Intravenous alteplase versus tenecteplase in patients with acute posterior circulation strokes: a secondary analysis from the AcT randomized controlled trial.

OBJECTIVES: There are limited data available demonstrating the safety and efficacy of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke in the posterior circulation. MATERIALS AND METHODS: This is a post-hoc analysis of the Alteplase compared to Tenecteplase(AcT) pragmatic, phase 3, registry-linked randomized controlled trial. Patients with any posterior circulation vessel occlusion on baseline imaging were included. Study outcomes included 90-day modified Rankin Scale(mRS) 0-1, mRS 0-2, ordinal mRS, death within 90 days, 24h symptomatic intracerebral haemorrhage(sICH) and successful reperfusion/recanalization. Mixed effects regression adjusting for age, sex and stroke severity was used to analyze differences in outcomes between patients administered tenecteplase vs. alteplase. Further, sensitivity analysis was conducted for basilar artery occlusion(BAO) alone. RESULTS: Of 1577 patients, 136(8.6%, 77:alteplase, 59:tenecteplase) had posterior circulation stroke. Baseline characteristics were similar[median age 71(IQR 60-81) vs. 72(IQR 65-82) years, 57.1% vs. 67.8% males, median baseline NIHSS 7(IQR 4-12) vs. 7(IQR 4-16) in alteplase vs. tenecteplase arms, respectively]. 28 patients(20.6%, 16:alteplase, 12:tenecteplase arm) underwent EVT. The median 90-120 days mRS was 2(IQR 1-4). There were no differences between alteplase and tenecteplase for 90-d mRS 0-1(adjRR 0.93;95%CI 0.63-1.36), 90-day mRS 0-2(adjRR 0.95; 95%CI 0.72-1.26), sICH(RR 0.65;95%CI 0.06-7.02) and mortality (RR 1.21;95%CI 0.61-2.38). Successful reperfusion eTICI 2b-3 and successful recanalization rAOL 2b-3 was achieved in 23/28(82%, 12:alteplase, 11:tenecteplase) and in 16/28(57%, 14:alteplase, 12:tenecteplase), respectively. Similar results were seen in 31 patients (22.8%) with BAO. CONCLUSION: Intravenous tenecteplase has a similar effect on outcome as alteplase, without increased safety concerns in patients with acute posterior circulation strokes.

Acceptability of an automated directly observed therapy (DOT) application for PrEP adherence support among young men who have sex with men: a qualitative exploration.

Pre-exposure prophylaxis (PrEP) adherence remains a challenge among young men who have sex with men (MSM). We developed and tested a smartphone application ("app"), "DOT Diary", which combines automated directly observed therapy (DOT) with information about PrEP protection levels, pill-taking reminders, a sexual behavior diary, and a PrEP dosing calendar. To contextualize trial results, we qualitatively explored participants' app experiences. The trial enrolled 100 young MSM in San Francisco and Atlanta. Participants were randomized 2:1 to DOT Diary versus standard-of-care and followed for 24 weeks. Interviews were conducted with 24 intervention participants. Data were analyzed using a memo-writing approach. Most expressed overall satisfaction with the app ("it was good for its purpose"), despite concerns about technical glitches. The most popular app features were the monthly calendar showing days PrEP was taken and information about level of protection based on pills taken. The DOT component helped participants establish PrEP routines. The reminders were "annoying but effective" at motivating dosing. Opinions about the sexual behavior diary varied. Overall, DOT Diary was acceptable; participants were willing to use it daily to record pill-taking. Critical components included the information about PrEP protection levels and calendar, while others may be modified to improve future success.Trial registration: ClinicalTrials.gov identifier: NCT03771638.

Comparative Effectiveness of Dupilumab and Omalizumab on Asthma Exacerbations and Systemic Corticosteroid Prescriptions: Real-World US ADVANTAGE Study.

BACKGROUND: In the US, dupilumab is approved for moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma, while omalizumab is approved for managing moderate-to-severe allergic asthma uncontrolled by inhaled corticosteroids. However, limited comparative effectiveness data exist for these biologics due to differing patient characteristics and treatment histories. OBJECTIVE: This analysis assessed the real-world effectiveness of dupilumab and omalizumab for asthma among patients in the US. METHODS: In this retrospective observational study, TriNetX Dataworks electronic medical record data were used to identify asthma patients (age: ≥12 years) who initiated (index) dupilumab or omalizumab between November 2018 and September 2020, and who had at least 12 months of pre- and post-index clinical information. Inverse probability of treatment weighting (IPTW) was applied to balance potential confounding in treatment groups. Asthma exacerbation rates and systemic corticosteroid (SCS) prescriptions were compared using a doubly robust negative binomial regression model, adjusting for baseline exacerbation/SCS rates and patient characteristics with ≥10% standardized differences after IPTW. RESULTS: Overall, 2,138 patients in dupilumab and 1,313 in omalizumab treatment groups met all inclusion and exclusion criteria. After weighting, the majority of baseline characteristics were balanced (standard difference <10%) between the two groups. Dupilumab was associated with a 44% lower asthma exacerbation rate (p<0.0001) than omalizumab. Additionally, dupilumab treatment significantly (p<0.05) reduced SCS prescriptions by 28% during the follow-up period compared to omalizumab treatment. CONCLUSION: The US ADVANTAGE real-world study demonstrated a significant reduction in severe asthma exacerbations and SCS prescriptions for patients prescribed dupilumab compared to those prescribed omalizumab during 12 months of follow-up.

An occupational health literacy intervention in nursing homes improved organizational health literacy - a quasi-experimental stepped wedge cluster trial.

OBJECTIVE: This study examined the effectiveness of a workplace health literacy intervention on individual, interpersonal, and organizational health literacy. METHOD: Using a quasi-experimental stepped wedge cluster design, we evaluated an intervention for 509 nursing home employees with two elements: 1) Courses for employees and management on pain prevention, management, and communication; 2) Structured dialogues between employees and supervisors, emphasizing pain prevention. RESULTS: One organizational health literacy item improved, with supervisors helping with pain prevention increasing by 0.42 points (95% CI 0.11;0.73). Positive trends were observed in supervisor actions when informed about pain (0.39 points, 95% CI -0.09;0.86), ease of finding workplace pain solutions (0.12 points, 95% CI -0.03;0.79), and employees having pain management information (0.44 points, 95% CI -0.03;0.92). CONCLUSION: The intervention improved one organizational health literacy item, with positive trends in three other items.

DiffPhys: Enhancing Signal-to-Noise Ratio in Remote Photoplethysmography Signal Using a Diffusion Model Approach.

Remote photoplethysmography (rPPG) is an emerging non-contact method for monitoring cardiovascular health based on facial videos. The quality of the captured videos largely determines the efficacy of rPPG in this application. Traditional rPPG techniques, while effective for heart rate (HR) estimation, often produce signals with an inadequate signal-to-noise ratio (SNR) for reliable vital sign measurement due to artifacts like head motion and measurement noise. Another pivotal factor is the overlooking of the inherent properties of signals generated by rPPG (rPPG-signals). To address these limitations, we introduce DiffPhys, a novel deep generative model particularly designed to enhance the SNR of rPPG-signals. DiffPhys leverages the conditional diffusion model to learn the distribution of rPPG-signals and uses a refined reverse process to generate rPPG-signals with a higher SNR. Experimental results demonstrate that DiffPhys elevates the SNR of rPPG-signals across within-database and cross-database scenarios, facilitating the extraction of cardiovascular metrics such as HR and HRV with greater precision. This enhancement allows for more accurate monitoring of health conditions in non-clinical settings.

Structural basis of RfaH-mediated transcription-translation coupling.

The NusG paralog RfaH mediates bacterial transcription-translation coupling in genes that contain a DNA sequence element, termed an ops site, required for pausing RNA polymerase (RNAP) and for loading RfaH onto the paused RNAP. Here, we report cryo-electron microscopy structures of transcription-translation complexes (TTCs) containing Escherichia coli RfaH. The results show that RfaH bridges RNAP and the ribosome, with the RfaH N-terminal domain interacting with RNAP and the RfaH C-terminal domain interacting with the ribosome. The results show that the distribution of translational and orientational positions of RNAP relative to the ribosome in RfaH-coupled TTCs is more restricted than in NusG-coupled TTCs because of the more restricted flexibility of the RfaH interdomain linker. The results further suggest that the structural organization of RfaH-coupled TTCs in the 'loading state', in which RNAP and RfaH are located at the ops site during formation of the TTC, is the same as the structural organization of RfaH-coupled TTCs in the 'loaded state', in which RNAP and RfaH are located at positions downstream of the ops site during function of the TTC. The results define the structural organization of RfaH-containing TTCs and set the stage for analysis of functions of RfaH during translation initiation and transcription-translation coupling.

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments.

PURPOSE OF THE REVIEW: Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. RECENT FINDINGS: Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

Physicochemical characterization of the metamorphosis of film-forming formulations of betamethasone-17-valerate.

Following topical application of a dermatological product, the loss (by evaporation and/or absorption through the skin) of volatile excipients will alter the composition of the formulation remaining on the tissue. This so-called metamorphosis impacts the concentration of the drug in the residual vehicle, (potentially) its physical form therein and, as a result, its uptake into and subsequent permeation through the skin. This research aimed to characterise - using primarily confocal Raman microspectroscopy - the metamorphosis of film-forming formulations of betamethasone-17-valerate (at different loadings) comprised of hydroxypropyl cellulose (film-forming agent), triethyl citrate (plasticizer) and ethanol (solvent). Dissolved and crystalline drug in the films were identified separately by their different characteristic Raman frequencies (1666 cm-1 and 1659 cm-1, respectively). These Raman measurements, as well as optical imaging, confirmed corticosteroid crystallisation in the residual films left after ethanol evaporation when drug concentration exceeded the saturation limit. In vitro release tests of either sprayed or pipette-deposited films into either aqueous or ethanolic receptor solutions revealed drug release kinetics dominated by the residual film post-metamorphosis. In particular, the rate and extent of drug release depends on the concentration of dissolved drug in the residual film, which is limited by drug saturation unless supersaturation occurs. For the simple films examined here, supersaturation was not detected and the solubility limit of drug in the films was sufficient to sustain drug release at a constant flux from the saturated films through a thin silicone elastomer membrane into an aqueous receptor solution for 30 h. Flux values were âˆ¼ 1 µg cm-2h-1 from saturated residual films independent of the amount of crystallized drug present. Flux from subsaturated films was reduced by an amount that was consistent with the lower degree of saturation.

SCG variability and spectral energy distribution during normal breathing and breath hold at different lung volumes and airway pressures.

Seismocardiographic (SCG) signals are chest wall vibrations induced by cardiac activity and are potentially useful for cardiac monitoring and diagnosis. SCG waveform is observed to vary with respiration, but the mechanism of these changes is poorly understood as alterations in autonomic tone, lung volume, heart location and intrathoracic pressure are all varying during the respiratory cycle. Understanding SCG variability and its sources may help reduce variability and increase SCG clinical utility. This study investigated SCG variability during breath holding (BH) at two different lung volumes (i.e., end inspiration and end expiration) and five airway pressures (i.e., 0, ± 2-4, and ± 15-20 cm H2O). Variability during normal breathing was also studied with and without grouping SCG beats into two clusters of similar waveform morphologies (performed using the K-medoid algorithm in an unsupervised machine learning fashion). The study included 15 healthy subjects (11 Females and 4 males, Age: 21 ± 2 y) where SCG, ECG, and spirometry were simultaneously acquired. SCG waveform variability was calculated at each experimental state (i.e., lung volume and airway pressure). Results showed that breath holding was more effective in reducing the intra-state variability of SCG than clustering normal breathing data. For the BH states, the intra-state variability increased as the airway pressure deviated from zero. The subaudible-to-audible energy ratio of the BH states increased as the airway pressure decreased below zero which may be related to the effect of the intrathoracic pressure on cardiac afterload and blood ejection. When combining the BH waveforms at end inspiration and end expiration states (at the same airway pressures) into one group, the intra-state variability increased, which suggests that the lung volume and associated change in heart location were a significant source of variability. The linear trend between airway pressure and waveform changes was found to be statistically significant for BH at end expiration. To confirm these findings, more studies are needed with a larger number of airway pressure levels and larger number of subjects.

Inhalational Agent Dosing Behaviors of Anesthesia Practitioners Cause Variability in End-Tidal Concentrations at the End of Surgery and Prolonged Times to Tracheal Extubation.

INTRODUCTION: Prolonged times to tracheal extubation are intervals from the end of surgery to extubation ≥15 minutes. We examined why there are associations with the end-tidal inhalational agent concentration as a proportion of the age­adjusted minimum alveolar concentration (MAC fraction) at the end of surgery. METHODS: The retrospective cohort study used 11.7 years of data from one hospital. All p­values were adjusted for multiple comparisons. RESULTS: There was a greater odds of prolonged time to extubation if the anesthesia practitioner was a trainee (odds ratio 1.68) or had finished fewer than five cases with the surgeon during the preceding three years (odds ratio 1.12) (both P<0.0001). There was a greater risk of prolonged time to extubation if the MAC fraction was >0.4 at the end of surgery (odds ratio 2.66, P<0.0001). Anesthesia practitioners who were trainees and all practitioners who had finished fewer than five cases with the surgeon had greater mean MAC fractions at the end of surgery and had greater relative risks of the MAC fraction >0.4 at the end of surgery (all P<0.0001). The source for greater MAC fractions at the end of surgery was not greater MAC fractions throughout the anesthetic because the means during the case did not differ among groups. Rather, there was substantial variability of MAC fractions at the end of surgery among cases of the same anesthesia practitioner, with the mean (standard deviation) among practitioners of each practitioner's standard deviation being 0.35 (0.05) and the coefficient of variation being 71% (13%). CONCLUSION: More prolonged extubations were associated with greater MAC fractions at the end of surgery. The cause of the large MAC fractions was the substantial variability of MAC fractions among cases of each practitioner at the end of surgery. That variability matches what was expected from earlier studies, both from variability among practitioners in their goals for the MAC fraction given at the start of surgical closure and from inadequate dynamic forecasting of the timing of when surgery would end. Future studies should examine how best to reduce prolonged extubations by using anesthesia machines' display of MAC fraction and feedback control of end-tidal agent concentration.

Patient-Reported Outcome Measure Development and Validation: A Primer for Clinicians.

A comprehensive definition of health includes the assessment of the patient's experience of a disease and its treatment. These patient experiences are best captured by standardized patient-reported outcome (PRO) instruments. A PRO is reported directly by the patient (or caregiver) and provides the patient's perspective into how a disease and its treatment impacts their lives. PRO instruments are typically standardized, validated questionnaires with items that are scaled and can be combined to represent an underlying health-related construct such as physical, social and role functioning, psychological well-being, symptoms, pain, and quality of life. Over the past few decades PROs have become increasingly used in clinical trials as endpoints to better understand treatment benefits from the patient's perspective and in clinical practice to identify unmet needs of patients, health risk surveillance, and monitor outcomes of care. In this paper, we describe the process for developing standardized PRO instruments, from conceptual model development through instrument validation.

Motion sickness resistant people showed suppressed steady-state visually evoked potential (SSVEP) under vection-inducing stimulation.

Visual stimulation can generate illusory self-motion perception (vection) and cause motion sickness among susceptible people, but the underlying neural mechanism is not fully understood. In this study, SSVEP responses to visual stimuli presented in different parts of the visual field are examined in individuals with different susceptibilities to motion sickness to identify correlates of motion sickness. Alpha band SSVEP data were collected from fifteen university students when they were watching roll-vection-inducing visual stimulation containing: (1) an achromatic checkerboard flickering at 8.6 Hz in the central visual field (CVF) and (2) rotating dots pattern flickering at 12 Hz in the peripheral visual field. Rotating visual stimuli provoked explicit roll-vection perception in all participants. The motion sickness resistant participants showed reduced SSVEP response to CVF checkerboard during vection, while the motion sickness susceptible participants showed increased SSVEP response. The changes of SSVEP in the presence of vection significantly correlated with individual motion sickness susceptibility and rated scores on simulator sickness symptoms. Discussion on how the findings can support the sensory conflict theory is presented. Results offer a new perspective on vection and motion sickness susceptibility. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09991-7.

Validity testing of the Korean version of the Health Literacy Questionnaire (HLQ) and its application in people with chronic diseases.

Health literacy plays a crucial role in promoting and maintaining the health of patients with chronic illnesses. Therefore, adequate assessments and the application of interventions based on people's health literacy strengths, needs, and preferences are required to improve health outcomes. This study aimed to evaluate the psychometrical properties of the Health Literacy Questionnaire (HLQ) in Koreans with chronic diseases. Data were collected from 278 patients (57.04±15.22 years) diagnosed with chronic disease, including kidney disease, hypertension, and diabetes, who visited the outpatient clinic of a university hospital from June to December 2020. For validity assessment, construct, convergent, and discriminant validities were evaluated, along with the HLQ reliability using Cronbach's α. One-way analysis of variance was used to evaluate mean differences in the HLQ scale scores based on patients' characteristics. The confirmatory factor analysis (CFA) indicated that all items were loaded on their respective factors. The model fit of a full nine-factor CFA model showed satisfactory or better fit compared with nine one-factor CFA model; χ2WLSMV (866) = 576.596 (p < .001), comparative normed fit index of 1.000 (reference: >0.950), Tucker-Lewis index of 0.981 (reference: >0.950), root mean square error of approximation of 0.066 (reference: <0.080), and standardized root mean square residual of 0.055 (reference: <0.080). All scales demonstrated good to excellent internal consistency (Cronbach's α ≥.757). Sociodemographic characteristic variables with significant score differences in HLQ scores were reported across nine scales, with the level of education and income showing significant score differences in 8 and 6 scales, respectively. This study revealed that the Korean version of the HLQ has many strong measurement properties among patients with chronic diseases. The validation indicated the HLQ as a robust tool that is used cross-culturally and is recommended for use in the Korean population.

The treatment effect across ASPECTS in acute ischemic stroke: Analysis from the AcT Trial.

BACKGROUND: Early ischemic changes on baseline imaging are commonly evaluated for acute stroke decision-making and prognostication. AIMS: We assess the association of early ischemic changes on clinical outcomes and whether it differs between intravenous tenecteplase versus Alteplase. METHODS: Data are from the phase 3, Alteplase compared to Tenecteplase (AcT) trial. Subjects with anterior circulation stroke were included. Early ischemic changes were assessed using the Alberta Stroke Program Early CT score (ASPECTS). Efficacy outcomes included modified Rankin scale (mRS) 0-1, mRS 0-2, and ordinal mRS at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage (sICH), any hemorrhage on follow-up scan, and 90-day mortality rate. Mixed effects logistic regression was used to assess the association of ASPECTS [continuous and categorical (0-4 vs. 5-7 vs. 8-10)] with outcomes and if these associations were modified by thrombolytic type after adjusting for age, sex, and baseline stroke severity. RESULTS: Of the 1577 patients in the trial, 901 patients (56.3%) (median age 75 years [IQR 65-84], 50.8% females, median NIHSS 14 [IQR 17-19]) with anterior circulation stroke were included. mRS 0-1 at 90d was achieved in 1/14 (0.3%), 43/160 (14.7%) and 252/726 (85.1%) in the ASPECTS 0-4, 5-7 and 8-10 groups respectively. Every 1-point decrease in ASPECTS was associated with 2.7% and 1.9% decrease in chances of mRS 0-1 and mRS 0-2 at 90 days, respectively, and 1.9% chances of increase in mortality at 90 days. Subgroup analysis in EVT treated population showed similar results. Thrombolytic type did not modify this association between ASPECTS and 90-day mRS 0-1 (P interaction 0.75). There was no significant interaction by thrombolytic type with any other outcome. CONCLUSIONS: Similar to prior studies, we found that every one-point decrease in ASPECTS was associated with poorer clinical and safety outcomes. This effect did not differ between alteplase and tenecteplase.

Measuring health literacy to inform actions to address health inequities: a cluster analysis approach based on the Australian national health literacy survey.

BACKGROUND: Measuring health literacy can inform interventions to address health inequities. This study used cluster analysis to examine health literacy data to determine if it can provide more insightful information than standard descriptive analysis to better inform intervention development. METHODS: Using data from the Australian National Health Survey (2018), this study compared descriptive analysis and cluster analysis results of two states-New South Wales (NSW) and Victoria-generated from the Health Literacy Questionnaire (HLQ). Based on the nine scale scores of the HLQ, a hierarchical cluster analysis using Ward's method for linkage was undertaken. RESULTS: The number of NSW and Victoria respondents was 1018 and 923, respectively. The nine HLQ scale full sample mean scores from both states were similar. However, the cluster analyses identified 11 clusters for NSW and 12 clusters for Victoria. While six clusters from each state presented similar health literacy patterns, five and six clusters from NSW and Victoria, respectively, displayed unique health literacy patterns. CONCLUSIONS: The results demonstrate that descriptive analysis only provides an overview and may lead to one-size-fits-all interventions. The varying health literacy patterns among subgroups resulting from the cluster analysis pave the way to inform tailored actions to improve health equity.

Testosterone, cortisol, and psychopathy: Further evidence with the Levenson self-report psychopathy scale and the inventory of callous unemotional traits.

The current study explored associations between testosterone, cortisol, and both the Levenson Self-Report Psychopathy Scale (LSRPS) and the Inventory of Callous Unemotional (ICU) traits. Data were gathered from a relatively large sample of university students (n = 522) and analyses considered direct and interactive associations between hormones and psychopathic traits, as well as interactions between these associations and the time of day at which samples were gathered and the sex of participants. Baseline cortisol had a negative association with LSRPS primary psychopathy scores. In addition, baseline cortisol interacted with the time of day in association with LSRPS total scores. Simple slopes analyses indicated cortisol had a negative association with LSRPS total scores in the morning but not the afternoon. Interactions among hormone measures were not statistically significant. There was also no evidence for the moderation of associations between hormones and psychopathic traits by sex.

Psychogenic non-epileptic (functional) seizures in adults with intellectual disability and epilepsy: A matched case-control study.

OBJECTIVE: To describe the characteristics of psychogenic non-epileptic (functional) seizures (PNES) in adults with epilepsy and intellectual disability (ID) and to establish differences and risk factors regarding psychosocial functioning between individuals with and without PNES. METHODS: Adults with ID and epilepsy living in epilepsy care facilities in The Netherlands were screened for PNES by a neurologist. A control group consisting of people with epilepsy and ID, without PNES, was matched according to age, sex, and level of ID. Objective data were retrieved retrospectively from clinical notes of the resident. Standardized questionnaires and tests, adjusted for people with ID, were obtained from participants and their nursing staff. Differences were analyzed using paired t tests, Wilcoxon signed-rank tests, or McNemar's tests, appropriate for matched case-control studies. Conditional logistic regression identified PNES risk factors. RESULTS: Five hundred forty individuals were screened, of which 42 had PNES (point prevalence 7.8%). In total, 35 cases and 35 controls gave consent. Proxy reports indicated that PNES impacted daily life in 79% by adjusting the individual's schedule, and caused minor injuries in one-third. Those with PNES were mainly female (69%); had a mild (46%) or moderate (37%) level of ID; showed more symptoms of depression (p = .024), anxiety (p = .030), self-injurious behavior (p = .015); and experienced more negative life events (p < .001). Clinically relevant predictors of PNES were the number of negative life events (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.12-2.53) and self-injurious behaviors (OR 5.27, 95% CI .97-28.81). SIGNIFICANCE: Previously, PNES in individuals with ID and epilepsy were described mainly as a reinforced behavioral pattern, due to limited associations with psychiatric disorders. Our results demonstrate that this population does show individual psychosocial vulnerabilities when measured with instruments adjusted for this population, as indicated by proxy reports from daily caregivers. Viewing PNES as an involuntary response, especially for stress-prone individuals with ID, could reduce stigma and improve treatment.

Addressing unmet need for primary care in Canada.

Primary care is the key health system strategy for improving health, enhancing patient and clinician experience, saving money, and promoting equity. Once a pioneer in primary care, Canada now fails to provide access to millions of people. This crisis is widely recognized, but policy responses are varied and mostly incremental and piecemeal. The goal of providing primary care to everyone seems unrealistic and elusive in Canada, yet it has long been attained in many other countries. Without an explicit policy goal of primary care for all, most likely on a geographic basis, Canada will continue to underinvest and underperform in primary care, with ramifications that include rapidly escalating costs, emergency department and hospital overcrowding and a growing and inequitable burden of preventable suffering. A commitment to work towards this goal is needed now to ensure that Canadians have access to high-quality well-organized care for everyone.