Reducing overdose deaths among persons with opioid use disorder in connecticut.

BACKGROUND: People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary. METHODS: We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons. RESULTS: Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime. CONCLUSIONS: Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.

Does the Association Between Stimulant use and High Risk Sexual Behavior Vary by Injection Drug Use, Sexual Minority Status, or HIV Infection Status? A Meta-analysis.

There is strong evidence linking stimulant use, namely methamphetamine use, to sexual risk behavior among sexual minority men (SMM); we do not, however, have a good understanding of this relationship among other at-risk populations. In this study, we systematically reviewed associations between stimulant use (i.e., methamphetamine, crack cocaine, cocaine) and sexual risk behaviors among populations facing elevated risk of HIV transmission and acquisition (i.e., SMM, people who inject drugs (PWID), and people living with HIV/AIDS (PLWH)). Random-effects meta-analyses and sensitivity analyses that included crude and adjusted estimates separately were conducted to evaluate the impact of potential confounding variables. The results showed strong relationships between stimulant use and condomless sex, transactional sex, and multiple sexual partners. Results were broadly consistent when analyses were stratified by type of stimulant (methamphetamine, crack cocaine, and other stimulants) and risk group. Sensitivity analyses with confounding variables did not greatly impact results. The results indicate that stimulant use is associated with numerous sexual risk behaviors regardless of risk group, suggesting prevention efforts focused on reducing methamphetamine-related HIV risk should target a range of at-risk populations.

A cluster-randomized, non-inferiority trial comparing use of misoprostol for universal prophylaxis vs. secondary prevention of postpartum hemorrhage among community level births in Egypt.

BACKGROUND: Previous community-based research shows that secondary prevention of postpartum hemorrhage (PPH) with misoprostol only given to women with above-average measured blood loss produces similar clinical outcomes compared to routine administration of misoprostol for prevention of PPH. Given the difficulty of routinely measuring blood loss for all deliveries, more operational models of secondary prevention are needed. METHODS: This cluster-randomized, non-inferiority trial included women giving birth with nurse-midwives at home or in Primary Health Units (PHUs) in rural Egypt. Two PPH management approaches were compared: 1) 600mcg oral misoprostol given to all women after delivery (i.e. primary prevention, current standard of care); 2) 800mcg sublingual misoprostol given only to women with 350-500 ml postpartum blood loss estimated using an underpad (i.e. secondary prevention). The primary outcome was mean change in pre- and post-delivery hemoglobin. Secondary outcomes included hemoglobin ≥2 g/dL and other PPH interventions. RESULTS: Misoprostol was administered after delivery to 100% (1555/1555) and 10.7% (117/1099) of women in primary and secondary prevention clusters, respectively. The mean drop in pre- to post-delivery hemoglobin was 0.37 (SD: 0.91) and 0.45 (SD: 0.76) among women in primary and secondary prevention clusters, respectively (difference adjusted for clustering = 0.01, one-sided 95% CI: < 0.27, p = 0.535). There were no statistically significant differences in secondary outcomes, including hemoglobin drop ≥2 g/dL, PPH diagnosis, transfer to higher level, or other interventions. CONCLUSIONS: Misoprostol for secondary prevention of PPH is comparable to universal prophylaxis and can be implemented using local materials, such as underpads. TRIAL REGISTRATION: Clinicaltrials.gov NCT02226588, date of registration 27 August 2014.

Intramuscular injection, intravenous infusion, and intravenous bolus of oxytocin in the third stage of labor for prevention of postpartum hemorrhage: a three-arm randomized control trial.

BACKGROUND: Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis. METHODS: In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial. RESULTS: Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, - 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, - 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm. CONCLUSIONS: Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis. TRIAL REGISTRATION: clinicaltrials.gov # NCT01914419 , posted August 2, 2013.

A randomized trial comparing the pharmacology of magnesium sulfate when used to treat severe preeclampsia with serial intravenous boluses versus a continuous intravenous infusion.

BACKGROUND: Magnesium sulfate is the preferred pharmacological intervention for the prevention and treatment of eclamptic seizures in pregnancy. Pain associated with intramuscular injections and the need for an electronic infusion pump for use intravenously represent significant barriers to broader utilization. We hypothesize that an alternative regimen based on serial intravenous (IV) boluses can produce serum concentrations comparable to those produced by a continuous infusion. METHODS: An open-label randomized trial was performed at two hospitals in Egypt. Women with severe preeclampsia were eligible and enrolled between January 2015 and February 2016. Two hundred subjects were randomized by random numbers generated centrally in distinct blocks and stratified by study site. They were assigned to a continuous infusion arm, (4 g loading dose with 1 g/hr. continuous infusion) or a serial IV bolus arm, (6 g loading dose with 2 g bolus every 2 h using a Springfusor® pump). Sparsely sampled magnesium serum concentrations were collected, nonlinear mixed effect modeling was conducted and Monte Carlo simulations were used to generate 200 simulated subjects in each treatment arm. The simulated populations were used to determine area under the concentration-time curve (AUC) as a measure of total drug exposure and compared. RESULTS: Simulated area under the magnesium serum concentration-time curve was significantly higher in the serial IV bolus arm than in the continuous infusion arm (1107 ± 461 mmol•min /L vs. 1010 ± 398 mmol•min /L, (P = 0.02)). Four percent of women in the serial bolus arm considered the treatment unacceptable or very unacceptable compared to 2% in the continuous infusion arm, (P = 0.68). CONCLUSIONS: Serial IV boluses achieve serum magnesium concentrations statistically significantly higher but clinically comparable to those achieved with a continuous infusion and offer a third option for the administration of MgSO4 to women with preeclampsia that may reduce barriers to utilization. TRIAL REGISTRATION: Trial no. NCT02091401, March 17, 2014.

Does smoking cessation reduce other substance use, psychiatric symptoms, and pain symptoms? Results from an emulated hypothetical randomized trial of US veterans.

BACKGROUND: Quitting smoking may lead to improvement in substance use, psychiatric symptoms, and pain, especially among high-risk populations who are more likely to experience comorbid conditions. However, causal inferences regarding smoking cessation and its subsequent benefits have been limited. METHODS: We emulated a hypothetical open-label randomized control trial of smoking cessation using longitudinal observational data of HIV-positive and HIV-negative US veterans from 2003-2015 in the Veterans Aging Cohort Study. We followed individuals from the first time they self-reported current cigarette smoking (baseline). We categorized participants as quitters or non-quitters at the first follow-up visit (approximately 1 year after baseline). Using inverse probability weighting to adjust for confounding and selection bias, we estimated odds ratios for improvement of co-occurring conditions (unhealthy alcohol use, cannabis use, illicit opioid use, cocaine use, depressive symptoms, anxiety symptoms, and pain symptoms) at second follow-up (approximately 2 years after baseline) for those who quit smoking compared to those who did not, among individuals who had the condition at baseline. RESULTS: Of 4,165 eligible individuals (i.e., current smokers at baseline), 419 reported no current smoking and 2,330 reported current smoking at the first follow-up. Adjusted odds ratios (95% confidence intervals) for associations between quitting smoking and improvement of each condition at second follow-up were: 2.10 (1.01, 4.35) for unhealthy alcohol use, 1.75 (1.00, 3.06) for cannabis use, 1.10 (0.58, 2.08) for illicit opioid use, and 2.25 (1.20, 4.24) for cocaine use, 0.78 (0.44, 1.38) for depressive symptoms, 0.93 (0.58, 1.49) for anxiety symptoms, and 1.31 (0.84, 2.06) for pain symptoms. CONCLUSIONS: While a causal interpretation of our findings may not be warranted, we found evidence for decreased substance use among veterans who quit cigarette smoking but none for the resolution of psychiatric conditions or pain symptoms. Findings suggest the need for additional resources combined with smoking cessation to reduce psychiatric and pain symptoms for high-risk populations.

Cessation of self-reported opioid use and impacts on co-occurring health conditions.

BACKGROUND: Among veterans in care reporting opioid use, we investigated the association between ceasing opioid use on subsequent reduction in report of other substance use and improvements in pain, anxiety, and depression. METHODS: Using Veterans Aging Cohort Study survey data collected between 2003 and 2012, we emulated a hypothetical randomized trial (target trial) of ceasing self-reported use of prescription opioids and/or heroin, and outcomes including unhealthy alcohol use, smoking, cannabis use, cocaine use, pain, and anxiety and depressive symptoms. Among those with baseline opioid use, we compared participants who stopped reporting opioid use at the first follow-up (approximately 1 year after baseline) with those who did not. We fit logistic regression models to estimate associations with change in each outcome at the second follow-up (approximately 2 years after baseline) among participants with that condition at baseline. We examined two sets of adjusted models that varied temporality assumptions. RESULTS: Among 2473 participants reporting opioid use, 872 did not report use, 606 reported use, and 995 were missing data on use at the first follow-up. Ceasing opioid use was associated with no longer reporting cannabis (adjusted odds ratio [AOR]=1.82, 95% confidence interval [CI] 1.10, 3.03) and cocaine use (AOR=1.93, 95% CI 1.16, 3.20), and improvements in pain (AOR=1.53, 95% CI 1.05, 2.24) and anxiety (AOR=1.56, 95% CI 1.01, 2.41) symptoms. CONCLUSION: Cessation of opioid misuse may be associated with subsequent cessation of other substances and reduction in pain and anxiety symptoms, which supports efforts to screen and provide evidence-based intervention where appropriate.

Abortion Aftercare Instructions in the United States: A Content Analysis of Patient Handouts.

BACKGROUND: At the clinical visit for abortion care, patients typically receive a handout with information about what to expect and how to care for themselves after the abortion. Published guidelines give little to no guidance regarding the content of postabortion instructions. METHODS: We collected aftercare instruction handouts for first trimester procedural and medication abortion from abortion clinics throughout the United States. Instructions were coded and analyzed using conventional content analysis. RESULTS: Of the 84 unique aftercare handouts we received, most included information about symptoms to expect (included in 98% of procedural handouts, 97% of medication handouts), how to manage symptoms (included in 100% of procedural handouts, 100% of medication handouts), and specific behaviors to avoid (included in 94% of procedural handouts, 66% of medication handouts). The most common behavioral avoidance instructions were "pelvic rest" (included in 90% of procedural handouts, 63% of medication handouts), avoiding strenuous activity (included in 61% of procedural handouts, 29% of medication handouts), and avoiding submersion in water (included in 41% of procedural handouts, 26% of medication handouts). Handouts varied with regard to the extent and duration of specific recommendations. They also varied in tone, word choice, and other characteristics. CONCLUSIONS: There exists a wide range of abortion aftercare instructions throughout the United States. Inconsistency among instructions may reflect a lack of published, evidence-based clinical guidelines. Standardizing aftercare instruction handouts based on patient-oriented evidence could improve patient experience after abortion.

Postpartum infection, pain and experiences with care among women treated for postpartum hemorrhage in three African countries: A cohort study of women managed with and without condom-catheter uterine balloon tamponade.

OBJECTIVE: We aimed to determine the risk of postpartum infection and increased pain associated with use of condom-catheter uterine balloon tamponade (UBT) among women diagnosed with postpartum hemorrhage (PPH) in three low- and middle-income countries (LMICs). We also sought women's opinions on their overall experience of PPH care. METHODS: This prospective cohort study compared women diagnosed with PPH who received and did not receive UBT (UBT group and no-UBT group, respectively) at 18 secondary level hospitals in Uganda, Egypt, and Senegal that participated in a stepped wedge, cluster-randomized trial assessing UBT introduction. Key outcomes were reported pain (on a scale 0-10) in the immediate postpartum period and receipt of antibiotics within four weeks postpartum (a proxy for postpartum infection). Outcomes related to satisfaction with care and aspects women liked most and least about PPH care were also reported. RESULTS: Among women diagnosed with PPH, 58 were in the UBT group and 2188 in the no-UBT group. Self-reported, post-discharge antibiotic use within four weeks postpartum was similar in the UBT (3/58, 5.6%) and no-UBT groups (100/2188, 4.6%, risk ratio = 1.22, 95% confidence interval [CI]: 0.45-3.35). A high postpartum pain score of 8-10 was more common among women in the UBT group (17/46, 37.0%) than in the no-UBT group (360/1805, 19.9%, relative risk ratio = 3.64, 95% CI:1.30-10.16). Most women were satisfied with their care (1935/2325, 83.2%). When asked what they liked least about care, the most common responses were that medications (580/1511, 38.4%) and medical supplies (503/1511, 33.3%) were unavailable. CONCLUSION: UBT did not increase the risk of postpartum infection among this population. Women who receive UBT may experience higher degrees of pain compared to women who do not receive UBT. Women's satisfaction with their care and stockouts of medications and other supplies deserve greater attention when introducing new technologies like UBT.

Empowerment evaluation: building prevention science and organizational capacity to prevent sexual violence.

The articles in this special issue all result from the employment of empowerment evaluation with the intention of furthering the field of sexual violence prevention. Centers for Disease Control and Prevention's goals were to build the science toward evidence-based programming and to build evaluation capacity among leaders in the sexual violence field. Other undefined benefits also resulted, including the facilitation of implementation of program improvements and the development of capacities that can be generalized across other aspects of the participants' work. These benefits are attributed to empowerment evaluation's intentional designation of evaluation activities to the same people responsible for program delivery. Empowerment evaluation's potential to make future contributions to the field of sexual violence prevention is discussed.

Developing teen dating violence prevention strategies: formative research with middle school youth.

Intimate partner violence (IPV) peaks in youth and young adulthood and is associated with multiple adolescent risk behaviors and negative health outcomes. Targeting youth with prevention messages before they start dating may avert teen dating violence and subsequent adult IPV. This article discusses findings from focus groups with middle school youth to determine behaviors and beliefs regarding dating violence. To develop effective prevention messages, participants were asked questions about characteristics of middle school dating relationships, healthy relationships, relationship norms, unhealthy relationships, emotional abuse, physical abuse, sexual abuse, intervening in violent situations, and trusted sources for information about dating violence. The recommendations for prevention efforts include an emphasis on skill building, tailoring efforts for particular subgroups, and identifying innovative ways of reaching youth.

Vaginal and Rectal Clostridium sordellii and Clostridium perfringens Presence Among Women in the United States.

OBJECTIVE: To characterize the presence of Clostridium sordellii and Clostridium perfringens in the vagina and rectum, identify correlates of presence, and describe strain diversity and presence of key toxins. METHODS: We conducted an observational cohort study in which we screened a diverse cohort of reproductive-aged women in the United States up to three times using vaginal and rectal swabs analyzed by molecular and culture methods. We used multivariate regression models to explore predictors of presence. Strains were characterized by pulsed-field gel electrophoresis and tested for known virulence factors by polymerase chain reaction assays. RESULTS: Of 4,152 participants enrolled between 2010 and 2013, 3.4% (95% confidence interval [CI] 2.9-4.0) were positive for C sordellii and 10.4% (95% CI 9.5-11.3) were positive for C perfringens at baseline. Among the 66% with follow-up data, 94.7% (95% CI 88.0-98.3) of those positive for C sordellii and 74.4% (95% CI 69.0-79.3) of those positive for C perfringens at baseline were negative at follow-up. At baseline, recent gynecologic surgery was associated with C sordellii presence, whereas a high body mass index was associated with C perfringens presence in adjusted models. Two of 238 C sordellii isolates contained the lethal toxin gene, and none contained the hemorrhagic toxin gene. Substantial strain diversity was observed in both species with few clusters and no dominant clones identified. CONCLUSION: The relatively rare and transient nature of C sordellii and C perfringens presence in the vagina and rectum makes it inadvisable to use any screening or prophylactic approach to try to prevent clostridial infection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01283828.