Neuronavigated Right Orbitofrontal 20 Hz Theta Burst Transcranial Magnetic Stimulation Augmentation for Obsessive-Compulsive Disorder with Comorbid Depression and Anxiety Disorders: An Open-Label Study.

BACKGROUND: Despite the availability of pharmacotherapy and psychotherapy for treating obsessive-compulsive disorder (OCD), alternative approaches need to be explored due to the high likelihood of treatment resistance. Neuronavigated 20 Hz theta burst stimulation (TBS-20 Hz), targeting the bilateral dorsolateral prefrontal cortex (DLPFC) augmented with the right orbitofrontal cortex (ROFC), was tested for treating OCD comorbid with depression and anxiety disorders. METHODS: A retrospective chart review was performed on fourteen patients treated for moderate-to-severe OCD in a private outpatient clinic. Twelve patients had comorbid major depressive disorder (MDD), and thirteen patients had either generalized anxiety disorder (GAD) or panic disorder (PD). Patients completed the Y-BOCS-SR, BDI-II, and BAI rating scales weekly, which were used to measure the changes in OCD, depression, and anxiety symptoms, respectively. RESULTS: Neuronavigated TBS-20 Hz was sequentially applied to the right DLPFC (RDLPFC), left DLPFC (LDLPFC), and ROFC. A total of 64% (9/14) of patients achieved remission from OCD (Y-BOCS-SR ≤ 14) in an average of 6.1 weeks of treatment (SD = 4.0). A total of 58% (7/12) of patients remitted from MDD (BDI < 13) in an average of 4.1 weeks (SD = 2.8), and 62% (8/13) of patients remitted from GAD/PD (BAI < 8) in an average of 4.3 weeks (SD = 2.5). CONCLUSIONS: The neuronavigated TBS-20 Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC, significantly reduced OCD, MDD, and GAD/PD symptoms. Randomized sham controls are warranted to validate these results.

Prevalence and burden of chronic cough in France.

Background: Chronic cough is a common condition that is associated with lower health-related quality of life and greater healthcare resource use. There are limited data on the prevalence, population characteristics and burden of chronic cough in France. Methods: This was a cross-sectional study based on responses from French adult residents to the 2020 National Health and Wellness Survey. Respondents with chronic cough were compared to 1:3 propensity score-matched controls without chronic cough. Results: The weighted lifetime and 12-month prevalence of chronic cough were estimated as 7.5% and 4.8%, respectively. Respondents with chronic cough reported significantly worse perceived health than matched controls, with lower mean±sd scores of 46.68±9.28 versus 50.42±8.26 on the physical health component and 40.32±9.87 versus 44.32± 9.69 on the mental health component of the Medical Outcomes Study 12-item Short Form Survey Version 2 survey (p<0.001 for both comparisons). Respondents with chronic cough also had higher rates of moderate-to-severe forms of anxiety (24.4% versus 12.4%) and depression (36.4% versus 20.2%); higher rates of multiple forms of sleep disturbance; greater impairment of work productivity (38.2% versus 25.5%) and other activities (41.8% versus 28.2%; p<0.001 for all comparisons). Respondents with chronic cough also had higher rates of all-cause healthcare resource use including emergency room visits, hospitalisation, and overall and specialist healthcare provider visits compared to controls (p<0.001 for all comparisons). Conclusion: Chronic cough is a common condition in France that is associated with lower health-related quality of life and greater healthcare resource utilisation.

Drivers and Barriers to Tolerable and Effective Treatment for ADHD: The Importance of Treatment Perseverance and Duration of Effect.

OBJECTIVE: To examine treatment outcomes for classes of ADHD drugs in conjunction with physicians' prescribing rationales and the utility of treatment perseverance in treatment effectiveness. METHODS: A retrospective non-interventional study using physician-provided chart data for treated adolescent and adult ADHD patients in the United States (April-June 2019). Multivariable analyses compared the effectiveness and tolerability of drug classes. RESULTS: Among the 1,232 ADHD patients included in this study, 37.7% experienced one, 11.8% two, and 6.7% three treatment changes post their first prescribed regimen. These changes were mostly attributed to lack of rapid onset and duration of effect. Achieving best response correlated with the number of previous treatments for adolescents, but not adults. Maintaining full response correlated with the length of current treatment for adolescents and adults. CONCLUSION: Physicians' prescribing rationales targeted duration of effect and tolerability. ER monotherapy demonstrated potential advantages over other regimens. Treatment perseverance is integral to effective ADHD management.

Tetraplegic spinal cord injury as a presentation of multiple myeloma: A case report.

Spinal cord injury is a devastating complication of cancers that exert physical compression on the spinal cord. Multiple myeloma is known predominantly as a condition that involves bony structures and can manifest with complications such as pathological fractures. However, involvement of other structures including spinal cord is a possible complication, with potentially catastrophic consequences. We describe a case of multiple myeloma presenting initially as severe paraplegia secondary to spinal cord compression in a 79-year-old man.

Burden of chronic cough in the UK: results from the 2018 National Health and Wellness Survey.

Background: Chronic cough, defined as daily cough for at least 8 weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the UK. Methods: Study participants were general population respondents to the 2018 UK National Health and Wellness Survey (NHWS). Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matchingon age, sex and the modified Charlson Comorbidity Index. Results: Of 15 000 NHWS respondents, 715 reported chronic cough in the previous 12 months and 918 during their lifetime. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence was 6.2%. Prevalence of chronic cough was higher among older respondents and those with smoking histories. Chronic cough respondents experienced higher rates of severe anxiety and depression in the past 2 weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents visited a healthcare provider in the past 6 months than respondents without chronic cough with a mean of 5.8 and 3.7 visits per respondent, respectively. Conclusion: Adults with chronic cough report lower quality of life, reduced work productivity and greater healthcare resource utilisation than matched controls without chronic cough.

Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid.

A metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR-Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I-mutant HTC cells. We demonstrate in cultured cells and a patient-derived xenograft model that small-molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration. SIGNIFICANCE: HTC is enriched in somatic mtDNA mutations predicted to affect complex I of the electron transport chain (ETC). We demonstrate that these mutations impair respiration and induce a therapeutically tractable reliance on aerobic fermentation for cell survival. This work provides a rationale for targeting fermentation in cancers harboring irreversible genetically encoded ETC defects. See related article by Gopal et al., p. 1904. This article is highlighted in the In This Issue feature, p. 1749.

Examining the impact of excessive daytime sleepiness on utility scores in patients with obstructive sleep apnoea and/or narcolepsy in five European countries.

BACKGROUND: Excessive daytime sleepiness (EDS) is a cardinal symptom of narcolepsy and affects many patients with obstructive sleep apnoea (OSA). EDS is associated with reduced quality of life, increased accident risk, and poor workplace performance. Given the impact of EDS, the ability to predict health-related utility from sleepiness is valuable for examining the cost effectiveness of novel treatments. The aim of this study was to examine the association between EDS and EQ-5D in patients with OSA and/or narcolepsy by modelling EQ-5D utility scores from Epworth Sleepiness Scale (ESS) scores. METHODS: Data were obtained from the Europe 2016/2017 National Health and Wellness Survey, an online, general population survey, designed to represent the age and gender composition of each country's adult population. Analyses included 2,348 patients self-reporting symptomatic and diagnosed OSA (n = 2,277), narcolepsy (n = 48), or both (n = 23). Multivariable models were used to examine ESS as a predictor of EQ-5D utility while adjusting for covariates of interest. Results were validated following the National Institute for Health and Care Excellence Decision Support Unit guidelines for predictive modelling. RESULTS: Utility decreased as EDS severity increased (no EDS: 0.711 ± 0.251, mild: 0.685 ± 0.261, moderate: 0.643 ± 0.268, severe: 0.559 ± 0.323). Whereas participants with only OSA or only narcolepsy did not differ in utility, those with both conditions had lower scores (0.685 ± 0.266 and 0.627 ± 0.325 vs. 0.439 ± 0.340, respectively). Piecewise linear regression identified a single breakpoint at ESS score of 11.29. In the final model, for each point increase in ESS score, the corresponding decrease in EQ-5D utility was larger among patients with ESS scores ≥ 12 compared to patients with ESS scores ≤ 11 (model slopes: -0.0131 vs. -0.0026, respectively). Findings from the validation sample confirmed these results. CONCLUSIONS: This study demonstrates the impact of sleepiness on quality of life (QoL) and its negative impact irrespective of sleep condition (OSA or narcolepsy). The breakpoint identified is relatively consistent with the established ESS cutoff score ≥ 11, which demarcates pathological sleepiness. Furthermore, as EDS severity worsens (increases) on the ESS, the impact on QoL is greater.

Humanistic and economic burden associated with depression in the United States: a cross-sectional survey analysis.

BACKGROUND: Depression (major depressive disorder [MDD]) affects the functioning of patients in many facets of life. Very few large-scale studies to date have compared health and economic related outcomes of those with versus without depression, and across various depression severity groups. We aimed to evaluate humanistic and economic burden in respondents with and without depression diagnosis, and across symptom severity groups. METHODS: Data from the 2017 US National Health and Wellness Survey (NHWS) were utilized. Of the adult respondents (N = 75,004), 59,786 were < 65 years old. Respondents not meeting eligibility criteria were excluded (e.g., those self-reporting bipolar disorder or experiencing depression in past 12 months but no depression diagnosis). Overall, data from 39,331 eligible respondents (aged 18-64 years) were analyzed; and comprised respondents 'with depression diagnosis' (n = 8853; self-reporting physician diagnosis of depression and experiencing depression in past 12 months) and respondents 'without depression diagnosis' (n = 30,478; no self-reported physician diagnosis of depression and not experiencing depression). Respondents with depression were further examined across depression severity based on Patient Health Questionnaire-9 (PHQ-9). Outcome measures included health-related quality-of-life (HRQoL; Medical Outcomes Study 36-item Short Form [SF-36v2]: mental and physical component summary [MCS and PCS]; Short-Form 6 Dimensions [SF-6D]; and EuroQol 5 Dimensions [EQ-5D]), work productivity and activity impairment (WPAI), and health resource utilization (HRU). Multivariate analysis was performed to examine group differences after adjusting covariates. RESULTS: Respondents with depression diagnosis reported significantly higher rates of diagnosed anxiety and sleep problems versus those without depression (for both; P < 0.001). Adjusted MCS, PCS, SF-6D, and EQ-5D scores were significantly lower in respondents with depression versus those without depression (all P < 0.001). Consistently, respondents with depression reported higher absenteeism, presenteeism, and overall WPAI, as well as greater number of provider visits, emergency room visits, and hospitalizations compared with those without depression (all P < 0.001). Further, burden of each outcome increased with an increase in disease severity. CONCLUSIONS: Diagnosed depression was associated with lower health-related quality-of-life and work productivity, and higher healthcare utilization than those without depression, and burden increased with an increase in symptom severity. The results show the burden of depression remains high even among those experiencing minimal symptoms.

TK216 targets microtubules in Ewing sarcoma cells.

Ewing sarcoma (EWS) is a pediatric malignancy driven by the EWSR1-FLI1 fusion protein formed by the chromosomal translocation t(11; 22). The small molecule TK216 was developed as a first-in-class direct EWSR1-FLI1 inhibitor and is in phase II clinical trials in combination with vincristine for patients with EWS. However, TK216 exhibits anti-cancer activity against cancer cell lines and xenografts that do not express EWSR1-FLI1, and the mechanism underlying cytotoxicity remains unresolved. We apply a forward-genetics screening platform utilizing engineered hypermutation in EWS cell lines and identify recurrent mutations in TUBA1B, encoding ⍺-tubulin, that prove sufficient to drive resistance to TK216. Using reconstituted microtubule (MT) polymerization in vitro and cell-based chemical probe competition assays, we demonstrate that TK216 acts as an MT destabilizing agent. This work defines the mechanism of cytotoxicity of TK216, explains the synergy observed with vincristine, and calls for a reexamination of ongoing clinical trials with TK216.

Prevalence of chronic cough and patient characteristics in adults in Spain: A population-based cross-sectional survey.

BACKGROUND: Chronic cough (CC) represents a significant health burden. This study assessed the prevalence of CC (defined as per international guidelines as cough duration >8 weeks) in Spanish adults and compared characteristics between CC and non-CC cohorts. METHODS: CC cohorts were compiled using data from adult respondents to the 2020 Spanish cross-sectional online National Health and Wellness Survey (NHWS). Using propensity scores, respondents experiencing CC during their lifetime and the previous 12 months were matched 3:1 to respondents without CC and their health characteristics were compared. The number of Spanish adults affected with CC was estimated using weighted CC prevalence. RESULTS: CC during their lifetime or the previous 12 months was experienced by 579 (8.2%) and 389 (5.5%) of 7074 NHWS respondents, of whom 233 (38.5%) and 171 (44.0%), respectively, had physician-diagnosed CC. Based on weighted prevalence rates, lifetime and 12-month CC were estimated to affect ≈3.3 million and ≈2.2 million Spanish adults, respectively. Relative to the non-CC cohort, the 12-month CC cohort consistently demonstrated poorer health status, poorer mental health, greater healthcare utilization, and lower productivity at work and home. CONCLUSION: This study contributes novel data regarding the prevalence of CC in Spain, suggests that CC is underdiagnosed, and reflects that CC and related comorbidities inflict a significant health burden in the affected population.

Chronic cough in Germany: results from a general-population survey.

BACKGROUND: Chronic cough (CC) which is defined ≥8 weeks is a common condition in clinical practice. However, estimates of prevalence and associated comorbidities in German adults and key subgroups of age and gender are lacking. METHODS: Cross-sectional study based on a representative panel of 15 020 adult subjects of the general population who completed the German National Health and Wellness Survey, reporting CC and questions about comorbidities. Lifetime and 12-month prevalence are presented as unweighted estimates. RESULTS: The lifetime CC prevalence was 6.5% (range across age groups 5.1%-8.3%) and the 12-month prevalence was 4.9% (range 3.7-5.7%). The prevalence of diagnosed CC was 2.8% (range 0.9-4.1%) and the prevalence of persons currently on any prescription to treat CC was 0.6% (range 0.2-1.4%). Respondents who experienced CC were 52.0±17.0 years old, with a higher prevalence in those aged 50 years and older. Persons with CC had higher morbidity scores and were diagnosed with an increased number of comorbidities, most frequently diagnoses of the respiratory system (71.0%), followed by digestive tract disorders (34.0%) and sleep disorders (37.6%). CONCLUSIONS: In a broadly representative sample of German adults, lifetime and 12-month prevalence of CC was greatest in current and former smokers and those older ≥50 years of age. Comorbidities are frequent and may complicate management of these patients.

Use of telehealth to increase treatment access for prisoners with chronic hepatitis C.

Prisons remain a priority population in the treatment of hepatitis C (HCV) in Australia. To improve treatment uptake, we created a novel telehealth-based model of care for prisoners with HCV that is both cost-effective and requires minimal infrastructure. Over a period of 30 months, a total of 332 patients was initiated on treatment, achieving a per protocol sustained virological response (SVR12) rate of 91%. A large number (29%) of patients was lost to follow up after release from prison - highlighting the vital opportunity for HCV treatment during incarceration. We propose that similar models of care can be used to improve HCV treatment access for other priority populations in Australia.

Prevalence and Burden of Chronic Cough in the United States.

BACKGROUND: Chronic cough is a common complaint but there are little population-based data on its burden in the United States. OBJECTIVE: To determine the prevalence of chronic cough and its burden on individuals and the health care system. METHODS: This was a survey of respondents who completed the 2018 National Health and Wellness Survey and questions about sleep and health care resource use. Chronic cough was defined as having a daily cough for 8 or more weeks. Respondents without chronic cough were selected through propensity score matching. Chronic cough prevalence was estimated using poststratification sampling weights calculated using U.S. Census data and post-data Horvitz-Thompson sampling weights to adjust for sampling bias. RESULTS: Of 74,977 National Health and Wellness Survey respondents, 3,654 had experienced chronic cough in the previous 12 months, for a weighted prevalence of 5.0%. Respondents with chronic cough were older and more predominantly female than respondents without chronic cough (both P < .001). Compared with matched respondents without chronic cough, those with chronic cough had lower mean scores on the Medical Outcomes Study 36-item Short Form Survey v2 physical (P < .001) and mental (P < .001) component summary scores. More respondents with chronic cough than matched controls experienced severe anxiety and severe depression in the past 2 weeks, work productivity impairment, impaired sleep quality and daytime sleepiness, as well as more emergency department visits and hospitalizations in the past 6 months (P < .001 for all comparisons). CONCLUSIONS: The burden of chronic cough manifests itself as reduced health-related quality of life, increased anxiety and depression, impaired sleep and work productivity, and greater health care utilization.

Increasing access to erectile dysfunction treatment via pharmacies to improve healthcare provider visits and quality of life: Results from a prospective real-world observational study in the United Kingdom.

OBJECTIVES: The Medicines and Healthcare Products Regulatory Agency in the United Kingdom (UK) formally reclassified sildenafil citrate 50 mg tablets as a pharmacy medicine (sildenafil-P) in 2017 for adult men with erectile dysfunction (ED). A 1-year prospective real-world observational study was conducted to track men's health behaviour, particularly their healthcare resource utilisation (HCRU) and quality of life (QoL) before and after the availability of sildenafil-P. METHODS: Adult men with ED aged ≥18 years provided data at baseline (prior to launch of sildenafil-P) and every 3 months after the launch. Demographics, health characteristics, treatments at baseline and HCRU, including number of pharmacist and physician/nurse practitioner visits over time are reported. QoL-related outcomes were assessed via the Self-Esteem and Relationship Questionnaire (SEAR), 2-Item Patient Health Questionnaire and ratings of sexual satisfaction. Generalised linear models were used to assess the association of sildenafil-P use with total physician/nurse practitioner and pharmacist visits and QoL-related outcomes at 12 months. RESULTS: Overall, 1162 men completed the survey at all 5 time points. The mean ± SD age was 59.02 ± 12.06 years; 55.42% reported having a moderate-to-severe ED. Hypertension (37.52%) and hypercholesterolaemia (31.50%) were the most common risk factors for ED. At baseline, 62.99% were not using any ED treatment. After adjusting for baseline visits/other covariates, mean physician/nurse practitioner (3.68 vs 2.87; P = .003) and pharmacist visits for any reason (2.10 vs 1.34; P < .001) at 12 months were significantly higher among sildenafil-P users than those who never used sildenafil-P. Sildenafil-P users also had significantly higher SEAR total and domain (sexual relationship and self-esteem) scores at 12 months. CONCLUSION: Following the reclassification to a pharmacy medicine in the UK, sildenafil-P was associated with a higher number of physician/nurse practitioner and pharmacist visits for any reason. Sildenafil-P use was also associated with better QoL, although group differences were small in magnitude.

Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries.

INTRODUCTION: The effect of erectile dysfunction (ED) on sexual planning behaviors and outcomes in men taking phosphodiesterase type 5 inhibitors (PDE5Is) is not well studied. AIMS: To assess sexual habits, behaviors, and treatment-related outcomes of PDE5I-treated men with ED. METHODS: This cross-sectional observational study recruited men aged 30 to 70 years with mild-to-severe ED from 8 diverse countries (the United States, the United Kingdom, Italy, Russia, Turkey, Israel, China, and Japan) to complete an approximately 15-minute survey. Differences were evaluated using bivariate analyses, and data were summarized using descriptive statistics. MAIN OUTCOME MEASURES: Self-reported data were collected for demographics, health characteristics, treatment, sexual habits, ED severity, ED-specific quality of life, and treatment satisfaction. RESULTS: The survey was completed by 1,575 men. Mean frequency of sexual intercourse was 5.7 times/month. Overall, 87.1% of men always, often, or sometimes planned for sexual activity. Of those planning in advance, 32.8% and 40.6% agreed or strongly agreed that they plan for specific days of the week and times of day, respectively. Sexual planning habits were similar for patients taking short-acting vs long-acting PDE5Is. The most commonly cited reasons for planning sexual activity were needing time to take medication (48.4%), needing to make sure medication has taken effect (43.4%), convenient time for sexual activity (34.9%), and needing the partner's agreement (33.4%). Mean Self-Esteem and Relationship Questionnaire total score was 56.4. CONCLUSIONS: The differences in ED burden and sexual planning behavior observed across countries were not influenced by the type of PDE5I being taken, suggesting that cultural differences are an important factor when considering types of ED treatment. These findings provide a better understanding of burden, sexual habits, planning behaviors, quality of life, and treatment-related outcomes among PDE5I-treated men with ED in 8 Western and non-Western countries and may aid healthcare providers in selecting optimal treatments. Goldstein I, Giraldi A, Maculaitis MC, Real-World Assessment of the Impact of Erectile Dysfunction on Sexual Planning Behavior and Health- and Treatment-Related Outcomes Among Men in 8 Countries. J Sex Med 2020;8:338-349.

Epidemiology Update of Erectile Dysfunction in Eight Countries with High Burden.

INTRODUCTION: Prior epidemiology studies on erectile dysfunction (ED) have varied in geography/place, time period, and methodology. Due to this variability, comparisons of data across studies are greatly limited. Additionally, little is known about the rates of comorbid ED and benign prostatic hyperplasia (BPH). AIM: To update the prevalence of ED and patient characteristics using a single methodology in 8 countries: Brazil, China, France, Germany, Italy, Spain, the United Kingdom, and the United States. METHODS: This retrospective cross-sectional study included men (≥18 years) who self-reported experiencing difficulty in achieving or maintaing an erection in the past 6 months in the 2015 and 2016 National Health and Wellness Surveys (N = 97,159). Pairwise comparisons between the United States and each of the other countries were performed among respondents with ED and no BPH, aged ≥18 years, and within the subset of men aged 40-70 years. MAIN OUTCOME MEASURES: ED prevalence (with BPH, with no BPH, and overall), health characteristics, and ED risk factors were assessed. RESULTS: ED with BPH was found to be < 6.0% in all countries. ED prevalence overall varied from 37.2% (Brazil) to 48.6% (Italy). Similar patterns were observed for the subset of men aged 40-70 years. Patients in Brazil were younger (aged ≥18: 43.85 vs. 52.35; aged 40-70: 52.94 vs. 56.76 years; for both, P < .05) than those in the United States. ED-related comorbidities were more common in European countries, comparatively. CONCLUSION: This study provides an important update and outlook to ED epidemiology in Brazil, China, France, Germany, Italy, Spain, the United Kingdom, and the United States. Overall, ED prevalence is high, relative to some previous estimates. Findings from this study highlight the continued burden ED plays in the lives of men in these countries. Goldstein I, Goren A, Li VW, et al. Epidemiology Update of Erectile Dysfunction in Eight Countries with High Burden. Sex Med Rev 2020;8:48-58.

Disparities in healthcare providers' interpretations and implementations of ACIP's meningococcal vaccine recommendations.

Invasive meningococcal disease (IMD) caused by the bacteria Neisseria meningitidis is rare but potentially fatal. For healthy adolescents, the US Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination with MenACWY and recommends MenB vaccination under shared clinical decision-making (previously "Category B"). The recommendation for MenB vaccination was the first category B recommendation in adolescents, and it is unclear how healthcare providers (HCPs) implement these guidelines. This 2017 web-based survey of US HCPs explored characteristics associated with prescribing or receiving MenB and MenACWY vaccines, HCP knowledge of vaccine recommendations, and real-world practice patterns. Of 529 respondents, 436 prescribed MenB vaccines to their eligible adolescent/young adult patients and 93 prescribed MenACWY vaccines only. MenB vaccine prescribers were more likely to be pediatricians compared with MenACWY vaccine only prescribers, and patients who received MenB vaccines were more likely to be non-Hispanic whites living in shared spaces (eg, college dormitories) than those not receiving the vaccine. Seventy-seven percent of HCPs indicated that they prescribe MenACWY vaccines consistently with ACIP recommendations (to all members of an age group), whereas only 7% indicated that they prescribe MenB vaccines consistently with ACIP recommendations (individual clinical decision making). Patient-related factors, disease-related factors, and guidelines all influenced HCP decisions to prescribe meningococcal vaccines. Providing HCPs with clear guidance on how to initiate discussion of MenB vaccines with patients and their caregivers may aid in fully protecting US adolescents against meningococcal disease caused by 5 of the disease-causing serogroups.

Structure-Activity Relationship Studies To Identify Affinity Probes in Bis-aryl Sulfonamides That Prolong Immune Stimuli.

Agents that safely induce, enhance, or sustain multiple innate immune signaling pathways could be developed as potent vaccine adjuvants or coadjuvants. Using high-throughput screens with cell-based nuclear factor κB (NF-κB) and interferon stimulating response element (ISRE) reporter assays, we identified a bis-aryl sulfonamide bearing compound 1 that demonstrated sustained NF-κB and ISRE activation after a primary stimulus with lipopolysaccharide or interferon-α, respectively. Here, we present systematic structure-activity relationship (SAR) studies on the two phenyl rings and amide nitrogen of the sulfonamide group of compound 1 focused toward identification of affinity probes. The murine vaccination studies showed that compounds 1 and 33 when used as coadjuvants with monophosphoryl lipid A (MPLA) showed significant enhancement in antigen ovalbumin-specific immunoglobulin responses compared to MPLA alone. SAR studies pointed to the sites on the scaffold that can tolerate the introduction of aryl azide, biotin, and fluorescent rhodamine substituents to obtain several affinity and photoaffinity probes which will be utilized in concert for future target identification and mechanism of action studies.

The association of erectile dysfunction with productivity and absenteeism in eight countries globally.

AIM: To evaluate the association of erectile dysfunction (ED) with work productivity loss, activity impairment and health-related quality of life (HRQoL) across Brazil, China, France, Germany, Italy, Spain, the UK and the US. METHODS: This cross-sectional observational study used data from adult men (40-70 years old; N = 52 697) from the 2015 and 2016 National Health and Wellness Surveys. ED assessment was based on self-reported difficulty in achieving or maintaining an erection in the past 6 months. Impairment to work and non-work activities and HRQoL were assessed for each country and compared against the US. Multivariable models tested interactions between ED status and country for each outcome. RESULTS: Overall ED prevalence was reported as 49.7%, with Italy reporting the highest rate (54.7%). Men with ED reported significantly higher absenteeism (7.1% vs 3.2%), presenteeism (22.5% vs 10.1%), overall work productivity impairment (24.8% vs 11.2%), activity impairment (28.6% vs 14.5%) and significantly lower Mental Component Summary scores (MCS; 46.7 vs 51.2), Physical Component Summary scores (PCS; 48.3 vs 53.0), and health state utilities (SF-6D: 0.693 vs 0.778; all, P < 0.001) than men with no ED. After adjusting for covariates, compared with the US, the association of ED status with overall work productivity impairment was greatest in the UK (26% higher; P < 0.05), and with MCS, PCS and SF-6D scores was greatest in China (-2.67, -1.58, and -0.043 points, respectively; all, P < 0.001). Greater ED severity was significantly associated with higher impairment to work and non-work activities and lower HRQoL, with China reporting the highest burden, compared with the US (most P < 0.05). CONCLUSION: ED poses a significant burden with respect to work productivity and HRQoL, with greater severity associated with worse outcomes. Better management and earlier detection may help reduce this burden, especially in countries reporting a strong association between ED and poor economic and health outcomes.