Public experiences and perspectives of primary care in Canada: results from a cross-sectional survey.

BACKGROUND: Through medicare, residents in Canada are entitled to medically necessary physician services without paying out of pocket, but still many people struggle to access primary care. We conducted a survey to explore people's experience with and priorities for primary care. METHODS: We conducted an online, bilingual survey of adults in Canada in fall 2022. We distributed an anonymous link through diverse channels and a closed link to 122 053 people via a national public opinion firm. We weighted completed responses to mirror Canada's population and adjusted for sociodemographic characteristics using regression models. RESULTS: We analyzed 9279 completed surveys (5.9% response rate via closed link). More than one-fifth of respondents (21.8%) reported having no primary care clinician, and among those who did, 34.5% reported getting a same or next-day appointment for urgent issues. Of respondents, 89.4% expressed comfort seeing another team member if their doctor recommended it, but only 35.9%, 9.5%, and 12.4% reported that their practice had a nurse, social worker, or pharmacist, respectively. The primary care attribute that mattered most was having a clinician who "knows me as a person and considers all the factors that affect my health." After we adjusted for respondent characteristics, people in Quebec, the Atlantic region, and British Columbia had lower odds of reporting a primary care clinician than people in Ontario (adjusted odds ratio 0.30, 0.33, and 0.39, respectively; p < 0.001). We also observed large provincial variations in timely access, interprofessional care, and walk-in clinic use. INTERPRETATION: More than 1 in 5 respondents did not have access to primary care, with large variation by province. Reforms should strive to expand access to relationship-based, longitudinal care in a team setting.

The cytochrome P4501A1 (CYP1A1) inhibitor bergamottin enhances host tolerance to multidrug-resistant Vibrio vulnificus infection.

PURPOSE: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. METHODS: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. RESULTS: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1ß: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1ß, IL-6, TNF-α in liver (IL-1ß: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1ß: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637). CONCLUSION: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Shelter Bans Among People Experiencing Homelessness: an Exploratory Study of Predictors in Two Large Canadian Datasets.

Emergency shelters are a core component of homeless service systems that address immediate basic needs. Service bans, which refer to temporary or permanent disallowances from a program or organization, are an underresearched phenomenon that can leave people experiencing homelessness without needed supports. This exploratory study examined the factors associated with shelter bans among people experiencing homelessness using secondary data from two Canadian studies: (1) a multisite randomized controlled trial of Housing First (At Home/Chez Soi Demonstration Project) and (2) a cross-sectional survey of youth experiencing homelessness across Canada (2019 Without a Home-National Youth Homelessness Survey). The two datasets were analyzed separately using logistic regression models with similar predictors to maximize the comparability of the results. Participants who experienced homelessness at an earlier age and had recent criminal justice system involvement were more likely to have shelter bans in both datasets. Impaired impulse control, more chronic medical conditions and living in Toronto were associated with increased likelihood of shelter bans in the At Home/Chez Soi dataset, whereas more adverse childhood experiences, physical violence victimization, engagement in survival sex behaviours and longer current episodes of homelessness were significant predictors of bans in the Without A Home dataset. Overall, the findings suggest that victimization and criminalization during homelessness may increase the risk of shelter loss from bans and further exclusion. The observed regional differences also highlight the potential limits of individual-level predictors. Further research is needed on shelter ban outcomes, as well as how capacity limits and organizational policies affect banning decisions.

Family physician practice patterns during COVID-19 and future intentions: Cross-sectional survey in Ontario, Canada.

OBJECTIVE: To determine the extent to which family physicians closed their doors altogether or for in-person visits during the pandemic, their future practice intentions, and related factors. DESIGN: Cross-sectional survey. SETTING: Six geographic areas in Toronto, Ont, aligned with Ontario Health Team regions. PARTICIPANTS: Family doctors practising office-based, comprehensive family medicine. MAIN OUTCOME MEASURES: Practice operations in January 2021, use of virtual care, and future plans. RESULTS: Of the 1016 (85.7%) individuals who responded to the survey, 99.7% (1001 of 1004) indicated their practices were open in January 2021, with 94.8% (928 of 979) seeing patients in person and 30.8% (264 of 856) providing in-person care to patients reporting COVID-19 symptoms. Respondents estimated spending 58.2% of clinical care time on telephone visits, 5.8% on video appointments, and 7.5% on e-mail or secure messaging. Among respondents, 17.5% (77 of 439) were planning to close their existing practices in the next 5 years. There were higher proportions of physicians who worked alone in clinics among those who did not see patients in person (27.6% no vs 12.4% yes, P<.05), among those who did not see symptomatic patients (15.6% no vs 6.5% yes, P<.001), and among those who planned to close their practices in the next 5 years (28.9% yes vs 13.9% no, P<.01). CONCLUSION: Most family physicians in Toronto were open to in-person care in January 2021, but almost one-fifth were considering closing their practices in the next 5 years. Policy makers need to prepare for a growing family physician shortage and better understand factors that support recruitment and retention.

Piezo2 channel in nodose ganglia neurons is essential in controlling hypertension in a pathway regulated directly by Nedd4-2.

Baroreflex plays a crucial role in regulation of arterial blood pressure (BP). Recently, Piezo1 and Piezo2, the mechanically-activated (MA) ion channels, have been identified as baroreceptors. However, the underlying molecular mechanism for regulating these baroreceptors in hypertension remains unknown. In this study, we used spontaneously hypertensive rats (SHR) and NG-Nitro-l-Arginine (L-NNA)- and Angiotensin II (Ang II)-induced hypertensive model rats to determine the role and mechanism of Piezo1 and Piezo2 in hypertension. We found that Piezo2 was dominantly expressed in baroreceptor nodose ganglia (NG) neurons and aortic nerve endings in Wistar-Kyoto (WKY) rats. The expression of Piezo2 not Piezo1 was significantly downregulated in these regions in SHR and hypertensive model rats. Electrophysiological results showed that the rapidly adapting mechanically-activated (RA-MA) currents and the responsive neuron numbers were significantly reduced in baroreceptor NG neurons in SHR. In WKY rats, the arterial BP was elevated by knocking down the expression of Piezo2 or inhibiting MA channel activity by GsMTx4 in NG. Knockdown of Piezo2 in NG also attenuated the baroreflex and increased serum norepinephrine (NE) concentration in WKY rats. Co-immunoprecipitation experiment suggested that Piezo2 interacted with Neural precursor cell-expressed developmentally downregulated gene 4 type 2 (Nedd4-2, also known as Nedd4L); Electrophysiological results showed that Nedd4-2 inhibited Piezo2 MA currents in co-expressed HEK293T cells. Additionally, Nedd4-2 was upregulated in NG baroreceptor neurons in SHR. Collectively, our results demonstrate that Piezo2 not Piezo1 may act as baroreceptor to regulate arterial BP in rats. Nedd4-2 induced downregulation of Piezo2 in baroreceptor NG neurons leads to hypertension in rats. Our findings provide a novel insight into the molecular mechanism for the regulation of baroreceptor Piezo2 and its critical role in the pathogenesis of hypertension.

Essential diabetes medicines and health outcomes in 127 countries.

AIM: Diabetes is the ninth leading cause of death. Improving access to diabetes medicines may decrease mortality. Diabetes medicines on national essential medicines lists (NEMLs) vary considerably. We examine the association between diabetes population health outcomes relating to mortality and the listing of diabetes medicines on national essential medicine lists for 127 countries. MATERIALS AND METHODS: We conducted a cross-sectional study. We determined the number of diabetes medicines on NEMLs and used multiple linear regression to analyse the association between diabetes health outcomes and the number of medicines on NEMLs. We used linear regression to assess the association between diabetes health outcomes and the listing of or not listing of medicines that were listed by 25-75% of countries. Diabetes prevalence, gross domestic product (GDP) per capita and mean expenditure per person with diabetes were controlled for in all analyses. RESULTS: The total number of diabetes medicines listed on NEMLs ranged from 0 to 16 (median: 4; interquartile range: 3-6). Diabetes health outcome scores were associated with the number of diabetes medicines on NEMLs [1.3-point increase (95% confidence interval, 95% CI 0.5-2.1) for every additional medicine on NEMLs; P = .002] and GDP per capita [19.5-point increase (95% CI 5.4-33.6) for every 10-fold increase in GDP; P = .003]. Diabetes expenditure was not associated with health outcome scores (P = .23). Increases in diabetes health outcomes score were associated with the listing of glimepiride (7.9-point increase, 95% CI 2.3-13.5, P = .006) and glipizide (5.8-point increase, 95% CI 0.03-11.6, P = .049) on NEMLs. CONCLUSIONS: Listing of diabetes medicines on NEMLs has the potential to improve population health outcomes related to mortality in countries with diverse incomes and diabetes prevalence without necessarily increasing diabetes health expenditure.

The Effect of a Housing First Intervention on Acute Health Care Utilization among Homeless Adults with Mental Illness: Long-term Outcomes of the At Home/Chez-Soi Randomized Pragmatic Trial.

We assessed the effects of the Toronto Site Housing First (HF) intervention on hospitalizations and emergency department (ED) visits among homeless adults with mental illness over 7 years of follow-up. The Toronto Site is part of an unblinded multi-site randomized pragmatic trial of HF for homeless adults with mental illness in Canada, which followed participants up to 7 years. Five hundred seventy-five participants were recruited and classified as having high (HN) or moderate need (MN) for mental health support services. Each group was randomized into intervention (HF) and treatment as usual groups, and 567 (98.6%) consented to link their data to health administrative databases. HF participants received a monthly rent supplement of $600 (Canadian) and assertive community treatment (ACT) support or intensive care management (ICM) support based on need level. Treatment as usual (TAU) participants had access to social, housing, and health services generally available in the community. Outcomes included all-cause and mental health-specific hospitalization, number of days in hospital, and ED visit. We used GEE models to estimate ratio of rate ratios (RRR). The results showed HF with ACT had no significant effect on hospitalization rates among HN participants, but reduced the number of days in hospital (RRR = 0.32, 95% CI 0.16-0.63) and number of ED visits (RRR = 0.57, 95% CI 0.34-0.95). HF with ICM resulted in an increase in the number of hospitalizations (RRR = 1.69, 95% CI 1.09-2.60) and ED visit rates (RRR = 1.42, 95% CI 1.01-2.01) but had no effect in days in hospital for MN participants. Addressing the health needs of this population and reducing acute care utilization remain system priorities. Trial registration: http://www.isrctn.com/identifier: ISRCTN42520374.

The Ontario Integrated Supervised Injection Services Cohort Study of People Who Inject Drugs in Toronto, Canada (OiSIS-Toronto): Cohort Profile.

The Ontario Integrated Supervised Injection Services cohort in Toronto, Canada (OiSIS-Toronto) is an open prospective cohort of people who inject drugs (PWID). OiSIS-Toronto was established to evaluate the impacts of supervised consumption services (SCS) integrated within three community health agencies on health status and service use. The cohort includes PWID who do and do not use SCS, recruited via self-referral, snowball sampling, and community/street outreach. From 5 November 2018 to 19 March 2020, we enrolled 701 eligible PWID aged 18+ who lived in Toronto. Participants complete interviewer-administered questionnaires at baseline and semi-annually thereafter and are asked to consent to linkages with provincial healthcare administrative databases (90.2% consented; of whom 82.4% were successfully linked) and SCS client databases. At baseline, 86.5% of participants (64.0% cisgender men, median ([IQR] age= 39 [33-49]) had used SCS in the previous 6 months, of whom most (69.7%) used SCS for <75% of their injections. A majority (56.8%) injected daily, and approximately half (48.0%) reported fentanyl as their most frequently injected drug. As of 23 April 2021, 291 (41.5%) participants had returned for follow-up. Administrative and self-report data are being used to (1) evaluate the impact of integrated SCS on healthcare use, uptake of community health agency services, and health outcomes; (2) identify barriers and facilitators to SCS use; and (3) identify potential enhancements to SCS delivery. Nested sub-studies include evaluation of "safer opioid supply" programs and impacts of COVID-19.

Associations of resilience with quality of life levels in adults experiencing homelessness and mental illness: a longitudinal study.

BACKGROUND: Homelessness constitutes a traumatic period that adversely impacts health and quality of life outcomes. The potential mitigating effects of resilience on quality of life levels in people experiencing homelessness are underresearched. This study assesses the longitudinal associations between resilience and quality of life scores among adults experiencing homelessness and mental illness. METHODS: This study is a secondary analysis of longitudinal data collected over 6 years from participants (N = 575) of the At Home/Chez Soi study on Housing First, Toronto site. Repeatedly measured resilience scores are the primary exposure and repeatedly measured global quality of life scores and mental health-specific quality of life scores are the primary outcomes. Mixed effect models were used to assess the association between the exposures and the outcomes. RESULTS: The majority of the participants were men (69.2%) and were on average 40.4 (± 11.8) years old at baseline. The average resilience score ranged between 5.00 to 5.62 over 8 data collection points across the 6-year follow-up period. After adjusting for gender, age, ethno-racial background, Housing First intervention, physical and mental comorbidities, and lifetime homelessness, higher resilience scores were positively associated with higher Global quality of life (Adjusted-coefficient: 0.23, 95% CI 0.19-0.27) and mental health-related quality of life values (Adjusted-coefficient: 4.15, 95% CI 3.35-4.95). CONCLUSION: In homeless adults with mental illness, higher resilience levels were positively associated with higher global and mental health related quality of life values. Further interventions and services aimed to enhance resilience mechanisms and strategies are warranted to enhance better mental health and quality of life outcomes of this population group. TRIAL REGISTRATION: At Home/Chez Soi trial was registered with ISRCTN, ISRCTN42520374. Registered 18 September 2009, http://www.isrctn.com/ISRCTN42520374.

Understanding disparities in primary care patient experience.

OBJECTIVE: To understand disparities in primary care patient experience. DESIGN: A serial cross-sectional study was conducted to understand disparities in patient experience at 2 time points (2014 and 2016). Disparities related to age, gender, neighbourhood income, and self-rated health were explored using 3 analytic approaches: stratification, logistic regression, and relative comparison across multiple demographic variables. SETTING: A multisite family health team in Toronto, Ont. PARTICIPANTS: Patients in the family medicine practice who completed e-mail surveys in 2014 (n = 1171, 19% response rate) and 2016 (n = 1823, 15% response rate). MAIN OUTCOME MEASURES: Patient-reported access (timely access when sick, access after hours) and patient-centredness (opportunity to ask questions, involvement in care decisions, enough time with provider). RESULTS: Performance for all measures improved between 2014 and 2016, with the greatest absolute improvement seen in access after hours (61% in 2014; 75% in 2016). Patients residing in low-income neighbourhoods reported worse patient experiences than those in high-income neighbourhoods did, as did patients with poor versus excellent self-rated health, even after adjustment for other variables. For example, in 2016, 60% of patients residing in low-income neighbourhoods reported timely access when sick versus 70% in high-income neighbourhoods (adjusted odds ratio of 0.67, 95% CI 0.47 to 0.95); 60% of patients with poor or fair self-rated health reported timely access when sick versus 72% with excellent self-rated health (adjusted odds ratio of 0.54, 95% CI 0.35 to 0.84). Comparing across demographic groups, patients with excellent self-rated health and poor or fair self-rated health reported the best and worst experiences, respectively, for all measures. In 2016, the average disparity between subgroups was largest for access after hours. CONCLUSION: In this setting, patient experience was worse for patients in lower-income neighbourhoods and those with poor or fair self-rated health. Access after hours demonstrated the greatest overall absolute improvement but also the greatest widening of disparities.

Electronic communication between family physicians and patients: Findings from a multisite survey of academic family physicians in Ontario.

OBJECTIVE: To assess the proportion of academic family physicians using e-mail with patients and to explore related attitudes, barriers, and facilitators. DESIGN: A 47-item questionnaire was created after a literature review, discussions with study team members, pretesting, and pilot testing. The questionnaire was disseminated electronically from June to August 2017. SETTING: Ontario. PARTICIPANTS: All family physicians affiliated with the Department of Family and Community Medicine at the University of Toronto. MAIN OUTCOME MEASURES: Physician practices using e-mail (including barriers to and facilitators of e-mail use with patients), use of e-mail with other health care providers, use of communication technologies other than e-mail, and demographic and practice information. RESULTS: A total of 1553 surveys were disseminated and 865 responses received (56% response rate). Overall, 610 respondents met inclusion criteria. Of these respondents, 43% (265 of 610) personally sent e-mails to patients in a typical week. An additional 21% (126 of 610) reported that they did not personally e-mail patients, but their clinic staff did. Patient convenience and a decrease in the need for telephone communication were the most commonly noted reasons for e-mail use. Facilitators of e-mail use included integration with the electronic medical record, enhanced e-mail access control, security features, and financial compensation. Barriers to e-mail use included privacy and security concerns, concerns about inappropriate e-mail use by patients, and the creation of unrealistic expectations about physician availability. CONCLUSION: E-mail use between academic family physicians and patients was found to be much higher than shown in previous studies of Canadian physicians. This finding might have been owing to unique aspects of academic medicine, remuneration via capitation, or other factors. Efforts to increase physician use of e-mail with patients should address concerns related to privacy and security, electronic medical record integration, and financial compensation.

Cannabidiol inhibits febrile seizure by modulating AMPA receptor kinetics through its interaction with the N-terminal domain of GluA1/GluA2.

Cannabidiol (CBD) is a major phytocannabinoid in Cannabis sativa. CBD is being increasingly reported as a clinical treatment for neurological diseases. Febrile seizure is one of the most common diseases in children with limited therapeutic options. We investigated possible therapeutic effects of CBD on febrile seizures and the underlying mechanism. Use of a hyperthermia-induced seizures model revealed that CBD significantly prolonged seizure latency and reduced the severity of thermally-induced seizures. Hippocampal neuronal excitability was significantly decreased by CBD. Further, CBD significantly reduced the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated evoked excitatory postsynaptic currents (eEPSCs) and the amplitude and frequency of miniature EPSCs (mEPSCs). Furthermore, CBD significantly accelerated deactivation in GluA1 and GluA2 subunits. Interestingly, CBD slowed receptor recovery from desensitization of GluA1, but not GluA2. These effects on kinetics were even more prominent when AMPAR was co-expressed with γ-8, the high expression isoform 8 of transmembrane AMPAR regulated protein (TARPγ8) in the hippocampus. The inhibitory effects of CBD on AMPAR depended on its interaction with the distal N-terminal domain of GluA1/GluA2. CBD inhibited AMPAR activity and reduced hippocampal neuronal excitability, thereby improving the symptoms of febrile seizure in mice. The putative binding site of CBD in the N-terminal domain of GluA1/GluA2 may be a drug target for allosteric gating modulation of AMPAR.

B12-dependent photoresponsive protein hydrogels for controlled stem cell/protein release.

Thanks to the precise control over their structural and functional properties, genetically engineered protein-based hydrogels have emerged as a promising candidate for biomedical applications. Given the growing demand for creating stimuli-responsive "smart" hydrogels, here we show the synthesis of entirely protein-based photoresponsive hydrogels by covalently polymerizing the adenosylcobalamin (AdoB12)-dependent photoreceptor C-terminal adenosylcobalamin binding domain (CarHC) proteins using genetically encoded SpyTag-SpyCatcher chemistry under mild physiological conditions. The resulting hydrogel composed of physically self-assembled CarHC polymers exhibited a rapid gel-sol transition on light exposure, which enabled the facile release/recovery of 3T3 fibroblasts and human mesenchymal stem cells (hMSCs) from 3D cultures while maintaining their viability. A covalently cross-linked CarHC hydrogel was also designed to encapsulate and release bulky globular proteins, such as mCherry, in a light-dependent manner. The direct assembly of stimuli-responsive proteins into hydrogels represents a versatile strategy for designing dynamically tunable materials.

Synthesis and Characterization of Ru-MOFs on Microelectrode for Trace Mercury Detection.

Mercury ions (Hg2+) pollution in the water environment can cause serious harm to human health. Trace Hg2+ detection is of vital importance for environmental monitoring. Herein, we report a novel design of Ru-MOFs modified gold microelectrode for Hg2+ determination. Ru-MOFs are synthesized directly by the cathodic method on gold microelectrode, with the covered area accurately controlled. Cathodic synthesized Ru-MOFs show good conductivity and are suitable to be used as the electrode surface material directly. The synergy of the pre-deposition process and the adsorption process of Ru-MOFs can effectively improves the performance of the sensor. The results show good linearity (R2 = 0.996) from 0.1 ppb to 5 ppb, with a high sensitivity of 0.583 µA ppb-1 mm-2. The limit of detection is found to be 0.08 ppb and the test process is within 6 min. Most importantly, the senor has a good anti-interference ability and the recoveries are satisfactory. This miniature electrochemical sensor has the potential for on-site detection of trace mercury in the field.

Anaplastic lymphoma kinase 5A4 immunohistochemistry as a diagnostic assay in lung cancer: A Canadian reference testing center's results in population-based reflex testing.

BACKGROUND: The presence of anaplastic lymphoma kinase (ALK) rearrangement predicts response to ALK tyrosine kinase inhibitor (TKI) therapy. Fluorescence in situ hybridization (FISH) was the initial reference standard to detect ALK rearrangement, but immunohistochemistry (IHC) using D5F3 has gained acceptance as an alternative diagnostic method. ALK IHC assays using other ALK antibodies have also been used as screening methods, but data supporting their utility as diagnostic tests have not been widely reported. METHODS: Data from reflexive clinical ALK IHC test using the 5A4 clone concurrent with epidermal growth factor receptor (EGFR) mutation testing were analyzed. ALK IHC results were reported as negative (-), equivocal, or positive (+), with equivocal or positive staining validated by FISH break-apart probe testing. Treatment outcomes were reviewed for ALK IHC+ patients. RESULTS: Between 2012 and 2015, 146 (2.5%) cases were reported as ALK IHC+, 188 (3.2%) were reported as equivocal, and 5624 (94.4%) were reported as ALK IHC-. Of the ALK IHC+ cases, 131/143(91.6%) were ALK FISH+. Excluding 6 cases in which FISH was inconclusive or not performed, the positive predictive value was 95.6%, and the negative predictive value was 100%. Most specimens (n = 5352 [89.6%]) were also successfully tested for EGFR. Clinical responses to ALK TKIs were noted in 49 ALK IHC+ patients, with a median progression-free survival of 9.9 months. CONCLUSIONS: ALK 5A4 IHC can serve as a robust diagnostic test for ALK-rearranged lung cancer and is associated with treatment response and survival. Optimized tissue allocation resulted in high success rates of combined reflex EGFR and ALK testing.

Comparison of essential medicines lists in 137 countries.

OBJECTIVE: To compare the medicines included in national essential medicines lists with the World Health Organization's (WHO's) Model list of essential medicines, and assess the extent to which countries' characteristics, such as WHO region, size and health care expenditure, account for the differences. METHODS: We searched the WHO's Essential Medicines and Health Products Information Portal for national essential medicines lists. We compared each national list of essential medicines with both the 2017 WHO model list and other national lists. We used linear regression to determine whether differences were dependent on WHO Region, population size, life expectancy, infant mortality, gross domestic product and health-care expenditure. FINDINGS: We identified 137 national lists of essential medicines that collectively included 2068 unique medicines. Each national list contained between 44 and 983 medicines (median 310: interquartile range, IQR: 269 to 422). The number of differences between each country's essential medicines list and WHO's model list ranged from 93 to 815 (median: 296; IQR: 265 to 381). Linear regression showed that only WHO region and health-care expenditure were significantly associated with the number of differences (adjusted R2 : 0.33; P < 0.05). Most medicines (1248; 60%) were listed by no more than 10% (14) of countries. CONCLUSION: The substantial differences between national lists of essential medicines are only partly explained by differences in country characteristics and thus may not be related to different priority needs. This information helps to identify opportunities to improve essential medicines lists.

Routine collection of sexual orientation and gender identity data: a mixed-methods study.

BACKGROUND: Sexual orientation and gender identity are key social determinants of health, but data on these characteristics are rarely routinely collected. We examined patients' reactions to being asked routinely about their sexual orientation and gender identity, and compared answers to the gender identity question against other data in the medical chart on gender identity. METHODS: We analyzed data on any patient who answered at least 1 question on a routinely administered sociodemographic survey between Dec. 1, 2013, and Mar. 31, 2016. We also conducted semistructured interviews with 27 patients after survey completion. RESULTS: The survey was offered to 15 221 patients and 14 247 (93.6%) responded to at least 1 of the sociodemographic survey questions. Most respondents answered the sexual orientation (90.6%) and gender identity (96.1%) questions. Many patients who had been classified as transgender or gender diverse in their medical chart did not self-identify as transgender, but rather selected female (22.9%) or male (15.4%). In the semistructured interviews, many patients expressed appreciation at the variety of options available, although some did not see their identities reflected in the options and some felt uncomfortable answering the questions. INTERPRETATION: We found a high response rate to questions about sexual orientation and gender identity. Fitting with other research, we suggest using a 2-part question to explore gender identity. Future research should evaluate the acceptability and feasibility of administering these questions in a variety of care settings. These data can help organizations identify health inequities related to sexual orientation and gender identity.

Interactions between Police and Persons Who Experience Homelessness and Mental Illness in Toronto, Canada: Findings from a Prospective Study.

OBJECTIVE: We aimed to describe interactions between police and persons who experience homelessness and serious mental illness and explore whether housing status is associated with police interactions. METHOD: We conducted a secondary analysis of 2008 to 2013 data from the Toronto, Canada, site of the At Home/Chez Soi study. Using police administrative data, we calculated the number and types of police interactions, the proportion of charges for acts of living and administration of justice, and the proportion of occurrences due to victimization, involuntary psychiatric assessment, and suicidal behavior. Using generalized estimating equations, we estimated the odds of police interaction by housing status. RESULTS: This study included 547 adults with mental illness who were homeless at baseline. In the year prior to randomization, 55.8% of participants interacted with police, while 51.7% and 43.0% interacted with police in Study Years 1 and 2, respectively. Of 2,228 charges against participants, 12.6% were due to acts of living and 21.2% were for administration of justice. Of 518 occurrences, 41.1% were for victimization, 45.6% were for mental health assessment, and 22.2% were for suicidal behavior. The odds of any police interaction during the past 90 days was 47% higher for those who were homeless compared to those who were stably housed (95% CI 1.26 to 1.73). CONCLUSIONS: For people who experience homelessness and mental illness in Toronto, Canada, interactions with police are common. The provision of stable housing and changes in policy and practice could decrease harms and increase health benefits associated with police interactions for this population.

Chronic intermittent hypobaric hypoxia provides vascular protection in the aorta of the 2-kidney, 1-clip rat model of hypertension.

Many studies have demonstrated that chronic intermittent hypobaric hypoxia (CIHH) can reduce blood pressure in spontaneously hypertensive rats and renovascular hypertensive (RVH) rats in which endothelial dysfunction is determined as a critical factor. However, whether CIHH can regulate vasodilation of the aorta in RVH rats remains unknown. The purpose of this study was to investigate the effect of CIHH on impaired relaxation of the aorta in the 2-kidney, 1-clip (2K1C) RVH rat model. The results showed CIHH improved the impaired endothelium-dependent relaxation in the 2K1C rat aorta. The endothelial dysfunction was prevented by the p38 antagonist SB203580, but not by the ERK1/2 antagonist PD98059 or JNK antagonist SP600125. Furthermore, the expression of p-eNOS, HIF-1α, and HIF-2α increased while that of p-p38 and BMP-4 decreased in CIHH-treated aortas from 2K1C rats. Finally, the p-eNOS expression was upregulated and the p-p38 expression was downregulated by pre-incubation of SB203580 or the BMP-4 antagonist Noggin with the aorta. CIHH ameliorated the impairment of endothelium-dependent relaxation through upregulating the expression of p-eNOS, which may be mediated by the inhibition of BMP-4/p-p38 MAPK, and upregulating the expression of HIFs in the 2K1C rat aorta.