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The relative risk of major gastrointestinal bleeding (GIB) among different direct oral anticoagulants (DOACs) is debatable. Randomized controlled trials (RCTs) comparing DOACs with each other are lacking. We performed network meta-analysis to assess whether the risk of major GIB differs based on type and dose of DOAC. Literature search of PubMed, EMBASE and Cochrane databases from inception to August 2019, limited to English publications, was conducted to identify RCTs comparing DOACs with warfarin or enoxaparin for any indication. Primary outcome of interest was major GIB risk. We used frequentist network meta-analysis through the random-effects model to compare DOACs with each other and DOACs by dose to isolate the impact on major GIB. Twenty-eight RCTs, including 139 587 patients receiving six anticoagulants, were selected. The risk of major GIB for DOACs was equal to warfarin. Comparison of DOACs with each other did not show risk differences. After accounting for dose, rivaroxaban 20 mg, dabigatran 300 mg and edoxaban 60 mg daily had 47, 40 and 22% higher rates of major GIB versus warfarin, respectively. Apixaban 5 mg twice daily had lower major GIB compared to dabigatran 300 mg (OR, 0.63; 95% CI, 0.44-0.88) and rivaroxaban 20 mg (OR, 0.60; 95% CI, 0.43-0.83) daily. Heterogeneity was low, and the model was consistent without publication bias (Egger's test: P = 0.079). All RCTs were high-quality with low risk of bias. DOACs at standard dose, except apixaban, had a higher risk of major GIB compared to warfarin. Apixaban had a lower rate of major GIB compared to dabigatran and rivaroxaban.

OBJECTIVE: Primary care physicians (PCPs) are positioned to mitigate opioid morbidity and mortality, but their engagement in primary, secondary, and tertiary opioid-related prevention behaviors is unclear. The objective of this study was to evaluate Tennessee PCPs' engagement in and intention to engage in multiple opioid-related prevention behaviors. METHODS: A survey instrument was developed, pretested, and pilot tested with practicing PCPs. Thereafter, a census of eligible Tennessee PCPs was conducted using a modified, four-wave tailored design method approach. Three patient scenarios were employed to assess physician intention to engage in 10 primary, secondary, and tertiary prevention behaviors. Respondents were asked to report, given 10 similar scenarios, the number of times (0-10) they would engage in prevention behaviors. Descriptive statistics were calculated using SPSS version 25. RESULTS: A total of 296 usable responses were received. Physician intention to engage in prevention behaviors varied across the 10 behaviors studied. Physicians reported frequently communicating risks associated with prescription opioids to patients (8.9 ± 2.8 out of 10 patients), infrequently utilizing brief questionnaires to assess for risk of opioid misuse (1.7 ± 3.3 out of 10 patients), and screening for current opioid misuse (3.1 ± 4.3 out of 10 patients). Physicians reported seldomly co-prescribing naloxone for overdose reversal and frequently discharging from practice patients presenting with an opioid use disorder. CONCLUSIONS: This study noted strengths and opportunities to increase engagement in prevention behaviors. Understanding PCPs' engagement in opioid-related prevention behaviors is important to effectively target and implement morbidity and mortality reducing interventions.

OBJECTIVE: Post-operative patients are at increased risk of becoming chronic users of opioids, and overprescribing can lead to abuse and diversion. Though data have shown a decrease in opioid prescriptions nationally, limited studies have specifically evaluated the influence of state legislation on this trend. This study aimed to assess the impact of legislation in the state of Tennessee on opioid prescribing amongst orthopedic surgeons. DESIGN: This retrospective cohort analysis evaluated patients who received opioids post-orthopedic surgery before and after the state legislation was passed. SETTING: A community teaching hospital. PATIENTS AND PARTICIPANTS: Two hundred and three post-orthopedic surgery patients were included, with 101 in the preleg-islation and 102 in the post-legislation groups. INTERVENTIONS: State legislation in Tennessee limiting amounts of prescribed opioids went into effect in July 2018. MAIN OUTCOME MEASURE(S): The primary outcome was total morphine milligram equivalents (MMEs) prescribed, with secondary outcomes of days' supply, dosage units, and MME per day. RESULTS: Orthopedic surgery patients in the post-legislation arm were prescribed significantly fewer MME than those in the prelegislation arm (median MME 375 vs. 562.5; p < 0.001). Prescription days' supply, number of dosage units, and MME per day were also significant lower in the post-legislation group. CONCLUSIONS: After orthopedic surgery, patients in the post-legislation arm were prescribed a median 187.5 MME less than those in the prelegislation arm. Our findings suggest that state opioid legislation is associated with a reduction in the amount of opioids prescribed in certain orthopedic surgery patients, though further studies evaluating adequacy of pain control are warranted.

BACKGROUND AND OBJECTIVES: Sexual minority individuals demonstrate disparate rates of substance use. Research suggests that bisexual women are vulnerable to substance use disorders when compared to other sexual minority groups. This study explored differences in prevalence of past-year alcohol use disorder (AUD) with and without concurrent past-year opioid and/or benzodiazepine misuse. METHODS: The present study utilized responses from the National Survey on Drug Use and Health (NSDUH) public dataset between the years 2015-2019 (N = 16,002) to examine the association between sexual orientation and concurrent misuse of opioids and/or benzodiazepines among individuals with past-year AUD, stratified by sex. RESULTS: Bisexual females demonstrated higher rates of concurrent opioid and benzodiazepine use compared to all other groups. Although there was no association between sexual orientation and concurrent substance use patterns among males, female respondents with past-year AUD endorsing past-year misuse of opioids and benzodiazepines, both alone and in combination, were more likely to be bisexual compared to heterosexual. Lesbians were less likely to endorse concurrent misuse of opioids and benzodiazepines compared to bisexual females. DISCUSSION AND CONCLUSIONS: In a national sample, bisexual females demonstrated higher odds of risky concurrent substance use patterns. Identifying sexual minority individuals who exhibit elevated risk of co-occurring alcohol, opioid, and/or benzodiazepine misuse is an important step to targeted prevention efforts and allocation of resources to combat rising overdose deaths. SCIENTIFIC SIGNIFICANCE: For the first time, this study explored risky concurrent alcohol, opioid, and benzodiazepine misuse patterns among individuals of different sexual orientations.

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