<p><strong>BACKGROUND: </strong>Children who undergo common outpatient surgeries are routinely prescribed opioids, although available evidence suggests opioids should be used with discretion for procedures associated with mild to moderate pain. The study assessed trends in postoperative opioid prescribing over time to determine if prescribing declined.</p>

<p><strong>METHODS: </strong>We used a private insurance database to study opioid-naïve patients under the age of 18 who underwent 1 of 8 surgical procedures from 2014 to 2019. The primary outcome was the likelihood of filling a prescription for opioids within 7 days of surgery, and the secondary outcome was the total amount of opioid dispensed. We used Joinpoint regression analysis to identify temporal shifts in trends.</p>

<p><strong>RESULTS: </strong>The study cohort included 124 249 opioid-naïve children. The percentage of children who filled an opioid prescription decreased from 78.2% (95% confidence interval [CI] 76.3-80.1) to 48.0% (95% CI 45.8-50.1) among adolescents, from 53.9% (95% CI 51.6-56.2) to 25.5% (95% CI 23.5-27.5) among school-aged children and 30.4% (95% CI 28.6-32.2) to 11.5% (95% CI 10.1-12.9) among preschool-aged children. The average morphine milligram equivalent dispensed declined from 228.9 (95% CI 220.1-237.7) to 110.8 (95% CI 105.6-115.9) among adolescents, 121.3 (95% CI 116.7-125.9) to 65.9 (95% CI 61.1-70.7) among school-aged children and 75.3 (95% CI 70.2-80.3) to 33.2 (95% CI 30.1-36.3) among preschool-aged children. Using Joinpoint regression, we identified rapid opioid deadoption beginning in late 2017, first in adolescents, then followed by school- and preschool-aged children.</p>

<p><strong>CONCLUSION: </strong>Opioid prescribing after surgery decreased gradually from 2014 to 2017, with a more pronounced decrease seen beginning in late 2017.</p>

<p><strong>Importance: </strong>While the 2016 US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic pain was not intended to address postoperative pain management, observers have noted the potential for the guideline to have affected postoperative opioid prescribing.</p>

<p><strong>Objective: </strong>To assess changes in postoperative opioid dispensing after vs before the CDC guideline release in March 2016.</p>

<p><strong>Design, Setting, and Participants: </strong>This cross-sectional study included 361 556 opioid-naive patients who received 1 of 8 common surgical procedures between March 16, 2014, and March 15, 2018. Data were retrieved from a private insurance database, and a retrospective interrupted time series analysis was conducted. Data analysis was conducted from March 2014 to April 2018.</p>

<p><strong>Exposure: </strong>Outcomes were measured before and after release of the 2016 CDC guideline.</p>

<p><strong>Main Outcomes and Measures: </strong>The primary outcome was the total amount of opioid dispensed in the first prescription filled within 7 days following surgery in morphine milligram equivalents (MMEs); secondary outcomes included the total amount of opioids prescribed and the incidence of any opioid refilled within 30 days after surgery. To characterize absolute opioid dispensing levels, the amount dispensed in initial prescriptions was compared with available procedure-specific recommendations.</p>

<p><strong>Results: </strong>The sample included 361 556 opioid-naive patients undergoing 8 general and orthopedic surgical procedures; 164 009 (45.4%) were male patients, and the median (interquartile range) age of the sample was 58 (45 to 69) years. The total amount of opioids dispensed in the first prescription after surgery decreased in the 2 years following the CDC guideline release, compared with an increasing trend in the 2 years prior (prerelease trend: 1.43 MME/month; 95% CI, 0.62 to 2.24 MME/month; P = .001; postrelease trend: -2.18 MME/month; 95% CI, -3.01 to -1.35 MME/month; P &lt; .001; trend change: -3.61 MME/month; 95% CI, -4.87 to -2.35 MME/month; P &lt; .001). Changes in initial dispensing amount trends were greatest for patients undergoing hip or knee replacement (-8.64 MME/month; 95% CI, -11.68 to -5.60 MME/month; P &lt; .001). Minimal changes were observed in rates of refills over time (net change: 0.14% per month; 95% CI, 0.06% to 0.23% per month; P = .001). Absolute amounts prescribed remained high throughout the period, with nearly half of patients (47.7%; 95% CI, 47.4%-47.9%) treated in the postguideline period receiving at least twice the initial opioid dose anticipated to treat postoperative pain based on available procedure-specific recommendations.</p>

<p><strong>Conclusions and Relevance: </strong>In this study, opioid dispensing after surgery decreased substantially after the 2016 CDC guideline release, compared with an increasing trend during the 2 years prior. Absolute amounts prescribed for surgery remained high during the study period, supporting the need for further efforts to improve postoperative pain management.</p>

<p><strong>OBJECTIVE: </strong>The authors sought to determine whether use of methylphenidate in adults is associated with elevated rates of serious cardiovascular events compared with rates in nonusers.</p>

<p><strong>METHOD: </strong>This was a cohort study of new users of methylphenidate based on administrative data from a five-state Medicaid database and a 14-state commercial insurance database. All new methylphenidate users with at least 180 days of prior enrollment were identified. Users were matched on data source, state, sex, and age to as many as four comparison subjects who did not use methylphenidate, amphetamines, or atomoxetine. A total of 43,999 new methylphenidate users were identified and matched to 175,955 nonusers. Events of primary interest were 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, and 4) a composite endpoint of stroke or myocardial infarction.</p>

<p><strong>RESULTS: </strong>The age-standardized incidence rate per 1,000 person-years of sudden death or ventricular arrhythmia was 2.17 (95% CI=1.63-2.83) in methylphenidate users and 0.98 (95% CI=0.89-1.08) in nonusers, for an adjusted hazard ratio of 1.84 (95% CI=1.33-2.55). Dosage was inversely associated with risk. Adjusted hazard ratios for stroke, myocardial infarction, and the composite endpoint of stroke or myocardial infarction did not differ statistically from 1.</p>

<p><strong>CONCLUSIONS: </strong>Although initiation of methylphenidate was associated with a 1.8-fold increase in risk of sudden death or ventricular arrhythmia, the lack of a dose-response relationship suggests that this association may not be a causal one.</p>

<p><strong>MAIN OBJECTIVE: </strong>To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users.</p>

<p><strong>METHODS: </strong>This was a retrospective cohort study of new amphetamines (n=38,586) or atomoxetine (n=20,995) users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n=238,183). The following events were primary outcomes of interest 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, 4) a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator.</p>

<p><strong>RESULTS: </strong>The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55-2.54) for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44-1.47) for stroke, 0.75 (95% CI: 0.42-1.35) for myocardial infarction, and 0.78 (95% CI: 0.51-1.19) for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10-1.75) for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52-3.29) for stroke, 0.56 (95% CI: 0.16-2.00) for myocardial infarction, and 0.92 (95% CI: 0.44-1.92) for stroke/myocardial infarction.</p>

<p><strong>CONCLUSIONS: </strong>Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.</p>

<p><strong>SETTING: </strong>The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear.</p>

<p><strong>OBJECTIVE: </strong>To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana.</p>

<p><strong>DESIGN: </strong>Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs).</p>

<p><strong>RESULTS: </strong>A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P &gt; 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4).</p>

<p><strong>CONCLUSION: </strong>We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.</p>