Physical health disparities and severe mental illness: A longitudinal comparative cohort study using hospital data in Northern Ireland

Abstract Background People with severe mental illness (SMI) die prematurely, mostly due to preventable causes. Objective To examine multimorbidity and mortality in people living with SMI using linked administrative datasets. Method Analysis of linked electronically captured routine hospital administrative data from Northern Ireland (2010–2021). We derived sex-specific age-standardised rates for seven chronic life-limiting physical conditions (chronic kidney disease, malignant neoplasms, diabetes mellitus, chronic obstructive pulmonary disease, chronic heart failure, myocardial infarction, and stroke) and used logistic regression to examine the relationship between SMI, socio-demographic indicators, and comorbid conditions; survival models quantified the relationship between all-cause mortality and SMI. Results Analysis was based on 929,412 hospital patients aged 20 years and above, of whom 10,965 (1.3%) recorded a diagnosis of SMI. Higher likelihoods of an SMI diagnosis were associated with living in socially deprived circumstances, urbanicity. SMI patients were more likely to have more comorbid physical conditions than non-SMI patients, and younger at referral to hospital for each condition, than non-SMI patients. Finally, in fully adjusted models, SMI patients had a twofold excess all-cause mortality. Conclusion Multiple morbidities associated with SMI can drive excess mortality. While SMI patients are younger at referral to treatment for these life-limiting conditions, their relatively premature death suggests that these conditions are also quite advanced. There is a need for a more aggressive approach to improving the physical health of this population

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Differences in African-American Maternal Self-Efficacy Regarding Practices Impacting Risk for Sudden Infant Death.

BACKGROUND: Sudden Infant Death Syndrome (SIDS) and other sleep-related deaths, including accidental suffocation, account for ~4000 U.S deaths annually. Parents may have higher self-efficacy with regards to preventing accidental suffocation than SIDS. OBJECTIVE: To assess self-efficacy in African-American mothers with regards to safe sleep practices and risk for SIDS and accidental suffocation. METHODS: As part of randomized clinical trial in African-American mothers of newborn infants, mothers completed a baseline survey about knowledge of and attitudes towards safe sleep recommendations, current intent, self-efficacy, and demographics. Tabular and adjusted, regression-based analyses of these cross-sectional data evaluated the impact of the message target (SIDS risk reduction vs suffocation prevention) on perceived self-efficacy. RESULTS: 1194 mothers were interviewed. Mean infant age was 1.5 days. 90.8% of mothers planned to place their infant supine, 96.7% stated that their infant would sleep in the same room, 3.6% planned to bedshare with the infant, and 72.9% intended to have soft bedding in the crib. Mothers were more likely to believe that prone placement (70.9% vs. 50.5%, p<0.001), bedsharing (73.5% vs. 50.1%, p<0.001), and having soft bedding in the sleep area (78.3% vs. 59.5%, p<0.001) increased their infant’s risk for suffocation than it did for SIDS. Mothers had higher self-efficacy, viz. increased confidence that their actions could keep their infant safe, with regards to suffocation than SIDS (88.0% vs. 79.4%, p<0.001). These differences remained significant when controlled for sociodemographics, grandmother in home, number of people in home, and breastfeeding intention. CONCLUSION: Maternal self-efficacy is higher with regards to prevention of accidental suffocation in African-Americans, regardless of sociodemographics. Healthcare professionals should discuss both SIDS risk reduction and prevention of accidental suffocation when advising African-American parents about safe sleep practices

Health Messaging and African-American Infant Sleep Location: A Randomized Controlled Trial.

BACKGROUND: Infant-parent bedsharing increases the risk of SIDS and other sleep-related deaths. Despite AAP recommendations to avoid bedsharing, public health efforts have been unsuccessful in changing behaviors. African-American infants are more than twice as likely to die from SIDS and other sleep-related deaths, and are also twice as likely to bedshare with their parents. Further, African-American parents have a high degree of self-efficacy with regards to preventing infant suffocation, but low self-efficacy with regards to SIDS risk reduction. It is unclear whether messages emphasizing suffocation prevention will decrease bedsharing. OBJECTIVES: To evaluate the impact of specific health messages on African-American parental decisions regarding infant sleep location. METHODS: We conducted a randomized, controlled trial of African-American mothers of infants. The control group received standard messaging emphasizing AAP-recommended safe sleep practices, including avoidance of bedsharing, for the purposes of SIDS risk reduction. The intervention group received enhanced messaging emphasizing safe sleep practices, including avoidance of bedsharing, for both SIDS risk reduction and suffocation prevention. Participants completed interviews at 2–3 weeks, 2–3 months, and 5–6 months after the infant’s birth. RESULTS: 1194 mothers were enrolled in the study, and 637 completed all interviews. Bedsharing, both usually (aOR 1.005 [95% CI 1.003, 1.006]) and last night (aOR 1.004 [95% CI 1.002, 1.007]) increased slightly but statistically significantly with infant age (p<0.001). Receipt of the enhanced message did not impact on sleep location. Maternal belief that bedsharing increased the risk of SIDS or suffocation declined over 6 months (p<0.001) and did not differ by group assignment. CONCLUSION: African-American mothers who received an enhanced message about SIDS risk reduction and suffocation prevention were no less likely to bedshare with their infants

Messaging Affects the Behavior of African American Parents with Regards to Soft Bedding in the Infant Sleep Environment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the impact of specific health messages on the decisions of African American parents regarding soft bedding use, specifically related to the high degree of self-efficacy that African American parents have with regards to preventing infant suffocation vs low self-efficacy with regards to sudden infant death syndrome (SIDS) risk reduction. STUDY DESIGN: We conducted a randomized, controlled clinical trial of African American mothers of infants. The control group received standard messaging emphasizing safe sleep practices recommended by the American Academy of Pediatrics for the purposes of SIDS risk reduction. The intervention group received enhanced messaging emphasizing safe sleep practices for both SIDS risk reduction and suffocation prevention. Participants completed interviews at 2–3 weeks, 2–3 months, and 5–6 months after the infant’s birth. RESULTS: Of 1194 mothers enrolled, 637 completed all interviews. The use of soft bedding both in the past week and last night declined with age (P < .001). Infants in the enhanced group had a lower rate of use of soft bedding in the past week (P = .006) and last night (P = .013). Mothers who received the enhanced message were more likely to state that they avoided soft bedding to protect their infant from suffocation. CONCLUSIONS: African American mothers who receive an enhanced message about SIDS risk reduction and suffocation prevention are less likely to use soft bedding in their infant’s sleep environment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01361880