Using "warm handoffs" to link hospitalized smokers with tobacco treatment after discharge: Study protocol of a randomized controlled trial

Abstract Background Post-discharge support is a key component of effective treatment for hospitalized smokers, but few hospitals provide it. Many hospitals and care settings fax-refer smokers to quitlines for follow-up; however, less than half of fax-referred smokers are successfully contacted and enrolled in quitline services. “Warm handoff” is a novel approach to care transitions in which health care providers directly link patients with substance abuse problems with specialists, using face-to-face or phone transfer. Warm handoff achieves very high rates of treatment enrollment for these vulnerable groups. Methods The aim of this study—“EQUIP” (Enhancing Quitline Utilization among In-Patients)—is to determine the effectiveness, and cost-effectiveness, of warm handoff versus fax referral for linking hospitalized smokers with tobacco quitlines. This study employs a two-arm, individually randomized design. It is set in two large Kansas hospitals that have dedicated tobacco treatment interventionists on staff. At each site, smokers who wish to remain abstinent after discharge will be randomly assigned to groups. For patients in the fax group, staff will provide standard in-hospital intervention and will fax-refer patients to the state tobacco quitline for counseling post-discharge. For patients in the warm handoff group, staff will provide brief in-hospital intervention and immediate warm handoff: staff will call the state quitline, notify them that a warm handoff inpatient from Kansas is on the line, then transfer the call to the patients’ mobile or bedside hospital phone for quitline enrollment and an initial counseling session. Following the quitline session, hospital staff provides a brief check-back visit. Outcome measures will be assessed at 1, 6, and 12 months post enrollment. Costs are measured to support cost-effectiveness analyses. We hypothesize that warm handoff, compared to fax referral, will improve care transitions for tobacco treatment, enroll more participants in quitline services, and lead to higher quit rates. We also hypothesize that warm handoff will be more cost-effective from a societal perspective. Discussion If successful, this project offers a low-cost solution for more efficiently linking millions of hospitalized smokers with effective outpatient treatment—smokers that might otherwise be lost in the transition to outpatient care. Trial registration Clinical Trials Registration NCT01305928Peer Reviewe

Using “warm handoffs” to link hospitalized smokers with tobacco treatment after discharge: study protocol of a randomized controlled trial

Post-discharge support is a key component of effective treatment for hospitalized smokers, but few hospitals provide it. Many hospitals and care settings fax-refer smokers to quitlines for follow-up; however, less than half of fax-referred smokers are successfully contacted and enrolled in quitline services. “Warm handoff” is a novel approach to care transitions in which health care providers directly link patients with substance abuse problems with specialists, using face-to-face or phone transfer. Warm handoff achieves very high rates of treatment enrollment for these vulnerable groups

Self-medication with antibiotics for the treatment of menstrual symptoms in southwest Nigeria: a cross-sectional study

Background: Self-medication with antibiotics is an important factor contributing to the development of bacterial antibiotic resistance. The purpose of this study was to evaluate the prevalence of self-medication with antibiotics for the treatment of menstrual symptoms among university women in Southwest Nigeria. Methods: A cross-sectional survey was administered to female undergraduate and graduate students (n = 706) at four universities in Southwest Nigeria in 2008. The universities were selected by convenience and the study samples within each university were randomly selected cluster samples. The survey was self-administered and included questions pertaining to menstrual symptoms, analgesic and antibiotic use patterns, and demographics. Data were analyzed using descriptive statistics and logistic regression. Results: The response rate was 95.4%. Eighty-six percent (95% CI: 83-88%) of participants experienced menstrual symptoms, and 39% (95% CI: 36-43%) reported using analgesics to treat them. Overall, 24% (95% CI: 21-27%) of participants reported self-medicated use of antibiotics to treat the following menstrual symptoms: cramps, bloating, heavy bleeding, headaches, pimples/acne, moodiness, tender breasts, backache, joint and muscle pain. Factors associated with this usage were: lower levels of education (Odds Ratio (OR): 2.8, 95% CI: 1.1-7.1, p-value: 0.03); nonscience major (OR: 1.58, 95% CI: 1.03-2.50, p-value: 0.04); usage of analgesics (OR: 3.17, 95% CI: 2.07-4.86, p-value: <0.001); and mild to extreme heavy bleeding (OR: 1.64, 95% CI: 1.01-2.67, p-value: 0.05) and pimples/acne (OR: 1.57, 95% CI: 0.98-2.54, p-value: 0.06). Ampicillin, tetracycline, ciprofloxacin and metronidazole were used to treat the most symptoms. Doctors or nurses (6%, 95% CI: 4-7%), friends (6%, 95% CI: 4-7%) and family members (7%, 95% CI: 5-8%) were most likely to recommend the use of antibiotics for menstrual symptoms, while these drugs were most often obtained from local chemists or pharmacists (10.2%, 95% CI: 8-12%). Conclusions: This is the first formal study to report that approximately 1 out of 4 university women surveyed in Southwest Nigeria self-medicate with antibiotics to treat menstrual symptoms. This practice could provide monthly, low-dose exposures to antibiotics among users. Further studies are necessary to evaluate the impacts of selfmedication on student health

Reversibility and Low Commitment to Forward Catalysis in the Conjugation of Lipid Alkenals by Glutathione Transferase A4-4

High concentrations of electrophilic lipid alkenals formed during oxidative stress are implicated in cytotoxicity and disease. However, low concentrations of alkenals are required to induce antioxidative stress responses. An established clearance pathway for lipid alkenals includes conjugation to glutathione (GSH) via Michael addition, which is catalyzed mainly by glutathione transferase isoform A4 (GSTA4-4). Based on the ability of GSTs to catalyze hydrolysis or retro-Michael addition of GSH conjugates, and the antioxidant function of low concentrations of lipid alkenals, we hypothesize that GSTA4-4 contributes a homeostatic role in lipid metabolism. Enzymatic kinetic parameters for retro-Michael addition with trans-2-Nonenal (NE) reveal the chemical competence of GSTA4-4 in this putative role. The forward GSTA4-4-catalyzed Michael addition occurs with the rapid exchange of the C2 proton of NE in D2O as observed by NMR. The isotope exchange was completely dependent on the presence of GSH. The overall commitment to catalysis, or the ratio of first order kcat,f for ‘forward’ Michael addition to the first order kcat,ex for H/D exchange is remarkably low, approximately 3:1. This behavior is consistent with the possibility that GSTA4-4 is a regulatory enzyme that contributes to steady-state levels of lipid alkenals, rather than a strict ‘one way’ detoxication enzyme

Reversibility and Low Commitment to Forward Catalysis in the Conjugation of Lipid Alkenals by Glutathione Transferase A4-4

High concentrations of electrophilic lipid alkenals formed during oxidative stress are implicated in cytotoxicity and disease. However, low concentrations of alkenals are required to induce antioxidative stress responses. An established clearance pathway for lipid alkenals includes conjugation to glutathione (GSH) via Michael addition, which is catalyzed mainly by glutathione transferase isoform A4 (GSTA4-4). Based on the ability of GSTs to catalyze hydrolysis or retro-Michael addition of GSH conjugates, and the antioxidant function of low concentrations of lipid alkenals, we hypothesize that GSTA4-4 contributes a homeostatic role in lipid metabolism. Enzymatic kinetic parameters for retro-Michael addition with trans-2-Nonenal (NE) reveal the chemical competence of GSTA4-4 in this putative role. The forward GSTA4-4-catalyzed Michael addition occurs with the rapid exchange of the C2 proton of NE in D2O as observed by NMR. The isotope exchange was completely dependent on the presence of GSH. The overall commitment to catalysis, or the ratio of first order kcat,f for &lsquo;forward&rsquo; Michael addition to the first order kcat,ex for H/D exchange is remarkably low, approximately 3:1. This behavior is consistent with the possibility that GSTA4-4 is a regulatory enzyme that contributes to steady-state levels of lipid alkenals, rather than a strict &lsquo;one way&rsquo; detoxication enzyme

The reproducibility of urinary ions in manganese exposed workers

PURPOSE: Manganese (Mn) is found in environmental and occupational settings, and can cause cognitive and motor impairment. Existing Mn exposure studies have not reached consensus on a valid and reproducible biomarker for Mn exposure. METHODS: Previously, global metabolomics data was generated from urine collected in October 2014 using mass spectrometry (MS). Nine ions were found to be different between persons exposed and unexposed to Mn occupationally, though their identity was not able to be determined. Here, we investigated these nine ions in a follow-up set of urine samples taken from the same cohort in January 2015, and in urine samples from a separate Mn-exposed cohort from Wisconsin. We fit an elastic net model fit using the nine ions found in the October 2014 data. RESULTS: The elastic net correctly predicted exposure status in 72% of the follow-up samples collected in January 2015, and the area under the curve of the receiver operating characteristic (ROC) curve was 0.8. In the Wisconsin samples, the elastic net performed no better than chance in predicting exposure, possibly due to differences in Mn exposure levels, or unmeasured occupational or environmental co-exposures. CONCLUSIONS: This work underscores the importance of taking repeat samples for replication studies when investigating the human urine metabolome, as both within- and between-person variances were observed. Validating and identifying promising results remains a challenge in harnessing global metabolomics for biomarker discovery in occupational cohorts

Pharmacometabonomic Prediction of Busulfan Clearance in Hematopoietic Cell Transplant Recipients

Intravenous (IV) busulfan doses are often personalized to a concentration at steady state (Css) using the patient’s clearance, which is estimated with therapeutic drug monitoring. We sought to identify biomarkers of IV busulfan clearance using a targeted pharmacometabonomics approach. A total of 200 metabolites were quantitated in 106 plasma samples, each obtained before IV busulfan administration in hematopoietic cell transplant (HCT) recipients. Both univariate linear regression with false discovery rate (FDR) and pathway enrichment analyses using the Global test were performed. In the univariate analysis, glycine, <i>N-</i>acetylglycine, 2-hydroxyisovaleric acid, creatine, serine, and tyrosine were statistically significantly associated with IV busulfan clearance at <i>P</i> < 0.05, with the first three satisfying the FDR of <i>q</i> < 0.1. Using pathway enrichment analysis, the glycine, serine, and threonine metabolism pathway was statistically significantly associated with IV busulfan clearance at <i>P</i> < 0.05 and <i>q</i> < 0.1, and a pathway impact >0.1. Glycine is a component of glutathione, which is conjugated with busulfan via glutathione transferase enzymes. These results demonstrate the potential utility of pharmacometabonomics to inform IV busulfan dosing. Future studies are required to validate these findings

Changing the default for tobacco-cessation treatment in an inpatient setting: study protocol of a randomized controlled trial

Abstract Background Most health care providers do not treat tobacco dependence routinely. This may in part be due to the treatment “default.” Current treatment guidelines recommend that providers (1) ask patients if they are willing to quit and (2) provide cessation-focused medications and counseling only to smokers who state that they are willing to quit. The default is that patients have to “opt in” to receive cessation assistance: providers ask smokers if they are willing to quit, and only offer medications and cessation support to those who say “yes.” This drastically limits the reach of cessation services because, at any given encounter, only one in three smokers say that they are ready to quit. The objective of this study is to determine the impact of providing all smokers with tobacco-cessation treatment unless they refuse it (OPT OUT) versus current practice—screening for readiness and only offering treatment to smokers who say they are ready to quit (OPT IN). Methods This individually randomized clinical trial is conducted in a tertiary-care hospital. We will conduct the trial among up to 1000 randomly selected hospitalized smokers to determine the population impact of changing the treatment default, identify mediators of outcome, and determine the cost-effectiveness of this new, highly proactive approach. This is a population-based study that targets an endpoint of vital interest; applies minimal eligibility criteria to broaden generalizability; and utilizes hospital staff for interventions to ensure long-term sustainability. The study employs delayed consent and an innovative Bayesian adaptive design to evaluate a major shift in our approach to care. If effective, this change would expand the reach of tobacco-cessation treatment from 30% to 100% of smokers. Discussion Regardless of outcome, the trial will provide a model of how to alter and evaluate the impact of health care defaults. If OPT OUT proves to be more effective, it will expand the population eligible for cessation treatment by over 300%. It will also simplify the tobacco-cessation treatment algorithm, and relieve busy health care providers of the burden of evaluating readiness to quit. Trial registration Clinical Trials Registration, ID: NCT02721082 . Registered on 22 March 2016