Opioids and benzodiazepines are commonly coprescribed medications. The mortality risk associated with their concurrent use is unknown.
To estimate the all-cause mortality risk for patients newly ...prescribed opioids and benzodiazepines concurrently relative to patients prescribed benzodiazepines only, opioids only, or neither medication.
This propensity score-matched, retrospective, cohort study included 17,476 patients receiving Veterans Affairs (VA) health care between October 1, 2009, and September 30, 2011, and diagnosed with posttraumatic stress disorder identified using ICD-9-CM code 309.81. One-year total and cause-specific mortality was assessed by hazard ratios and subhazard ratios, adjusted for propensity score, age, baseline psychiatric and medical comorbidity, and daily medication dose.
Concurrent users (n = 4,369) were propensity score matched 1:1 with benzodiazepine-only users, opioid-only users, and nonusers. One year after medication start, the concurrent cohort had higher rates of all-cause mortality (116 deaths) relative to benzodiazepine-only (75 deaths; adjusted hazard ratio = 1.52; 95% CI, 1.14-2.03), opioid-only (67 deaths; 1.76; 95% CI, 1.32-2.35), and nonuser (60 deaths; 1.85; 95% CI, 1.30-2.64) cohorts. Risk of overdose death was greater among patients in the concurrent cohort relative to patients in the benzodiazepine-only (adjusted subhazard ratio = 2.59; 95% CI, 1.00-6.66), opioid-only (2.58; 95% CI, 1.09-6.11), and nonuser (9.16; 95% CI, 2.27-37.02) cohorts. For circulatory disease-related deaths, the adjusted subhazard ratio for concurrent medication users was 1.81 (95% CI, 1.01-3.24) relative to nonusers.
New coprescription of opioids and benzodiazepines was associated with increased all-cause mortality and overdose death compared with new prescription of benzodiazepines only, opioids only, or neither medication and increased circulatory disease-related death relative to neither medication.
IntroductionMobile apps can increase access to alcohol-related care but only if patients actively engage with them. Peers have shown promise for facilitating patients’ engagement with mobile apps. ...However, the effectiveness of peer-based mobile health interventions for unhealthy alcohol use has yet to be evaluated in a randomised controlled trial. The goal of this hybrid I effectiveness-implementation study is to test a mobile app (‘Stand Down–Think Before You Drink’), with and without peer support, to improve drinking outcomes among primary care patients.Methods and analysisIn two US Veterans Health Administration (VA) medical centres, 274 primary care patients who screen positive for unhealthy alcohol use and are not currently in alcohol treatment will be randomised to receive usual care (UC), UC plus access to Stand Down (App), or UC plus Peer-Supported Stand Down (PSSD—four peer-led phone sessions over the initial 8 weeks to enhance app engagement). Assessments will occur at baseline and 8-, 20- and 32-weeks postbaseline. The primary outcome is total standard drinks; secondary outcomes include drinks per drinking day, heavy drinking days and negative consequences from drinking. Hypotheses for study outcomes, as well as treatment mediators and moderators, will be tested using mixed effects models. Semi-structured interviews with patients and primary care staff will be analysed using thematic analysis to identify potential barriers and facilitators to implementation of PSSD in primary care.Ethics and disseminationThis protocol is a minimal risk study and has received approval from the VA Central Institutional Review Board. The results have the potential to transform the delivery of alcohol-related services for primary care patients who engage in unhealthy levels of drinking but rarely seek treatment. Study findings will be disseminated through collaborations with healthcare system policymakers as well as publications to scholarly journals and presentations at scientific conferences.Trial registration numberNCT05473598.
The US is confronted with a rise in opioid use disorder (OUD), opioid misuse, and opioid-associated harms. Medication treatment for opioid use disorder (MOUD)-including methadone, buprenorphine and ...naltrexone-is the gold standard treatment for OUD. MOUD reduces illicit opioid use, mortality, criminal activity, healthcare costs, and high-risk behaviors. The Veterans Health Administration (VHA) has invested in several national initiatives to encourage access to MOUD treatment. Despite these efforts, by 2017, just over a third of all Veterans diagnosed with OUD received MOUD. VHA OUD specialty care is often concentrated in major hospitals throughout the nation and access to this care can be difficult due to geography or patient choice. Recognizing the urgent need to improve access to MOUD care, in the Spring of 2018, the VHA initiated the Stepped Care for Opioid Use Disorder, Train the Trainer (SCOUTT) Initiative to facilitate access to MOUD in VHA non-SUD care settings. The SCOUTT Initiative's primary goal is to increase MOUD prescribing in VHA primary care, mental health, and pain clinics by training providers working in those settings on how to provide MOUD and to facilitate implementation by providing an ongoing learning collaborative. Thirteen healthcare providers from each of the 18 VHA regional networks across the VHA were invited to implement the SCOUTT Initiative within one facility in each network. We describe the goals and initial activities of the SCOUTT Initiative leading up to a two-day national SCOUTT Initiative conference attended by 246 participants from all 18 regional networks in the VHA. We also discuss subsequent implementation facilitation and evaluation plans for the SCOUTT Initiative. The VHA SCOUTT Initiative could be a model strategy to implement MOUD within large, diverse health care systems.
Objective:The U.S. Department of Veterans Affairs (VA) health care system established policies to include patient record flags (PRFs) for high suicide risk in the electronic medical record to alert ...providers and to increase health care contacts. This study identified predictors of new PRFs and described health care utilization before and after PRF initiation among VA patients with substance use disorders.Methods:The sample included patients ages ≥18 who received a substance use disorder diagnosis in 2012 (N=474,946). Demographic, clinical, and utilization predictors of PRFs were identified by multivariable logistic regression. Changes in short-term (three months) and longer-term (12 months) health care utilization before and after PRF initiation were compared by negative binomial regression.Results:A total of 8,913 patients received PRFs. Demographic predictors of PRF initiation included being younger than 35, white, and homeless. Clinical predictors were cocaine, opioid, and sedative use disorders; posttraumatic stress, psychotic, bipolar, and depressive disorders; and diagnosis of a suicide attempt. Patients with PRFs averaged 1.33 (95% confidence interval CI=1.29–1.38) times more primary care visits, 2.29 (CI=2.24–2.34) times more mental health visits, 4.10 (CI=3.80–4.42) times more substance use visits, and fewer (incidence rate ratio=.55, CI=.53–.58) emergency department visits in the three months following compared with the three months before PRF initiation. Modest increases in mental health– and substance use–related days hospitalized were observed.Conclusions:Veterans received significantly more health care services after PRF initiation. Further research is warranted on the effects of PRFs on clinical outcomes, such as suicide behaviors.
Insulin resistance occurs in 20%–25% of the human population, and the condition is a chief component of type 2 diabetes mellitus and a risk factor for cardiovascular disease and certain forms of ...cancer. Herein, we demonstrate that the sphingolipid ceramide is a common molecular intermediate linking several different pathological metabolic stresses (i.e., glucocorticoids and saturated fats, but not unsaturated fats) to the induction of insulin resistance. Moreover, inhibition of ceramide synthesis markedly improves glucose tolerance and prevents the onset of frank diabetes in obese rodents. Collectively, these data have two important implications. First, they indicate that different fatty acids induce insulin resistance by distinct mechanisms discerned by their reliance on sphingolipid synthesis. Second, they identify enzymes required for ceramide synthesis as therapeutic targets for combating insulin resistance caused by nutrient excess or glucocorticoid therapy.
The absence of insulin results in oscillating hyperglycemia and ketoacidosis in type 1 diabetes. Remarkably, mice genetically deficient in the glucagon receptor (Gcgr) are refractory to the ...pathophysiological symptoms of insulin deficiency, and therefore, studies interrogating this unique model may uncover metabolic regulatory mechanisms that are independent of insulin. A significant feature of Gcgr-null mice is the high circulating concentrations of GLP-1. Hence, the objective of this report was to investigate potential noninsulinotropic roles of GLP-1 in mice where GCGR signaling is inactivated. For these studies, pancreatic β-cells were chemically destroyed by streptozotocin (STZ) in Gcgr(-/-):Glp-1r(-/-) mice and in Glp-1r(-/-) animals that were subsequently treated with a high-affinity GCGR antagonist antibody that recapitulates the physiological state of Gcgr ablation. Loss of GLP-1 action substantially worsened nonfasting glucose concentrations and glucose tolerance in mice deficient in, and undergoing pharmacological inhibition of, the GCGR. Further, lack of the Glp-1r in STZ-treated Gcgr(-/-) mice elevated rates of endogenous glucose production, likely accounting for the differences in glucose homeostasis. These results support the emerging hypothesis that non-β-cell actions of GLP-1 analogs may improve metabolic control in patients with insulinopenic diabetes.
For effective resolution of regional subacute inflammation and prevention of biofouling formation, we have developed a polymeric implant that can release meloxicam, a selective cyclooxygenase (COX)-2 ...inhibitor, in a sustained manner. Meloxicam-loaded polymer matrices were produced by hot-melt extrusion, with commercially available biocompatible polymers, poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(ethylene vinyl acetate) (EVA). PLGA and EVA had a limited control over the drug release rate partly due to the acidic microenvironment and hydrophobicity, respectively. PCL allowed for sustained release of meloxicam over two weeks and was used as a carrier of meloxicam. Solid-state and image analyses indicated that the PCL matrices encapsulated meloxicam in crystalline clusters, which dissolved in aqueous medium and generated pores for subsequent drug release. The subcutaneously implanted meloxicam-loaded PCL matrices in rats showed pharmacokinetic profiles consistent with their in vitro release kinetics, where higher drug loading led to faster drug release. This study finds that the choice of polymer platform is crucial to continuous release of meloxicam and the drug release rate can be controlled by the amount of drug loaded in the polymer matrices.
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•A meloxicam-loaded polymeric implant was developed for control of local inflammation.•Meloxicam was loaded in three polymeric matrices by hot-melt extrusion.•Of three polymers, PCL allowed for sustained release of meloxicam over two weeks.•Meloxicam was encapsulated in clusters, producing pores in matrices upon dissolution.•In vitro in vivo correlation of meloxicam-loaded PCL matrices was confirmed in rats.
Background: Alcohol screening and brief interventions (BIs) are ranked the third highest US prevention priority, but effective methods of implementing BI into routine care have not been described. ...Objectives: This study evaluated the prevalence of documented BI among Veterans Affairs (VA) outpatients with alcohol misuse before, during, and after implementation of a national performance measure (PM) linked to incentives and dissemination of an electronic clinical reminder (CR) for BI. Methods: VA outpatients were included in this study if they were randomly sampled for national medical record reviews and screened positive for alcohol misuse (Alcohol Use Disorders Identification Test-Consumption score ≥ 5) between July 2006 and September 2008 (N = 6788). Consistent with the PM, BI was defined as documented advice to reduce or abstain from drinking plus feedback linking drinking to health. The prevalence of BI was evaluated among outpatients who screened positive for alcohol misuse during 4 successive phases of BI implementation: baseline year (n = 3504), after announcement (n = 753) and implementation (n = 697) of the PM, and after CR dissemination (n = 1834), unadjusted and adjusted for patient characteristics. Results: Among patients with alcohol misuse, the adjusted prevalence of BI increased significantly over successive phases of BI implementation, from 5.5% (95% CI 4.1%-7.5%), 7.6% (5.6%-10.3%), 19.1% (15.4%-23.7%), to 29.0% (25.0%-33.4%) during the baseline year, after PM announcement, PM implementation, and CR dissemination, respectively (test for trend P < 0.001). Conclusions: A national PM supported by dissemination of an electronic CR for BI was associated with meaningful increases in the prevalence of documented brief alcohol interventions.
FGF-21 as a novel metabolic regulator Kharitonenkov, Alexei; Shiyanova, Tatiyana L; Koester, Anja ...
The Journal of clinical investigation,
06/2005, Letnik:
115, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Diabetes mellitus is a major health concern, affecting more than 5% of the population. Here we describe a potential novel therapeutic agent for this disease, FGF-21, which was discovered to be a ...potent regulator of glucose uptake in mouse 3T3-L1 and primary human adipocytes. FGF-21-transgenic mice were viable and resistant to diet-induced obesity. Therapeutic administration of FGF-21 reduced plasma glucose and triglycerides to near normal levels in both ob/ob and db/db mice. These effects persisted for at least 24 hours following the cessation of FGF-21 administration. Importantly, FGF-21 did not induce mitogenicity, hypoglycemia, or weight gain at any dose tested in diabetic or healthy animals or when overexpressed in transgenic mice. Thus, we conclude that FGF-21, which we have identified as a novel metabolic factor, exhibits the therapeutic characteristics necessary for an effective treatment of diabetes.
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