Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence.

BACKGROUND: Although many large, randomized controlled trials (RCT) have been conducted on antibiotic therapy for patients with primary C. difficile infections (CDI), few RCTs have been performed for patients with recurrent CDI (rCDI). In addition, fecal microbial transplant (FMT) is neither FDA-approved or guideline-recommended for patients with pauci-rCDI (first or second recurrences). Therefore, a rigorous RCT of sufficient size was designed to determine the optimal treatment among three antibiotic regimens in current practice for treatment of pauci-rCDI. METHODS: VA Cooperative Studies Program (CSP) #596 is a prospective, double-blind, multi-center clinical trial of veteran patients with pauci-rCDI comparing fidaxomicin (FDX) 200 mg twice daily for 10 days and vancomycin (VAN) 125 mg four times daily for 10 days followed by a 3-week vancomycin taper and pulse (VAN-T/P) regimen to a standard course of VAN 125 mg four times daily for 10 days. The primary endpoint is sustained clinical response at day 59, with sustained response measured as a diarrhea composite outcome (D-COM) that includes symptom resolution during treatment (before day 10) without recurrence of diarrhea or other clinically important outcomes through day 59. DISCUSSION: CSP study 596 is designed to compare three current antibiotic treatments for recurrent CDI that are in clinical practice, but which lack high-quality evidence to support strong guideline recommendations. The design of the study which included a pilot phase initiated at six sites with expansion to 24 sites is described along with protocol modifications based on early trial experience and clinical realities including the COVID-19 pandemic. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov (Identifier: NCT02667418).

Characteristics of Marijuana Use During Pregnancy - Eight States, Pregnancy Risk Assessment Monitoring System, 2017.

Marijuana is the most commonly used illicit substance under federal law in the United States (1); however, many states have legalized medical and adult nonmedical use. Evidence regarding the safety and health effects of cannabis use during pregnancy is largely inconclusive (2). Potential adverse health effects to exposed infants (e.g., lower birthweight) have been documented (2). To provide population-based estimates of use surrounding pregnancy, identify reasons for and mode of use, and understand characteristics of women who continue versus cease marijuana use during pregnancy, CDC analyzed data from eight states participating in the 2017 Pregnancy Risk Assessment Monitoring System (PRAMS) marijuana supplement. Overall, 9.8% of women self-reported marijuana use before pregnancy, 4.2% during pregnancy, and 5.5% after pregnancy. The most common reasons for use during pregnancy were to relieve stress or anxiety, nausea or vomiting, and pain. Smoking was the most common mode of use. In multivariable models that included age, race/ethnicity, marital status, education, insurance status, parity, trimester of entry into prenatal care, and cigarette and e-cigarette use during pregnancy, women who continued versus ceased marijuana use during pregnancy were more likely to be non-Hispanic white or other race/ethnicity than non-Hispanic black, be unmarried, have ≤12 years of education, and use cigarettes during pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) recommend refraining from marijuana use during pregnancy and lactation (3,4). Given the increasing number of states legalizing medical and adult nonmedical marijuana use, surveillance of perinatal marijuana use can inform clinical guidance, provider and patient education, and public health programs to support evidence-based approaches to addressing substance use.

Indication-Specific Opioid Prescribing for US Patients With Medicaid or Private Insurance, 2017.

Importance: Although opioids can be effective medications in certain situations, they are associated with harms, including opioid use disorder and overdose. Studies have revealed unexplained prescribing variation and prescribing mismatched with patient-reported pain for many indications. Objective: To summarize opioid prescribing frequency, dosages, and durations, stratified across numerous painful medical indications. Design, Setting, and Participants: Retrospective cross-sectional analysis of 2017 US administrative claims data among outpatient clinical settings, including postsurgical discharge. Participants had any of 41 different indications associated with nonsurgical acute or chronic pain or postsurgical pain or pain associated with sickle cell disease or active cancer and were enrolled in either private insurance (including Medicare Advantage) in the OptumLabs Data Warehouse data set (n = 18 016 259) or Medicaid in the IBM MarketScan Multi-State Medicaid Database (n = 11 453 392). OptumLabs data were analyzed from October 2018 to March 2019; MarketScan data were analyzed from January to April 2019. Exposures: Nonsurgical acute or chronic pain or postsurgical pain; pain related to sickle cell disease or active cancer. Main Outcomes and Measures: Indication-specific opioid prescribing rates; days' supply per prescription; daily opioid dosage in morphine milligram equivalents; and for chronic pain indications, the number of opioid prescriptions. Results: During the study period, of 18 016 259 eligible patients with private insurance, the mean (95% CI) age was 42.7 (42.7-42.7) years, and 50.3% were female; of 11 453 392 eligible Medicaid enrollees, the mean (95% CI) age was 20.4 (20.4-20.4) years, and 56.1% were female. A pain-related indication under study occurred in at least 1 visit among 6 380 694 patients with private insurance (35.4%) and 3 169 831 Medicaid enrollees (27.7%); 2 270 596 (35.6% of 6 380 694) privately insured patients and 1 126 508 (35.5% of 3 169 831) Medicaid enrollees had 1 or more opioid prescriptions. Nonsurgical acute pain opioid prescribing rates were lowest for acute migraines (privately insured, 4.6% of visits; Medicaid, 6.6%) and highest for rib fractures (privately insured, 44.8% of visits; Medicaid, 56.3%), with variable days' supply but similar daily dosage across most indications. Opioid prescribing for a given chronic pain indication varied depending on a patient's opioid use history. Days' supply for postoperative prescriptions was longest for combined spinal decompression and fusion (privately insured, 9.5 days [95% CI, 9.4-9.7 days]) or spinal fusion (Medicaid, 9.1 days [95% CI, 8.9-9.2 days]) and was shortest for vaginal delivery (privately insured, 4.1 days [95% CI, 4.1-4.1 days] vs Medicaid, 4.2 days [95% CI, 4.2-4.2 days]). Conclusions and Relevance: Indication-specific opioid prescribing rates were not always aligned with existing guidelines. Potential inconsistencies between prescribing practice and clinical recommendations, such as for acute and chronic back pain, highlight opportunities to enhance pain management and patient safety.

Adverse Childhood Experiences Increase Risk for Prescription Opioid Misuse.

The United States is in the midst of an opioid overdose epidemic, with a significant portion of the burden associated with prescription opioids. In response, the CDC released a Guideline for Prescribing Opioids for Chronic Pain, which promotes access to treatment for opioid use disorder. Decades of research have linked childhood adversity to negative health and risk behavior outcomes, including substance misuse. Our present study builds upon this work to examine the relationship between adverse childhood experiences (ACEs) and prescription opioid misuse. We compiled data from the Behavioral Risk Factor Surveillance System implemented by Montana and Florida in 2010 and 2011, respectively. Logistic regressions (run in 2017) tested the associations between ACEs and subsequent prescription pain medicine/opioid misuse outcomes in adulthood. ACEs were prevalent, with 62.7% of respondents in Montana and 50% in Florida reporting at least one ACE. The presence of ACEs was positively associated with prescription opioid misuse across both samples. Respondents reporting three or more ACEs had increased odds of taking opioids more than prescribed, without a prescription, and for the feeling they cause. Our results support a strong link between ACEs and prescription opioid misuse. Opportunities to prevent opioid misuse start with assuring safe, stable, nurturing relationships and environments in childhood and across the lifespan to prevent ACEs from occurring, and intervening appropriately when they do occur. Substance use prevention programs for adolescents, appropriate pain management and opioid prescribing protocols, and treatments for opioid use disorder can address ACEs by enhancing treatment safety and effectiveness and can reduce the intergenerational continuity of early adversity.

Evidence for state, community and systems-level prevention strategies to address the opioid crisis.

BACKGROUND: Practitioners and policy makers need evidence to facilitate the selection of effective prevention interventions that can address the ongoing opioid overdose epidemic in the United States. METHODS: We conducted a systematic review of publications reporting on rigorous evaluations of systems-level interventions to address provider and patient/public behavior and prevent prescription and illicit opioid overdose. A total of 251 studies were reviewed. Interventions studied included 1) state legislation and regulation, 2) prescription drug monitoring programs (PDMPs), 3) insurance strategies, 4) clinical guideline implementation, 5) provider education, 6) health system interventions, 7) naloxone education and distribution, 8) safe storage and disposal, 9) public education, 10) community coalitions, and 11) interventions employing public safety and public health collaborations. RESULTS: The quality of evidence supporting selected interventions was low to moderate. Interventions with the strongest evidence include PDMP and pain clinic legislation, insurance strategies, motivational interviewing in clinical settings, feedback to providers on opioid prescribing behavior, intensive school and family-based programs, and patient education in the clinical setting. CONCLUSIONS: Although evidence is growing, further high-quality research is needed. Investigators should aim to identify strategies that can prevent overdose, as well as influence public, patient, and provider behavior. Identifying which strategies are most effective at addressing prescription compared to illicit opioid misuse and overdose could be fruitful, as well as investigating synergistic effects and unintended consequences.

Vital Signs: Pharmacy-Based Naloxone Dispensing - United States, 2012-2018.

BACKGROUND: The CDC Guideline for Prescribing Opioids for Chronic Pain recommends considering prescribing naloxone when factors that increase risk for overdose are present (e.g., history of overdose or substance use disorder, opioid dosages ≥50 morphine milligram equivalents per day [high-dose], and concurrent use of benzodiazepines). In light of the high numbers of drug overdose deaths involving opioids, 36% of which in 2017 involved prescription opioids, improving access to naloxone is a public health priority. CDC examined trends and characteristics of naloxone dispensing from retail pharmacies at the national and county levels in the United States. METHODS: CDC analyzed 2012-2018 retail pharmacy data from IQVIA, a health care, data science, and technology company, to assess U.S. naloxone dispensing by U.S. Census region, urban/rural status, prescriber specialty, and recipient characteristics, including age group, sex, out-of-pocket costs, and method of payment. Factors associated with naloxone dispensing at the county level also were examined. RESULTS: The number of naloxone prescriptions dispensed from retail pharmacies increased substantially from 2012 to 2018, including a 106% increase from 2017 to 2018 alone. Nationally, in 2018, one naloxone prescription was dispensed for every 69 high-dose opioid prescriptions. Substantial regional variation in naloxone dispensing was found, including a twenty-fivefold variation across counties, with lowest rates in the most rural counties. A wide variation was also noted by prescriber specialty. Compared with naloxone prescriptions paid for with Medicaid and commercial insurance, a larger percentage of prescriptions paid for with Medicare required out-of-pocket costs. CONCLUSION: Despite substantial increases in naloxone dispensing, the rate of naloxone prescriptions dispensed per high-dose opioid prescription remains low, and overall naloxone dispensing varies substantially across the country. Naloxone distribution is an important component of the public health response to the opioid overdose epidemic. Health care providers can prescribe or dispense naloxone when overdose risk factors are present and counsel patients on how to use it. Efforts to improve naloxone access and distribution work most effectively with efforts to improve opioid prescribing, implement other harm-reduction strategies, promote linkage to medications for opioid use disorder treatment, and enhance public health and public safety partnerships.

Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children.

Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States. Objective: To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI. Evidence Review: The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015. Findings: The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment. Conclusions and Relevance: This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations.

Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review.

Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study. Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI. Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search. Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking. Conclusions and Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management.

What Pediatricians Need to Know About the CDC Guideline on the Diagnosis and Management of mTBI.

Pediatric traumatic brain injury (TBI) is a growing health concern, with over half a million TBI-related emergency department (ED) visits annually. However, this is likely an underestimate of the true incidence, with many children presenting to their pediatrician. The Centers for Disease Control and Prevention (CDC) published a guideline on the diagnosis and management of pediatric mild traumatic brain injury (mTBI). We outline key points and a decision checklist for pediatricians based on this evidence-based guideline.

Technical Packages in Injury and Violence Prevention to Move Evidence Into Practice: Systematic Reviews and Beyond.

Injury and violence prevention strategies have greater potential for impact when they are based on scientific evidence. Systematic reviews of the scientific evidence can contribute key information about which policies and programs might have the greatest impact when implemented. However, systematic reviews have limitations, such as lack of implementation guidance and contextual information, that can limit the application of knowledge. "Technical packages," developed by knowledge brokers such as the federal government, nonprofit agencies, and academic institutions, have the potential to be an efficient mechanism for making information from systematic reviews actionable. Technical packages provide information about specific evidence-based prevention strategies, along with the estimated costs and impacts, and include accompanying implementation and evaluation guidance to facilitate adoption, implementation, and performance measurement. We describe how systematic reviews can inform the development of technical packages for practitioners, provide examples of technical packages in injury and violence prevention, and explain how enhancing review methods and reporting could facilitate the use and applicability of scientific evidence.

Teens and seat belt use: What makes them click?

PROBLEM: Motor vehicle crashes kill more adolescents in the United States than any other cause, and often the teen is not wearing a seat belt. METHODS: Using data from the 2011 Youth Risk Behavior Surveys from 38 states, we examined teens' self-reported seat belt use while riding as a passenger and identified individual characteristics and environmental factors associated with always wearing a seat belt. RESULTS: Only 51% of high school students living in 38 states reported always wearing a seat belt when riding as a passenger; prevalence varied from 32% in South Dakota to 65% in Delaware. Seat belt use was 11 percentage points lower in states with secondary enforcement seat belt laws compared to states with primary enforcement laws. Racial/ethnic minorities, teens living in states with secondary enforcement seat belt laws, and those engaged in substance use were least likely to always wear their seat belts. The likelihood of always being belted declined steadily as the number of substance use behaviors increased. DISCUSSION: Seat belt use among teens in the United States remains unacceptably low. Results suggest that environmental influences can compound individual risk factors, contributing to even lower seat belt use among some subgroups. PRACTICAL APPLICATIONS: This study provides the most comprehensive state-level estimates to date of seat belt use among U.S. teens. This information can be useful when considering policy options to increase seat belt use and for targeting injury prevention interventions to high-risk teens. States can best increase teen seat belt use by making evidence-informed decisions about state policy options and prevention strategies.

CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016.

IMPORTANCE: Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose. OBJECTIVE: To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care. PROCESS: The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category. EVIDENCE SYNTHESIS: Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects. RECOMMENDATIONS: There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone. CONCLUSIONS AND RELEVANCE: The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.