An explainable machine learning framework for predicting the risk of buprenorphine treatment discontinuation for opioid use disorder among commercially insured individuals.

OBJECTIVES: Buprenorphine is an effective evidence-based medication for opioid use disorder (OUD). Yet premature discontinuation undermines treatment effectiveness, increasing the risk of mortality and overdose. We developed and evaluated a machine learning (ML) framework for predicting buprenorphine care discontinuity within 12 months following treatment initiation. METHODS: This retrospective study used United States (US) 2018-2021 MarketScan commercial claims data of insured individuals aged 18-64 who initiated buprenorphine between July 2018 and December 2020 with no buprenorphine prescriptions in the previous six months. We measured buprenorphine prescription discontinuation gaps of ≥30 days within 12 months of initiating treatment. We developed predictive models employing logistic regression, decision tree classifier, random forest, extreme gradient boosting, Adaboost, and random forest-extreme gradient boosting ensemble. We applied recursive feature elimination with cross-validation to reduce dimensionality and identify the most predictive features while maintaining model robustness. For model validation, we used several statistics to evaluate performance, such as C-statistics and precision-recall curves. We focused on two distinct treatment stages: at the time of treatment initiation and one and three months after treatment initiation. We employed SHapley Additive exPlanations (SHAP) analysis that helped us explain the contributions of different features in predicting buprenorphine discontinuation. We stratified patients into risk subgroups based on their predicted likelihood of treatment discontinuation, dividing them into decile subgroups. Additionally, we used a calibration plot to analyze the reliability of the models. RESULTS: A total of 30,373 patients initiated buprenorphine and 14.98% (4551) discontinued treatment. C-statistic varied between 0.56 and 0.76 for the first-stage models including patient-level demographic and clinical variables. Inclusion of proportion of days covered (PDC) measured after one month and three months following treatment initiation significantly increased the models' discriminative power (C-statistics: 0.60 to 0.82). Random forest (C-statistics: 0.76, 0.79 and 0.82 with baseline predictors, one-month PDC and three-months PDC, respectively) outperformed other ML models in discriminative performance in all stages (C-statistics: 0.56 to 0.77). Most influential risk factors of discontinuation included early stage medication adherence, age, and initial days of supply. CONCLUSION: ML algorithms demonstrated a good discriminative power in identifying patients at higher risk of buprenorphine care discontinuity. The proposed framework may help healthcare providers optimize treatment strategies and deliver targeted interventions to improve buprenorphine care continuity.

Clinical effectiveness of spindle-view intracytoplasmic sperm injection compared to conventional intracytoplasmic sperm injection in patients with poor ovarian response and previous implantation failure.

OBJECTIVE: This study aimed to determine the clinical advantage of spindle-view intracytoplasmic sperm injection (SVICSI; a novel technology) over conventional intracytoplasmic sperm injection (cICSI) in patients with poor ovarian response (POR) and previous implantation failure. METHODS: The study included 37 patients who underwent SVICSI followed by fresh embryo transfer (FET) at a single fertility clinic from January to December 2022, 58 patients who underwent cICSI followed by FET at the same fertility clinic from January to December 2021 as a control group. All study participants met the Bologna criteria for POR and had at least three or more previous failed embryo transfers. RESULTS: The number of blastocyst transfers was significantly higher in the SVICSI group than in the cICSI group. A good-quality cleavage embryo rate, blastocyst rate, and good-quality blastocyst rate were also significantly higher in the SVICSI group than in the cICSI group. There were no significant differences in the rates of fertilization, implantation, clinical pregnancy, or clinical abortion between the two groups. CONCLUSION: In patients with POR, those who underwent SVICSI appeared to have better embryos than those who underwent cICSI. However, whether SVICSI improved clinical outcomes such as implantation and pregnancy rates cannot be proven.

Trends in Attention-Deficit Hyperactivity Disorder Diagnosis and Pharmacotherapy Among Adults With Opioid Use Disorder.

OBJECTIVE: This study aimed to assess nationwide trends in attention-deficit hyperactivity disorder (ADHD) diagnoses and pharmacotherapy among patients with opioid use disorder and ADHD and to examine factors predicting receipt of stimulant medications among patients receiving medications for opioid use disorder (MOUDs). METHODS: A claims-based database of commercially insured patients ages 13-64 was used to conduct two analyses: an annual cross-sectional study of 387,980 patients diagnosed as having opioid use disorder (2007-2017) to estimate the prevalence of ADHD diagnoses and pharmacotherapy, and a retrospective cohort study of 158,591 patients receiving MOUDs to test, with multivariable regression, the association between patient characteristics and receipt of stimulant medication. RESULTS: From 2007 to 2017, the prevalence of ADHD diagnoses increased from 4.6% to 15.1% and the rate of ADHD pharmacotherapy increased from 42.6% to 51.8% among patients with opioid use disorder. Among all patients receiving MOUDs, 10.5% received at least one prescription stimulant during the study period. Female sex; residence in the southern United States; and ADHD, mood, and anxiety disorder diagnoses were associated with increased likelihood of stimulant receipt. Stimulant use disorder and other substance use disorder diagnoses were associated with decreased likelihood of stimulant receipt. CONCLUSIONS: ADHD diagnoses and pharmacotherapy among patients with opioid use disorder have increased. A minority of patients with ADHD and taking MOUDs received a stimulant. Further study is needed of the benefits and risks of ADHD pharmacotherapy for patients with opioid use disorder.

Proline-Hinged α-Helical Peptides Sensitize Gram-Positive Antibiotics, Expanding Their Physicochemical Properties to Be Used as Gram-Negative Antibiotics.

The outer membrane (OM) of Gram-negative bacteria is the most difficult obstacle for small-molecule antibiotics to reach their targets in the cytosol. The molecular features of Gram-negative antibiotics required for passing through the OM are that they should be positively charged rather than neutral, flat rather than globular, less flexible, or more increased amphiphilic moment. Because of these specific molecular characteristics, developing Gram-negative antibiotics is difficult. We focused on sensitizer peptides to facilitate the passage of hydrophobic Gram-positive antibiotics through the OM. We explored ways of improving the sensitizing ability of proline-hinged α-helical peptides by adjusting their length, hydrophobicity, and N-terminal groups. A novel peptide, 1403, improves the potentiation of rifampicin in vitro and in vivo and potentiates most Gram-positive antibiotics. The "sensitizer" approach is more plausible than those that rely on conventional drug discovery methods concerning drug development costs and the development of drug resistance.

Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21-100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10-20%/weekday followed by 2.5-10%/weekday over three weeks to (2) 10-25%/1-4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2-4 weeks, followed by 2-8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI-BZD, and 4 provided conflicting recommendations on the OPI-BZD deprescribing sequence. Thirty-five states' websites provided resources for opioid deprescription and three states' websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI-BZD deprescription.

Pre-Paid Phone Distribution: A Tool for Improving Healthcare Engagement for People with Substance Use Disorder.

BACKGROUND: The COVID-19 pandemic drove significant disruptions in access to substance use disorder (SUD) treatment and harm reduction services. Healthcare delivery via telemedicine has increasingly become the norm, rendering access to a phone essential for engagement in care. METHODS: Adult patients with SUD who lacked phones (n = 181) received a free, pre-paid phone during encounters with inpatient and outpatient SUD programs. We evaluated changes in healthcare engagement including completed in-person and telemedicine outpatient visits and telephone encounters 30 days before and after phone receipt. We used descriptive statistics, where appropriate, and paired t-tests to assess the change in healthcare engagement measures. RESULTS: Patients were predominantly male (64%) and white (62%) with high rates of homelessness (81%) and opioid use disorder (89%). When comparing 30 days before to 30 days after phone receipt, there was a significant increased change in number of telemedicine visits by 0.3 (95% CL [0.1,0.4], p < 0.001) and telephone encounters by 0.2 (95% CL [0.1,0.3], p = 0.004). There was no statistically significant change in in-person outpatient visits observed. CONCLUSIONS: Pre-paid phone distribution to patients with SUD was associated with an increased healthcare engagement including telemedicine visits and encounters.

Ambivalence and Stigma Beliefs About Medication Treatment Among Young Adults With Opioid Use Disorder: A Qualitative Exploration of Young Adults' Perspectives.

PURPOSE: Young adults with opioid use disorder (OUD) have low engagement in treatment with medication for opioid use disorder (MOUD). The objective of this study is to explore the beliefs and attitudes about MOUD among young adults. METHODS: We conducted a single-site qualitative study of 20 young adults ages 18-29 years with a diagnosis of OUD receiving care at an outpatient program and who spoke English. We used a flexible interview guide with the following domains: experience with MOUD, sources and impact of stigma, and interactions with family, healthcare professionals, and social networks. We conducted a thematic analysis based on deductive codes related to the domains and emergent codes from the interviews. RESULTS: We identified three themes. First, participants perceived being on MOUD as stigmatizing. They regarded MOUD as lifesaving but ultimately as a "crutch" hindering their full recovery. Second, young adults expressed ambivalence, distinct from stigma, about MOUD. This ambivalence was related to fear of withdrawal symptoms and concerns about their ability to live independent lives, side effects, and unknown treatment duration. Third, participants felt that MOUD was more than just a means to reduce risk of overdose, it was a means to become fully functioning in their lives. DISCUSSION: In this study of young adults in treatment for OUD, we found that stigma and ambivalence concerning MOUD could explain young adults' low engagement in care. Interventions addressing concerns about the stigmatizing effects of MOUD and the ambivalence young adults experience related to MOUD could improve engagement and retention of young adults.

An Exploration of Young Adults With Opioid Use Disorder and How Their Perceptions of Family Members' Beliefs Affects Medication Treatment.

BACKGROUND: Young adults with opioid use disorder (OUD) have low engagement and retention in medication treatment. Families are uniquely situated to play an important role in treatment decisions. This qualitative study explored how young adults with OUD perceive their families' beliefs about OUD and medication treatment, and how those beliefs impacted young adults' beliefs about their own treatment decisions. METHODS: We conducted a qualitative study of a convenience sample of 20 English-speaking young adults with OUD receiving care from an urban safety net hospital in Massachusetts. We explored young adults' perceptions of how families viewed medication treatment. We conducted semi-structured interviews that were recorded and transcribed. We analyzed interviews using hybrid inductive and deductive categorization to support thematic analysis. RESULTS: We identified 3 themes. First, family history of substance use disorder and treatment negatively impacted how young adults perceive their OUD and medication treatment. Second, young adults shared that many families held negative or stigmatizing views of medication treatment. Finally, acceptance by family was important but young adults acknowledged that keeping treatment decisions from family was sometimes necessary. CONCLUSIONS: In this qualitative exploration of young adults with OUD, we found that young adults felt that their families held important beliefs about the kind of treatment family members found most appropriate, and these perceived family beliefs impacted their treatment choices. Future research to improve engagement and retention of youth adults with OUD could target the beliefs of family members.

"My Life Isn't Defined by Substance Use": Recovery Perspectives Among Young Adults with Substance Use Disorder.

BACKGROUND: While substance use disorder remains a leading cause of morbidity and mortality for young adults, low rates of treatment engagement and retention persist. One explanation is that substance use disorder treatment approaches do not match young adults' expectations for recovery. While the concept of recovery has been explored among adult populations, less is known about how young adults think about recovery. OBJECTIVE: To describe perspectives of recovery among young adults with substance use disorder. DESIGN: Qualitative, in-depth interviews exploring young adults' definitions of recovery. PARTICIPANTS: Twenty English-speaking young adults (7 women; 21-29 years old) diagnosed with substance use disorder recruited from an urban safety net hospital in Massachusetts. APPROACH: Interviews were recorded and transcribed verbatim. An iterative categorization analytic approach was used to identify and interpret themes. KEY RESULTS: Four themes related to recovery were identified. First, young adults described recovery as a way to grow up and live a normal life not defined by the substance use. A second theme was recovery had to include multiple components, such as mental health treatment, to be successful. Third, young adults described recovery as a self-motivated process, and it was important that young adults had agency in recovery decision-making. Fourth, recovery was described as a lifelong pursuit that required vigilance and commitment. CONCLUSIONS: In this qualitative study of young adults with substance use disorder, participants identified themes that have implications for treatment models. Participants recognized recovery as a complex and individually motivated process that includes multiple components such as mental health treatment and re-engagement in regular daily activities. Models of care for young adults should consider incorporating these treatment elements to improve engagement and retention.

"It could potentially be dangerous... but nothing else has seemed to help me.": Patient and clinician perspectives on benzodiazepine use in opioid agonist treatment.

BACKGROUND: Benzodiazepine use among patients receiving opioid agonist treatment (OAT) presents a conundrum: benzodiazepines increase overdose risk, yet can treat anxiety and insomnia. How best to balance the risks and benefits of benzodiazepines among OAT patients is unclear. Using qualitative methods, we examined patient motivations for benzodiazepine use and understanding of risks, and the context in which benzodiazepine use and prescribing occurs. METHODS: We conducted semi-structured interviews with 26 OAT patients using benzodiazepines and 10 OAT clinicians. Participants were recruited from an office-based buprenorphine clinic at an academic medical center and a methadone opioid treatment program using purposive sampling. The study team reviewed transcripts and double-coded 100% of interviews. Data analysis combined both deductive and inductive methods. RESULTS: Major emergent themes were: 1) patients focus on benefits over risks of benzodiazepines, 2) patients can learn to use benzodiazepines safely, 3) patients want to use benzodiazepines now but discontinue in the future, 4) clinicians and patients weigh the risks and benefits of benzodiazepine use differently, 5) clinicians and patient have differences in treatment goals, and 6) clinicians struggle with benzodiazepine discontinuation. CONCLUSIONS: OAT patients and clinicians can weigh the risks and benefits of benzodiazepines differently leading to a difference in treatment goals. The risk-benefit analysis of benzodiazepine prescribing may depend on whether the patient is engaged in opioid treatment. Future work among patients and clinicians is warranted to determine how to better balance patient and clinician priorities in order to deliver safer prescribing practices and maintain patient engagement in care.

Adaptation of a System of Treatment for Substance Use Disorders During the COVID-19 Pandemic.

The Grayken Center for Addiction at Boston Medical Center includes programs across the care continuum for people with substance use disorders (SUDs), serving both inpatients and outpatients. These programs had to innovate quickly during the COVID-19 outbreak to maintain access to care. Federal and state regulatory flexibility allowed these programs to initiate treatment for people experiencing homelessness and maximize patient safety through physical distancing practices. Programs switched to telehealth with high levels of acceptability and patient retention. Some programs also maintained some face-to-face clinic visits to see patients with complex problems and to provide injectable medications. Text-messaging proved invaluable with adolescent and young adult clients, and a mobile-health outreach program was initiated to reach mother/child dyads affected by SUDs. A 24-hour hotline was implemented to support seamless access to treatment for hundreds released from incarceration early due to the pandemic. Boston Medical Center also launched the COVID Recuperation Unit to allow patients experiencing homelessness to recover from mild to moderate COVID-19 infection in an environment that took a harm-reduction approach to SUDs and provided rapid initiation of medication treatment. Many of these innovations increased access to treatment and retention of patients during the pandemic. Maintaining the revised regulations would allow flexibility to provide telehealth, extended prescriptions, and remote access to buprenorphine initiation to support and engage more patients with SUDs.

Correlation between patient health questionnaire-2 and postoperative pain in laparoscopic cholecystectomy.

BACKGROUND: Postoperative pain is affected by preoperative depression. If the risk of postoperative pain associated with depression can be predicted preoperatively, anesthesiologists and/or surgeons can better manage it with personalized care. The objective of this study was to determine the efficacy of Patient Health Questionnaire-2 (PHQ-2) depression screening tool as a predictor of postoperative pain. METHODS: A total of 50 patients scheduled for elective laparoscopic cholecystectomy with an American Society of Anesthesiologists physical status 1 or 2 were enrolled. They answered the PHQ-2, which consists of two questions, under the supervision of a researcher on the day before the surgery. The numerical rating scale (NRS) scores were assessed at post-anesthesia care unit (PACU), at 24, and 48 postoperative hours, and the amount of intravenous patient-controlled analgesia (IV-PCA) administered was documented at 24, 48, and 72 postoperative hours. At 72 h, the IV-PCA device was removed and the final dosage was recorded. RESULTS: The NRS score in PACU was not significantly associated with the PHQ-2 score (correlation coefficients: 0.13 [P = 0.367]). However, the use of analgesics after surgery was higher in patients with PHQ-2 score of 3 or more (correlation coefficients: 0.33 [P = 0.018]). CONCLUSIONS: We observed a correlation between the PHQ-2 score and postoperative pain. Therefore, PHQ-2 could be useful as a screening test for preoperative depression. Particularly, when 3 points were used as the cut-off score, the PHQ-2 score was associated with the dosage of analgesics, and the analgesic demand could be expected to be high with higher PHQ-2 scores.

Proline Hinged Amphipathic α-Helical Peptide Sensitizes Gram-Negative Bacteria to Various Gram-Positive Antibiotics.

Gram-negative bacteria are becoming resistant to almost all currently available antibiotics. Systemically designed antimicrobial peptides (AMPs) are attractive agents to enhance the activities of antibiotics. We constructed a small Pro-scanning library using amphipathic model peptides. Measurements of minimum inhibitory concentration (MIC) against Escherichia coli and hemolytic activities showed that one of the Pro-hinged peptides, KL-L9P, displays the highest specificity toward E. coli. Moreover, KL-L9P sensitizes E. coli to be responsive to most antibiotics that are not active against Gram-negative bacteria. The results of biochemical experiments show that KL-L9P promotes the rearrangement of the bacterial membrane that enables hydrophobic antibiotics to permeate. Finally, the results of animal tests demonstrate that KL-L9P strongly sensitizes Gram-negative bacteria to linezolid (Lzd), rifampicin (Rif), or clarithromycin (Clr). Thus, KL-L9P operates as a sensitizer to extend the antibacterial activity of most antibiotics to Gram-negative bacteria.

Associations between prescribed benzodiazepines, overdose death and buprenorphine discontinuation among people receiving buprenorphine.

BACKGROUND AND AIMS: Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. DESIGN AND SETTING: This was a retrospective cohort study using five individually linked data sets from Massachusetts, United States government agencies. PARTICIPANTS: We studied 63 389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015. MEASUREMENTS: Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment. FINDINGS: Of the 63 345 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one per cent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) = 2.92, 95% confidence interval (CI) = 2.10-4.06, non-fatal opioid overdose, adjusted HR = 2.05, 95% CI, 1.68-2.50, all-cause mortality, adjusted HR = 1.90, 95% CI, 1.48-2.44 and a decreased risk of buprenorphine discontinuation, adjusted HR = 0.87, 95% CI, 0.85-0.89. CONCLUSIONS: Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.

A Preliminary Survey on Clinical Practice for Children and Adolescents with Gender Dysphoria in Japan: Current Situation and Challenges.

Little is known about the treatment of gender dysphoria among children and adolescents in Japan. This preliminary survey aims to improve understanding of current clinical practice for treatment of children with gender dysphoria. Subjects were 315 certified child and adolescent psychiatrists in Japan. The questionnaire asked about clinical experiences concerning gender dysphoria and gender identityrelated concerns. A total of 128 psychiatrists responded to the questionnaire. Mean length of clinical experience was 24.2±10.0 years in total and 16.9±11.5 years as child and adolescent psychiatry specialists. Among the respondents, 74 (57.8%) had seen children and adolescents with DSM-5 gender dysphoria, and 87 (67.7%) had examined cases with gender identity-related concerns. The mean number of experienced cases with gender dysphoria was 1.80±2.3 per respondent. We found that even among certified child and adolescent psychiatrists in Japan, experience with treatment of children with gender dysphoria was limited.

Stigma associated with medication treatment for young adults with opioid use disorder: a case series.

BACKGROUND: Opioid-related overdose deaths have risen sharply among young adults. Despite this increase, access to evidence-based medication for opioid agonist treatment (OAT) for youth remains low. Among older adults, barriers to OAT include the paucity of buprenorphine-waivered prescribers and low rates of prescribing among waivered physicians. We have increasingly found in our clinical practice significant stigma related to using OAT to treat addiction for young adults. In this series, we describe three cases of young adults who faced significant stigma related to their treatment. CASE PRESENTATIONS: The first case is a young male with a history of significant trauma and a severe opioid use disorder. He started buprenorphine and has found a job, stayed abstinent, and began a healthy relationship. At each step in his recovery, he has faced resistance to taking medication from other treatment providers, directors of sober houses, and his parents. The second case is a young woman who presented to a substance use treatment program after a relapse. She was unable to restart buprenorphine despite our calling to ask that it be restarted. Ultimately, she left against medical advice and was stabilized as an outpatient on buprenorphine. The final case is a young woman who stopped buprenorphine after being told she was "not sober" while attending 12-step group but restarted after conversations with her clinical team. In each case, the patient has continued their medication treatment and are stable. CONCLUSIONS: Opioid-related deaths continue to rise among all age groups, including young adults. Stigma related to medication treatment can be a substantial barrier for many young adult patients but there are concrete steps that providers and communities can take to address this stigma.

Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells.

CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulates CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While the overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased the expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetylcysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing the CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated the claudin-1 and MUC1 expressions, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway. [BMB Reports 2017; 50(10): 516-521].

Debate: Are Benzodiazepines Appropriate Treatments for Patients with Substance Use Disorders? Yes.

Benzodiazepines are a controversial treatment for anxiety in patients with substance use disorders. Concerns include risk of addiction, overdose, and diversion. But benzodiazepines are among the most effective and well-tolerated treatments for anxiety, and are safe for the majority of patients who take them. Though not appropriate for all cases, particularly in those with an active opioid use disorder, benzodiazepines should be considered as a treatment for patients with substance use disorders after careful weighing of benefits and harms.

Opioid Overdose: Risk Assessment and Mitigation in Outpatient Treatment.

The present clinical case discussion focuses on a patient with comorbid substance use disorder (SUD) and chronic pain, who experienced an overdose of heroin. The case illustrates the complex array of risk factors that contribute to overdose risk, discusses the use of naloxone, and highlights the need for further risk mitigation interventions in patients at risk for overdose.

Understanding Risk Factors for Opioid Overdose in Clinical Populations to Inform Treatment and Policy.

Overdoses involving opioid analgesics represent a significant public health problem in the United States. We reviewed the literature on risk factors for overdose, with a focus on studies that examine clinical populations of patients receiving opioids for pain and potential risk factors for overdose in these populations. A structured review resulted in 15 articles published between 2007 and 2015 that examined risk factors for fatal and nonfatal overdose in patients receiving opioid analgesics. Opioid dosage was the factor most consistently analyzed and also associated with increased risk of overdose. Other risk factors include concurrent use of sedative-hypnotics, use of extended-release/long-acting opioids, and the presence of substance use and other mental health disorder comorbidities. Future research is needed to better characterize populations taking opioids for pain to help clarify discrepancies between existing studies and identify previously unexplored risk factors for overdose. Given that policy and clinical practice have shifted as a result of prior studies reviewed here, further efforts in understanding patient groups and opioid-related prescribing practices associated with overdose risk have great potential to impact policy and practice in the treatment of pain while improving the safety around opioid prescribing.