Ascertaining the Francophone population in Ontario: validating the language variable in health data.

BACKGROUND: Language barriers can impact health care and outcomes. Valid and reliable language data is central to studying health inequalities in linguistic minorities. In Canada, language variables are available in administrative health databases; however, the validity of these variables has not been studied. This study assessed concordance between language variables from administrative health databases and language variables from the Canadian Community Health Survey (CCHS) to identify Francophones in Ontario. METHODS: An Ontario combined sample of CCHS cycles from 2000 to 2012 (from participants who consented to link their data) was individually linked to three administrative databases (home care, long-term care [LTC], and mental health admissions). In total, 27,111 respondents had at least one encounter in one of the three databases. Language spoken at home (LOSH) and first official language spoken (FOLS) from CCHS were used as reference standards to assess their concordance with the language variables in administrative health databases, using the Cohen kappa, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV). RESULTS: Language variables from home care and LTC databases had the highest agreement with LOSH (kappa = 0.76 [95%CI, 0.735-0.793] and 0.75 [95%CI, 0.70-0.80], respectively) and FOLS (kappa = 0.66 for both). Sensitivity was higher with LOSH as the reference standard (75.5% [95%CI, 71.6-79.0] and 74.2% [95%CI, 67.3-80.1] for home care and LTC, respectively). With FOLS as the reference standard, the language variables in both data sources had modest sensitivity (53.1% [95%CI, 49.8-56.4] and 54.1% [95%CI, 48.3-59.7] in home care and LTC, respectively) but very high specificity (99.8% [95%CI, 99.7-99.9] and 99.6% [95%CI, 99.4-99.8]) and predictive values. The language variable from mental health admissions had poor agreement with all language variables in the CCHS. CONCLUSIONS: Language variables in home care and LTC health databases were most consistent with the language often spoken at home. Studies using language variables from administrative data can use the sensitivity and specificity reported from this study to gauge the level of mis-ascertainment error and the resulting bias.

Prevalence and patterns of multimorbidity among linguistic groups of patients receiving home care in Ontario: a retrospective cohort study.

BACKGROUND: Prior studies have demonstrated the negative impact of language barriers on access, quality, and safety of healthcare, which can lead to health disparities in linguistic minorities. As the population ages, those with multiple chronic diseases will require increasing levels of home care and long-term services. This study described the levels of multimorbidity among recipients of home care in Ontario, Canada by linguistic group. METHODS: Population-based retrospective cohort of 510,685 adults receiving home care between April 1, 2010, to March 31, 2018, in Ontario, Canada. We estimated and compared prevalence and characteristics of multimorbidity (2 or more chronic diseases) across linguistic groups (Francophones, Anglophones, Allophones). The most common combinations and clustering of chronic diseases were examined. Logistic regression models were used to explore the main predictors of 'severe' multimorbidity (defined as the presence of five or more chronic diseases). RESULTS: The proportion of home care recipients with multimorbidity and severe multimorbidity was 92% and 44%, respectively. The prevalence of multimorbidity was slightly higher among Allophones (93.6%) than among Anglophones (91.8%) and Francophones (92.4%). However, Francophones had higher rates of cardiovascular and respiratory disease (64.9%) when compared to Anglophones (60.2%) and Allophones (61.5%), while Anglophones had higher rates of cancer (34.2%) when compared to Francophones (25.2%) and Allophones (24.3%). Relative to Anglophones, Allophones were more likely to have severe multimorbidity (adjusted OR = 1.04, [95% CI: 1.02-1.06]). CONCLUSIONS: The prevalence of multimorbidity among Ontarians receiving home care services is high; especially for whose primary language is a language other than English or French (i.e., Allophones). Understanding differences in the prevalence and characteristics of multimorbidity across linguistic groups will help tailor healthcare services to the unique needs of patients living in minority linguistic situations.

Patient-physician language concordance and quality and safety outcomes among frail home care recipients admitted to hospital in Ontario, Canada.

BACKGROUND: When patients and physicians speak the same language, it may improve the quality and safety of care delivered. We sought to determine whether patient-physician language concordance is associated with in-hospital and postdischarge outcomes among home care recipients who were admitted to hospital. METHODS: We conducted a population-based study of a retrospective cohort of 189 690 home care recipients who were admitted to hospital in Ontario, Canada, between 2010 and 2018. We defined patient language (obtained from home care assessments) as English (Anglophone), French (Francophone) or other (allophone). We obtained physician language from the College of Physicians and Surgeons of Ontario. We defined hospital admissions as language concordant when patients received more than 50% of their care from physicians who spoke the patients' primary language. We identified in-hospital (adverse events, length of stay, death) and post-discharge outcomes (emergency department visits, readmissions, death within 30 days of discharge). We used regression analyses to estimate the adjusted rate of mean and the adjusted odds ratio (OR) of each outcome, stratified by patient language, to assess the impact of language-concordant care within each linguistic group. RESULTS: Allophone patients who received language-concordant care had lower risk of adverse events (adjusted OR 0.25, 95% confidence interval [CI] 0.15-0.43) and in-hospital death (adjusted OR 0.44, 95% CI 0.29-0.66), as well as shorter stays in hospital (adjusted rate of mean 0.74, 95% CI 0.66-0.83) than allophone patients who received language-discordant care. Results were similar for Francophone patients, although the magnitude of the effect was smaller than for allophone patients. Language concordance or discordance of the hospital admission was not associated with significant differences in postdischarge outcomes. INTERPRETATION: Patients who received most of their care from physicians who spoke the patients' primary language had better in-hospital outcomes, suggesting that disparities across linguistic groups could be mitigated by providing patients with language-concordant care.

Socioeconomic and Geographic Disparities in Emergency Department Visits due to Alcohol in Ontario: A Retrospective Population-level Study from 2003 to 2017.

OBJECTIVE: While the overall health system burden of alcohol is large and increasing in Canada, little is known about how this burden differs by sociodemographic factors. The objectives of this study were to assess sociodemographic patterns and temporal trends in emergency department (ED) visits due to alcohol to identify emerging and at-risk subgroups. METHODS: We conducted a retrospective population-level cohort study of all individuals aged 10 to 105 living in Ontario, Canada. We identified ED visits due to alcohol between 2003 and 2017 using defined International Classification of Diseases, 10th edition, codes from a pre-existing indicator. We calculated annual age- and sex-standardized, and age- and sex-specific rates of ED visits and compared overall patterns and changes over time between urban and rural settings and income quintiles. RESULTS: There were 829,662 ED visits due to alcohol over 15 years. Rates of ED visits due to alcohol were greater for individual living in the lowest- compared to the highest-income quintile neighbourhoods, and disparities (rate ratio lowest to highest quintile) increased with age from 1.22 (95% CI, 1.19 to 1.25) in 15- to 18-year-olds to 4.17 (95% CI, 4.07 to 4.28) in 55- to 59-year-olds. Rates of ED visits due to alcohol were significantly greater in rural settings (56.0 per 10,000 individuals, 95% CI, 55.7 to 56.4) compared to urban settings (44.8 per 10,000 individuals, 95% CI, 44.7 to 44.9), particularly for young adults. Increases in rates of visits between 2003 and 2017 were greater in rural versus urban settings (82 vs. 68% increase in age- and sex-standardized rates) and varied across sociodemographic subgroups with the largest annual increases in rates of visits in young (15 to 29) low-income women (6.9%, 95%CI, 6.7 to 7.3) and the smallest increase in older (45 to 59) high-income men (2.7, 95%CI, 2.4 to 3.0). CONCLUSION: Alcohol harms display unique patterns with the highest burden in rural and lower-income populations. Rural-urban and income-based disparities differ by age and sex and have increased over time, which offers an imperative and opportunity for further interventions by clinicians and policy makers.

Suicide and Self-Harm Among Physicians in Ontario, Canada.

BACKGROUND: Studies of occupation-associated suicide suggest physicians may be at a higher risk of suicide compared to nonphysicians. We set out to assess the risk of suicide and self-harm among physicians and compare it to nonphysicians. METHODS: We conducted a population-based, retrospective cohort study using registration data from the College of Physicians and Surgeons of Ontario from 1990 to 2016 with a follow-up to 2017, linked to Ontario health administrative databases. Using age- and sex-standardized rates and inverse probability-weighted, cause-specific hazards regression models, we compared rates of suicide, self-harm, and a composite of either event among all newly registered physicians to nonphysician controls. RESULTS: Among 35,989 physicians and 6,585,197 nonphysicians, unadjusted suicide events (0.07% vs. 0.11%) and rates (9.44 vs. 11.55 per 100,000 person-years) were similar. Weighted analyses found a hazard ratio of 1.05 (95% confidence interval: 0.69 to 1.60). Self-harm requiring health care was lower among physicians (0.22% vs. 0.46%; hazard ratio: 0.65, 95% confidence interval: 0.52 to 0.82), as was the composite of suicide or self-harm (hazard ratio: 0.70, 95% confidence interval: 0.57 to 0.86). The composite of suicide or self-harm was associated with a history of a mood or anxiety disorder (odds ratio: 2.84, 95% confidence interval: 1.17 to 6.87), an outpatient mental health visit in the past year (odds ratio: 3.08, 95% confidence interval: 1.34 to 7.10) and psychiatry visit in the preceding year (odds ratio: 3.87, 95% confidence interval: 1.67 to 8.95). INTERPRETATION: Physicians in Ontario are at a similar risk of suicide deaths and a lower risk of self-harm requiring health care relative to nonphysicians. Risk factors associated with suicide or self-harm may help inform prevention programs.

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

RATIONALE & OBJECTIVES: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. EXPOSURES: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. OUTCOMES: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. ANALYTICAL APPROACH: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. RESULTS: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. LIMITATIONS: Observational design, BP measurement data unavailable. CONCLUSIONS: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.

The Impact of Language on Emergency Department Visits, Hospitalizations, and Length of Stay Among Home Care Recipients.

BACKGROUND: Research considering the impact of language on health care utilization is limited. We conducted a population-based study to: (1) investigate the association between residents' preferred language and hospital-based health care utilization; and (2) determine whether this association is modified by dementia, a condition which can exacerbate communication barriers. METHODS: We used administrative databases to establish a retrospective cohort study of home care recipients (2015-2017) in Ontario, Canada, where the predominant language is English. Residents' preferred language (obtained from in-person home care assessments) was coded as English (Anglophones), French (Francophones), or other (Allophones). Diagnoses of dementia were ascertained with a previously validated algorithm. We identified all emergency department (ED) visits and hospitalizations within 1 year. RESULTS: Compared with Anglophones, Allophones had lower annual rates of ED visits (1.3 vs. 1.8; P<0.01) and hospitalizations (0.6 vs. 0.7; P<0.01), while Francophones had longer hospital stays (9.1 vs. 7.6 d per admission; P<0.01). After adjusting for potential confounders, Francophones and Allophones were less likely to visit the ED or be hospitalized than Anglophones. We found evidence of synergism between language and dementia; the average length of stay for Francophones with dementia was 25% (95% confidence interval: 1.10-1.39) longer when compared with Anglophones without dementia. CONCLUSIONS: Residents whose preferred language was not English were less frequent users of hospital-based health care services, a finding that is likely attributable to cultural factors. Francophones with dementia experienced the longest stays in hospital. This may be related to the geographic distribution of Francophones (predominantly in rural areas) or to suboptimal patient-provider communication.

Health Care Provider Utilization of Prescription Monitoring Programs: A Systematic Review and Meta-Analysis.

OBJECTIVE: To synthesize the literature on the proportion of health care providers who access and use prescription monitoring program data in their practice, as well as associated barriers to the use of such data. DESIGN: We performed a systematic review using a standard systematic review method with meta-analysis and qualitative meta-summary. We included full-published peer-reviewed reports of study data, as well as theses and dissertations. METHODS: We identified relevant quantitative and qualitative studies. We synthesized outcomes related to prescription monitoring program data use (i.e., ever used, frequency of use). We pooled the proportion of health care providers who had ever used prescription monitoring program data by using random effects models, and we used meta-summary methodology to identify prescription monitoring program use barriers. RESULTS: Fifty-three studies were included in our review, all from the United States. Of these, 46 reported on prescription monitoring program use and 32 reported on barriers. The pooled proportion of health care providers who had ever used prescription monitoring program data was 0.57 (95% confidence interval: 0.48-0.66). Common barriers to prescription monitoring program data use included time constraints and administrative burdens, low perceived value of prescription monitoring program data, and problems with prescription monitoring program system usability. CONCLUSIONS: Our study found that health care providers underutilize prescription monitoring program data and that many barriers exist to prescription monitoring program data use.

Risk of Cardiovascular Events and Mortality Among Elderly Patients With Reduced GFR Receiving Direct Oral Anticoagulants.

RATIONALE & OBJECTIVE: Evidence for the efficacy of direct oral anticoagulants (DOACs) to prevent cardiovascular (CV) events and mortality in older individuals with a low estimated glomerular filtration rate (eGFR) is lacking. We sought to characterize the association of oral anticoagulant use with CV morbidity in elderly patients with or without reductions in eGFRs, comparing DOACs with vitamin K antagonists (VKAs). STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: All individuals 66 years or older with an initial prescription for oral anticoagulants dispensed in Ontario, Canada, from 2009 to 2016. EXPOSURE: DOACs (apixaban, dabigatran, and rivaroxaban) compared with VKAs by eGFR group (≥60, 30-59, and<30mL/min/1.73m2). OUTCOMES: The primary outcome was a composite of a CV event (myocardial infarction, revascularization, or ischemic stroke) or mortality. Secondary outcomes were CV events alone, mortality, and hemorrhage requiring hospitalization. ANALYTICAL APPROACH: High-dimensional propensity score matching of DOAC to VKA users and Cox proportional hazards regression. RESULTS: 27,552 new DOAC users were matched to 27,552 new VKA users (median age, 78 years; 49% women). There was significantly lower risk for CV events or mortality among DOAC users compared with VKA users (event rates of 79.78 vs 99.77 per 1,000 person-years, respectively; HR, 0.82 [95% CI, 0.75-0.90]) and lower risk for hemorrhage (event rates of 10.35 vs 16.77 per 1,000 person-years, respectively; HR, 0.73 [95% CI, 0.58-0.91]). There was an interaction between eGFR and the association of anticoagulant class with the primary composite outcome (P<0.02): HRs of 1.01 [95% CI, 0.92-1.12], 0.83 [95% CI, 0.75-0.93], and 0.75 [95% CI, 0.51-1.10] for eGFRs of≥60, 30 to 59, and<30mL/min/1.73m2. No interaction was detected for the outcome of hemorrhage. LIMITATIONS: Retrospective observational study design limits causal inference; dosages of DOACs and international normalized ratio values were not available; low event rates in some subgroups limited statistical power. CONCLUSIONS: DOACs compared with VKAs were associated with lower risk for the composite of CV events or mortality, an association for which the strength was most apparent among those with reduced eGFRs. The therapeutic implications of these findings await further study.

The impact of dementia and language on hospitalizations: a retrospective cohort of long-term care residents.

BACKGROUND: Hospitalizations carry considerable risks for frail, elderly patients; this is especially true for patients with dementia, who are more likely to experience delirium, falls, functional decline, iatrogenic complications, and infections when compared to their peers without dementia. Since up to two thirds of patients in long-term care (LTC) facilities have dementia, there is interest in identifying factors associated with transitions from LTC facilities to hospitals. The purpose of this study was to investigate the association between dementia status and incidence of hospitalization among residents in LTC facilities in Ontario, Canada, and to determine whether this association is modified by linguistic factors. METHODS: We used linked administrative databases to establish a prevalent cohort of 81,188 residents in 628 LTC facilities from April 1st 2014 to March 31, 2017. Diagnoses of dementia were identified with a previously validated algorithm; all other patient characteristics were obtained from in-person assessments. Residents' primary language was coded as English or French; facility language (English or French) was determined using language designation status according to the French Language Services Act. We identified all hospitalizations within 3 months of the first assessment performed after April 1st 2014. We performed multivariate logistic regression analyses to determine the impact of dementia and resident language on the incidence of hospitalization; we also considered interactions between dementia and both resident language and resident-facility language discordance. RESULTS: The odds of hospitalization were 39% lower for residents with dementia compared to residents without dementia (OR 0.61, 95% CI 0.57-0.65). Francophones had lower odds of hospitalization than Anglophones, but this difference was not statistically significant (OR 0.91, 95% CI 0.81-1.03). However, Francophones without dementia were significantly less likely to be hospitalized compared to Anglophones without dementia (OR 0.71, 95% CI 0.53-0.94). Resident-facility language discordance did not significantly affect hospitalizations. CONCLUSIONS: Residents in LTC facilities were generally less likely to be hospitalized if they had dementia, or if their primary language was French and they did not have dementia. These findings could be explained by differences in end-of-life care goals; however, they could also be the result of poor patient-provider communication.

The impact of hospital language on the rate of in-hospital harm. A retrospective cohort study of home care recipients in Ontario, Canada.

BACKGROUND: Patients who live in minority language situations are generally more likely to experience poor health outcomes, including harmful events. The delivery of healthcare services in a language-concordant environment has been shown to mitigate the risk of poor health outcomes related to chronic disease management in primary care. However, data assessing the impact of language-concordance on the risk of in-hospital harm are lacking. We conducted a population-based study to determine whether admission to a language-discordant hospital is a risk factor for in-hospital harm. METHODS: We used linked administrative health records to establish a retrospective cohort of home care recipients (from 2007 to 2015) who were admitted to a hospital in Eastern or North-Eastern Ontario, Canada. Patient language (obtained from home care assessments) was coded as English (Anglophone group), French (Francophone group), or other (Allophone group); hospital language (English or bilingual) was obtained using language designation status according to the French Language Services Act. We identified in-hospital harmful events using the Hospital Harm Indicator developed by the Canadian Institute for Health Information. RESULTS: The proportion of hospitalizations with at least 1 harmful event was greater for Allophones (7.63%) than for Anglophones (6.29%, p <  0.001) and Francophones (6.15%, p <  0.001). Overall, Allophones admitted to hospitals required by law to provide services in both French and English (bilingual hospitals) had the highest rate of harm (9.16%), while Francophones admitted to these same hospitals had the lowest rate of harm (5.93%). In the unadjusted analysis, Francophones were less likely to experience harm in bilingual hospitals than in hospitals that were not required by law to provide services in French (English-speaking hospitals) (RR = 0.88, p = 0.048); the opposite was true for Anglophones and Allophones, who were more likely to experience harm in bilingual hospitals (RR = 1.17, p <  0.001 and RR = 1.41, p <  0.001, respectively). The risk of harm was not significant in the adjusted analysis. CONCLUSIONS: Home care recipients residing in Eastern and North-Eastern Ontario were more likely to experience harm in language-discordant hospitals, but the risk of harm did not persist after adjusting for confounding variables.

The effectiveness of prescription drug monitoring programs at reducing opioid-related harms and consequences: a systematic review.

BACKGROUND: In order to address the opioid crisis in North America, many regions have adopted preventative strategies, such as prescription drug monitoring programs (PDMPs). PDMPs aim to increase patient safety by certifying that opioids are prescribed in appropriate quantities. We aimed to synthesize the literature on changes in opioid-related harms and consequences, an important measure of PDMP effectiveness. METHODS: We completed a systematic review. We conducted a narrative synthesis of opioid-related harms and consequences from PDMP implementation. Outcomes were grouped into categories by theme: opioid dependence, opioid-related care outcomes, opioid-related adverse events, and opioid-related legal and crime outcomes. RESULTS: We included a total of 22 studies (49 PDMPs) in our review. Two studies reported on illicit and problematic use but found no significant associations with PDMP status. Eight studies examined the association between PDMP status and opioid-related care outcomes, of which two found that treatment admissions for prescriptions opioids were lower in states with PDMP programs (p < 0.05). Of the thirteen studies that reported on opioid-related adverse events, two found significant (p < 0.001 and p < 0.05) but conflicting results with one finding a decrease in opioid-related overdose deaths after PDMP implementation and the other an increase. Lastly, two studies found no statistically significant association between PDMP status and opioid-related legal and crime outcomes (crime rates, identification of potential dealers, and diversion). CONCLUSION: Our study found limited evidence to support overall associations between PDMPs and reductions in opioid-related consequences. However, this should not detract from the value of PDMPs' larger role of improving opioid prescribing.

Severe autoimmune hemolytic anemia with renal neoplasm.

Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

Place of Death and Place of Care at the End of Life: Are They Correlated? A Retrospective Cohort Study of Ontario Decedents.

Background: Dying in nonpalliative acute care is generally considered inappropriate and avoidable. Place of death, a commonly reported big-dot indicator of end-of-life care quality, is often used as a proxy for place of care despite no empirical evidence for their correlations. Thus, we examined the correlations between place of death and place of care in the last month of life. We also investigated anecdotal claims that individuals cared in acute care often get discharged to die at home, and vice versa. Methods: We conducted a retrospective cohort study of Ontario decedents (18+) who died between January 1, 2015 and December 31, 2017. We identified individuals who died in nonpalliative acute care, palliative care unit, subacute care, long-term care (LTC), and the community. We calculated the number of days decedents spent in each setting in their last month of life, and used descriptive analyses to investigate their correlations. Results: Decedent's place of death generally correlated with their place of care in the last month of life-individuals who died in a particular setting spent more time in that setting than individuals who died elsewhere. Furthermore, 75.0% of individuals who spent more than two weeks of their last month in acute care died in acute care. Among individuals who died in the community and in LTC, 65.4% and 75.0%, respectively, spent zero days in acute care. Interpretation: We showed that place of death can be a useful high-level performance indicator, by itself and as a proxy for place of care, to gauge end-of-life quality and service provision/implementation.

Stent-assisted Woven EndoBridge embolization for the treatment of pulsatile tinnitus caused by an ipsilateral high-riding jugular bulb.

PURPOSE: Pulsatile tinnitus can be caused by a high-riding jugular bulb (HRJB), characterized by the superior position of the jugular bulb in the petrous temporal bone. The anatomical position and morphology of this entity make it challenging for endovascular treatment. We report our experience with two patients successfully treated with a stent-assisted Woven EndoBridge (WEB; Microvention, Tustin, CA, USA) device. MATERIALS AND METHODS: We describe two cases of HRJB in patients presenting with disabling pulsatile tinnitus. Temporary balloon occlusion of the jugular bulb prior to the intervention reduced tinnitus intensity. Both patients were subsequently treated under general anesthesia with the WEB device deployed in the HRJB which was held by a stent deployed in the sigmoid sinus. RESULTS: Both procedures were successful with good positioning of the WEB device and no procedural complications. Both patients had complete resolution of pulsatile tinnitus immediately after the procedure. Follow-up imaging showed successful occlusion of the venous cavity with a widely patent stent. CONCLUSION: Among patients with pulsatile tinnitus caused by an ipsilateral HRJB, a stent-assisted WEB device seems to be a viable endovascular option with angiographic and clinical success.

An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.

Antibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition. In part, this is because limited experimental platforms exist for assessing quantitative and simultaneous sequence-function relationships for multiple antibodies. Here we present MAGMA-seq, an integrated technology that combines multiple antigens and multiple antibodies and determines quantitative biophysical parameters using deep sequencing. We demonstrate MAGMA-seq on two pooled libraries comprising mutants of ten different human antibodies spanning light chain gene usage, CDR H3 length, and antigenic targets. We demonstrate the comprehensive mapping of potential antibody development pathways, sequence-binding relationships for multiple antibodies simultaneously, and identification of paratope sequence determinants for binding recognition for broadly neutralizing antibodies (bnAbs). MAGMA-seq enables rapid and scalable antibody engineering of multiple lead candidates because it can measure binding for mutants of many given parental antibodies in a single experiment.

An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries.

Antibodies are engineerable quantities in medicine. Learning antibody molecular recognition would enable the in silico design of high affinity binders against nearly any proteinaceous surface. Yet, publicly available experiment antibody sequence-binding datasets may not contain the mutagenic, antigenic, or antibody sequence diversity necessary for deep learning approaches to capture molecular recognition. In part, this is because limited experimental platforms exist for assessing quantitative and simultaneous sequence-function relationships for multiple antibodies. Here we present MAGMA-seq, an integrated technology that combines multiple antigens and multiple antibodies and determines quantitative biophysical parameters using deep sequencing. We demonstrate MAGMA-seq on two pooled libraries comprising mutants of nine different human antibodies spanning light chain gene usage, CDR H3 length, and antigenic targets. We demonstrate the comprehensive mapping of potential antibody development pathways, sequence-binding relationships for multiple antibodies simultaneously, and identification of paratope sequence determinants for binding recognition for broadly neutralizing antibodies (bnAbs). MAGMA-seq enables rapid and scalable antibody engineering of multiple lead candidates because it can measure binding for mutants of many given parental antibodies in a single experiment.

Common framework mutations impact antibody interfacial dynamics and flexibility.

Introduction: With the flood of engineered antibodies, there is a heightened need to elucidate the structural features of antibodies that contribute to specificity, stability, and breadth. While antibody flexibility and interface angle have begun to be explored, design rules have yet to emerge, as their impact on the metrics above remains unclear. Furthermore, the purpose of framework mutations in mature antibodies is highly convoluted. Methods: To this end, a case study utilizing molecular dynamics simulations was undertaken to determine the impact framework mutations have on the VH-VL interface. We further sought to elucidate the governing mechanisms by which changes in the VH-VL interface angle impact structural elements of mature antibodies by looking at root mean squared deviations, root mean squared fluctuations, and solvent accessible surface area. Results and discussion: Overall, our results suggest framework mutations can significantly shift the distribution of VH-VL interface angles, which leads to local changes in antibody flexibility through local changes in the solvent accessible surface area. The data presented herein highlights the need to reject the dogma of static antibody crystal structures and exemplifies the dynamic nature of these proteins in solution. Findings from this work further demonstrate the importance of framework mutations on antibody structure and lay the foundation for establishing design principles to create antibodies with increased specificity, stability, and breadth.

Race, Poverty, and Foster Care Placement in the United States: Longitudinal and Cross-Sectional Perspectives.

Although the connections between race, poverty, and foster care placement seem obvious, the link has not in fact been studied extensively. To address this gap, we view poverty and placement through longitudinal and cross-sectional lenses to more accurately capture how changes in poverty rates relate to changes in placement frequency. The longitudinal study examines the relationship between poverty rate changes and changes in the placement of Black and White children between 2000 and 2015. The cross-sectional study extends the longitudinal analysis by using a richer measure of socio-ecological diversity and more recent foster care data. Using Poisson regression models, we assess the extent to which changes in race-differentiated child poverty rates are correlated with Black and White child placement frequencies and placement disparities. Regardless of whether one looks longitudinally or cross-sectionally, we find that Black children are placed in foster care more often than White children. Higher White child poverty rates are associated with substantially reduced placement differences; however, higher Black child poverty rates are associated with relatively small changes in placement disparity. Black and White child placement rates are more similar in counties with the fewest socio-ecological assets.

Adverse Gastrointestinal Events With Sodium Polystyrene Sulfonate Use in Patients on Maintenance Hemodialysis: An International Cohort Study.

Background: There are concerns regarding the gastrointestinal (GI) safety of sodium polystyrene sulfonate (SPS), a medication commonly used in the management of hyperkalemia. Objective: To compare the risk of GI adverse events among users versus non-users of SPS in patients on maintenance hemodialysis. Design: International prospective cohort study. Setting: Seventeen countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018). Patients: 50 147 adults on maintenance hemodialysis. Measurements: An adverse GI event defined by a GI hospitalization or GI fatality with SPS prescription compared with no SPS prescription. Methods: Overlap propensity score-weighted Cox models. Results: Sodium polystyrene sulfonate prescription was present in 13.4% of patients and ranged from 0.42% (Turkey) to 20.6% (Sweden) with 12.5% use in Canada. A total of 935 (1.9%) adverse GI events (140 [2.1%] with SPS, 795 [1.9%] with no SPS; absolute risk difference 0.2%) occurred. The weighted hazard ratio (HR) of a GI event was not elevated with SPS use compared with non-use (HR = 0.93, 95% confidence interval = 0.83-1.6). The results were consistent when examining fatal GI events and/or GI hospitalization separately. Limitations: Sodium polystyrene sulfonate dose and duration were unknown. Conclusions: Sodium polystyrene sulfonate use in patients on hemodialysis was not associated with a higher risk of an adverse GI event. Our findings suggest that SPS use is safe in an international cohort of maintenance hemodialysis patients.

Contexte: Des préoccupations sont soulevées quant à l'innocuité gastro-intestinale (GI) du sulfonate de polystyrène sodique (SPS), un médicament couramment utilisé dans la gestion de l'hyperkaliémie. Objectif: Comparer dans une population de patients sous hémodialyse d'entretien le risque d'effets indésirables gastro-intestinaux chez les utilisateurs du SPS par rapport aux patients non-utilisateurs. Conception: Étude de cohorte prospective internationale. Cadre: 17 pays (phases 2 à 6 de l'essai DOPPS [de 2002 à 2018]). Sujets: 50 147 adultes sous hémodialyse d'entretien. Mesures: La comparaison entre les événements gastro-intestinaux indésirables, définis par une hospitalisation ou un décès en lien avec un problème gastro-intestinal, selon que les patients avaient ou non une prescription de SPS. Méthodologie: Modèles de Cox pondérés par le score de propension au chevauchement. Résultats: Dans l'ensemble de la cohorte, 13,4 % des patients avaient une prescription de SPS; l'usage de SPS variait selon les pays entre 0,42 % (Turquie) et 20,6 % (Suède) avec 12,5 % au Canada. En tout, 935 (1,9 %) événements GI indésirables sont survenus dans l'ensemble de la cohorte, soit 140 (2,1 %) chez les patients avec prescription de SPS et 795 (1,9 %) chez les patients sans prescription de SPS (différence de risque absolue: 0,2 %). Le rapport de risque (RR) pondéré d'un événement GI n'était pas plus élevé avec l'utilisation de SPS (RR = 0,93; IC 95 %: 0,83-1,6). Les résultats étaient cohérents lorsque l'on a examiné séparément les événements gastro-intestinaux (hospitalisation et/ou décès). Limites: La dose et la durée du traitement par SPS étaient inconnues. Conclusion: L'utilisation de SPS chez les patients sous hémodialyse n'a pas été associée à un risque plus élevé d'événements indésirables d'origine gastro-intestinale. Nos résultats suggèrent que l'utilisation du SPS est sans danger dans la cohorte internationale de patients sous hémodialyse d'entretien étudiée.