased systolic and diastolic cardiac function, neuropathy and nephropathy. Changes to bone composition and the skeleton increase the risk of bone fractures. Zucker Diabetic-Sprague Dawley rats have not yet achieved widespread use by researchers. We highlight sex-related differences in the ZDSD phenotype and gaps in knowledge for future studies. Overall, scientific data support the premise that the phenotype and disease progression in ZDSD rats models the characteristics in humans. We conclude that ZDSD rats are an advantageous model to advance understanding and discovery of treatments for T2D through preclinical research.

Timing and durability of response to erenumab in patients with episodic migraine.

OBJECTIVE: We sought to evaluate temporal response patterns to erenumab treatment in patients with episodic migraine. BACKGROUND: Although many patients treated with erenumab experience onset of efficacy as early as 1 week, clinical benefits of migraine preventive therapies may accrue with continued treatment. Furthermore, details about the maintenance of clinical responses have not been reported. METHODS: This was a post hoc analysis of a 6-month, randomized, double-blind, placebo-controlled, phase 3 study of erenumab for the prevention of episodic migraine. We analyzed temporal responses to erenumab using a threshold of ≥50% reduction from baseline in monthly migraine days (MMDs). RESULTS: During the 6-month treatment period, 73.7% (230/312) and 79.6% (253/318) of patients in the erenumab 70 mg (n = 312) and 140 mg (n = 318) groups, respectively, achieved a response in at least 1 month. In this group of responders, at least half reached first monthly response (first month with ≥50% reduction from baseline in MMDs) by month 2 and at least 75% of them by month 3. The remainder responded in months 4-6. Of patients in the erenumab 70 and 140 mg groups, 35.3% (110/312) and 41.8% (133/318), respectively, responded over months 1-3 (mean response over first 3 months). Of these patients, 81.8% (90/110) and 81.9% (109/133) maintained this response over months 4-6 (mean response over last 3 months) in the 70 and 140 mg groups, respectively. Many patients who did not achieve an initial response (≥50% reduction from baseline in MMDs during month 1) responded later with continued treatment, with approximately one-half or more of initial nonresponders responding by months 4-6. CONCLUSIONS: These results support guidelines recommending at least 3 months following the initiation of erenumab for migraine prevention before the assessment of response.

The Evolution of Rumors on a Closed Social Networking Platform During COVID-19: Algorithm Development and Content Study.

BACKGROUND: In 2020, the COVID-19 pandemic put the world in a crisis regarding both physical and psychological health. Simultaneously, a myriad of unverified information flowed on social media and online outlets. The situation was so severe that the World Health Organization identified it as an infodemic in February 2020. OBJECTIVE: The aim of this study was to examine the propagation patterns and textual transformation of COVID-19-related rumors on a closed social media platform. METHODS: We obtained a data set of suspicious text messages collected on Taiwan's most popular instant messaging platform, LINE, between January and July 2020. We proposed a classification-based clustering algorithm that could efficiently cluster messages into groups, with each group representing a rumor. For ease of understanding, a group is referred to as a "rumor group." Messages in a rumor group could be identical or could have limited textual differences between them. Therefore, each message in a rumor group is a form of the rumor. RESULTS: A total of 936 rumor groups with at least 10 messages each were discovered among 114,124 text messages collected from LINE. Among 936 rumors, 396 (42.3%) were related to COVID-19. Of the 396 COVID-19-related rumors, 134 (33.8%) had been fact-checked by the International Fact-Checking Network-certified agencies in Taiwan and determined to be false or misleading. By studying the prevalence of simplified Chinese characters or phrases in the messages that originated in China, we found that COVID-19-related messages, compared to non-COVID-19-related messages, were more likely to have been written by non-Taiwanese users. The association was statistically significant, with P<.001, as determined by the chi-square independence test. The qualitative investigations of the three most popular COVID-19 rumors revealed that key authoritative figures, mostly medical personnel, were often misquoted in the messages. In addition, these rumors resurfaced multiple times after being fact-checked, usually preceded by major societal events or textual transformations. CONCLUSIONS: To fight the infodemic, it is crucial that we first understand why and how a rumor becomes popular. While social media has given rise to an unprecedented number of unverified rumors, it also provides a unique opportunity for us to study the propagation of rumors and their interactions with society. Therefore, we must put more effort into these areas.

Tackling exclusion: A pilot mixed method quasi-experimental identity capital intervention for young people exiting homelessness.

BACKGROUND: Longitudinal studies examining the life trajectories of young people after they have exited homelessness have identified concerns with persistent social and economic exclusion, struggles to shake off identities of homelessness, and housing instability. This pilot study sought to explore the feasibility of improving socioeconomic inclusion outcomes by bolstering identity capital (sense of purpose and control, self-efficacy and self-esteem) among young people who had experienced homelessness. METHODS: Nineteen individuals (aged 18-26) who had transitioned out of homelessness within the past three years participated in a six-week, six-session program focused on building identity capital. The study employed a mixed method prospective cohort hybrid design with an intervention group (Group One) and a delayed intervention comparison group (Group Two). Participants were interviewed every three months until nine months post-intervention. RESULTS: None of the youth who began the intervention dropped out of the program, with the exception of one participant who moved across the country and was unable to continue. Immediately after participating in the intervention, Group One had statistically significant improvements (p < .05) and large to very large effect sizes in self-esteem (d = 1.16) and physical community integration (d = 1.79) compared to changes in Group Two over the same period, which had not yet begun the intervention. In the pooled analysis, small to moderate effect sizes in hopelessness, physical community integration, and self-esteem were observed at all post-intervention time points. Notably, at six- and nine-months post-intervention, statistically significant improvements (p < .05) and moderate effect sizes in hopelessness (d = -0.73 and d = -0.60 respectively) and self-esteem (d = 0.71 and d = 0.53 respectively) were observed. Youth shared they appreciated the normalizing (vs. pathologizing) of strategies they needed to learn and spoke of the importance of framing new skills as something one needs "to have a better life" vs. "to get better." CONCLUSIONS: These early findings signal that targeting identity capital is feasible and may be a promising approach to incorporate into a more complex intervention that includes housing, education, and employment supports to help youth transition out of homelessness. Future research could build on these findings through a sufficiently powered randomized controlled trial.

Timing and durability of response to erenumab in patients with chronic migraine.

BACKGROUND: Erenumab is a human anti-calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. We sought to further assess the temporal patterns of response to erenumab in patients with chronic migraine (CM), specifically the onset and sustainability of monthly migraine day (MMD) response. METHODS: This is a post hoc analysis of a 12-week, randomized, double-blind, placebo-controlled study of erenumab for migraine prevention in patients with CM (≥15 headache days/month, including ≥8 migraine days/month). Onset and sustainability were assessed according to MMD reduction from baseline, with the following response categories: responders (≥50% reduction), partial responders (≥30% and <50%), or nonresponders (<30%). RESULTS: Among the erenumab 140 mg group (n = 187), 54.0% (101/187) achieved a response at any month during the study with a median time to onset of monthly response of 1 month. This improvement was maintained in most patients with continued treatment. An initial response was achieved at Month 1 by 28.3% (53/187) of patients; 69.8% (37/53) of whom maintained a response at Months 2 and 3. Although many patients responded early, some patients required longer treatment to achieve a response; 79.4% (27/34) of initial partial responders and 21.0% (21/100) of initial nonresponders subsequently achieved a response. Similar findings were observed for the erenumab 70mg group (n = 188). CONCLUSION: A majority of erenumab-treated patients with CM who achieved an initial response at Month 1 sustained this benefit. Many patients responded later with continued treatment. Our data support recommendations to assess outcomes after ≥3 months of preventive treatment with erenumab in CM.

Factors Associated with Readmission Among General Internal Medicine Patients Experiencing Homelessness.

BACKGROUND: People who are homeless have a higher burden of illness and higher rates of hospital admission and readmission compared to the general population. Identifying the factors associated with hospital readmission could help healthcare providers and policymakers improve post-discharge care for homeless patients. OBJECTIVE: To identify factors associated with hospital readmission within 90 days of discharge from a general internal medicine unit among patients experiencing homelessness. DESIGN: This prospective observational study was conducted at an urban academic teaching hospital in Toronto, Canada. Interviewer-administered questionnaires and chart reviews were completed to assess medical, social, processes of care, and hospitalization data. Multivariable logistic regression with backward selection was used to identify factors associated with a subsequent readmission and estimate odds ratios and 95% confidence intervals. PARTICIPANTS: Adults (N = 129) who were admitted to the general internal medicine service between November 2017 and November 2018 and who were homeless at the time of admission. MAIN MEASURES: Unplanned all-cause readmission to the study hospital within 90 days of discharge. KEY RESULTS: Thirty-five of 129 participants (27.1%) were readmitted within 90 days of discharge. Factors associated with lower odds of readmission included having an active case manager (adjusted odds ratios [aOR]: 0.31, 95% CI, 0.13-0.76), having informal support such as friends and family (aOR: 0.25, 95% CI, 0.08-0.78), and sending a copy of the patient's discharge plan to a primary care physician who had cared for the patient within the last year (aOR: 0.44, 95% CI, 0.17-1.16). A higher number of medications prescribed at discharge was associated with higher odds of readmission (aOR: 1.12, 95% CI, 1.02-1.23). CONCLUSION: Interventions to reduce hospital readmission for people who are homeless should evaluate tailored discharge planning and dedicated resources to support implementation of these plans in the community.

Dental problems and chronic diseases in mentally ill homeless adults: a cross-sectional study.

BACKGROUND: Dental problems (DPs) and physical chronic diseases (CDs) are highly prevalent and incident in people with low socioeconomic status such as homeless individuals. Yet, evidence on the association between DPs and physical CDs in this population is limited. In the present study, we assessed the association between DPs and type and number of CDs in individuals experienced chronic homelessness and serious mental health problems. METHODS: We analyzed cross-sectional baseline data from 575 homeless adults with serious mental health problems participating in the Toronto site of the At Home/Chez Soi randomized controlled trial. Chronic DPs (lasting at least 6 months) were the primary exposure variable. Presence of self-reported CDs, including heart disease, effect of stroke, hypertension, diabetes, asthma, chronic bronchitis/emphysema, stomach or intestinal ulcer, inflammatory bowel disease, migraine, thyroid problems, arthritis, kidney/bladder problems, liver disease (other than hepatitis), and iron-deficiency anemia, were the primary outcomes. The total number of CDs was also analyzed as a secondary outcome. Logistic regression models were used to assess the association between DPs with each of the studied CDs, and negative binomial regression was used to test the association between DPs with the number of CDs. RESULTS: In our 575 homeless participants (68.5% males) with mean age 40.3 (11.8) years, a high proportion had DPs (42.5%). The presence of DPs was positively associated with heart disease (adjusted odds ratio (AOR):4.19,1.67-10.52), diabetes (AOR:2.17,1.13-4.17), chronic bronchitis (AOR:2.34,1.28-4.29), stomach or intestinal ulcer (AOR:3.48,1.80-6.73), inflammatory bowel disease (AOR:2.52,1.38-4.60), migraine (AOR:1.80,1.20-2.72), arthritis (AOR:2.71,1.71-4.29), kidney/bladder problems (AOR:2.43,1.30-4.54), and iron-deficiency anemia (AOR:3.28,1.90-5.65). DPs were also associated with a higher number of CDs (IRR: 1.62,1.38-1.90). CONCLUSION: Dental health problems in homeless individuals with serious mental disorders are associated with several CDs. Dental care should be better integrated into existing social and health programs serving this population to improve their overall health status. The AH/CS study is registered with the International Standard Randomized Control Trial Number Register (ISRCTN42520374).

Denosumab in postmenopausal women with osteoporosis and diabetes: Subgroup analysis of FREEDOM and FREEDOM extension.

PURPOSE: Diabetes and osteoporosis occur frequently in older adults and are both associated with increased fracture risk. Denosumab treatment reduced new vertebral, nonvertebral, and hip fractures over 3 years, with continued low fracture incidence for up to 10 years in postmenopausal women with osteoporosis. However, its effects in diabetic subjects with osteoporosis have not yet been investigated. METHODS: Post hoc analysis of the 3-year, placebo-controlled FREEDOM study and 7-year Extension included postmenopausal women with osteoporosis and diabetes. Effects on BMD, vertebral, and nonvertebral fracture incidence were evaluated. RESULTS: Of 7808 subjects in FREEDOM, 508 with diabetes received denosumab (n = 266) or placebo (n = 242). Among those, BMD increased significantly with denosumab versus placebo in FREEDOM, and continued to increase during the Extension in long-term (continuing denosumab) and crossover (placebo to denosumab) denosumab subjects. In FREEDOM, denosumab-treated subjects with diabetes had significantly lower new vertebral fracture rates (1.6%) versus placebo (8.0%) (RR: 0.20 [95% CI 0.07-0.61]; p = .001). Nonvertebral fracture incidence was higher with denosumab (11.7%) versus placebo (5.9%) (HR: 1.94 [95% CI 1.00-3.77]; p = .046), although there were fewer hip fractures with denosumab (World Health Organization, 2017 [1]) than placebo (4; nonsignificant). During the first 3 years in FREEDOM Extension, new vertebral and nonvertebral fracture incidences were low in long-term and crossover denosumab diabetic groups (≤6%), consistent with the overall Extension population; yearly nonvertebral fracture incidence was comparable to the FREEDOM placebo group. CONCLUSION: Denosumab significantly increased BMD and decreased vertebral fracture risk in subjects with osteoporosis and diabetes. No reduction in nonvertebral fractures was observed.

Comparison of glycoprotein separation reveals greater impact of carbohydrates and disulfides on electrophoretic mobility for CE-SDS versus SDS-PAGE.

Capillary electrophoresis sodium dodecyl sulfate (CE-SDS) has emerged as an indispensable tool in biopharmaceutical analysis to supersede the conventional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Despite the comparable migration behaviors of native proteins on the two platforms, the correlation has not been evaluated systematically for biotherapeutic proteins, which are often confounded by the presence of glycans and disulfides. Here we studied various mammalian glycoproteins using the two techniques under both reduced and non-reduced conditions. The results revealed substantial reduction in electrophoretic mobility under the capillary mode. Moreover, the migration order was found to be reversed between the reduced and nonreduced runs compared to SDS-PAGE. Such effects appeared to be independent of the content of sialylation. Our work unveiled complex interplays between the gel matrix, proteins and glycans which provide important guidance to biopharmaceutical analysis.

Evaluating the Effects of a Rent Subsidy and Mentoring Intervention for Youth Transitioning Out of Homelessness: Protocol for a Mixed Methods, Community-Based Pilot Randomized Controlled Trial.

BACKGROUND: Although the risk factors associated with young people entering and becoming entrenched in street life have been thoroughly investigated, peer-reviewed evidence is scarce to nonexistent for rigorous interventions targeting social integration outcomes for young people who have experienced homelessness. From the limited research that has been done, emerging evidence signals that, although structural supports such as subsidized housing and social service providers are important, these resources alone are insufficient to help young people integrate into the mainstream society. OBJECTIVE: The overarching aim of this study is to assess whether and how rent subsidies and mentorship influence social integration outcomes for formerly homeless young people living in market rent housing in 3 Canadian cities. The primary outcome measures for this study are community integration (psychological and physical) and self-esteem at 18 months. Secondary outcomes include social connectedness, hope, and academic and vocational participation at 18 months. Exploratory outcomes include income, perceived housing quality, engulfment, psychiatric symptoms, and participant perspectives of intervention barriers and facilitators. METHODS: This is a convergent mixed methods, open-label, 2-arm parallel randomized controlled trial (RCT) with 1:1 allocation embedded within a community-based participatory action research (CBPAR) framework. The intervention will provide 24 young people (aged 16-26 years), who have transitioned out of homelessness and into market rent housing within the past year, with rent subsidies for 24 months. Half of the young people will also be randomly assigned an adult mentor who has been recruited and screened by 1 of our 3 community partners. Data collection will occur every 6 months, and participants will be followed for 30 months. RESULTS: Ethical approval for this study has been obtained from the Providence, St Joseph's, and St Michael's Healthcare Research Ethics Board (number 18-251). Enrollment took place from April 2019 to September 2019. Preliminary analysis of the baseline quantitative and qualitative data is underway. CONCLUSIONS: This pilot RCT will be the first to test the impact of economic and social support on meaningful social integration for formerly homeless young people living in market rent housing. We believe that the mixed methods design will illuminate important contextual factors that must be considered if the intervention is to be scaled up and replicated elsewhere. Importantly, the CBPAR framework will incorporate the perspectives of the community, including formerly homeless young people, who are in the best position to determine what might work best in the context of their lives. TRIAL REGISTRATION: Clinicaltrials.gov NCT03779204; https://clinicaltrials.gov/ct2/show/NCT03779204. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15557.