Association between a diagnosis of diabetes mellitus and smoking abstinence: An analysis of the National Health Interview Survey.

OBJECTIVE: Both diabetes and smoking significantly increase the risk of cardiovascular disease (CVD). Understanding whether a diagnosis of diabetes can be leveraged to promote smoking cessation is a gap in the literature. METHODS: We used data from the US National Health Interview Survey, 2006 to 2018, to investigate the relationship between self-report of diagnosis of diabetes and subsequent smoking abstinence among 142,884 respondents who reported regular smoking at baseline. Effect sizes were presented as hazard ratios (HRs) derived from multivariable Cox regression models adjusted for potential confounders using diabetes as a time-dependent covariate. Subgroup-specific estimates were obtained using interaction terms between diabetes and variables of interest. RESULTS: A self-reported diagnosis of diabetes was associated with smoking abstinence (HR: 1.21; 95% CI: 1.16 to 1.27). The strength of the association varied based on race (P for interaction: 0.004), where it was strongest in African Americans (HR: 1.44; 95% CI: 1.29 to 1.60); income (P for interaction <0.001), where it was strongest in those with a yearly income less than $35,000 (HR: 1.45; 95% CI: 1.36 to 1.53); and educational attainment (P for interaction <0.001), where it was strongest in those who did not attend college (HR: 1.48; 95% CI: 1.40 to 1.57). CONCLUSION: Among adults who smoke, a diagnosis of diabetes is significantly associated with subsequent smoking abstinence. The association is strongest in socially disadvantaged demographics, including African Americans, low-income individuals, and those who did not attend college.

Evaluating strategies to recruit health researchers to participate in online survey research.

BACKGROUND: Engaging researchers as research subjects is key to informing the development of effective and relevant research practices. It is important to understand how best to engage researchers as research subjects. METHODS: A 24 factorial experiment, as part of a Multiphase Optimization Strategy, was performed to evaluate effects of four recruitment strategy components on participant opening of an emailed survey link and survey completion. Participants were members of three US-based national health research consortia. A stratified simple random sample was used to assign potential survey participants to one of 16 recruitment scenarios. Recruitment strategy components were intended to address both intrinsic and extrinsic sources of motivation, including: $50 gift, $1,000 raffle, altruistic messaging, and egoistic messaging. Multivariable generalized linear regression analyses adjusting for consortium estimated component effects on outcomes. Potential interactions among components were tested. Results are reported as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). RESULTS: Surveys were collected from June to December 2023. A total of 418 participants were included from the consortia, with final analytical sample of 400 eligible participants. Out of the final sample, 82% (341) opened the survey link and 35% (147) completed the survey. Altruistic messaging increased the odds of opening the survey (aOR 2.02, 95% CI: 1.35-2.69, p = 0.033), while egoistic messaging significantly reduced the odds of opening the survey (aOR 0.56, 95%CI 0.38-0.75, p = 0.08). The receipt of egoistic messaging increased the odds of completing the survey once opened (aOR 1.81, 95%CI: 1.39-2.23, p < 0.05). There was a significant negative interaction effect between the altruistic appeal and egoistic messaging strategies for survey completion outcome. Monetary incentives did not a have a significant impact on survey completion. CONCLUSION: Intrinsic motivation is likely to be a greater driver of health researcher participation in survey research than extrinsic motivation. Altruistic and egoistic messaging may differentially impact initial interest and survey completion and when combined may lead to improved rates of recruitment, but not survey completion. Further research is needed to determine how to best optimize message content and whether the effects observed are modified by survey burden.

Switching to e-cigarettes as harm reduction among individuals with chronic disease who currently smoke: Results of a pilot randomized controlled trial.

INTRODUCTION: E-cigarettes (ECs) may be an effective harm reduction strategy for individuals with conditions like chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), and peripheral arterial disease (PAD) who smoke combustible cigarettes (CCs). Our aim was to examine how individuals with chronic conditions transition from CCs to ECs and its impact on health outcomes. METHODS: In a pilot randomized controlled trial (RCT), patients with COPD, asthma, CAD/PAD who currently smoke CCs and have not used nicotine replacement therapy (NRT) or ECs in the past 14 days were randomized to receive ECs or combination NRT with behavioral counselling. Disease symptoms, acceptability/satisfaction (TSQM-9) and feasibility, and cigarettes per day (CPD), and/or EC use were collected at baseline, 3-, and 6-months. Descriptive statistics and a linear regression were conducted to explore changes in CPD and chronic condition-specific assessments (CAT, SAQ-7, ACT) that assess COPD, asthma, and CAD/PAD symptom change. RESULTS: At 3-months, the EC group (n=63, mean CPD=9±11) reduced their CPD by 54% vs. 60% in the NRT group (n=58, mean CPD=7±6), p=0.56. At 6-months, 17.5% had switched completely to ECs while 23% quit smoking in the NRT arm. CAT scores showed a significant 6-point reduction in the EC arm (p=0.03). Participants scored an average of 69±27 for EC effectiveness, 87±23 for convenience, and 75±27 for overall satisfaction. CONCLUSIONS: This pilot study suggests that ECs may be a safer alternative for chronic condition patients using CCs and warrants further research on expected smoking cessation/reduction among individuals who use ECs. IMPLICATIONS: The findings from this pilot RCT hold significant implications with chronic conditions such as COPD, asthma, CAD and PAD who smoke CCs. The observed reduction in cigarettes per day and improvement in respiratory symptoms suggest that switching to ECs appears feasible and acceptable among those with chronic diseases. These results suggest that ECs may offer an alternative for individuals struggling to quit CC smoking through existing pharmacotherapies. This study supports further exploration of switching to ECs as a harm reduction strategy among CC users who have been unsuccessful at quitting by other means.

Prevalence and factors associated with second hand smoke exposure among a sample of pregnant women in Cairo, Egypt.

PURPOSE: This study estimated the prevalence of and factors associated with secondhand smoke (SHS) exposure, and assessed attitudes and knowledge about SHS among pregnant women in Cairo, Egypt. METHODS: Pregnant women in the third trimester were recruited to participate in a survey assessing tobacco smoking and SHS exposure during their current pregnancy. Participants were recruited from three antenatal clinics in Cairo, Egypt, from June 2015 to May 2016. We examined differences in sociodemographic characteristics and SHS exposure, attitudes, and knowledge by smoking/SHS status. We used multivariable ordinary least squares regression to examine the association between husbands' smoking and pregnant women's mean daily hours of SHS exposure, adjusting for women's smoking status, age group, education, and urban (vs. suburban/rural) residence. RESULTS: Of two hundred pregnant women aged 16-37 years, about two-thirds (69%) had a husband who smoked tobacco. During their current pregnancy, most women reported being non-smokers (71%), and 38% of non-smokers reported being SHS-exposed. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. In adjusted analyses, having a husband who smoked was significantly associated with a greater mean number of hours of SHS exposure per day exposed, and this difference was driven by husbands who smoked in the home (p < 0.001). Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. CONCLUSION: Among our sample of pregnant women in Cairo, Egypt, there was a high rate of SHS exposure as well as misconceptions about the safety of SHS exposure to a developing fetus. Our findings suggest a need for targeted education and gender-sensitive messaging about SHS exposure, along with improved enforcement of existing tobacco control policies.

Exposure to secondhand smoke (SHS) remains a major contributor to health problems in pregnant women and their children. Using a survey, this study sought to estimate how many pregnant women in Cairo Metropolitan Area, Egypt, were exposed to SHS and the factors contributing to that exposure, and to assess attitudes towards SHS. During their current pregnancy, 38% of non-smokers reported being exposed to SHS. Non-smokers exposed to SHS tended to live in more rural areas and have husbands who smoked in the home. Having a husband who smoked as well as a husband who smoked in the home was significantly associated with a greater average number of SHS exposure hours per day. Women in the SHS-exposed group were less likely than other groups to agree that SHS exposure was harmful to their own or their future child's health; however, all groups agreed that SHS was harmful to newborn health. Among pregnant women in Cairo, Egypt, there is a high rate of SHS exposure­often driven by SHS exposure in the home­as well as misconceptions about the safety of SHS exposure to a developing fetus. There is a need for targeted education and gender-sensitive messaging about SHS exposure along, with improved enforcement of existing tobacco control policies.

Considerations for using predictive models that include race as an input variable: The case study of lung cancer screening.

Indiscriminate use of predictive models incorporating race can reinforce biases present in source data and lead to an exacerbation of health disparities. In some countries, such as the United States, there is therefore a push to remove race from prediction models; however, there are still many prediction models that use race as an input. Biomedical informaticists who are given the responsibility of using these predictive models in healthcare environments are likely to be faced with questions like how to deal with race covariates in these models. Thus, there is a need for a pragmatic framework to help model users think through how to include race in their chosen model so as to avoid inadvertently exacerbating disparities. In this paper, we use the case study of lung cancer screening to propose a simple framework to guide how model users can approach the use (or non-use) of race inputs in the predictive models they are tasked with leveraging in electronic health records and clinical workflows.

Inhibition Predicts the Course of Depression and Anxiety Symptoms Among Adolescents: The Moderating Role of Familial Risk.

ABSTRACT: Numerous theoretical models suggest that inhibition difficulties-the inability to moderate automatic responses-contribute to the onset and/or maintenance of internalizing symptoms. Inhibition deficits and internalizing disorders run in families and share overlapping genetic risk factors, suggesting that inhibition deficits may be particularly prognostic of internalizing symptoms in those with high familial risk. This study tested this hypothesis in a longitudinal sample during the transition from adolescence to early adulthood. As hypothesized, prospective associations between inhibition and anxiety and depressive symptoms 8 years later were moderated by familial risk for depression. Specifically, poorer inhibition prospectively predicted greater anxiety and depressive symptoms in those at high (but not low) familial risk for major depressive disorder. These findings provide preliminary support for impaired inhibition as an indicator of risk for later internalizing symptoms in those at high familial risk.

Reducing prescribing of antibiotics for acute respiratory infections using a frontline nurse-led EHR-Integrated clinical decision support tool: protocol for a stepped wedge randomized control trial.

BACKGROUND: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model. METHODS: Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested is: Implementation of RN-led iCPR tools will reduce antibiotic prescribing across diverse primary care settings. Specifically, this study aims to: (1) determine the impact of iCPRs on rapid strep test and chest x-ray ordering and antibiotic prescribing rates when used by RNs; (2) examine resource use patterns and cost-effectiveness of RN visits across diverse clinical settings; (3) determine the impact of iCPR-guided care on patient satisfaction; and (4) ascertain the effect of the intervention on RN and physician burnout. DISCUSSION: This study represents an innovative approach to using an iCPR model led by RNs and specifically designed to address inappropriate antibiotic prescribing. This study has the potential to provide guidance on the effectiveness of delegating care of low-acuity patients with ARIs to RNs to increase use of iCPRs and reduce antibiotic overprescribing for ARIs in outpatient settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255303, Registered February 5 2020, https://clinicaltrials.gov/ct2/show/NCT04255303 .

Estimation of the intraoperative blood loss in dogs undergoing enucleation.

PURPOSE: To quantify the surgical blood loss during canine enucleation and to investigate the relationship between this and any patient, surgical, and anesthetic factors. METHODS: A prospective observational analysis was conducted on 121 client-owned dogs (130 eyes) undergoing enucleation at a referral ophthalmology clinic. Blood loss was estimated by the gravimetric method (weight difference between dry and blood-containing surgical materials) to provide absolute blood loss (ABL) in milliliters, expressed as a percentage of circulating blood volume, to establish relative blood loss (RBL). RESULTS: Median ABL was 12 ml (1.6-116 ml), and median RBL was 1.3% (0.1%-6.7%). A higher RBL was associated with the following: use of a bupivacaine splash block versus retrobulbar nerve block (1.9 vs. 1%; p < .001), transpalpebral versus subconjunctival approach (2.2 vs. 1.3%; p = .003), and small versus large breed dogs (1.7% vs. 1.1%; p = .001). Both ABL and RBL differed significantly between surgeons. There was no significant difference in hemorrhage associated with the presence of ocular hypertension, systemic illness, surgical time, administration of meloxicam or choice of pre-medicant (acepromazine vs medetomidine). No dog required supportive intervention in response to surgical hemorrhage. CONCLUSIONS: This study has established a surgical blood loss estimate for dogs undergoing enucleation at an ophthalmology referral centre. Subconjunctival enucleation may be preferred for patients at greater risk of haemodynamic complications.

Recognizing the value of meta-research and making it easier to find.

Meta-research is a bourgeoning field studying topics with significant relevance to health sciences librarianship, such as research reproducibility, peer review, and open access. As a discipline that studies research itself and the practices of researchers, meta-research spans disciplines and encompasses a broad spectrum of topics and methods. The breadth of meta-research presents a significant challenge for identifying published meta-research studies. Introducing a subject heading for meta-research in the controlled vocabularies of literature databases has the potential to increase the visibility of meta-research, further advance the field, and expand its impact on research practices. Given the relatively recent designation of meta-research as a field and its expanding use as a term, now is the time to develop appropriate indexing vocabulary. We seek to call attention to the value of meta-research for health sciences librarianship, describe the challenges of identifying meta-research literature with currently available key terms, and highlight the need to establish controlled vocabulary specific to meta-research.

Test-of-Cure After Treatment of Pharyngeal Gonorrhea in Durham, North Carolina, 2021-2022.

BACKGROUND: In December 2020, the Centers for Disease Control and Prevention updated its treatment guidelines for gonococcal infection and, for the first time, recommended universal test-of-cure for all individuals treated for pharyngeal gonorrhea. After the release of these guidelines, data are lacking on rates of return for the test-of-cure, particularly in populations other than men who have sex with men. METHODS: We analyzed the demographic characteristics, clinical characteristics, rate of return for the recommended test-of-cure, and percent positivity for Neisseria gonorrhoeae on repeat pharyngeal specimens at a local public health department in Durham, NC. RESULTS: Of 101 individuals treated for pharyngeal gonorrhea between March 2021 and April 2022, 54.5% were men, 71.2% Black or African American, and 58.4% between the ages of 20 and 29 years. Most identified as either women who have sex with men (38.6%), men who have sex with men (24.8%), or men who have sex with women (22.8%). Of these individuals, 41 (40.6%) returned for a test-of-cure, with LGBTQ+ individuals more likely to return than men who have sex with women and women who have sex with men. Of those who returned for the test-of-cure, 4.9% of pharyngeal samples were equivocal and 2.4% positive for N. gonorrhoeae by nucleic acid amplification testing, likely reflecting false-positive tests. CONCLUSION: Despite recommendations to perform a test-of-cure 7 to 14 days after treatment of pharyngeal gonorrhea, rates of return continue to be low. Alternative strategies should be investigated to increase test-of-cure rates.

A targeted approach to using e-cigarettes for harm reduction in adults.

Smoking remains the leading preventable cause of death and disease in the US. While e-cigarettes (EC) are undeniably harmful when used by adolescents and nonsmokers, the perpetuation of the increasing negative perceptions of EC and widespread false belief that EC are equal or more harmful than combustible cigarettes (CC) represents a significant missed public health opportunity. EC have great potential to serve as a mechanism for smoking harm reduction among hard-to-treat populations of smokers who have failed to quit with currently available treatments. In this paper, we outline why we need to overcome the hostile EC research environment to explore the potential use of EC as a harm-reduction strategy in hard-to-treat populations.

A new patient-derived iPSC model for dystroglycanopathies validates a compound that increases glycosylation of α-dystroglycan.

Dystroglycan, an extracellular matrix receptor, has essential functions in various tissues. Loss of α-dystroglycan-laminin interaction due to defective glycosylation of α-dystroglycan underlies a group of congenital muscular dystrophies often associated with brain malformations, referred to as dystroglycanopathies. The lack of isogenic human dystroglycanopathy cell models has limited our ability to test potential drugs in a human- and neural-specific context. Here, we generated induced pluripotent stem cells (iPSCs) from a severe dystroglycanopathy patient with homozygous FKRP (fukutin-related protein gene) mutation. We showed that CRISPR/Cas9-mediated gene correction of FKRP restored glycosylation of α-dystroglycan in iPSC-derived cortical neurons, whereas targeted gene mutation of FKRP in wild-type cells disrupted this glycosylation. In parallel, we screened 31,954 small molecule compounds using a mouse myoblast line for increased glycosylation of α-dystroglycan. Using human FKRP-iPSC-derived neural cells for hit validation, we demonstrated that compound 4-(4-bromophenyl)-6-ethylsulfanyl-2-oxo-3,4-dihydro-1H-pyridine-5-carbonitrile (4BPPNit) significantly augmented glycosylation of α-dystroglycan, in part through upregulation of LARGE1 glycosyltransferase gene expression. Together, isogenic human iPSC-derived cells represent a valuable platform for facilitating dystroglycanopathy drug discovery and therapeutic development.

Posttraumatic Stress Disorder Symptom Cluster Structure in Prolonged Exposure Therapy and Virtual Reality Exposure.

The emotional processing theory of posttraumatic stress disorder (PTSD) posits that avoidance is central to PTSD development and maintenance. Prolonged exposure (PE) therapy, which clinically focuses on avoidance reduction, has strong empirical support as a PTSD treatment. Virtual reality exposure (VRE) has been utilized to accelerate avoidance reduction by increasing multisensory engagement. Although some exposure therapy studies have found associations between avoidance and PTSD symptoms, others have indicated that reexperiencing or hyperarousal symptoms drive symptom trajectories. Using a cross-lagged panel design, the present secondary data analysis examined temporal associations between clinician-assessed PTSD symptom clusters during treatment with PE, VRE, or a waitlist control condition. There were no significant differences between PE and VRE regarding symptom clusters at any assessment. Compared to the waitlist condition, individuals who received VRE or PE exhibited earlier reductions in avoidance/numbing symptoms, ß = -.19, 95% CI [-.33, -.05], followed by reductions in hyperarousal symptoms, ß = -.21, 95% CI [-.33, -.09]. Hyperarousal symptoms predicted changes in later avoidance/numbing and reexperiencing outcomes across treatment: pretreatment to midtreatment, ß = .29, 95% CI [.17, .42]; midtreatment to posttreatment, ß = .23, 95% CI [.07, .39]. Reexperiencing symptoms predicted changes in hyperarousal outcomes earlier in treatment, ß = .22, 95% CI [.02, .37], whereas avoidance/numbing symptoms predicted changes in hyperarousal outcomes later in treatment, ß = .18, 95% CI [.04, .32]. These findings support the efficacy of exposure therapy in addressing avoidance/numbing symptoms and highlight the potential importance of hyperarousal symptoms in relation to other symptom clusters.

Current State of the Evidence: Examining the Effects of Orton-Gillingham Reading Interventions for Students With or at Risk for Word-Level Reading Disabilities.

Over the past decade, parent advocacy groups led a grassroots movement resulting in most states adopting dyslexia-specific legislation, with many states mandating the use of the Orton-Gillingham approach to reading instruction. Orton-Gillingham is a direct, explicit, multisensory, structured, sequential, diagnostic, and prescriptive approach to reading for students with or at risk for word-level reading disabilities (WLRD). Evidence from a prior synthesis and What Works Clearinghouse reports yielded findings lacking support for the effectiveness of Orton-Gillingham interventions. We conducted a meta-analysis to examine the effects of Orton-Gillingham reading interventions on the reading outcomes of students with or at risk for WLRD. Findings suggested Orton-Gillingham reading interventions do not statistically significantly improve foundational skill outcomes (i.e., phonological awareness, phonics, fluency, spelling; effect size [ES] = 0.22; p = .40), although the mean ES was positive in favor of Orton-Gillingham-based approaches. Similarly, there were not significant differences for vocabulary and comprehension outcomes (ES = 0.14; p = .59) for students with or at risk for WLRD. More high-quality, rigorous research with larger samples of students with WLRD is needed to fully understand the effects of Orton-Gillingham interventions on the reading outcomes for this population.

Cost-effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection and a Combined Intervention of Syringe Access and Medication-assisted Therapy for Opioid Use Disorders in an Injection Drug Use Population.

BACKGROUND: There are too many plausible permutations and scale-up scenarios of combination hepatitis C virus (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used a computer simulation to project the health and economic impacts of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct antiviral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+). METHODS: We performed an allocative efficiency study, using a mathematical model to simulate the progression of HCV in PWID and its related consequences. We combined 2 previously validated simulations to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health-sector and societal perspective, with a 15-year time horizon and a discount rate of 3%. RESULTS: From a health-sector perspective (excluding criminal justice system-related costs), 4 potential strategies fell on the cost-efficiency frontier. At 20% coverage, DAAs had an incremental cost-effectiveness ratio (ICER) of $27 251/quality-adjusted life-year (QALY). Combinations of DAA at 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165 985/QALY, $325 860/QALY, and $399 189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA at 20% with MAT+ at 80% was the most effective intervention and was cost saving. While DAA at 20% with MAT+ at 80% was more expensive (eg, less cost saving) than MAT+ at 80% alone without DAA, it offered a favorable value compared to MAT+ at 80% alone ($23 932/QALY). CONCLUSIONS: When considering health-sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together became the most cost-effective intervention.

Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases.

The delta isoform of phosphoinositide 3-kinase (PI3Kδ) regulates various lymphocyte functions. Considering the key pro-inflammatory role of IL-17A and IL-17F cytokines in psoriasis and spondyloarthritis (SpA), we investigated the potential of PI3Kδ blockade to suppress IL-17A, IL-17F and associated pro-inflammatory cytokines that could synergize with IL-17A and IL-17F. Using in vitro studies with primary human cells and ex vivo studies with inflamed target tissues, we assessed if seletalisib, a selective PI3Kδ inhibitor, suppresses cytokine production by T cells and innate-like lymphocytes, and if seletalisib modulates the inflammatory responses in stromal cell populations in psoriasis (human dermal fibroblasts (HDF)) and SpA (fibroblast-like synoviocytes (FLS)). In vitro, seletalisib inhibited the production of pro-inflammatory cytokines, including IL-17A and IL-17F, from peripheral blood mononuclear cells (PBMCs), T helper 17 (Th17) cells as well as γδ-T cells and mucosal-associated invariant T cells. This inhibition resulted in decreased inflammatory activation of HDF in co-culture systems. Seletalisib was also efficacious in inhibiting SpA PBMCs and synovial fluid mononuclear cells (SFMCs) from producing pro-inflammatory cytokines. Furthermore, supernatant derived from cultured seletalisib-treated Th17 cells showed reduced potency for activating inflammatory responses from cultured SpA FLS and decreased their osteogenic differentiation capacity. Finally, analysis of inflamed SpA synovial tissue biopsies revealed activation of the PI3K-Akt-mTOR pathway. We observed that ex vivo seletalisib treatment of inflamed synovial tissue reduced IL-17A and IL-17F expression. Collectively, inhibition of PI3Kδ reduces the production of pro-inflammatory cytokines from IL-17-producing adaptive and innate-like lymphocytes and thereby inhibits downstream inflammatory and tissue remodeling responses. PI3Kδ-targeting may therefore represent a novel therapeutic avenue for the treatment of IL-17-mediated chronic inflammatory diseases such as psoriasis and SpA.

The Impact of Exposure Therapy on Resting Heart Rate and Heart Rate Reactivity Among Active-Duty Soldiers With Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is linked to poor health, including cardiovascular disease. These effects may be a result of increased tonic cardiovascular function and cardiovascular reactivity. Despite PTSD's negative health burden, relatively little is known about whether frontline treatments for PTSD may alleviate cardiovascular risk. METHODS: The current study was a secondary analysis of a larger intervention study of active-duty soldiers with PTSD (n = 104; mean [SD] age = 30.6 [6.7] years; 6% women) randomized to an exposure therapy-either prolonged exposure (PE) or virtual reality exposure (VRE)-or a waitlist control condition. We examined change in participants' resting heart rate (HR) and HR reactivity from baseline (before randomization) to midtreatment and posttreatment using residualized change regression models. RESULTS: The results of the study demonstrated decreased resting HR (B = -5.06, p = .024) and HR reactivity (B = -2.46, p = .005) from baseline to posttreatment of PE and VRE relative to waitlist. Exploratory analyses found that changes in resting HR and HR reactivity were not significantly correlated with either self-reported or clinician-rated PTSD symptom change. CONCLUSIONS: These results suggest that PE and VRE for PTSD may alleviate some cardiovascular health risk associated with PTSD, improving cardiovascular functioning.RCT Registration: ClinicalTrials.gov (identifier: NCT01193725).

Does Reducing Drinking in Patients with Unhealthy Alcohol Use Improve Pain Interference, Use of Other Substances, and Psychiatric Symptoms?

BACKGROUND: We aimed to investigate the impact of reducing drinking in patients with unhealthy alcohol use on improvement of chronic pain interference, substance use, and psychiatric symptoms. METHODS: We analyzed longitudinal data from 2003 to 2015 in the Veterans Aging Cohort Study, a prospective, multisite observational study of US veterans, by emulating a hypothetical randomized trial (a target trial). Alcohol use was assessed using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and outcome conditions were assessed via validated survey items. Individuals were followed from the first time their AUDIT score was ≥ 8 (baseline), a threshold consistent with unhealthy alcohol use. We compared individuals who reduced drinking (AUDIT < 8) at the next follow-up visit with individuals who did not (AUDIT ≥ 8). We fit separate logistic regression models to estimate odds ratios for improvement of each condition 2 years postbaseline among individuals who had that condition at baseline: moderate or severe pain interference symptoms, tobacco smoking, cannabis use, cocaine use, depressive symptoms, and anxiety symptoms. Inverse probability weighting was used to account for potential selection bias and confounding. RESULTS: Adjusted 2-year odds ratios (95% confidence intervals) for associations between reducing drinking and improvement or resolution of each condition were as follows: 1.49 (0.91, 2.42) for pain interference symptoms, 1.57 (0.93, 2.63) for tobacco smoking, 1.65 (0.92, 2.95) for cannabis use, 1.83 (1.03, 3.27) for cocaine use, 1.11 (0.64, 1.92) for depressive symptoms, and 1.33 (0.80, 2.22) for anxiety symptoms. CONCLUSIONS: We found some evidence for improvement of pain interference symptoms and substance use after reducing drinking among US veterans with unhealthy alcohol use, but confidence intervals were wide.

The Effects of a Paraphrasing and Text Structure Intervention on the Main Idea Generation and Reading Comprehension of Students with Reading Disabilities in Grades 4 and 5.

This study examined the effects of a small group intervention targeting paraphrasing and text structure instruction on the main idea generation and reading comprehension of students with reading disabilities in Grades 4 and 5. Students (N = 62) were randomly assigned to receive the Tier 2-type intervention or business-as-usual instruction. Students in the intervention received 25, 40-minute lessons focused on paraphrasing sections of text by identifying the main topic and the most important idea about that topic. Students utilized the text structure organization to inform their main idea generation. Results yielded statistically significant, positive effects in favor of the intervention group on near-transfer and mid-transfer measures of text structure identification (g = 0.75) and main idea generation (g = 0.70), but no statistically significant effect on a far-transfer measure of reading comprehension. These findings provide initial support for utilizing this instruction to improve students' main idea generation on taught and untaught structures.

Development and Evaluation of an 18F-Radiolabeled Monocyclam Derivative for Imaging CXCR4 Expression.

In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation for detection and treatment of the disease. Peptidic antagonists have been labeled with a variety of radioisotopes for the detection of CXCR4, but the methodology utilizing small molecules has predominantly used radiometals. We report here the development of a 18F-radiolabeled cyclam-based small molecule radioprobe, [18F]MCFB, for imaging CXCR4 expression. The IC50 value of [19F]MCFB for CXCR4 was similar to that of AMD3465 (111.3 and 89.8 nM, respectively). In vitro binding assays show that the tracer depicted a differential CXCR4 expression, which was blocked in the presence of AMD3465, demonstrating the specificity of [18F]MCFB. Positron emission tomography (PET) imaging studies showed a distinct uptake of the radioprobe in lymphoma and breast cancer xenografts. High liver and kidney uptakes were seen with [18F]MCFB, leading us to further examine the basis of its pharmacokinetics in relation to the tracer's cationic nature and thus the role of organic cation transporters (OCTs). Substrate competition following the intravenous injection of metformin led to a marked decrease in the urinary excretion of [18F]MCFB, with moderate changes observed in other organs, including the liver. Our results suggest involvement of OCTs in the renal elimination of the tracer. In conclusion, the 18F-radiolabeled monocyclam, [18F]MCFB, has potential to detect tumor CXCR4 in nonhepatic tissues.