High-cost gene therapies strain the sustainability of healthcare budgets. Despite the potential long-term savings promised by certain gene therapies, realizing these savings faces challenges due to uncertainties regarding the treatment’s durability and a lesser-discussed factor: the true potential for cost offset. Our study aims to assess the cost-offset uncertainty for US Medicaid regarding recently approved gene therapies in hemophilia A and B.

The analysis used 2018 to 2022 Colorado Department of Health Care Policy & Financing data to determine direct costs of standard of care (factor replacement therapy or emicizumab). Cost-simulation models over five- and ten-year time horizons estimated Colorado Medicaid costs if patients switched to gene therapy (valoctocogene roxaparvovec or etranacogene dezaparvovec) versus maintaining standard of care. Patients were included if aged 18 and over with ICD-10-CM codes D66 (hemophilia A) and D67 (hemophilia B). In the base case, severe hemophilia A was defined as requiring greater than or equal to six yearly factor VIII or emicizumab claims and moderate/severe hemophilia B requiring greater than or equal to four factor IX replacement therapy claims annually.

Annual standard-of-care costs were USD426,000 (SD USD353,000) for hemophilia A and USD546,000 (SD USD542,000) for hemophilia B. Valoctocogene roxaparvovec (hemophilia A) had incremental costs of USD880,000 at five years and −USD481,000 at 10 years. Sensitivity analysis revealed a 23 percent chance of break-even within five years and 48 percent within 10 years. Etranacogene dezaparvovec (hemophilia B) showed incremental costs of USD429,000 at five years and −USD2,490,000 at 10 years. Simulation indicated a 32 percent chance of break-even within five years and 59 percent within 10 years. Varying eligibility (≥4 to ≥15 standard-of-care claims) notably affected break-even; for example, valoctocogene roxaparvovec: 40 percent to 77 percent chance of break-even in 10 years.

Our study highlights significant cost variation in the standard of care of patients eligible for gene therapies, adding to the uncertainty surrounding cost estimation and highlighting the importance of addressing this factor in risk-sharing agreements. The impact of varying eligibility criteria on cost offsets emphasizes the importance of carefully defining eligibility when using real-world data in the context of health technology assessment.

Migration is a well-established risk factor for psychotic disorders, and migrant language has been proposed as a novel factor that may improve our understanding of this relationship. Our objective was to explore the association between indicators of linguistic distance and the risk of psychotic disorders among first-generation migrant groups.

Using linked health administrative data, we constructed a retrospective cohort of first-generation migrants to Ontario over a 20-year period (1992–2011). Linguistic distance of the first language was categorized using several approaches, including language family classifications, estimated acquisition time, syntax-based distance scores, and lexical-based distance scores. Incident cases of non-affective psychotic disorder were identified over a 5- to 25-year period. We used Poisson regression to estimate incidence rate ratios (IRR) for each language variable, after adjustment for knowledge of English at arrival and other factors.

Our cohort included 1 863 803 first-generation migrants. Migrants whose first language was in a different language family than English had higher rates of psychotic disorders (IRR = 1.08, 95% CI 1.01–1.16), relative to those whose first language was English. Similarly, migrants in the highest quintile of linguistic distance based on lexical similarity had an elevated risk of psychotic disorder (IRR = 1.15, 95% CI 1.06–1.24). Adjustment for knowledge of English at arrival had minimal effect on observed estimates.

We found some evidence that linguistic factors that impair comprehension may play a role in the excess risk of psychosis among migrant groups; however, the magnitude of effect is small and unlikely to fully explain the elevated rates of psychotic disorder across migrant groups.

Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Studies have shown mixed results regarding social capital and the risk of developing a psychotic disorder, and this has yet to be studied in North America. We sought to examine the relationship between neighbourhood-level marginalisation, social capital, and the incidence of schizophrenia and schizoaffective disorder in Toronto, Canada.

We used a retrospective population-based cohort to identify incident cases of schizophrenia and schizoaffective disorder over a 10 year period and accounted for neighbourhood-level marginalisation and a proxy indicator of neighbourhood social capital. Mixed Poisson regression models were used to estimate adjusted incidence rate ratios (aIRRs).

In the cohort (n = 649 020) we identified 4841 incident cases of schizophrenia and schizoaffective disorder. A 27% variation in incidence was observed between neighbourhoods. All marginalisation dimensions, other than ethnic concentration, were associated with incidence. Compared to areas with low social capital, areas with intermediate social capital in the second [aIRR = 1.17, 95% confidence interval (CI) 1.03–1.33] and third (aIRR = 1.23, 95% CI 1.08–1.40) quintiles had elevated incidence rates after accounting for marginalisation. There was a higher risk associated with the intermediate levels of social capital (aIRR = 1.18, 95% CI 1.00–1.39) when analysed in only the females in the cohort, but the CI includes the possibility of a null effect.

The risk of developing schizophrenia and schizoaffective disorder in Toronto varies by neighbourhood and is associated with socioenvironmental exposures. Social capital was not linearly associated with risk, and risk differs by sex and social capital quintile. Future research should examine these relationships with different forms of social capital and examine how known individual-level risk factors impact these findings.

To assess the effect of individual compared to clinic-level feedback on guideline-concordant care for 3 acute respiratory tract infections (ARTIs) among family medicine clinicians caring for pediatric patients.

Cluster randomized controlled trial with a 22-month baseline, 26-month intervention period, and 12-month postintervention period.

In total, 26 family medicine practices (39 clinics) caring for pediatric patients in Virginia, North Carolina, and South Carolina were selected based upon performance on guideline-concordance for 3 ARTIs, stratified by practice size. These were randomly allocated to a control group (17 clinics in 13 practices) or to an intervention group (22 clinics in 13 practices).

All clinicians received an education session and baseline then monthly clinic-level rates for guideline-concordant antibiotic prescribing for ARTIs: upper respiratory tract infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). For the intervention group only, individual clinician performance was provided.

Both intervention and control groups demonstrated improvement from baseline, but the intervention group had significantly greater improvement compared with the control group: URI (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.37–1.92; P < 0.01); ABS (OR, 1.45; 95% CI, 1.11–1.88; P < 0.01); and AOM (OR, 1.59; 95% CI, 1.24–2.03; P < 0.01). The intervention group also showed significantly greater reduction in broad-spectrum antibiotic prescribing percentage (BSAP%): odds ratio 0.80, 95% CI 0.74-0.87, P < 0.01. During the postintervention year, gains were maintained in the intervention group for each ARTI and for URI and AOM in the control group.

Monthly individual peer feedback is superior to clinic-level only feedback in family medicine clinics for 3 pediatric ARTIs and for BSAP% reduction.

ClinicalTrials.gov identifier: NCT04588376, Improving Antibiotic Prescribing for Pediatric Respiratory Infection by Family Physicians with Peer Comparison.

Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.

MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.

VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.

Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students.

An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health.

Twenty-two higher education institutions.

College students (n 17 686) enrolled at one of twenty-two participating universities.

Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P < 0·0001) and reported more days with poor mental (P < 0·0001) and physical (P < 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P < 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04).

College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes.

There is currently no universally accepted measure for population-based surveillance of mood and anxiety disorders. As such, the use of multiple linked measures could provide a more accurate estimate of population prevalence. Our primary objective was to apply Bayesian methods to two commonly employed population measures of mood and anxiety disorders to make inferences regarding the population prevalence and measurement properties of a combined measure.

We used data from the 2012 Canadian Community Health Survey – Mental Health linked to health administrative databases in Ontario, Canada. Structured interview diagnoses were obtained from the survey, and health administrative diagnoses were identified using a standardised algorithm. These two prevalence estimates, in addition to data on the concordance between these measures and prior estimates of their psychometric properties, were used to inform our combined estimate. The marginal posterior densities of all parameters were estimated using Hamiltonian Monte Carlo (HMC), a Markov Chain Monte Carlo technique. Summaries of posterior distributions, including the means and 95% equally tailed posterior credible intervals, were used for interpretation of the results.

The combined prevalence mean was 8.6%, with a credible interval of 6.8–10.6%. This combined estimate sits between Bayesian-derived prevalence estimates from administrative data-derived diagnoses (mean = 7.4%) and the survey-derived diagnoses (mean = 13.9%). The results of our sensitivity analysis suggest that varying the specificity of the survey-derived measure has an appreciable impact on the combined posterior prevalence estimate. Our combined posterior prevalence estimate remained stable when varying other prior information. We detected no problematic HMC behaviour, and our posterior predictive checks suggest that our model can reliably recreate our data.

Accurate population-based estimates of disease are the cornerstone of health service planning and resource allocation. As a greater number of linked population data sources become available, so too does the opportunity for researchers to fully capitalise on the data. The true population prevalence of mood and anxiety disorders may reside between estimates obtained from survey data and health administrative data. We have demonstrated how the use of Bayesian approaches may provide a more informed and accurate estimate of mood and anxiety disorders in the population. This work provides a blueprint for future population-based estimates of disease using linked health data.

The utility and efficacy of bolus dose vasopressors in hemodynamically unstable patients is well-established in the fields of general anesthesia and obstetrics. However, in the prehospital setting, minimal evidence for bolus dose vasopressor use exists and is primarily limited to critical care transport use. Hypotensive episodes, whether traumatic, peri-intubation-related, or septic, increase patient mortality. The purpose of this study is to assess the efficacy and adverse events associated with prehospital bolus dose epinephrine use in non-cardiac arrest, hypotensive patients treated by a single, high-volume, ground-based Emergency Medical Services (EMS) agency.

This is a retrospective, observational study of all non-cardiac arrest EMS patients treated for hypotension using bolus dose epinephrine from September 12, 2018 through September 12, 2019. Inclusion criteria for treatment with bolus dose epinephrine required a systolic blood pressure (SBP) measurement <90mmHg. A dose of 20mcg every two minutes, as needed, was allowed per protocol. The primary data source was the EMS electronic medical record.

Forty-two patients were treated under the protocol with a median (IQR) initial SBP immediately prior to treatment of 78mmHg (65-86) and a median (IQR) initial mean arterial pressure (MAP) of 58mmHg (50-66). The post-bolus SBP and MAP increased to 93mmHg (75-111) and 69mmHg (59-83), respectively. The two most common patient presentations requiring protocol use were altered mental status (55%) and respiratory failure (31%). Over one-half of the patients treated required both advanced airway management (62%) and multiple bolus doses of vasopressor support (55%). A single episode of transient severe hypertension (SBP>180mmHg) occurred, but there were no episodes of unstable tachyarrhythmia or cardiac arrest while en route or upon arrival to the receiving hospitals.

These preliminary data suggest that the administration of bolus dose epinephrine may be effective at rapidly augmenting hypotension in the prehospital setting with a minimal incidence of adverse events. Paramedic use of bolus dose epinephrine successfully increased SBP and MAP without clinically significant side effects. Prospective studies with larger sample sizes are needed to further investigate the effects of prehospital bolus dose epinephrine on patient morbidity and mortality.

Many institutions are attempting to implement patient-reported outcome (PRO) measures. Because PROs often change clinical workflows significantly for patients and providers, implementation choices can have major impact. While various implementation guides exist, a stepwise list of decision points covering the full implementation process and drawing explicitly on a sociotechnical conceptual framework does not exist.

To facilitate real-world implementation of PROs in electronic health records (EHRs) for use in clinical practice, members of the EHR Access to Seamless Integration of Patient-Reported Outcomes Measurement Information System (PROMIS) Consortium developed structured PRO implementation planning tools. Each institution pilot tested the tools. Joint meetings led to the identification of critical sociotechnical success factors.

Three tools were developed and tested: (1) a PRO Planning Guide summarizes the empirical knowledge and guidance about PRO implementation in routine clinical care; (2) a Decision Log allows decision tracking; and (3) an Implementation Plan Template simplifies creation of a sharable implementation plan. Seven lessons learned during implementation underscore the iterative nature of planning and the importance of the clinician champion, as well as the need to understand aims, manage implementation barriers, minimize disruption, provide ample discussion time, and continuously engage key stakeholders.

Highly structured planning tools, informed by a sociotechnical perspective, enabled the construction of clear, clinic-specific plans. By developing and testing three reusable tools (freely available for immediate use), our project addressed the need for consolidated guidance and created new materials for PRO implementation planning. We identified seven important lessons that, while common to technology implementation, are especially critical in PRO implementation.

Ethnic minority groups often have more complex and aversive pathways to mental health care. However, large population-based studies are lacking, particularly regarding involuntary hospitalisation. We sought to examine the risk of involuntary admission among first-generation ethnic minority groups with early psychosis in Ontario, Canada.

Using health administrative data, we constructed a retrospective cohort (2009–2013) of people with first-onset non-affective psychotic disorder aged 16–35 years. This cohort was linked to immigration data to ascertain migrant status and country of birth. We identified the first involuntary admission within 2 years and compared the risk of involuntary admission for first-generation migrant groups to the general population. To control for the role of migrant status, we restricted the sample to first-generation migrants and examined differences by country of birth, comparing risk of involuntary admission among ethnic minority groups to a European reference. We further explored the role of migrant class by adjusting for immigrant vs refugee status within the migrant cohort. We also explored effect modification of migrant class by ethnic minority group.

We identified 15 844 incident cases of psychotic disorder, of whom 19% (n=3049) were first-generation migrants. Risk of involuntary admission was higher than the general population in five of seven ethnic minority groups. African and Caribbean migrants had the highest risk of involuntary admission (African: risk ratio (RR) = 1.52, 95% CI = 1.34–1.73; Caribbean: RR = 1.58, 95% CI = 1.37–1.82), and were the only groups where the elevated risk persisted when compared to the European reference group within the migrant cohort (African: RR=1.24, 95% CI = 1.04–1.48; Caribbean: RR=1.29, 95% CI = 1.07–1.56). Refugee status was independently associated with involuntary admission (RR=1.16, 95% CI = 1.02–1.32); however, this risk varied by ethnic minority group, with Caribbean refugees having an elevated risk of involuntary admission compared with Caribbean immigrants (RR=1.72, 95% CI = 1.15–2.58).

Our findings are consistent with the international literature showing increased rates of involuntary admission among some ethnic minority groups with early psychosis. Interventions aimed at improving pathways to care could be targeted at these groups to reduce disparities.

The family physician is key to facilitating access to psychiatric treatment for young people with first-episode psychosis, and this involvement can reduce aversive events in pathways to care. Those who seek help from primary care tend to have longer intervals to psychiatric care, and some people receive ongoing psychiatric treatment from the family physician.

Our objective is to understand the role of the family physician in help-seeking, recognition and ongoing management of first-episode psychosis.

We will use a mixed-methods approach, incorporating health administrative data, electronic medical records (EMRs) and qualitative methodologies to study the role of the family physician at three points on the pathway to care. First, help-seeking: we will use health administrative data to examine access to a family physician and patterns of primary care use preceding the first diagnosis of psychosis; second, recognition: we will identify first-onset cases of psychosis in health administrative data, and look back at linked EMRs from primary care to define a risk profile for undetected cases; and third, management: we will examine service provision to identified patients through EMR data, including patterns of contacts, prescriptions and referrals to specialised care. We will then conduct qualitative interviews and focus groups with key stakeholders to better understand the trends observed in the quantitative data.

These findings will provide an in-depth description of first-episode psychosis in primary care, informing strategies to build linkages between family physicians and psychiatric services to improve transitions of care during the crucial early stages of psychosis.

None.

Discrepancies between population-based estimates of the incidence of psychotic disorder and the treated incidence reported by early psychosis intervention (EPI) programs suggest additional cases may be receiving services elsewhere in the health system. Our objective was to estimate the incidence of non-affective psychotic disorder in the catchment area of an EPI program, and compare this to EPI-treated incidence estimates.

We constructed a retrospective cohort (1997–2015) of incident cases of non-affective psychosis aged 16–50 years in an EPI program catchment using population-based linked health administrative data. Cases were identified by either one hospitalization or two outpatient physician billings within a 12-month period with a diagnosis of non-affective psychosis. We estimated the cumulative incidence and EPI-treated incidence of non-affective psychosis using denominator data from the census. We also estimated the incidence of first-episode psychosis (people who would meet the case definition for an EPI program) using a novel approach.

Our case definition identified 3245 cases of incident non-affective psychosis over the 17-year period. We estimate that the incidence of first-episode non-affective psychosis in the program catchment area is 33.3 per 100 000 per year (95% CI 31.4–35.1), which is more than twice as high as the EPI-treated incidence of 18.8 per 100 000 per year (95% CI 17.4–20.3).

Case ascertainment strategies limited to specialized psychiatric services may substantially underestimate the incidence of non-affective psychotic disorders, relative to population-based estimates. Accurate information on the epidemiology of first-episode psychosis will enable us to more effectively resource EPI services and evaluate their coverage.

Identify factors referred to as barriers and facilitators that can prevent or assist safe injection practices in ambulatory care settings to guide quality improvement.

In this mixed-methods study, we utilized observations and interviews.

This study was conducted at ambulatory clinics at a midwestern academic medical center from May through August 2017. Sites included a variety of clinical settings that performed intramuscular, intradermal, intravenous, or intra-articular injections.

Direct observations of injections and interviews of ambulatory care staff were conducted. An observation checklist was created, including standards of injection safety from nationally recognized guidelines. Interview questions were developed using the System Engineering Initiative for Patient Safety (SEIPS) model. Interviews were recorded, transcribed, and then coded by 2 investigators.

In total, 106 observations and 36 interviews were completed at 21 clinics. Injection safety standards with the lowest adherence included using needleless access devices to prepare injections (33%) and the proper use of multidose vials (<80%). Of 819 coded interview segments, 461 (56.3%) were considered facilitators of safe injection practices. The most commonly identified barriers were patient movement during administration, feeling rushed, and inadequate staffing. The most commonly identified facilitators were availability of supplies, experience in the practice area, and availability of safety needles and prefilled syringes.

Perceived barriers and facilitators to infection control elements of injection safety are interconnected with SEIPS elements of persons, organizations, technologies, tasks, and environment. Direct observations demonstrated that knowledge of safety injection standards does not necessarily translate to best practices and may not match self-reported data.

Infect Control Hosp Epidemiol 2018;39:841–848