Addressing Smoking in Musculoskeletal Specialty Care.

➤: Physicians who advise patients to quit smoking substantially improve cessation rates, but cessation counseling is currently underperformed. ➤: Counseling, pharmacotherapy, and additional interventions can improve the chance of successful smoking cessation. Most patients require multiple attempts at quitting to be successful. ➤: A list of referral contacts and resources should be developed and routinely offered to these patients. The national Quitline (1-800-QUIT-NOW) provides free access to trained counselors and "quit coaches" for each state program in the United States. ➤: Government and private insurance plans in the United States are required (in most cases) to cover the cost of 2 quitting attempts per year including counseling referrals and medications. ➤: Several biopsychosocial factors that affect orthopaedic outcomes (weight, anxiety, depression, etc.) are also relevant to smoking cessation; management of these factors is thus potentially aggregately advantageous.

The Effects of Immune Modulators on Amodiaquine-Induced Liver Injury.

If idiosyncratic drug-induced liver injury (IDILI) is immune mediated, then it is logical that immune modulators may be able to affect liver injury caused by a drug. We have previously shown that modulating the immune system by impairing programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling, both receptors involved in immune tolerance, was capable of producing an animal model of amodiaquine (AQ) IDILI with characteristics very similar to IDILI in humans. Other immune modulators may also increase liver injury caused by drugs that cause IDILI in humans. In this study, myeloid derived suppressor cells (MDSCs), transforming growth factor beta (TGF-ß), and lymphocyte-activation gene 3 (LAG3) were targeted with antibodies, with and without PD-1 and CTLA-4 impairment. We found that anti-Gr1 antibodies used to deplete MDSCs led to a significant increase in AQ-induced liver injury in wild-type mice; however, the injury was actually less in PD-1-/- mice, with or without anti-CTLA-4, and it was less than we have previously observed in PD-1-/- mice combined with anti-CTLA-4 without anti-Gr1. Addition of anti-LAG3 or anti-TGF-ß antibodies produced a small increase ALT in AQ-treated wild-type mice. There was a significant increase in ALT in PD-1-/- mice co-treated with anti-LAG3 or anti-TGF-ß relative to AQ-treated wild-type mice. In the case of TGF-ß, this was further increased by the addition of anti-CTLA-4, but if anything, there appeared to be a paradoxical decrease when anti-CTLA-4 was combined with anti-LAG3. Overall, the results from this study were not always as expected, and they highlight the complexity of the immune response, in particular immune tolerance, which appears to be the dominant immune response to drugs that cause IDILI.

Medications for opioid use disorder in the Department of Veterans Affairs (VA) health care system: Historical perspective, lessons learned, and next steps.

The US Department of Veterans Affairs (VA), the largest health care system in the US, has been confronted with the health care consequences of opioid disorder (OUD). Increasing access to quality OUD treatment, including pharmacotherapy, is a priority for the VA. We examine the history of medications (e.g., methadone, buprenorphine, injectable naltrexone) used in the treatment of OUD within VA, document early and ongoing efforts to increase access and build capacity, primarily through the use of buprenorphine, and summarize research examining barriers and facilitators to prescribing and medication receipt. We find that there has been a slow but steady increase in the use of medications for OUD and, despite system-wide mandates and directives, uneven uptake across VA facilities and within patient sub-populations, including some of those most vulnerable. We conclude with recommendations intended to support the greater use of medication for OUD in the future, both within VA as well as other large health care systems.

Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

Rising overdose fatalities among U.S. veterans suggest veterans taking prescription opioids may be at risk for overdose. However, it is unclear whether veterans prescribed chronic opioids are aware of this risk. The objective of this study was to identify risk factors and determine awareness of risk for opioid overdose in veterans treated with opioids for chronic pain, using veterans treated with methadone or buprenorphine for opioid use disorder as a high-risk comparator group. In the current study, 90 veterans on chronic opioid medication, for either opioid use disorder or pain management, completed a questionnaire assessing risk factors, knowledge, and self-estimate of risk for overdose. Nearly all veterans in both groups had multiple overdose risk factors, although individuals in the pain management group had on average a significantly lower total number of risk factors than did individuals in the opioid use disorder group (5.9 versus 8.5, p < .0001). On average, participants treated for pain management scored slightly but significantly lower on knowledge of opioid overdose risk factors (12.1 versus 13.5, p < .01). About 70% of participants, regardless of group, believed their overdose risk was below that of the average American adult. There was no significant relationship between self-estimate of overdose risk and either number or knowledge of opioid overdose risk factors. Our results suggest that veterans in both groups underestimated their risk for opioid overdose. Expansion of overdose education to include individuals on chronic opioids for pain management and a shift in educational approaches to overdose prevention may be indicated.

Deoxyribozyme-based logic gates.

We report herein a set of deoxyribozyme-based logic gates capable of generating any Boolean function. We construct basic NOT and AND gates, followed by the more complex XOR gate. These gates were constructed through a modular design that combines molecular beacon stem-loops with hammerhead-type deoxyribozymes. Importantly, as the gates have oligonucleotides as both inputs and output, they open the possibility of communication between various computation elements in solution. The operation of these gates is conveniently connected to a fluorescent readout.