S100-alarmin-induced innate immune programming protects newborn infants from sepsis.

The high risk of neonatal death from sepsis is thought to result from impaired responses by innate immune cells; however, the clinical observation of hyperinflammatory courses of neonatal sepsis contradicts this concept. Using transcriptomic, epigenetic and immunological approaches, we demonstrated that high amounts of the perinatal alarmins S100A8 and S100A9 specifically altered MyD88-dependent proinflammatory gene programs. S100 programming prevented hyperinflammatory responses without impairing pathogen defense. TRIF-adaptor-dependent regulatory genes remained unaffected by perinatal S100 programming and responded strongly to lipopolysaccharide, but were barely expressed. Steady-state expression of TRIF-dependent genes increased only gradually during the first year of life in human neonates, shifting immune regulation toward the adult phenotype. Disruption of this critical sequence of transient alarmin programming and subsequent reprogramming of regulatory pathways increased the risk of hyperinflammation and sepsis. Collectively these data suggest that neonates are characterized by a selective, transient microbial unresponsiveness that prevents harmful hyperinflammation in the delicate neonate while allowing for sufficient immunological protection.

Functional genomic screens with death rate analyses reveal mechanisms of drug action.

A common approach for understanding how drugs induce their therapeutic effects is to identify the genetic determinants of drug sensitivity. Because 'chemo-genetic profiles' are performed in a pooled format, inference of gene function is subject to several confounding influences related to variation in growth rates between clones. In this study, we developed Method for Evaluating Death Using a Simulation-assisted Approach (MEDUSA), which uses time-resolved measurements, along with model-driven constraints, to reveal the combination of growth and death rates that generated the observed drug response. MEDUSA is uniquely effective at identifying death regulatory genes. We apply MEDUSA to characterize DNA damage-induced lethality in the presence and absence of p53. Loss of p53 switches the mechanism of DNA damage-induced death from apoptosis to a non-apoptotic death that requires high respiration. These findings demonstrate the utility of MEDUSA both for determining the genetic dependencies of lethality and for revealing opportunities to potentiate chemo-efficacy in a cancer-specific manner.

Taming Molecular Folding: Anion-Templated Foldamers with Tunable Quaternary Structures.

Higher-order foldamers represent a unique class of supramolecules at the forefront of molecular design. Herein we control quaternary folding using a novel approach that combines halogen bonding (XBing) and hydrogen bonding (HBing). We present the first anion-templated double helices induced by halogen bonds (XBs) and stabilized by "hydrogen bond enhanced halogen bonds" (HBeXBs). Our findings demonstrate that the number and orientation of hydrogen bond (HB) and XB donors significantly affect the quaternary structure and guest selectivity of two similar oligomers. This research offers new design elements to engineer foldamers and tailor their quaternary structure for specific guest binding.

A phase II study of FOLFOX combined with nab-paclitaxel in the treatment of metastatic or advanced unresectable gastric, gastroesophageal junction adenocarcinoma: a Big Ten Cancer Research Consortium trial.

BACKGROUND: Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability. PATIENTS AND METHODS: Eligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate. RESULTS: The study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each). CONCLUSIONS: FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.

A retrospective study of a novel 3-session rush venom immunotherapy protocol.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment for life-threatening stinging-insect hypersensitivity. Rush VIT protocols allow patients to reach maintenance dosing faster, thus conferring protection sooner. The published protocols vary in dosing regimens, monitoring parameters, and safety profiles. OBJECTIVE: To describe a novel 3-session outpatient rush VIT protocol with full therapeutic dosing achieved at the end of session 3. METHODS: We conducted a retrospective chart review of adult patients treated with rush VIT in an outpatient university allergy/immunology clinic. Demographic and clinical data, including the type of sting reaction, the number of venom allergens, and any systemic reactions (SRs) during VIT, were analyzed. RESULTS: Over a 14-year period, 55 patients (28 females and 27 males) with a median age of 47 years underwent our VIT protocol. A total of 46 patients (84%) tolerated the procedure without SR, and 53 (96%) attained full maintenance dosing. All reactions during rush were Brown anaphylaxis criteria grade 1 or 2. Although the most common venom allergy was yellow jacket, most patients had multiple venom allergies and received therapy with more than 1 venom. Furthermore, 10 patients were re-stung while on maintenance with only 1 patient having a mild SR. CONCLUSION: Our 3-session outpatient rush VIT protocol is effective and safe. Most patients had no SR and attained maintenance dosing. Compared with other 3-session rush protocols, our protocol requires non-invasive monitoring, and patients achieved monthly maintenance dosing immediately on completion.

Generation of nanobodies acting as silent and positive allosteric modulators of the α7 nicotinic acetylcholine receptor.

The α7 nicotinic acetylcholine receptor (nAChR), a potential drug target for treating cognitive disorders, mediates communication between neuronal and non-neuronal cells. Although many competitive antagonists, agonists, and partial-agonists have been found and synthesized, they have not led to effective therapeutic treatments. In this context, small molecules acting as positive allosteric modulators binding outside the orthosteric, acetylcholine, site have attracted considerable interest. Two single-domain antibody fragments, C4 and E3, against the extracellular domain of the human α7-nAChR were generated through alpaca immunization with cells expressing a human α7-nAChR/mouse 5-HT3A chimera, and are herein described. They bind to the α7-nAChR but not to the other major nAChR subtypes, α4ß2 and α3ß4. E3 acts as a slowly associating positive allosteric modulator, strongly potentiating the acetylcholine-elicited currents, while not precluding the desensitization of the receptor. An E3-E3 bivalent construct shows similar potentiating properties but displays very slow dissociation kinetics conferring quasi-irreversible properties. Whereas, C4 does not alter the receptor function, but fully inhibits the E3-evoked potentiation, showing it is a silent allosteric modulator competing with E3 binding. Both nanobodies do not compete with α-bungarotoxin, localizing at an allosteric extracellular binding site away from the orthosteric site. The functional differences of each nanobody, as well as the alteration of functional properties through nanobody modifications indicate the importance of this extracellular site. The nanobodies will be useful for pharmacological and structural investigations; moreover, they, along with the extracellular site, have a direct potential for clinical applications.

Prevalence of probable substance use disorders among children in Ugandan health facilities.

BACKGROUND: Globally, there is a concerning surge in the prevalence of substance use among adolescents and children, creating a substantial public health problem. Despite the magnitude of this issue, accessing healthcare explicitly for substance use remains challenging, even though many substance users frequently visit healthcare institutions for other health-related issues. To address this gap, proactive screening for substance use disorders has emerged as a critical strategy for identifying and engaging patients at risk of substance use. The purpose of this study was to investigate the prevalence of probable alcohol and other substance use disorders, and associated factors, among children aged 6 to 17 years old attending health facilities in Mbale, Uganda. METHODS: We conducted a health facility cross-sectional study, involving 854 children aged 6-17 years. The prevalence of probable alcohol and other substance use disorders was assessed using a validated Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) screening tool. Univariable and multivariable modified Poisson regression analyses were performed using STATA 15 software. RESULTS: The overall prevalence of probable alcohol use disorders (AUD) and other substance use disorders (SUD) was 27.8% (95% CI 1.24-1.31) while that of probable AUD alone was 25.3% (95% CI 1.22-1.28). Peer substance use (APR = 1.24, 95% CI 1.10-1.32), sibling substance use (APR = 1.14, 95% CI 1.06-1.23), catholic caregiver religion (APR = 1.07 95% CI 1.01-1.13), caregiver income of more than $128 (APR = 0.90, 95% CI 0.82-0.98), having no parental reprimand for substance use (APR = 1.05, 95% CI 1.01-1.10) and having no knowledge of how to decline an offer to use substances (APR = 1.06, 95% CI 1.01-1.12) were found to be significantly associated with probable AUD/SUD. CONCLUSIONS: Our findings suggest a high prevalence of probable AUD and SUD among children and adolescents visiting healthcare facilities for other conditions, along with a strong link between AUD and SUD prevalence and social factors. The implication for our healthcare system is to actively screen for and treat these conditions at primary healthcare facilities.

Family pressure and support on young adults' eating behaviors and body image: The role of gender.

Families play a key role in establishing eating habits of children, yet whether families continue to influence eating behaviors of young adults remains an open question. It is also not clear whether associations between family variables (i.e., support and pressure) are similar for adult sons and daughters regarding eating pathology. The present cross-sectional study examined family correlates on disordered eating, body satisfaction, and drive for muscularity. The aim was to examine the associations of family support and family pressure with eating pathology, and to determine whether gender moderated the associations. Among 365 undergraduates (Mage = 18.9 years, 62 % Caucasian, 48 % female), neither family pressure nor family support were significantly associated with the drive for muscularity, whereas both were associated with disordered eating, and family pressure was associated with body satisfaction. Gender moderated the relationship of family pressure and body satisfaction (p = 0.03) and, unexpectedly, the relationship of family support and disordered eating (p = 0.02). Contrary to prediction, family pressure had stronger associations with body satisfaction for men (i.e., men had a more robust association (beta = -0.31, p < .001) than women (beta = -0.19, p = 0.004)). For women, the relationship of family support and disordered eating was not significant (beta = 0.07, p = 0.452); but, was significant for men (beta = -0.25, p < .001). These findings suggest that family pressure and support are associated with eating pathology among young adults, and that in some instances the associations were larger for men, thus highlighting the importance of including men in eating pathology research. Pending replication, these results suggest that family attitudes, behaviors, and support may be necessary topics to address when designing prevention programs for young adults.

Information-theoretic measures of superconductivity in a two-dimensional doped Mott insulator.

A key open issue in condensed-matter physics is how quantum and classical correlations emerge in an unconventional superconductor from the underlying normal state. We study this problem in a doped Mott insulator with information-theory tools on the two-dimensional (2D) Hubbard model at finite temperature with cluster dynamical mean-field theory. We find that the local entropy detects the superconducting state and that the difference in the local entropy between the superconducting and normal states follows the same difference in the potential energy. We find that the thermodynamic entropy is suppressed in the superconducting state and monotonically decreases with decreasing doping. The maximum in entropy found in the normal state above the overdoped region of the superconducting dome is obliterated by superconductivity. The total mutual information, which quantifies quantum and classical correlations, is amplified in the superconducting state of the doped Mott insulator for all doping levels and shows a broad peak versus doping, as a result of competing quantum and classical effects.

Pollen effects in a changing climate: Ragweed pollen exposure and sleepiness in immunotherapy patients of a Southeastern Michigan allergy clinic.

Allergic rhino-conjunctivitis (AR) is a globally relevant health disorder characterized by sneezing, rhinorrhea and sleep disturbance. Ragweed (Ambrosia artemisiifolia) is a plant common to North America and an important allergen. Coarse methods of measuring airborne pollen counts are used to predict seasonal allergy symptoms. This research used a longitudinal study design with a novel, model-based raster of predicted pollen counts to test associations with self-reported symptoms of AR collected from patients receiving immunotherapy for pollen allergies at an allergy clinic. Researchers visited a clinic six times over three weeks. Immunotherapy patients were asked to fill out a brief intake survey on allergic and symptomatic profiles, daytime sleepiness, housing quality, and demographics. Participants responded to a daily, emailed survey on sleepiness and asthma symptoms for 21 days. Using the date and location of responses, ragweed pollen counts were extracted from a prognostic, model based raster (25km pixels). Lag associations of pollen counts with sleepiness were tested using a logistic regression model , adjusted for housing and demographic characteristics, in a distributed lag non-linear model (DLNM) framework. 49 people participated in the study. 26 (52%) were female. The mean age was 37.9 years. Asthma/allergy symptoms were not associated with ragweed pollen but sleepiness was highest two days after exposure (Estimate: 0.33 [0.04,0.62]). Subjects traveled widely during the study period. Intense exposures to ragweed pollen may be associated with daytime sleepiness within small exposure windows. Model-based predicted pollen counts could be used to study health impacts of pollen in people with disease severe enough to receive immunotherapy. Daytime sleepiness can affect productivity and injury risk, and pollen season length and allergenicity may be increasing with climate change. Thus our results may have important implications for population health.

The Effectiveness of Collaborative Advanced Practice Nursing in Primary Hypertension Management: A Randomized Controlled Trial.

BACKGROUND: Hypertension is a global health concern that is best managed at the primary care level. In low- and middle-income countries (LMICs) facing resource constraints, collaboration between well-prepared entry-level advanced practice nurses (APNs) and physicians (medical doctors [MDs]) can enhance the care of patients with primary hypertension. OBJECTIVE: The purpose of this study was to evaluate the effectiveness of collaborative entry-level APNs in primary hypertension management, including patient knowledge, physiological and behavioral outcomes, consultation length, and patient satisfaction. METHODS: Sixty-three eligible patients were randomly assigned to either an entry-level APN intervention group or a control group with MDs. Three master's-prepared nurses, trained in hypertension management, acted as entry-level APNs, following the Joint National Committee guidelines in collaboration with a physician. The control group underwent standard clinic consultations. After 1 month, a mixed analysis of variance was used to assess intervention effectiveness, examining both between-groups and within-groups outcomes. RESULTS: Both groups shared similar sociodemographic and baseline characteristics. Significant improvements in blood pressure, body mass index, knowledge, self-management, and medication adherence were found at the 1-month follow-up, with no significant differences in outcomes or patient satisfaction between the entry-level APN and MD groups. However, clinical consultation time was significantly longer for entry-level APNs than for MDs. CONCLUSIONS: Collaborative entry-level APNs managing primary hypertension are comparable with MD care; however, larger, longer trials are essential for a thorough assessment. Strengthening the development of entry-level advanced practice nursing roles in low- and middle-income countries is crucial for addressing service gaps in primary hypertension and other chronic diseases.

Systematic Evaluation of Regiochemistry and Lipidation of Aryl Trehalose Mincle Agonists.

The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand-receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound 4d, tri-substituted and five carbons long, induced significantly greater levels of interleukin-1ß (IL-1ß), tumor necrosis factor- α (TNF-α), interleukin-23 (IL-23), and interferon- γ (IFN-γ) than the other compounds tested in this study. An in silico assessment of 4d highlighted the capability of this analogue to bind to the human Mincle carbohydrate recognition domain (CRD) efficiently. Together, these data highlight important structure-activity findings regarding Mincle-specific cytokine induction, generating a lead adjuvant candidate for future formulations and immunological evaluations.

3D Mapping of the DMEK Detachment Area from OCT Scans of the Anterior Segment of the Eye - Clinical Applications. / 3D-Kartierung der DMEK-Abhebungsfläche aus OCT-Scans des vorderen Augensegmentes mit klinischen Anwendungen.

Graft detachment is the most common complication after Descemet membrane endothelial keratoplasty (DMEK). To assess the amount of graft detachment, precision is limited when using slit-lamp biomicroscopy. Detachment of DMEK grafts can be assessed automatically on anterior segment optical coherence tomography (AS OCT) images and allows visualization of the area and volume of detachment using 3D maps. This article provides an overview of its applications such as accurately assessing the course of natural graft attachment, identification of potential risk factors for detachment and evaluation of the long-term effect of graft detachment. The 3D map of DMEK detachment may support researchers and clinicians in precise quantification of the area and volume of graft detachment even in large data sets, and the intuitive, fast and reliable evaluation.

Lymphedema is associated with CELSR1 in Phelan-McDermid syndrome.

Lymphedema is a troubling condition present in many disorders including the rare genetic disorder known as Phelan-McDermid syndrome (PMS). The neurobehavioral features of PMS, also known as 22q13.3 deletion syndrome, have been investigated, but little research exists on lymphedema in PMS. In this investigation, clinical and genetic data from 404 people with PMS were reviewed from the PMS-International Registry revealing a prevalence of 5% with lymphedema. Lymphedema was reported in 1 out of 47 people (2.1%) with PMS due to a SHANK3 variant and 19 out of 357 people (5.3%) with PMS due to 22q13.3 deletions. Lymphedema was more common among those in their teens or adulthood (p = 0.0011) and those with deletions >4 Mb. People with lymphedema had significantly larger deletions (mean 5.375 Mb) than those without lymphedema (mean 3.464 Mb, p = 0.00496). Association analysis identified a deletion of the CELSR1 gene to be the biggest risk factor (OR = 12.9 95% CI [2.9-56.2]). Detailed assessment of 5 subjects identified all had deletions of CELSR1, developed symptoms of lymphedema starting at age 8 or older, and typically responded well to standard therapy. In conclusion, this is the largest assessment of lymphedema in PMS to date and our results suggest that individuals with deletions >4 Mb or those with CELSR1 deletions should be assessed for lymphedema.

Raman Probing the Local Ultrastrong Coupling of Vibrational Plasmon Polaritons on Metallic Gratings.

Strong coupling of molecular vibrations with light creates polariton states, enabling control over many optical and chemical properties. However, the near-field signatures of strong coupling are difficult to map as most cavities are closed systems. Surface-enhanced Raman microscopy of open metallic gratings under vibrational strong coupling enables the observation of spatial polariton localization in the grating near field, without the need for scanning probe microscopies. The lower polariton is localized at the grating slots, displays a strongly asymmetric line shape, and gives greater plasmon-vibration coupling strength than measured in the far field. Within these slots, the local field strength pushes the system into the ultrastrong coupling regime. Models of strong coupling which explicitly include the spatial distribution of emitters can account for these effects. Such gratings enable exploration of the rich physics of polaritons, its impact on polariton chemistry under flow conditions, and the interplay between near- and far-field properties through vibrational polariton-enhanced Raman scattering.

How Blackouts during Heat Waves Amplify Mortality and Morbidity Risk.

The recent concurrence of electrical grid failure events in time with extreme temperatures is compounding the population health risks of extreme weather episodes. Here, we combine simulated heat exposure data during historical heat wave events in three large U.S. cities to assess the degree to which heat-related mortality and morbidity change in response to a concurrent electrical grid failure event. We develop a novel approach to estimating individually experienced temperature to approximate how personal-level heat exposure changes on an hourly basis, accounting for both outdoor and building-interior exposures. We find the concurrence of a multiday blackout event with heat wave conditions to more than double the estimated rate of heat-related mortality across all three cities, and to require medical attention for between 3% (Atlanta) and more than 50% (Phoenix) of the total urban population in present and future time periods. Our results highlight the need for enhanced electrical grid resilience and support a more spatially expansive use of tree canopy and high albedo roofing materials to lessen heat exposures during compound climate and infrastructure failure events.

The pregnancy research on inflammation, nutrition, & city environment: systematic analyses study (PRINCESA) cohort, 2009-2015.

The Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses Study (PRINCESA) cohort was set up to evaluate associations between air pollution and birth outcomes among pregnant persons in Mexico City. Specifically, the study was designed to improve air pollution exposure assessment and elucidate biological mechanisms underlying associations between maternal exposures and adverse pregnancy outcomes. Pregnant persons (all women) (N = 935) between ages 18-45 who lived and/or worked in metropolitan Mexico City, Mexico, from 2009 to 2015 and liveborn singleton infants (N = 815) of participants who completed follow-up were enrolled in the cohort. We followed participants monthly from enrollment to delivery and the following categories of data were obtained: demographic, medical and obstetric history, geo-referenced data, repeated measures on daily activity patterns, reported food intake, anthropometric, clinical and obstetric data, 20 serum and 20 cervicovaginal cytokines, and lower reproductive tract infection. Repeated ultrasound measures of fetal parameters and infant birth data are also included in the study's database. In addition, PRINCESA investigators calculated air pollution exposure measures for six pollutants measured by the Mexico City Atmospheric Monitoring System (SIMAT). These estimates utilize participants' addresses to account for spatial variation in exposure (nearest monitor, inverse distance weighting, and kriging) and are available daily during pregnancy for participants. To date, associations between environmental and nutritional impacts on maternal and child health outcomes have been evaluated. PRINCESA has a comprehensive database of maternal and infant data and biological samples and offers collaboration opportunities to study associations between environmental and other factors, including nutrition and pregnancy outcomes.

Health outcomes among offspring of US Coast Guard responders to the Deepwater Horizon oil spill, 2010-2011.

OBJECTIVE: To evaluate the potential for adverse health outcomes among infants born to US Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill disaster. METHODS: Department of Defense Birth and Infant Health Research programme data identified a cohort of singleton infants born 2010-2011 to USCG personnel in the DWH Oil Spill Coast Guard Cohort study. Infants were included if their military parent ('sponsor') responded to the oil spill during a selected reproductive exposure window (ie, 3 months preconception for male sponsors and periconception through pregnancy for female sponsors), or if their sponsor was a non-responder. χ2 tests and multivariable log-binomial regression were used to compare the demographic and health characteristics of infants born to spill responders and non-responders. RESULTS: Overall, 1974 infants with a male sponsor (n=182 responder, n=1792 non-responder) and 628 infants with a female sponsor (n=35 responder, n=593 non-responder) in the DWH Oil Spill Coast Guard Cohort were identified. Health outcomes were similar among the offspring of male responders and non-responders. The frequency of any poor live birth outcome (ie, low birth weight, preterm birth or birth defect) was higher among infants born to female responders (17.1%, n=6) than non-responders (8.9%, n=53); the maternal age-adjusted association was suggestively elevated (risk ratio 1.93, 95% CI 0.89 to 4.16). CONCLUSION: Infant health outcomes were comparable between the offspring of male USCG oil spill responders and non-responders. Findings were limited by the small number of infants identified, particularly among female responders, and should be interpreted with caution.

Impact of lifestyle and socioeconomic position on use of non-steroidal anti-inflammatory drugs: A population-based cohort study.

PURPOSE: Lifestyle and socioeconomic position may confound the link between non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular events, if associated with NSAID use. We examined this association. METHODS: We conducted a cohort study of all adult first-time responders to the Danish National Health Surveys of 2010, 2013, or 2017 without an NSAID prescription within 3 months before survey completion (n = 407 395). Study exposures were weight, smoking status, alcohol consumption, binge drinking frequency, physical activity level, marital status, highest achieved level of education, income, and employment status. We used a Cox model to compute hazard ratios of time to first redemption of an NSAID prescription and a cumulative odds model to compute odds ratios (ORs) of redeeming one additional NSAID prescription in the year after survey completion. RESULTS: Total follow-up time was 1 931 902 years. The odds of redeeming one additional NSAID prescription in the year after survey completion varied within all categories of lifestyle and socioeconomic position. The largest ORs were observed within categories of weight (1.70, 95% CI: 1.65-1.74 for obesity vs. normal weight), smoking status (1.24, 95% CI: 1.21-1.27 for current vs. never use), and education (1.44, 95% CI: 1.39-1.49 for primary or other vs. university or higher education). The Cox model showed consistent results. CONCLUSIONS: Markers of unhealthy lifestyle and low socioeconomic position were associated with initiation and prolonged NSAID use. Consideration of lifestyle and socioeconomic markers as potential confounders in NSAID studies is therefore recommended.