Cluster Analysis of the Highest Users of Medical, Behavioral Health, and Social Services in San Francisco.

BACKGROUND: In the City and County of San Francisco, frequent users of emergent and urgent services across different settings (i.e., medical, mental health (MH), substance use disorder (SUD) services) are referred to as high users of multiple systems (HUMS). While often grouped together, frequent users of the health care system are likely a heterogenous population composed of subgroups with differential management needs. OBJECTIVE: To identify subgroups within this HUMS population using a cluster analysis. DESIGN: Cross-sectional study of HUMS patients for the 2019-2020 fiscal year using the Coordinated Care Management System (CCMS), San Francisco Department of Public Health's integrated data system. PARTICIPANTS: We calculated use scores based on nine types of urgent and emergent medical, MH, and SUD services and identified the top 5% of HUMS patients. Through k-medoids cluster analysis, we identified subgroups of HUMS patients. MAIN MEASURES: Subgroup-specific demographic, comorbidity, and service use profiles. KEY RESULTS: The top 5% of HUMS patients in the study period included 2657 individuals; 69.7% identified as men and 66.5% identified as non-White. We detected 5 subgroups: subgroup 1 (N = 298, 11.2%) who were relatively younger with prevalent MH and SUD comorbidities, and MH services use; subgroup 2 (N = 478, 18.0%), who were experiencing homelessness, with multiple comorbidities, and frequent use of medical services; subgroup 3 (N = 449, 16.9%), who disproportionately self-identified as Black, with prolonged homelessness, multiple comorbidities, and persistent HUMS status; subgroup 4 (N = 690, 26.0%), who were relatively older, disproportionately self-identified as Black, with prior homelessness, multiple comorbidities, and frequent use of medical services; and subgroup 5 (N=742, 27.9%), who disproportionately self-identified as Latinx, were housed, with medical comorbidities and frequent medical service use. CONCLUSIONS: Our study highlights the heterogeneity of HUMS patients. Interventions must be tailored to meet the needs of these diverse patient subgroups.

Coronavirus Disease 2019 Outbreak in a San Francisco Homeless Shelter.

We report the public health response to a coronavirus disease 2019 (COVID-19) outbreak in a San Francisco shelter where 67% of residents and 17% of staff tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the limited utility of case investigation, person-based contact tracing and symptom screening, and the benefits of mass testing in outbreak response.

Comparison of infection control strategies to reduce COVID-19 outbreaks in homeless shelters in the United States: a simulation study.

BACKGROUND: COVID-19 outbreaks have occurred in homeless shelters across the US, highlighting an urgent need to identify the most effective infection control strategy to prevent future outbreaks. METHODS: We developed a microsimulation model of SARS-CoV-2 transmission in a homeless shelter and calibrated it to data from cross-sectional polymerase chain reaction (PCR) surveys conducted during COVID-19 outbreaks in five homeless shelters in three US cities from March 28 to April 10, 2020. We estimated the probability of averting a COVID-19 outbreak when an exposed individual is introduced into a representative homeless shelter of 250 residents and 50 staff over 30 days under different infection control strategies, including daily symptom-based screening, twice-weekly PCR testing, and universal mask wearing. RESULTS: The proportion of PCR-positive residents and staff at the shelters with observed outbreaks ranged from 2.6 to 51.6%, which translated to the basic reproduction number (R0) estimates of 2.9-6.2. With moderate community incidence (~ 30 confirmed cases/1,000,000 people/day), the estimated probabilities of averting an outbreak in a low-risk (R0 = 1.5), moderate-risk (R0 = 2.9), and high-risk (R0 = 6.2) shelter were respectively 0.35, 0.13, and 0.04 for daily symptom-based screening; 0.53, 0.20, and 0.09 for twice-weekly PCR testing; 0.62, 0.27, and 0.08 for universal masking; and 0.74, 0.42, and 0.19 for these strategies in combination. The probability of averting an outbreak diminished with higher transmissibility (R0) within the simulated shelter and increasing incidence in the local community. CONCLUSIONS: In high-risk homeless shelter environments and locations with high community incidence of COVID-19, even intensive infection control strategies (incorporating daily symptom screening, frequent PCR testing, and universal mask wearing) are unlikely to prevent outbreaks, suggesting a need for non-congregate housing arrangements for people experiencing homelessness. In lower-risk environments, combined interventions should be employed to reduce outbreak risk.

Understanding the association between frequent emergency department use and jail incarceration: A cross-sectional analysis.

BACKGROUND: Frequent emergency department (ED) use and incarceration can be driven by underlying structural factors and social needs. If frequent ED users are at increased risk for incarceration, ED-based interventions could be developed to mitigate this risk. The objective of this study was to determine whether frequent ED use is associated with incarceration. METHODS: We conducted a retrospective cross-sectional study of 46,752 individuals in San Francisco Department of Public Health's interagency, integrated Coordinated Care Management System (CCMS) during fiscal year 2018-2019. The primary exposure was frequency of ED visits, and the primary outcome was presence of any county jail incarceration during the study period. We performed descriptive and multivariable analysis to determine the association between the frequency of ED use and jail encounters. RESULTS: The percentage of those with at least one episode of incarceration during the study period increased with increasing ED visit frequency. Unadjusted odds of incarceration increased with ED use frequency: odds ratio (OR) = 2.14 (95% confidence interval [CI] = 1.94-2.35) for infrequent use, OR = 4.98 (95% CI = 4.43-5.60) for those with frequent ED use, and OR = 12.33 (95% CI = 9.59-15.86) for those with super-frequent ED use. After adjustment for observable confounders, the odds of incarceration for those with super-frequent ED use remained elevated at 2.57 (95% CI = 1.94-3.41). Of those with super-frequent ED use and at least one jail encounter, 18% were seen in an ED within 30 days after release from jail and 25% were seen in an ED within 30 days prior to arrest. CONCLUSIONS: Frequent ED use is independently associated with incarceration. The ED may be a site for intervention to prevent incarceration among frequent ED users by addressing unmet social needs.

Mortality Among People Experiencing Homelessness in San Francisco During the COVID-19 Pandemic.

Importance: There has been recent media attention on the risk of excess mortality among homeless individuals during the COVID-19 pandemic, yet data on these deaths are limited. Objectives: To quantify and describe deaths among people experiencing homelessness in San Francisco during the COVID-19 pandemic and to compare the characteristics of these deaths with those in prior years. Design, Setting, and Participants: A cross-sectional study tracking mortality among people experiencing homelessness from 2016 to 2021 in San Francisco, California. All deceased individuals who were homeless in San Francisco at the time of death and whose deaths were processed by the San Francisco Office of the Chief Medical Examiner were included. Data analysis was performed from August to October 2021. Exposure: Homelessness, based on homeless living status in an administrative database. Main Outcomes and Measures: Descriptive statistics were used to understand annual trends in demographic characteristics, cause and manner of death (based on autopsy), substances present in toxicology reports, geographic distribution of deaths, and use of health and social services prior to death. Total estimated numbers of people experiencing homelessness in San Francisco were assessed through semiannual point-in-time counts. The 2021 point-in-time count was postponed owing to the COVID-19 pandemic. Results: In San Francisco, there were 331 deaths among people experiencing homelessness in the first year of the COVID-19 pandemic (from March 17, 2020, to March 16, 2021). This number was more than double any number in previous years (eg, 128 deaths in 2016, 128 deaths in 2017, 135 deaths in 2018, and 147 deaths in 2019). Most individuals who died were male (268 of 331 [81%]). Acute drug toxicity was the most common cause of death in each year, followed by traumatic injury. COVID-19 was not listed as the primary cause of any deaths. The proportion of deaths involving fentanyl increased each year (present in 52% of toxicology reports in 2019 and 68% during the pandemic). Fewer decedents had contacts with health services in the year prior to their death during the pandemic than in prior years (13% used substance use disorder services compared with 20% in 2019). Conclusions and Relevance: In this cross-sectional study, the number of deaths among people experiencing homelessness in San Francisco increased markedly during the first year of the COVID-19 pandemic. These findings may guide future interventions to reduce mortality among individuals experiencing homelessness.

Association of Shelter-in-Place Hotels With Health Services Use Among People Experiencing Homelessness During the COVID-19 Pandemic.

Importance: Some jurisdictions used hotels to provide emergency noncongregate shelter and support services to reduce the risk of COVID-19 infection among people experiencing homelessness (PEH). A subset of these shelter-in-place (SIP) hotel guests were high users of acute health services, and the association of hotel placement with their service use remains unknown. Objective: To evaluate the association of SIP hotel placements with health services use among a subset of PEH with prior high acute health service use. Design, Setting, and Participants: This study used a matched retrospective cohort design comparing health services use between PEH with prior high service use who did and did not receive a SIP hotel placement, from April 2020 to April 2021. The setting was 25 SIP hotels in San Francisco, California, with a daily capacity of 2500 people. Participants included PEH who were among the top 10% high users of acute medical, mental health, and substance use services and who had 3 or more emergency department (ED) visits in the 9 months before the implementation of the SIP hotel program. Data analysis for this study was performed from February 2021 to May 2022. Exposures: SIP hotel placement with on-site supportive services. Main Outcomes and Measures: The primary outcomes were ED visits, hospitalizations and bed days, psychiatric emergency visits, psychiatric hospitalizations, outpatient mental health and substance use visits, and outpatient medical visits. Results: Of 2524 SIP guests with a minimum of 90-day stays, 343 (13.6%) met criteria for high service use. Of 686 participants with high service use (343 SIP group; 343 control), the median (IQR) age was 54 (43-61) years, 485 (70.7%) were male, 283 (41.3%) were Black, and 337 (49.1%) were homeless for more than 10 years. The mean number of ED visits decreased significantly in the high-user SIP group (1.84 visits [95% CI, 1.52-2.17 visits] in the 90 days before SIP placement to 0.82 visits [95% CI, 0.66-0.99 visits] in the 90 days after SIP placement) compared with high-user controls (decrease from 1.33 visits [95% CI, 1.39-1.58 visits] to 1.00 visits [95% CI, 0.80-1.20 visits]) (incidence rate ratio [IRR], 0.60; 95% CI, 0.47-0.75; P < .001). The mean number of hospitalizations decreased significantly from 0.41 (95% CI, 0.30-0.51) to 0.14 (95% CI, 0.09-0.19) for SIP guests vs 0.27 (95% CI, 0.19-0.34) to 0.22 (95% CI, 0.15-0.29) for controls (IRR, 0.41; 95% CI, 0.27-063; P < .001). Inpatient hospital days decreased significantly from a mean of 4.00 (95% CI, 2.44-5.56) to 0.81 (95% CI, 0.40-1.23) for SIP guests vs 2.27 (95% CI, 1.27-3.27) to 1.85 (95% CI, 1.06-2.65) for controls (IRR, 0.25; 95% CI, 0.12-0.54; P < .001), as did psychiatric emergency visits, from a mean of 0.03 (95% CI, 0.01-0.05) to 0.01 (95% CI, 0.00-0.01) visits for SIP guests vs no change in the control group (IRR, 0.25; 95% CI, 0.11-0.51; P < .001). Conclusions and Relevance: These findings suggest that in a population of PEH with high use of acute health services, SIP hotel placement was associated with significantly reduced acute care use compared with high users without a placement.

Analysis of Emergency Department Encounters Among High Users of Health Care and Social Service Systems Before and During the COVID-19 Pandemic.

Importance: Although the general US population had fewer emergency department (ED) visits during the COVID-19 pandemic, patterns of use among high users are unknown. Objectives: To examine natural trends in ED visits among high users of health and social services during an extended period and assess whether these trends differed during COVID-19. Design, Setting, and Participants: This retrospective cohort study combined data from 9 unique cohorts, 1 for each fiscal year (July 1 to June 30) from 2012 to 2021, and used mixed-effects, negative binomial regression to model ED visits over time and assess ED use among the top 5% of high users of multiple systems during COVID-19. Data were obtained from the Coordinated Care Management System, a San Francisco Department of Public Health platform that integrates medical and social information with service use. Exposures: Fiscal year 2020 was defined as the COVID-19 year. Main Outcomes and Measures: Measured variables were age, gender, language, race and ethnicity, homelessness, insurance status, jail health encounters, mental health and substance use diagnoses, and mortality. The main outcome was annual mean ED visit counts. Incidence rate ratios (IRRs) were used to describe changes in ED visit rates both over time and in COVID-19 vs non-COVID-19 years. Results: Of the 8967 participants, 3289 (36.7%) identified as White, 3005 (33.5%) as Black, and 1513 (16.9%) as Latinx; and 7932 (88.5%) preferred English. The mean (SD) age was 46.7 (14.2) years, 6071 (67.7%) identified as men, and 7042 (78.5%) had experienced homelessness. A statistically significant decrease was found in annual mean ED visits among high users for every year of follow-up until year 8, with the largest decrease occurring in the first year of follow-up (IRR, 0.41; 95% CI, 0.40-0.43). However, during the pandemic, ED visits decreased 25% beyond the mean reduction seen in prepandemic years (IRR, 0.75; 95% CI, 0.72-0.79). Conclusions and Relevance: In this study, multiple cohorts of the top 5% of high users of multiple health care systems in San Francisco had sustained annual decreases in ED visits from 2012 to 2021, with significantly greater decreases during COVID-19. Further research is needed to elucidate pandemic-specific factors associated with these findings and understand how this change in use was associated with health outcomes.

Male/Female Differences in the Impact of Caring for Elderly Relatives on Labor Market Attachment and Hours of Work: 1997-2015.

OBJECTIVES: Using representative samples of the Canadian labor market (N = 5,871,850), this study examined male/female differences in the impact of informal care on labor market attachment, and the extent to which differences in labor market participation and employment relationships explained these differences over a 19-year period. METHODS: We examined four outcomes related to labor market impacts associated with caring for elderly relatives: leaving the labor market, working part-time, taking time off work in the previous week, and the amount of time taken off from work. Regression models examined differences between men and women, and the extent to which gendered labor market roles accounted for these differences. RESULTS: We observed an increase in all labor market outcomes over the study period. Women were more likely than men to experience each outcome. Adjusting for labor market role variables did not change these estimates appreciably. After adjustment for differences in labor market roles women were 73% more likely to leave the labor market, more than 5 times more likely to work part-time, and twice as likely to take time off in the last week due to informal care. Further, for temporary absences to provide care, women took an average of 160 min more per week than men. DISCUSSION: Taken together, these results suggest an increasing impact of informal care on labor market participation in Canada between 1997 and 2005, and it remains gendered.

Effect of a Health System-Sponsored Mobile App on Perinatal Health Behaviors: Retrospective Cohort Study.

BACKGROUND: Pregnancy mobile apps are becoming increasingly popular, with parents-to-be seeking information related to their pregnancy and their baby through mobile technology. This increase raises the need for prenatal apps with evidence-based content that is personalized and reliable. Previous studies have looked at whether prenatal apps impact health and behavior outcomes among pregnant and postpartum individuals; however, research has been limited. OBJECTIVE: The primary objective of this study is to assess whether the use of a health system-sponsored mobile app-Circle by Providence-aimed at providing personalized and reliable health information on pregnancy, postpartum recovery, and infant care is associated with improved health outcomes and increased healthy behaviors and knowledge among users. METHODS: This observational study compared app users and app nonusers using a self-reported survey and electronic medical records. The study took place over 18 months and was conducted at Providence St. Joseph Health in Portland, Oregon. The sample included patients who received prenatal care at one of seven Providence clinics and had a live birth at a Providence hospital. Recruitment occurred on a rolling basis and only those who completed the survey were included. Survey respondents were separated into app users and app nonusers, and survey responses and clinical outcomes were compared across groups using univariate and adjusted multivariate logistic regression. RESULTS: A total of 567 participants were enrolled in the study-167 in the app user group and 400 in the nonuser group. We found statistically significant differences between the two groups for certain behavior outcomes: subjects who used the app had 75% greater odds of breastfeeding beyond 6 months postpartum (P=.012), were less likely to miss prenatal appointments (P=.046), and were 50% more likely to exercise 3 or more times a week during pregnancy (P=.04). There were no differences in nutritional measures, including whether they took prenatal vitamins, ate 5 fruits or vegetables a day, or drank caffeine. We found no differences in many of the infant care outcomes; however, there was an increase in awareness of "purple crying." Finally, there were no significant differences in measured clinical health outcomes, including cesarean births, length of hospital stays (in minutes), low birth weight infants, preterm births, small-for-gestational-age births, large-for-gestational-age births, and neonatal intensive care unit stays. CONCLUSIONS: The use of the Circle app, which provides access to personalized and evidence-based health information, was associated with an increase in certain healthy behaviors and health knowledge, although there was no impact on clinical health outcomes. More research is needed to determine the impact of mobile prenatal apps on healthy pregnancies, clinical health outcomes, and infant care.

Frequent Emergency Department Users: Focusing Solely On Medical Utilization Misses The Whole Person.

Frequent emergency department (ED) users often have complex behavioral health and social needs. However, policy makers often focus on this population's medical system use without examining its use of behavioral health and social services systems. To illuminate the wide-ranging needs of frequent ED users, we compared medical, mental health, substance use, and social services use among nonelderly nonfrequent, frequent, and superfrequent ED users in San Francisco County, California. We linked administrative data for fiscal years 2013-15 for beneficiaries of the county's Medicaid managed care plan to a county-level integrated data system. Compared to nonfrequent users, frequent users were disproportionately female, white or African American/black, and homeless. They had more comorbidities and annual outpatient mental health visits (11.93 versus 4.16), psychiatric admissions (0.73 versus 0.07), and sobering center visits (0.17 versus <0.01), as well as disproportionate use of housing and jail health services. Our findings point to the need for shared knowledge across domains, at the patient and population levels. Integrated data can serve as a systems improvement tool and help identify patients who might benefit from coordinated care management. To deliver whole-person care, policy makers should prioritize improvements in data sharing and the development of integrated medical, behavioral, and social care systems.

Assessing a ban on the use of UV tanning devices among adolescents in Ontario, Canada: first-year results.

OBJECTIVES: To describe the effect of the first year of a ban on UV tanning device (beds, lamps) use among those under 18 years of age in Ontario, Canada. METHODS: Online questionnaires were completed by adolescents in grades 7 to 12, aged less than 18 years: one when the ban was enacted (May 2014) and a second a year later (May 2015). Questionnaires asked grade, age, sex, and about use of UV tanning devices in the previous year. Recent users were asked about length, frequency, and location of use; service refusals and reasons; awareness of signs/warning labels; and use of eye protection. Weighted estimates and confidence intervals were generated. RESULTS: There were 1561 participants in 2014 and 2305 in 2015. No reduction was observed in UV tanning device use (6.9% vs. 7.9%) in the 12 months preceding the survey. In 2015, most respondents used UV tanning devices in beauty establishments, which was a shift away from gyms and fitness centres as seen in 2014. Non-significant increases occurred in the proportions noticing warning signs/labels (57% vs. 71%), required to wear eye protection (92% vs. 99%), and refused service (17% vs. 21%). Most adolescents who were refused service did not use tanning devices that year (72%). CONCLUSION: Use did not change in the year following enactment of a ban on UV tanning devices among youth in Ontario. The ban did lead to improvements in service refusal, awareness of warning signage, and use of eye protection. As service refusal deterred future use, enhanced enforcement is important.

Cancer risk factors and screening in First Nations in Ontario. / Facteurs de risque et dépistage du cancer chez les Premières Nations en Ontario.

INTRODUCTION: A lack of identifiers in health administrative databases limits our understanding of the cancer burden in First Nations. This study compares cancer risk factors and screening between First Nations in Ontario (on and off reserve) and non-Aboriginal Ontarians using two unique health surveys. METHODS: We measured age-standardized prevalence estimates using the First Nations Regional Health Survey (RHS) Phase 2, 2008/10 (for First Nations on reserve) and the Canadian Community Health Survey (CCHS), 2007-2013 (for First Nations off reserve and non-Aboriginal Ontarians). We used prevalence rate ratios (RR) and Pearson's chisquare tests for differences in proportions to compare estimates between First Nations (on and off reserve) and non-Aboriginal Ontarians. RESULTS: A higher proportion of First Nation men, women and adolescents on reserve smoked (RR = 1.97, 2.78 and 7.21 respectively) and were obese (RR = 1.73, 2.33 and 3.29 respectively) compared to their non-Aboriginal counterparts. Similar patterns were observed for First Nations off reserve. Frequent binge drinking was also more prevalent among First Nation men and women living on reserve (RR = 1.28 and 2.22, respectively) and off reserve (RR = 1.70 and 1.45, respectively) than non-Aboriginal Ontarians. First Nation men and women on reserve were about half as likely to consume fruit at least twice per day and vegetables at least twice per day compared to non-Aboriginal men and women (RR = 0.53 and 0.54, respectively). Pap test uptake was similar across all groups, while First Nation women on reserve were less likely to have had a mammogram in the last five years than non-Aboriginal women (RR = 0.85). CONCLUSION: First Nations, especially those living on reserve, have an increased risk for cancer and other chronic diseases compared to non-Aboriginal Ontarians. These results provide evidence to support policies and programs to reduce the future burden of cancer and other chronic diseases in First Nations in Ontario.

INTRODUCTION: L'absence d'identificateurs, dans les bases de données administratives sur la santé, nous empêche de bien comprendre le fardeau du cancer chez les Premières Nations. Notre étude compare les facteurs de risque et le dépistage du cancer chez les membres des Premières Nations en Ontario (vivant dans des réserves et hors réserves) et chez les Ontariens non autochtones, en s'appuyant sur deux enquêtes sur la santé. MÉTHODOLOGIE: L'absence d'identificateurs, dans les bases de données administratives sur la santé, nous empêche de bien comprendre le fardeau du cancer chez les Premières Nations. Notre étude compare les facteurs de risque et le dépistage du cancer chez les membres des Premières Nations en Ontario (vivant dans des réserves et hors réserves) et chez les Ontariens non autochtones, en s'appuyant sur deux enquêtes sur la santé. RÉSULTATS: Une proportion plus élevée d'hommes, de femmes et d'adolescents des Premières Nations vivant dans des réserves fumaient (RT = 1,97, 2,78 et 7,21 respectivement) et souffraient d'obésité (RT = 1,73, 2,33 et 3,29 respectivement), comparativement à leurs homologues non autochtones. Des tendances similaires ont été observées chez les membres des Premières Nations vivant hors réserves. La consommation excessive ponctuelle d'alcool fréquente était également plus répandue chez les hommes et les femmes des Premières Nations vivant dans des réserves (RT = 1,28 et 2,22, respectivement) et hors réserves (RT = 1,70 et 1,45, respectivement) que chez les Ontariens non autochtones. Les hommes et les femmes des Premières Nations vivant dans des réserves étaient deux fois moins susceptibles de consommer des fruits au moins deux fois par jour et des légumes au moins deux fois par jour que les hommes et les femmes non autochtones (RT = 0,53 et 0,54, respectivement). La participation au test de Pap était similaire dans tous les groupes, mais les femmes des Premières Nations étaient moins susceptibles que les femmes non autochtones (RT = 0,85) d'avoir subi une mammographie au cours des cinq années précédant l'enquête. CONCLUSION: Comparativement aux Ontariens non autochtones, les membres des Premières Nations, en particulier ceux qui vivent dans une réserve, présentent un risque accru de cancer et d'autres maladies chroniques. Ces résultats fournissent des éléments probants à l'appui de politiques et de programmes visant à réduire le fardeau futur du cancer et d'autres maladies chroniques chez les Premières Nations en Ontario.

Noradrenaline acting on astrocytic ß2-adrenoceptors induces neurite outgrowth in primary cortical neurons.

The neurotransmitter noradrenaline (NA) has anti-inflammatory properties and promotes expression of neurotrophic factors in the central nervous system (CNS) via activation of glial adrenoceptors. Here we examined the ability of conditioned media (CM) from NA-treated glial cells to impact upon neuronal complexity. Primary rat cortical neurons were treated either directly with NA (1-10 µM), or treated with CM from NA-stimulated primary mixed glial cells. Neuronal complexity was assessed using Sholl analysis. Exposure of neurons to CM from NA-stimulated glial cells increased all indices of neuronal complexity, whereas direct exposure of neurons to NA did not. CM from NA-stimulated astrocytes, but not microglia, also increased neuronal complexity indicating a key role for astrocytes. The ß-adrenergic subtype was implicated in this response as the increase was blocked by the ß-adrenoceptor antagonist propanolol, but not by the α-adrenoceptor antagonist phentolamine. CM from glial cells treated with the ß2-adrenoceptor agonists salmeterol and clenbuterol, but not the ß1-adrenoceptor agonist xamoterol, mimicked the ability of NA to increase neuronal complexity. NA induced expression of a range of growth factors (BDNF, NGF-ß, GDNF, FGF-2 and IL-6) in glial cells. In addition to this, the phosphatidylinositol 3-kinase (PI3K), mitogen activated protein kinase (MAPK) and JAK-STAT signalling pathways are implicated in NA CM-induced neuritic growth as inhibition of these pathways attenuated NA CM-induced neuritic growth. In conclusion, this study indicates a novel role for NA acting at glial ß2-adrenoceptors to induce neuritic growth through the expression of soluble factors that elicit a neurotrophic action and increase neuronal complexity.