A Cost-Utility Analysis of Add-On Cannabidiol Versus Usual Care Alone for the Treatment of Seizures Associated with Tuberous Sclerosis Complex in England and Wales.

OBJECTIVES: The aim of this study was to evaluate the cost effectiveness of plant-derived highly purified cannabidiol (Epidyolex® in the UK; 100 mg/mL oral solution) as an add-on treatment to usual care for the management of treatment-refractory seizures associated with tuberous sclerosis complex (TSC) in patients aged ≥ 2 years. METHODS: A cohort-based model was developed using a National Health Service perspective and lifetime horizon. Health states were based on weekly seizure frequency and seizure-free days, utilizing patient-level data from the GWPCARE6 trial (ClinicalTrials.gov identifier: NCT02544763). Two independent regression models were applied to individual patient-level data to predict seizure-free days and seizure frequency. Healthcare resource utilization data were sourced from a Delphi panel, and patient and caregiver health-related quality of life values were elicited using vignettes valued by the general public. Outcomes relating to TSC-associated neuropsychiatric disorders were modeled with costs and quality-adjusted life-years sourced from published literature. RESULTS: In the base case, compared with usual care alone, 12 mg/kg/day cannabidiol was associated with an incremental cost-effectiveness ratio (ICER) of £23,797. The National Institute for Health and Care Excellence disease severity modifier reduced the ICER to £19,831. Probabilities of cost effectiveness at willingness-to-pay thresholds of £20,000 and £30,000 were 30% and 52%, respectively, for the base case and 39% and 66%, respectively, for the disease severity modifier. Results were robust to sensitivity and scenario analyses. CONCLUSIONS: At 12 mg/kg/day and an ICER threshold of £20,000-£30,000, we provide evidence for the cost effectiveness of add-on cannabidiol treatment for patients with TSC-associated seizures aged ≥ 2 years who are refractory to current treatment.

Design, Recruitment, and Implementation of Research Interventions Among Youth Experiencing Homelessness: A Systematic Review.

Transitional age youth experiencing homelessness (TAY-EH) represent an underserved and understudied population. While an increasing number of empirical interventions have sought to address the high burden of psychopathology in this population, findings remain mixed regarding intervention effectiveness. In this systematic review of behavioral health interventions for TAY-EH, we sought to examine the structural framework in which these interventions take place and how these structures include or exclude certain populations of youth. We also examined implementation practices to identify how interventions involving youth and community stakeholders effectively engage these populations. Based on PRISMA guidelines, searches of Medline, PsycInfo, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov databases were conducted, including English language literature published before October 2022. Eligible studies reported on interventions for adolescent or young adult populations ages 13-25 years experiencing homelessness. The initial search yielded 3850 citations; 353 underwent full text review and 48 met inclusion criteria, of which there were 33 unique studies. Studies revealed a need for greater geographic distribution of empirically based interventions, as well as interventions targeting TAY-EH in rural settings. Studies varied greatly regarding their operationalizations of homelessness and their method of intervention implementation, but generally indicated a need for increased direct-street outreach in participant recruitment and improved incorporation of youth feedback into intervention design. To our knowledge, this is the first systematic review to examine the representation of various groups of TAY-EH in the literature on substance use and mental health interventions. Further intervention research engaging youth from various geographic locations and youth experiencing different forms of homelessness is needed to better address the behavioral health needs of a variety of TAY-EH.

Attitudes Toward School-Based Surveillance of Adolescents' Social Media Activity: Convergent Parallel Mixed Methods Survey.

BACKGROUND: US schools increasingly implement commercially available technology for social media monitoring (SMM) of students, purportedly to address youth mental health and school safety. However, little is known about how SMM is perceived by stakeholders, including the students who are the focus of these efforts. OBJECTIVE: We aimed to assess attitudes toward SMM in schools among 4 stakeholder groups and examine reasons for holding supportive, neutral, or unsupportive views toward the technology. We also sought to explore whether any differences in attitudes were associated with binary sex, race, ethnicity, sexual orientation, or gender identity. METHODS: In October 2019, we conducted a convergent parallel mixed methods web-based survey of young adults (aged 18-22 y; n=206), parents (n=205), teachers (n=77), and school administrators (n=41) via Qualtrics web-based panels. We included Likert-type survey items to assess perceived benefits, risks, and overall support of SMM in schools and test for differences based on stakeholder group or demographic characteristics. We also included open-ended questions, and the responses to these items were analyzed using thematic content analysis of reasons given for holding supportive, neutral, or unsupportive views. RESULTS: The tests of group differences showed that young adults perceived lower benefit (P<.001) as well as higher risk (P<.001) and expressed lower overall support (P<.001) of the use of SMM in schools than all other stakeholder groups. Individuals identifying as nonheterosexual also perceived lower benefit (P=.002) and higher risk (P=.02) and expressed lower overall support (P=.02) than their heterosexual counterparts; respondents who identified as people of racial and ethnic minorities also perceived higher risk (P=.04) than their White counterparts. Qualitative thematic content analysis revealed greater nuance in concerns about SMM. Specifically, the primary reasons given for not supporting SMM across all stakeholder groups were (1) skepticism about its utility, (2) perceived privacy violations, and (3) fears of inappropriate or discriminatory use of the data. Within the young adult group in particular, concerns were also raised about (4) unintended and adverse consequences, including the erosion of trust between students and school institutions and administrators, and the chronic adverse effects of constant or prolonged surveillance. Thematic analysis also showed that individuals in every stakeholder group who indicated overall support of SMM were likely to cite the potential for enhanced school safety as the reason. Young adults' overall stances toward SMM were the most polarized, either strongly for or strongly against SMM, and responses from teachers indicated similar polarization but more often favored support of SMM in schools. CONCLUSIONS: This study found differing perspectives among stakeholder groups regarding SMM in schools. More work is needed to assess the ways in which this type of surveillance is being implemented and the range and complexity of possible effects, particularly on students.

A systematic review of substance use screening in outpatient behavioral health settings.

OBJECTIVE: Despite the frequent comorbidity of substance use disorders (SUDs) and psychiatric disorders, it remains unclear if screening for substance use in behavioral health clinics is a common practice. The aim of this review is to examine what is known about systematic screening for substance use in outpatient behavioral health clinics. METHODS: We conducted a PRISMA-based systematic literature search assessing substance use screening in outpatient adult and pediatric behavioral health settings in PubMed, Embase, and PsycINFO. Quantitative studies published in English before May 22, 2020 that reported the percentage of patients who completed screening were included. RESULTS: Only eight articles met our inclusion and exclusion criteria. Reported prevalence of screening ranged from 48 to 100%, with half of the studies successfully screening more than 75% of their patient population. There were limited data on patient demographics for individuals who were and were not screened (e.g., gender, race) and screening practices (e.g., electronic versus paper/pencil administration). CONCLUSIONS: The results of this systematic review suggest that successful screening for substance use in behavioral health settings is possible, yet it remains unclear how frequently screening occurs. Given the high rates of comorbid SUD and psychopathology, future research is necessary regarding patient and clinic-level variables that may impact the successful implementation of substance use screening. Trial registry A methodological protocol was registered with the PROSPERO systematic review protocol registry (ID: CRD42020188645).

Examining the clinical correlates of conduct disorder in youth with bipolar disorder.

BACKGROUND: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. METHODS: 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives. RESULTS: Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LIMITATIONS: The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. CONCLUSIONS: Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.

A systematic review of virtual reality therapies for substance use disorders: Impact on secondary treatment outcomes.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) therapy may be an effective tool in treating urges and cravings in substance use disorder (SUD). Given the high co-occurrence of difficulties with mood, anxiety, and emotional dysregulation with SUD, this review sought to examine the extant literature on the efficacy of VR for SUD in improving these secondary treatment outcomes. METHODS: A systematic literature review was conducted following PRISMA guidelines in PubMed, PsychInfo, and Embase. Studies were included if they utilized immersive VR, were conducted with individuals with substance use disorder/dependence/misuse, and included measures of mood, anxiety, depression, emotional dysregulation, or retention in treatment. RESULTS: Seven articles met our inclusion criteria. Five studies were conducted on patients using nicotine and utilized a cue-exposure intervention. VR was effective at reducing substance use and cravings in the majority of studies. Results on the efficacy of VR for improving mood, anxiety, and emotional regulation were mixed. Work examining retention in treatment was limited. DISCUSSION AND CONCLUSIONS: VR for SUD has the potential to improve mood and anxiety symptoms as well as retention in treatment for patients with SUD, particularly if the therapy targets these psychological symptoms. Future studies examining components of VR for SUD in individuals with drug use disorders, as well as examinations of targeted interventions for associated mood, emotional dysregulation, and retention in treatment, are necessary. SCIENTIFIC SIGNIFICANCE: This is the first systematic review of the impact of VR on mood, anxiety, and emotional dysregulation for individuals with substance use.

Substance Use Disorders and Psychiatric Illness Among Transitional Age Youth Experiencing Homelessness.

Objective: Transitional age youth experiencing homelessness (TAY-EH) bear a high burden of substance use disorders (SUDs) and psychopathology. However, limited data exist on the co-occurrence and interactions between these diagnoses in this marginalized group. This study sought to identify rates of single and co-occurring SUDs and psychiatric diagnoses among a sample of TAY-EH and to investigate associations between psychopathology and prevalence and severity of SUDs in this group. Method: TAY-EH accessing a low-threshold social service agency in a large metropolitan area completed psychosocial and diagnostic interviews to assess for SUDs and psychopathology. Analyses examined rates of single and co-occurring disorders and associations between burden of psychopathology and presence and severity of SUDs. Results: The assessment was completed by 140 TAY-EH; the majority were youth of color (54% Black/African American, 16% Latinx), and 57% identified as male. Rates of single and co-occurring psychiatric disorders and specific SUDs (cannabis use disorder [CUD] and alcohol use disorder [AUD]) were notably high. An increasing number of psychiatric diagnoses was significantly associated with elevated CUD/AUD prevalence and severity. Mood, anxiety, attention-deficit/hyperactivity, and antisocial personality disorders were significantly associated with elevated CUD/AUD prevalence and severity, as was suicidality (all p < .05). Conclusion: This study reveals a complex overlay of SUDs and psychopathology facing TAY-EH, with a significant association between co-occurring psychopathology and severity of CUD/AUD. To the authors' knowledge, this is the first study to examine associations between specific psychopathology and severity of SUDs among TAY-EH. Further research into the mechanistic and temporal links between these conditions is needed to inform tailored treatment interventions.

Systematic review: Rates of psychopathology, substance misuse, and neuropsychological dysfunction among transitional age youth experiencing homelessness.

BACKGROUND AND OBJECTIVES: Transitional age youth experiencing homelessness (TAY-EH) bear a disproportionate burden of morbidity and mortality related to psychopathology, substance use disorders (SUD), and neuropsychological dysfunction. Prior reviews examining these conditions are now nearly a decade old, have focused on younger adolescent populations, or have utilized nonsystematic approaches. To our knowledge, no prior reviews have reported on all three of these domains in an integrated fashion. Here, we provide a contemporary, critical synthesis of the literature on the functioning of TAY-EH in North America within these three domains. METHODS: Based upon PRISMA guidelines, a search of PubMed, Medline, and PsycInfo databases was conducted, including literature published between January 2015 and June 2021. RESULTS: The initial search yielded 2024 citations; 104 underwent full text review and 32 met inclusion criteria, with a final aggregate sample size of 13,516. Studies revealed elevated rates of mood disorders, PTSD, anxiety disorders, and alcohol misuse. There is insufficient data to draw generalizable conclusions regarding neuropsychological functioning, other SUD, or other psychiatric diagnoses. No studies reported on co-occurrence of disorders among or between the domains of psychopathology, SUD, and neuropsychological dysfunction. Four studies used structured interviews for diagnoses, with the remainder relying upon brief screeners or self-report measures. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: To our knowledge, this is the first systematic review to provide integrated findings on psychopathology, SUD, and neuropsychological dysfunction among TAY-EH. Further research using structured, DSM-based tools is needed to characterize rates of single and co-occurring conditions to inform tailored treatment interventions.

The Relationship Between Cannabis Use and Self-Reported Trait Anger in Treatment-Seeking Young People.

Objective: Trait anger has been shown to be predictive of emotion-focused coping and alcohol use. Yet, the connection between cannabis use and trait anger remains poorly characterized. The present study sought to investigate the relationship between cannabis use and self-reported trait anger in youth seeking substance use treatment. Methods: A retrospective chart review was conducted on youth (n=168) aged 14-26 presenting for an initial evaluation at an outpatient substance use treatment program. Patients self-reported trait anger score (TAS) and lifetime, recent, and Diagnostic and Statistics Manual-5th Edition diagnostic status of cannabis use were assessed. Clinician-coded psychiatric and substance use patterns were collected, along with urine carboxy delta-9-tetrahydrocannabinol (THC) concentration levels. Additional measures of anxiety, depression, and demographic variables were assessed. Results: Higher self-reported TAS were associated with cannabis use, cannabis use disorder (CUD), and more recent and frequent cannabis use. The presence of a CUD was independently associated with TAS after controlling for the presence of other substance use disorders and co-occurring depression and anxiety disorders. Higher urine THC concentration levels were associated with higher TAS. Conclusions: Findings support an association between heavy, chronic cannabis use and elevated self-reported trait anger at intake. There may be important neurological consequences of heavy, chronic cannabis use that impact anger regulation. It is also plausible that trait anger maybe a predisposing factor for elevated cannabis use. Better controlled prospective research is needed to help determine directionality. Treatment programs should target both cannabis use and anger regulation in youth.

The Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders.

Background and Objective: Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. Methods: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development. Results: Our search terms yielded 21 studies examining the impact of pharmacotherapy and later SUD in attention-deficit/hyperactivity disorder (ADHD), two studies on Major Depressive Disorder, and three studies on psychotic disorders. The majority of these studies reported reductions in SUD (N = 14 sides) followed by no effects (N = 10) and enhanced rates of SUD (N = 2). Studies in ADHD also reported that earlier-onset and longer-duration treatment was associated with the largest risk reduction for later SUD. Conclusions: Overall, pharmacological treatments for psychiatric disorders appear to mitigate the development of SUD, especially when treatment is initiated early and for longer durations. More studies on the development of SUD linked to the effects of psychotherapy alone and in combination with medication, medication initiation and duration, adequacy of treatment, non-ADHD disorders, and psychiatric comorbidity are necessary.

Discrimination is associated with C-reactive protein among young sexual minority men.

This report examines associations between everyday discrimination, microaggressions, and CRP to gain insight on potential mechanisms that may underlie increased CVD risk among sexual minority male young adults. The sample consisted of 60 participants taken from the P18 cohort between the ages of 24 and 28 years. Multinomial logistic regression models were used to examine the association between perceived everyday discrimination and LGBQ microaggressions with C-reactive protein cardiovascular risk categories of low-, average-, and high-risk, as defined by the American Heart Association and Centers for Disease Control. Adjustments were made for BMI. Individuals who experienced more everyday discrimination had a higher risk of being classified in the high-risk CRP group compared to the low-risk CRP group (RRR = 3.35, p = 0.02). Interpersonal LGBQ microaggressions were not associated with CRP risk category. Everyday discrimination, but not specific microaggressions based on sexual orientation, were associated with elevated levels of CRP among young sexual minority men (YSMM). Thus, to implement culturally and age-appropriate interventions, further researcher is needed to critically examine the specific types of discrimination and the resultant impact on YSMM's health.

A characteristic optical variability time scale in astrophysical accretion disks.

Accretion disks around supermassive black holes in active galactic nuclei produce continuum radiation at ultraviolet and optical wavelengths. Physical processes in the accretion flow lead to stochastic variability of this emission on a wide range of time scales. We measured the optical continuum variability observed in 67 active galactic nuclei and the characteristic time scale at which the variability power spectrum flattens. We found a correlation between this time scale and the black hole mass extending over the entire mass range of supermassive black holes. This time scale is consistent with the expected thermal time scale at the ultraviolet-emitting radius in standard accretion disk theory. Accreting white dwarfs lie close to this correlation, suggesting a common process for all accretion disks.

Social Media Surveillance in Schools: Rethinking Public Health Interventions in the Digital Age.

Growing public concern about student safety and well-being has led schools and school districts to contract private companies to implement new technologies that target and surveil students' activity on social media websites. Although innovative solutions for addressing student safety and health are needed, it is unclear whether the implementation of social media surveillance in schools is an effective strategy. Currently, there is no evidence to support the claims made by social media surveillance companies, as well as the schools that hire them, that these technologies can address the myriad of public health issues facing today's students. Instead, these digital surveillance systems may only serve to exacerbate the problems that youth-especially those from historically marginalized groups-already face.

Disentangling the Social Context of Nonmedical Use of Prescription Stimulants in College Students.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the social context of nonmedical use of prescription stimulants (NMUPS) among college students who endorsed NMUPS with co-occurring substance use disorders (SUD) compared with those without co-occurring SUDs. METHODS: Presented here are new analyses based on data previously collected from college students aged 18 to 28 years derived from the Boston metropolitan area who endorsed NMUPS (N = 100) at least once in their lifetime. Differences between those with lifetime history of SUD (N = 46) and without a history of SUD (N = 54) on the Massachusetts General Hospital ADHD Medication Misuse and Diversion Assessment were analyzed using the Student t test, the Pearson χ2 test, and the Wilcoxon rank-sum test. RESULTS: College students who endorsed NMUPS with co-occurring SUD were more likely than those without SUD to have bought or traded stimulants, bought or traded in their car, used at parties with drugs/alcohol, or used intranasally (all P < .05). Intranasal administration was common (38% of all students endorsing NMUPS) and was associated with misuse at a party and simultaneous use with cocaine (P = .04), marijuana (P < .001), and alcohol (P < .001), compared with only oral use. DISCUSSION AND CONCLUSIONS: Notable characteristics were identified among individuals who engaged in NMUPS in the type, amount, cost, and ascertainment of stimulants. SCIENTIFIC SIGNIFICANCE: The concurrence of SUD and/or intranasal administration appear to represent a more severe phenotype of NMUPS that should be considered in the implementation of future prevention and intervention protocols on college campuses. (Am J Addict 2020;29:476-484).

Does Extended PET Acquisition in PET/MRI Rectal Cancer Staging Improve Results?

OBJECTIVE: The purpose of this study was to determine if extended PET acquisition times in the pelvis during PET/MRI increase detection rates of potentially metastatic lymph nodes in patients with rectal cancer. MATERIALS AND METHODS: Our study was approved by the institutional review board of the University of California, San Francisco. Twenty-two patients with biopsy-proven rectal cancer underwent imaging via simultaneous 3-T time-of-flight PET/MRI, with seven undergoing two separate PET/MRI examinations, for a total of 29 studies. Each examination included both a whole-body PET/MRI and a dedicated pelvic PET/MRI with both 3- and 15-minute PET acquisitions for the pelvis. Three radiologists interpreted each examination with PET only, MRI only, then combined PET and MRI examinations, using all available images. Additionally, the 3- and 15-minute PET acquisitions of the pelvis were reviewed separately by a single radiologist. RESULTS: A total of 94 lymph nodes were identified as abnormal on PET, all with MRI anatomic correlates. Of these, 37 (39.4%) were seen only on the dedicated 15-minute acquisition. Fifty-seven (60.6%) nodes measured 5 mm or less, including 29 (30.9%) seen only on the 15-minute acquisition. Thirty-one (33.0%) nodes measured 5.1-10 mm, including eight (25.8%) seen only on the 15-minute acquisition. Of the 17 subjects imaged for initial staging, 11 (64.7%) were upstaged as a result of the increased PET acquisition time (10 from N1 to N2 and one from N0 to N1). CONCLUSION: Longer PET acquisition times during PET/MRI for rectal cancer increases the number of FDG-avid lymph nodes detected without increasing scan time.

Polarizable Molecular Dynamics and Experiments of 1,2-Dimethoxyethane Electrolytes with Lithium and Sodium Salts: Structure and Transport Properties.

The structure and transport properties of electrolyte solutions of 1,2-dimethoxyethane (DME) having salts of Li+ with bis(trifluoromethanesulfonyl)imide ([TFSI]-) or Na+ with [TFSI]- are investigated with polarizable molecular dynamics and experiments. Polarizable force fields for Li+ and Na+ with DME and [TFSI]- were developed based on quantum chemistry calculations, ab initio molecular dynamics simulations, and thermodynamic liquid-state properties. Simulation results for density, viscosity, self-diffusion coefficient, and conductivity of the electrolytes all agree well with the trends and magnitudes of available experimental data for a wide range of salt concentrations. As the concentration of salt increases, the electrolytes become more viscous and molecular species become less mobile. Ionic conductivity does not change monotonically with salt concentration and exhibits a maximum between 0.5 and 1.0 M for both Li[TFSI] and Na[TFSI] electrolytes. Comparatively, both cations are solvated by 5-6 DME or [TFSI]- oxygen atoms and exhibit similar diffusivities and conductivities. The solvation shell of Na+ is found to be more weakly bound and to have a lower binding residence time than that of Li+. The transport of Li+ therefore is more vehicular, through the motion of the solvation shell, while the transport of Na+ is based more on exchange, through the replacement of solvating species. The atomistic insight provided by this work can be used as the basis for future rational design of improved electrolyte solvents for lithium-oxygen, sodium-oxygen, and lithium-sulfur batteries.

ATP synthase F1 subunits recruited to centromeres by CENP-A are required for male meiosis.

The histone H3 variant CENP-A epigenetically defines the centromere and is critical for chromosome segregation. Here we report an interaction between CENP-A and subunits of the mitochondrial ATP synthase complex in the germline of male Drosophila. Furthermore, we report that knockdown of CENP-A, as well as subunits ATPsyn-α, -ßlike (a testis-specific paralogue of ATPsyn-ß) and -γ disrupts sister centromere cohesion in meiotic prophase I. We find that this disruption is likely independent of reduced ATP levels. We identify that ATPsyn-α and -ßlike localise to meiotic centromeres and that this localisation is dependent on the presence of CENP-A. We show that ATPsyn-α directly interacts with the N-terminus of CENP-A in vitro and that truncation of its N terminus perturbs sister centromere cohesion in prophase I. We propose that the CENP-A N-terminus recruits ATPsyn-α and -ßlike to centromeres to promote sister centromere cohesion in a nuclear function that is independent of oxidative phosphorylation.

Cost-effectiveness of indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination for patients with moderate-to-severe chronic obstructive pulmonary disease: a LANTERN population analysis from Singapore.

INTRODUCTION: In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting. METHODS: A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis. RESULTS: Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC. CONCLUSION: IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

Poly(vinylidene fluoride) (PVDF) Binder Degradation in Li-O2 Batteries: A Consideration for the Characterization of Lithium Superoxide.

We show that a common Li-O2 battery cathode binder, poly(vinylidene fluoride) (PVDF), degrades in the presence of reduced oxygen species during Li-O2 discharge when adventitious impurities are present. This degradation process forms products that exhibit Raman shifts (∼1133 and 1525 cm-1) nearly identical to those reported to belong to lithium superoxide (LiO2), complicating the identification of LiO2 in Li-O2 batteries. We show that these peaks are not observed when characterizing extracted discharged cathodes that employ poly(tetrafluoroethylene) (PTFE) as a binder, even when used to bind iridium-decorated reduced graphene oxide (Ir-rGO)-based cathodes similar to those that reportedly stabilize bulk LiO2 formation. We confirm that for all extracted discharged cathodes on which the 1133 and 1525 cm-1 Raman shifts are observed, only a 2.0 e-/O2 process is identified during the discharge, and lithium peroxide (Li2O2) is predominantly formed (along with typical parasitic side product formation). Our results strongly suggest that bulk, stable LiO2 formation via the 1 e-/O2 process is not an active discharge reaction in Li-O2 batteries.