Is nicotine vaping associated with subsequent initiation of cannabis or other substances from adolescence into young adulthood?

Prior studies estimating longitudinal associations between nicotine vaping and subsequent initiation of cannabis and other substances (e.g., cocaine, heroin) have been limited by short follow-up periods, convenience sampling, and possibly inadequate confounding control. We sought to address some of these gaps using the nationally representative Population Assessment of Tobacco and Health Study (PATH) to estimate longitudinal associations between nicotine vaping and the initiation of cannabis or other substances among adolescents transitioning to adulthood from2013 to 2019, adjusting for treatment-confounder feedback. Estimands like the longitudinal average treatment effect were not identified because of extensive practical positivity violations. Therefore, we estimated longitudinal incremental propensity score effects, which were identified. We found that reduced odds of nicotine vaping were associated with decreased risks of cannabis or other substance initiation; these associations strengthened over time. For example, by the final wave (2018-19), cannabis and other substance initiation risks were 6.2 (95%CI:4.6-7.7) and 1.8 (95%CI:0.4-3.2) percentage points lower when odds of nicotine vaping were reduced to be 90% lower in all preceding waves (2013-14 to 2016-18), as compared with observed risks. Strategies to lower nicotine vaping prevalence during this period may have resulted in fewer young people initiating cannabis and other substances.

The role of prescription opioid and cannabis supply policies on opioid overdose deaths.

Mandatory prescription drug monitoring programs and cannabis legalization have been hypothesized to reduce overdose deaths. We examined associations between prescription monitoring programs with access mandates ("must-query PDMPs"), legalization of medical and recreational cannabis supply, and opioid overdose deaths in United States counties in 2013-2020. Using data on overdose deaths from the National Vital Statistics System, we fit Bayesian spatiotemporal models to estimate risk differences and 95% credible intervals (CrI) in county-level opioid overdose deaths associated with enactment of these state policies. Must-query PDMPs were independently associated with on average 0.8 (95% CrI: 0.5, 1.0) additional opioid-involved overdose deaths per 100,000 person-years. Legal cannabis supply was not independently associated with opioid overdose deaths in this time period. Must-query PDMPs enacted in the presence of legal (medical or recreational) cannabis supply were associated with 0.7 (95% CrI: 0.4, 0.9) more opioid-involved deaths, relative to must-query PDMPs without any legal cannabis supply. In a time when overdoses are driven mostly by non-prescribed opioids, stricter opioid prescribing policies and more expansive cannabis legalization were not associated with reduced overdose death rates.

The Combined Relationship of Prescription Drug Monitoring Program Enactment and Medical Cannabis Laws with Chronic Pain-Related Healthcare Visits.

BACKGROUND: U.S. state electronic prescription drug monitoring programs (PDMPs) are associated with reduced opioid dispensing among people with chronic pain and may impact use of other chronic pain treatments. In states with medical cannabis laws (MCLs), patients can use cannabis for chronic pain management, reducing their need for chronic-pain related treatment visits and moderating effects of PDMP laws. OBJECTIVE: Given high rates of chronic pain among Medicaid enrollees, we examined associations between PDMP enactment in the presence or absence of MCL on chronic pain-related outpatient and emergency department (ED) visits. DESIGN: We created annual cohorts of Medicaid enrollees with chronic pain diagnoses using national Medicaid claims data from 2002-2013 and 2016. Negative binomial hurdle models produced adjusted odds ratios (aOR) for the likelihood of any chronic pain-related outpatient or ED visit and incident rate ratios (IRR) for the rate of visits among patients with ≥ 1 visit. PARTICIPANTS: Medicaid enrollees aged 18-64 years with chronic pain (N = 4,878,462). MAIN MEASURES: A 3-level state-year variable with the following categories: 1) no PDMP, 2) PDMP enactment in the absence of MCL, or 3) PDMP enactment in the presence of MCL. Healthcare codes for chronic pain-related outpatient and ED visits each year. KEY RESULTS: The sample was primarily female (67.2%), non-Hispanic White (51.2%), and ages 40-55 years (37.2%). Compared to no-PDMP states, PDMP enactment in the absence of MCL was not associated with chronic pain-related outpatient visits but PDMP enactment in the presence of MCL was associated with lower odds of chronic pain-related outpatient visits (aOR = 0.81, 95% CI:0.71-0.92). PDMP enactment was not associated with ED visits, irrespective of MCL. CONCLUSIONS: During a period of PDMP and MCL expansion, our findings suggest treatment shifts for persons with chronic pain away from outpatient settings, potentially related to increased use of cannabis for chronic pain management.

Changing adolescent activity patterns and the correlation of self-esteem and externalizing mental health symptoms across time: results from the USA from 1991 through 2020.

BACKGROUND: Common adolescent psychiatric symptoms cluster into two dominant domains: internalizing and externalizing. Both domains are linked to self-esteem, which serves as a protective factor against a wide range of internalizing and externalizing problems. This study examined trends in US adolescents' self-esteem and externalizing symptoms, and their correlation, by sex and patterns of time use. METHODS: Using Monitoring the Future data (N = 338 896 adolescents, grades:8/10/12, years:1991-2020), we generated six patterns of time use using latent profile analysis with 17 behavior items (e.g. sports participation, parties, paid work). Groups were differentiated by high/low engagement in sports and either paid work or high/low peer socialization. Within each group, we mapped annual, sex-stratified means of (and correlation between) self-esteem and externalizing factors. We also examined past-decade rates of change for factor means using linear regression and mapped proportions with top-quartile levels of poor self-esteem, externalizing symptoms, or both. RESULTS: We found consistent increases in poor self-esteem, decreases in externalizing symptoms, and a positive correlation between the two across nearly all activity groups. We also identified a relatively constant proportion of those with high levels of both in every group. Increases in poor self-esteem were most pronounced for female adolescents with low levels of socializing, among whom externalizing symptoms also increased. CONCLUSIONS: Rising trends in poor self-esteem are consistent across time use groups, as is the existence of a group facing poor self-esteem and externalizing symptoms. Effective interventions for adolescents' poor self-esteem/co-occurring symptoms are needed broadly, but especially among female adolescents with low peer socialization.

Trends in Nonfatal Overdose Rates Due to Alcohol and Prescription and Illegal Substances in Colombia, 2010‒2021.

Objectives. To examine drug overdoses in Colombia by type of substance, sex, age, and intent using data from a health surveillance system from 2010 to 2021. Methods. We characterized data by year, type of substance, and sociodemographic variables. We calculated age-adjusted overdose rates by substance type, sex, age groups, and intent. We used Poisson regression models to examine trend differences across sex and age groups. Results. Age-adjusted rates of drug overdoses increased from 8.51 to 40.52 per 100 000 during 2010 to 2021. Men, compared with women, had higher overdose rates for every substance, except for opioids and psychotropics. Drug overdose rates involving cannabis and stimulants increased steadily until 2017 but decreased afterward. Overdose rates involving psychotropic medication increased greatly during 2018 to 2021, mainly because of intentional overdoses in young women. Conclusions. Overdoses involving illegal drugs decreased in recent years in Colombia; however, the continuous increase in intentional psychotropic overdose rates highlights the need for prevention efforts to curb this trend. Health surveillance systems are an important tool that can guide overdose prevention efforts in countries with limited data resources. (Am J Public Health. 2024;114(11):1252-1260. https://doi.org/10.2105/AJPH.2024.307786).

TNF blockers alone and associated with Benznidazole impact in vitro cytokine dynamics in chronic Chagas disease.

Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.

Neighborhood and Individual Disparities in Community-Based Naloxone Access for Opioid Overdose Prevention.

Improving access to naloxone for laypersons is a cornerstone of the US strategy to reduce opioid overdose deaths. This study evaluated change in distance to opioid overdose prevention programs (OOPPs) providing walk-in naloxone across two time points. We also explored individual and neighborhood disparities in distance to OOPPs, associations between 2020 OOPP locations and 2018 overdoses, and associations between OOPPs and neighborhood fatal overdose rates. Using fatal opioid overdose locations in 2018 (n = 1167) and 2020 (n = 2045) in New York City, we mapped OOPP locations and fatal overdose locations to visualize areas of unmet naloxone need. We used logistic regression to assess individual (age, sex, race/ethnicity) and neighborhood correlates of odds of an overdose occurring within walking distance (≤ 0.5 miles or 0.8 km) of an OOPP and negative binomial regression to assess the relationship between census tract-level OOPP counts and overdose rates. Distance to OOPPs significantly improved over time, with average distance decreasing by 1.7 miles (2.7 km) (p < 0.001). OOPPs were more likely to be located in neighborhoods with higher poverty in both years and in closer proximity to Latinos in 2020-suggesting improved access for Latinos and in higher poverty neighborhoods. OOPP locations in 2020 were significantly positively associated with overdose locations in 2018. OOPPs were not well-situated in neighborhoods with elevated overdose rates in 2018 but were better situated in 2020, controlling for other neighborhood variables. Community lay naloxone access through OOPPs improved over time and could have promising effects for improved overdose rates in the future.

Recreational cannabis legalization and immigration enforcement: a state-level analysis of arrests and deportations in the United States, 2009-2020.

BACKGROUND: Recreational cannabis laws (RCL) in the United States (US) can have important implications for people who are non-citizens, including those with and without formal documentation, and those who are refugees or seeking asylum. For these groups, committing a cannabis-related infraction, even a misdemeanor, can constitute grounds for status ineligibility, including arrest and deportation under federal immigration policy-regardless of state law. Despite interconnections between immigration and drug policy, the potential impacts of increasing state cannabis legalization on immigration enforcement are unexplored. METHODS: In this repeated cross-sectional analysis, we tested the association between state-level RCL adoption and monthly, state-level prevalence of immigration arrests and deportations related to cannabis possession. Data were from the Transactional Records Access Clearinghouse. Immigration arrest information was available from Oct-2014 to May-2018 and immigration deportation information were available from Jan-2009 to Jun-2020 for. To test associations with RCLs, we fit Poisson fixed effects models that controlled for pre-existing differences between states, secular trends, and potential sociodemographic, sociopolitical, and setting-related confounders. Sensitivity analyses explored potential violations to assumptions and sensitivity to modeling specifications. RESULTS: Over the observation period, there were 7,739 immigration arrests and 48,015 deportations referencing cannabis possession. By 2020, 12 stated adopted recreational legalization and on average immigration enforcement was lower among RCL compared to non-RCL states. In primary adjusted models, we found no meaningful changes in arrest prevalence, either immediately following RCL adoption (Prevalence Ratio [PR]: 0.84; [95% Confidence Interval [CI]: 0.57, 1.11]), or 1-year after the law was effective (PR: 0.88 [CI: 0.56, 1.20]). For the deportation outcome, however, RCL adoption was associated with a moderate relative decrease in deportation prevalence in RCL versus non-RCL states (PR: 0.68 [CI: 0.56, 0.80]; PR 1-year lag: 0.68 [CI: 0.54, 0.82]). Additional analyses were mostly consistent by suggested some sensitivities to modeling specification. CONCLUSIONS: Our findings suggest that decreasing penalties for cannabis possession through state RCLs may reduce some aspects of immigration enforcement related to cannabis possession. Greater attention to the immigration-related consequences of current drug control policies is warranted, particularly as more states weigh the public health benefits and drawbacks of legalizing cannabis.

BRCA1 and BRCA2 germline mutation analysis from a cohort of 1267 patients at high risk for breast cancer in Brazil.

We determined the frequency and mutational spectrum of BRCA1 and BRCA2 in a series of patients at high risk for developing breast cancer from Brazil. A total of 1267 patients were referred for BRCA genetic testing, and no obligation of fulfilling criteria of mutation probability methods for molecular screening was applied. Germline deleterious mutations in BRCA1/2 (i.e., pathogenic/likely pathogenic variants) were identified in 156 out of 1267 patients (12%). We confirm recurrent mutations in BRCA1/2, but we also report three novel mutations in BRCA2, not previously reported in any public databases or other studies. Variants of unknown significance (VUS) represent only 2% in this dataset and most of them were detected in BRCA2. The overall mutation prevalence in BRCA1/2 was higher in patients diagnosed with cancer at age > 35 years old, and with family history of cancer. The present data expand our knowledge of BRCA1/2 germline mutational spectrum, and it is a valuable clinical resource for genetic counseling and cancer management programs in the country.

Changes in Opioid and Benzodiazepine Poisoning Deaths After Cannabis Legalization in the US: A County-level Analysis, 2002-2020.

BACKGROUND: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 SUGGESTION FOR REPHRASING: In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

Cannabis Recreational Legalization and Prevalence of Simultaneous Cannabis and Alcohol Use in the United States.

BACKGROUND: Simultaneous cannabis/alcohol use, using both substances within a short time interval so that their effects overlap, has a greater risk of potential negative consequences than single-substance use and is more common in younger age. Relationships between recreational cannabis laws (RCLs) and changes in simultaneous cannabis/alcohol use prevalence remain untested. OBJECTIVE: To examine trends in simultaneous cannabis/alcohol use from 2008 to 2019, and investigate associations between implementation of RCLs (i.e., presence of active legal dispensaries or legal home cultivation) and simultaneous cannabis/alcohol use in the United States (U.S.). DESIGN: Repeated cross-sectional samples from the 2008-2019 U.S. National Survey on Drug Use and Health (NSDUH). PARTICIPANTS: Respondents (51% female) aged 12 and older. INTERVENTIONS: Changes in simultaneous cannabis/alcohol use before and after RCL implementation (controlling for medical cannabis law implementation) were compared in different age groups (12-20, 21-30, 31-40, 41-50, 51+), using adjusted multi-level logistic regression with state random intercepts and an RCL/age group interaction. MEASUREMENTS: Self-reported simultaneous cannabis/alcohol use. RESULTS: From 2008 to 2019, the overall prevalence of simultaneous cannabis/alcohol use declined among those aged 12-20 but increased in adults aged 21+. Model-based simultaneous cannabis/alcohol use prevalence increased after RCL implementation among respondents aged 21-30 years (+1.2%; aOR= 1.15 [95%CI = 1.04-1.27]), 31-40 years (+1.0; 1.15 [1.04-1.27]), and 41-50 years (+1.75; 1.63 [1.34-1.98]), but not in individuals aged <21 or 51+ years. CONCLUSIONS: Implementation of recreational cannabis policies resulted in increased simultaneous use of cannabis and alcohol, supporting the complementarity hypothesis, but only among adults aged 21+. Efforts to minimize harms related to simultaneous cannabis/alcohol use are critical, especially in states with RCLs. Future studies should investigate cultural norms, perceived harm, and motives related to simultaneous use.

Risks of opioid overdose among New York State Medicaid recipients with chronic pain before and during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic contributed to healthcare disruptions for patients with chronic pain. Following initial disruptions, national policies were enacted to expand access to long-term opioid therapy (LTOT) for chronic pain and opioid use disorder (OUD) treatment services, which may have modified risk of opioid overdose. We examined associations between LTOT and/or OUD with fatal and non-fatal opioid overdoses, and whether the pandemic moderated overdose risk in these groups. METHODS: We analyzed New York State Medicaid claims data (3/1/2019-12/31/20) of patients with chronic pain (N = 236,391). We used generalized estimating equations models to assess associations between LTOT and/or OUD (neither LTOT or OUD [ref], LTOT only, OUD only, and LTOT and OUD) and the pandemic (03/2020-12/2020) with opioid overdose. RESULTS: The pandemic did not significantly (ns) affect opioid overdose among patients with LTOT and/or OUD. While patients with LTOT (vs. no LTOT) had a slight increase in opioid overdose during the pandemic (pre-pandemic: aOR:1.65, 95% CI:1.05, 2.57; pandemic: aOR:2.43, CI:1.75,3.37, ns), patients with OUD had a slightly attenuated odds of overdose during the pandemic (pre-pandemic: aOR:5.65, CI:4.73, 6.75; pandemic: aOR:5.16, CI:4.33, 6.14, ns). Patients with both LTOT and OUD also experienced a slightly reduced odds of opioid overdose during the pandemic (pre-pandemic: aOR:5.82, CI:3.58, 9.44; pandemic: aOR:3.70, CI:2.11, 6.50, ns). CONCLUSIONS: Findings demonstrated no significant effect of the pandemic on opioid overdose among people with chronic pain and LTOT and/or OUD, suggesting pandemic policies expanding access to chronic pain and OUD treatment services may have mitigated the risk of opioid overdose.

HIV stigma and disclosure of alcohol use to physicians: examining the mediating role of depression among persons living with HIV.

Alcohol use among persons living with HIV (PWH) can lead to poor disease outcomes. Disclosure of alcohol consumption to physicians is critical to inform HIV care. HIV stigma is associated with poor care engagement, and this relationship is partially mediated by depression. However, less is known about how HIV stigma and depression affect reporting of alcohol use to care providers. We used baseline data from an HIV intervention trial of 330 adult PWH in Baltimore, MD. We fit a path model to examine whether HIV stigma was associated with increased depression symptoms and whether higher levels of depression were, in turn, associated with underreporting of alcohol use to physicians. Among PWH reporting past 6-month alcohol use (n = 182, 55%), 64% met symptom criteria for probable depression, 58% met criteria for hazardous drinking, and 10% reported not disclosing alcohol use to their physician. HIV stigma was associated with higher levels of depression (ß = 0.99, p < .0001); depression was associated with a lower likelihood of alcohol disclosure (ß = -0.04, p < .0001); and depression mediated the indirect pathway from stigma to alcohol disclosure (ß = -0.04, p < .01). Methods to augment or strengthen alcohol self-report may be useful in HIV care, particularly among PWH experiencing HIV stigma and depression.

Maternal Tobacco Smoking During Pregnancy and Children's Emotional and Behavioral Trajectories: The EDEN Mother-Child Birth Cohort Study.

INTRODUCTION: The nature of the relationship between maternal tobacco smoking during pregnancy and the occurrence of children's behavioral problems is still a matter of controversy. We tested this association using data collected among a sample of pregnant women and their offspring followed up from birth to early adolescence (age 12 years), accounting for multiple parent, child, and family characteristics. AIMS AND METHODS: Data come from 1424 mother-child pairs participating in the Étude des Déterminants pré et post-natals précoces du développement psychomoteur et de la santé de l'ENfant mother-child cohort in France. Using repeated measures (3, 5.5, 8, and 11.5 years) of the mother-reported Strengths and Difficulties Questionnaire, we estimated trajectories of children's emotional and behavioral difficulties. Two aspects of maternal smoking were studied: The timing (nonsmoker, smoking during the periconceptional period, or throughout pregnancy) and the level of use (cigarettes/day) during the first trimester of pregnancy. Robust Poisson regression models controlled for confounding factors including maternal mental health and socioeconomic characteristics using propensity scores with the overlap weighting technique. RESULTS: Contrary to bivariate analyses, in propensity score-controlled regression models, maternal smoking throughout pregnancy was no longer significantly associated with offspring emotional or behavioral difficulties. Maternal heavy smoking (≥10 cigarettes/day) remained significantly associated with intermediate levels of conduct problems (RR 1.25, 95% CI 1.19 to 1.31). CONCLUSIONS: The association between maternal smoking in pregnancy and offspring's emotional and behavioral difficulties appears to be largely explained by women's other characteristics. However, maternal heavy smoking appears to be related to offspring behavioral difficulties beyond the role of confounding characteristics. IMPLICATIONS: The relationship between maternal smoking during pregnancy (in two modalities: Timing and level of smoking) and behavioral difficulties in children is still a matter of debate. While the relationship between any maternal tobacco use and offspring behavioral difficulties appears to be largely explained by confounding factors, heavy maternal smoking in the first trimester of pregnancy seems to be associated with offspring behavioral difficulties beyond the socioeconomic and mental health characteristics transmitted across generations.

Role of monocytes and dendritic cells in cardiac reverse remodelling after cardiac resynchronization therapy.

BACKGROUND AND AIMS: Monocytes and dendritic cells (DC) are both key inflammatory cells, with recognized effects on cardiac repair. However, there are distinct subsets of monocytes with potential for beneficial or detrimental effects on heart failure (HF) pathogenesis. The connection between reverse cardiac remodelling, the potential anti-inflammatory effect of cardiac resynchronization therapy (CRT) and monocytes and DC homeostasis in HF is far from being understood. We hypothesized that monocytes and DC play an important role in cardiac reverse remodelling and CRT response. Therefore, we aimed to assess the potential role of baseline peripheral levels of blood monocytes and DC subsets and their phenotypic and functional activity for CRT response, in HF patients. As a secondary objective, we aimed to evaluate the impact of CRT on peripheral blood monocytes and DC subsets, by comparing baseline and post CRT circulating levels and phenotypic and functional activity. METHODS: Forty-one patients with advanced HF scheduled for CRT were included in this study. The quantification and phenotypic determination of classical (cMo), intermediate (iMo) and non-classical monocytes (ncMo), as well as of myeloid (mDC) and plasmacytoid DC (pDC) were performed by flow cytometry in a FACSCanto™II (BD) flow cytometer. The functional characterization of total monocytes and mDC was performed by flow cytometry in a FACSCalibur flow cytometer, after in vitro stimulation with lipopolysaccharide from Escherichia coli plus interferon (IFN)-γ, in the presence of Brefeldina A. Comparisons between the control and the patient group, and between responders and non-responders to CRT were performed. RESULTS: Compared to the control group, HF population presented a significantly lower frequency of pDC at baseline and a higher proportion of monocytes and mDC producing IL-6 and IL-1ß, both before and 6-months after CRT (T6). There was a remarkable decrease of cMo and an increase of iMo after CRT, only in responders. The responder group also presented higher ncMo values at T6 compared to the non-responder group. Both responders and non-responders presented a decrease in the expression of CD86 in all monocyte and DC populations after CRT. Moreover, in non-responders, the increased frequency of IL-6-producing DC persisted after CRT. CONCLUSION: Our study provides new knowledge about the possible contribution of pDC and monocytes subsets to cardiac reverse remodelling and response to CRT. Additionally, CRT is associated with a reduction on CD86 expression by monocytes and DC subsets and in their potential to produce pro-inflammatory cytokines, contributing, at least in part, for the well described anti-inflammatory effects of CRT in HF patients.

Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy.

BACKGROUND: T cells have been implicated in the development and progression of inflammatory processes in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure (HF) patients. METHODS: Thirty-nine HF patients were evaluated before CRT (T0) and six months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry. RESULTS: T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08 ± 0.50 versus (heart failure patients (HFP)-T0: 0.69 ± 0.40, P = 0.022) and remaining diminished after CRT (HFP-T6: 0.61 ± 0.29, P = 0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52 ± 12.55 versus NR: 24.71 ± 11.66, P = 0.006). After CRT, HF patients presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50 ± 16.62 versus R: 61.47 ± 20.54, P = 0.014; and HG: 40.62 ± 15.36 versus R: 52.39 ± 18.66, P = 0.049, respectively). CONCLUSION: The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response. Even after CRT, it seems that the inflammatory condition underlying CHF continues to evolve with the progression of the disease. This could be due, at least in part, to the inability to restore Treg cells levels. TRIAL REGISTRATION: Observational and prospective study with no trial registration.

Evaluating chronic pain as a risk factor for COVID-19 complications among New York State Medicaid beneficiaries: a retrospective claims analysis.

OBJECTIVE: To assess whether chronic pain increases the risk of COVID-19 complications and whether opioid use disorder (OUD) differentiates this risk among New York State Medicaid beneficiaries. DESIGN, SETTING, AND SUBJECTS: This was a retrospective cohort study of New York State Medicaid claims data. We evaluated Medicaid claims from March 2019 through December 2020 to determine whether chronic pain increased the risk of COVID-19 emergency department (ED) visits, hospitalizations, and complications and whether this relationship differed by OUD status. We included beneficiaries 18-64 years of age with 10 months of prior enrollment. Patients with chronic pain were propensity score-matched to those without chronic pain on demographics, utilization, and comorbidities to control for confounders and were stratified by OUD. Complementary log-log regressions estimated hazard ratios (HRs) of COVID-19 ED visits and hospitalizations; logistic regressions estimated odds ratios (ORs) of hospital complications and readmissions within 0-30, 31-60, and 61-90 days. RESULTS: Among 773 880 adults, chronic pain was associated with greater hazards of COVID-related ED visits (HR = 1.22 [95% CI: 1.16-1.29]) and hospitalizations (HR = 1.19 [95% CI: 1.12-1.27]). Patients with chronic pain and OUD had even greater hazards of hospitalization (HR = 1.25 [95% CI: 1.07-1.47]) and increased odds of hepatic- and cardiac-related events (OR = 1.74 [95% CI: 1.10-2.74]). CONCLUSIONS: Chronic pain increased the risk of COVID-19 ED visits and hospitalizations. Presence of OUD further increased the risk of COVID-19 hospitalizations and the odds of hepatic- and cardiac-related events. Results highlight intersecting risks among a vulnerable population and can inform tailored COVID-19 management.

Mind The Gap: Differences in Alcohol Use Screening And Discussions Among Adults Comparing Asian American And Other Racial And Ethnic Subgroups in the United States, 2015-2019.

AIMS: Asian Americans are the fastest growing racial and ethnic subgroup in the USA but are underrepresented in the alcohol literature, partially due to misconceptions and racial stereotypes. We estimated any alcohol screening/discussions with providers among Asian Americans and other racial and ethnic subgroups and tested associations with alcohol treatment. METHODS: Weighted prevalences of any alcohol screening or discussions with providers included US adults reporting past-year alcohol use and > =1 healthcare visit in the 2015-2019 National Survey on Drug Use and Health (n = 123,002). Multinomial logistic regressions estimated adjusted associations between alcohol use screening/discussions (ref: no screening/discussion) comparing Asian Americans to other racial and ethnic adult subgroups. Among adults with alcohol use disorder (AUD), we estimated adjusted odds of alcohol treatment and perceived treatment need by screening/discussions and racial and ethnic subgroup. RESULTS: Among Asian American adults who reported past-year alcohol use and a healthcare visit, 24.7% reported any screening only and 51.4% discussed alcohol with providers. All racial and ethnic subgroups were more likely than Asian Americans to report alcohol screening/discussions (e.g. white adults, screening adjusted relative risk ratio [aRRR] = 1.48, 95% CI: 1.28-1.72; discussions aRRR = 1.92, 95% CI: 1.74-2.10). AUD treatment use and perceived need were about two times higher among people reporting alcohol discussions. CONCLUSIONS: Asian Americans were less likely to report discussing alcohol with providers than all other racial and ethnic subgroups. Alcohol discussions were associated with treatment use and perceived need. Efforts to increase equitable alcohol screening and discussions with clinicians are needed.

Alcohol use disorders in patients with bipolar disorder: a systematic review and meta-analysis.

Alcohol consumption has a key role in more than 200 diseases and health injuries, being an important factor for social and public health costs. Studies with clinical populations show an association between alcohol use disorders (AUD) and bipolar disorder. In this meta-analysis we included studies, reports, or summaries identified in Google Scholar, Lilacs, Medline, and MedCaribe that reported original data published up to 31 January 2023. We included cross-sectional and longitudinal observational studies that investigated the prevalence of AUD in patients with bipolar disorder. We calculated the prevalence rates and conducted a meta-analysis using a random effects model. The meta-analysis included 20 unique studies conducted in 12 countries, with a total sample of 32,886 individuals with bipolar disorder, comprising 17,923 women and 13,963 men, all aged 18 years or older. The prevalence of AUD in individuals with bipolar disorder was found to be 29.12%, while the prevalence of Alcohol Dependence (AD) was 15.87% and the prevalence of Alcohol Abuse (AA) was 18.74%. The high prevalence of AUD individuals with bipolar disorder is important because it highlights the need for targeted interventions to prevent and address comorbid conditions, which may improve treatment outcomes, reduce harm, and promote public health.