Recently Published Projects

Objectives: Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds (PBCs) to treat chronic pain. Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request, were searched to July, 2021. Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect, or small, moderate, and large effects. Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short-term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI], −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI, −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic high-THC to CBD was associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant, high-THC to CBD (oral) was associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported. Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio cannabis products in short-term treatment (1 to 6 months). Evidence for other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment indicate that more research is needed.

Objectives: Objectives. To review the association between malnutrition and clinical outcomes among hospitalized patients, evaluate effectiveness of measurement tools for malnutrition on clinical outcomes, and assess effectiveness of hospital-initiated interventions for patients diagnosed with malnutrition. Data sources. We searched electronic databases (EMBASE, MEDLINE, PubMed, and the Cochrane Library) from January 1, 2000 to June 3, 2021. We hand-searched reference lists of relevant studies and searched for unpublished studies in ClinicalTrials.gov. Review methods. Using predefined criteria and dual review, we selected 1) existing systematic reviews (SRs) to assess the association between malnutrition and clinical outcomes, 2) randomized and non-randomized studies to evaluate the effectiveness of malnutrition measurement tools on clinical outcomes, and 3) randomized controlled trials (RCTs) to assess effectiveness of hospital-initiated treatments for malnutrition. Clinical outcomes of interest included mortality, length of stay, 30-day readmission, quality of life, functional status, activities of daily living, hospital acquired conditions, wound healing, and discharge disposition. When appropriate, we conducted meta-analysis to quantitatively summarize study findings; otherwise, data were narratively synthesized. When available, we used pooled estimates from existing SRs to determine the association between malnutrition with clinical outcomes and assessed the strength of evidence. Results. Six existing SRs (including 43 unique studies) provided evidence on the association between malnutrition and clinical outcomes. Low to moderate strength of evidence (SOE) showed an association between malnutrition and increased hospital mortality and prolonged hospital length of stay. This association was observed across patients hospitalized for an acute medical event requiring ICU care, heart failure, and cirrhosis. Literature searches found no studies that met inclusion criteria and assessed effectiveness of measurement tools. The primary reason studies did not meet inclusion criteria is because they lacked an appropriate control group. Moderate SOE from 11 RCTs found that hospital-initiated malnutrition interventions likely reduce mortality compared with usual care among hospitalized patients diagnosed with malnutrition. Low SOE indicated that hospital-initiated malnutrition interventions may also improve quality of life compared to usual care. Conclusions. Evidence shows an association between malnutrition and increased mortality and prolonged length of hospital stay among hospitalized patients identified as malnourished. However, the strength of this association varied depending on patient population and tool used to identify malnutrition. Evidence indicates malnutrition-focused hospital-initiated interventions likely reduce mortality and may improve quality of life compared to usual care among patients diagnosed with malnutrition. Research is needed to assess the clinical utility of measurement tools for malnutrition.

Objectives: To assess benefits and harms of antipsychotics for the prevention and treatment of delirium in adult patient populations.

Objectives: Objective. To conduct a systematic review of the literature on the safety of vaccines recommended for routine immunization in the United States, updating the 2014 Agency for Healthcare Research and Quality (AHRQ) report on the topic. Data sources. We searched MEDLINE®, Embase®, CINAHL®, Cochrane CENTRAL, Web of Science, and Scopus through November 9, 2020, building on the prior 2014 report; reviewed existing reviews, trial registries, and supplemental material submitted to AHRQ; and consulted with experts. Review methods. This report addressed three Key Questions (KQs) on the safety of vaccines currently in use in the United States and included in the Centers for Disease Control and Prevention’s (CDC) recommended immunization schedules for adults (KQ1), children and adolescents (KQ2), and pregnant women (KQ3). The systematic review was supported by a Technical Expert Panel that identified key adverse events of particular concern. Two reviewers independently screened publications; data were extracted by an experienced subject matter expert. Studies of vaccines that used a comparator and reported the presence or absence of adverse events were eligible. We documented observed rates and assessed the relative risks for key adverse events. We assessed the strength of evidence (SoE) across the existing findings from the prior 2014 report and the new evidence from this update. The systematic review is registered in PROSPERO (CRD42020180089). Results. A large body of evidence is available to evaluate adverse events following vaccination. Of 56,608 reviewed citations, 189 studies met inclusion criteria for this update, adding to data in the prior 2014 report, for a total of 338 included studies reported in 518 publications. Regarding vaccines recommended for adults (KQ1), we found either no new evidence of increased risk for key adverse events with varied SoE or insufficient evidence in this update, including for newer vaccines such as recombinant influenza vaccine, adjuvanted inactivated influenza vaccine, and recombinant adjuvanted zoster vaccine. The prior 2014 report noted a signal for anaphylaxis for hepatitis B vaccines in adults with yeast allergy and for tetanus, diphtheria, and acellular pertussis vaccines. Regarding vaccines recommended for children and adolescents (KQ2), we found either no new evidence of increased risk for key adverse events with varied SoE or insufficient evidence, including for newer vaccines such as 9-valent human papillomavirus vaccine and meningococcal B vaccine. The prior 2014 report noted signals for rare adverse events—such as anaphylaxis, idiopathic thrombocytopenic purpura, and febrile seizures—with some childhood vaccines. Regarding vaccines recommended for pregnant women (KQ3), we found no evidence of increased risk for key adverse events with varied SoE among either pregnant women or their infants following administration of tetanus, diphtheria, and acellular pertussis vaccines during pregnancy. Conclusion. Across this large body of research, we found no new evidence of increased risk since the prior 2014 report for key adverse events following administration of vaccines that are routinely recommended. Signals from the prior report remain unchanged for rare adverse events, which include anaphylaxis in adults and children, and febrile seizures and idiopathic thrombocytopenic purpura in children. There is no evidence of increased risk of adverse events for vaccines currently recommended in pregnant women. There remains insufficient evidence to draw conclusions about some rare potential adverse events.

Objectives: Background. Opioid-related harms are increasing among older adults. Until we better understand the factors contributing to this trend, we will be unable to design and implement effective interventions to optimally manage opioid use and its potential harms among older adults. Although considerable research has been done in younger or mixed-age populations, the degree to which it is directly applicable to older adults is uncertain. Objectives. To provide a framework for understanding how to reduce adverse outcomes of opioid use among older adults, and to describe the evidence available for different factors associated with and interventions to reduce adverse outcomes related to opioid use in this population. Approach. With input from a diverse panel of content experts and other stakeholders, we developed a conceptual framework and evidence map to characterize empirical studies of factors associated with opioid-related outcomes and interventions to reduce opioid-related harms in older adults. We identified relevant literature among older adults (age ≥60 years) for an evidence map by systematically searching PubMed, PsycINFO, and CINAHL for studies published in English between 2000 and May 6, 2020. Findings. We identified 5,933 citations, from which we identified 41 studies with multivariable models of factors associated with opioid-related outcomes and 16 studies of interventions in older adults. More than half (22/41) of the multivariable analysis studies evaluated factors associated with long-term opioid use (which, though not a harm per se, may increase the risk of harms if not appropriately managed). Prior or early postoperative opioid use, or greater amounts of prescribed opioids (high number of opioid prescriptions or higher opioid dose), were consistently (100% agreement) and strongly (measure of association ≥2.0) associated with long- term opioid use. Back pain, depression, concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), and fibromyalgia also had consistent, but weaker, associations with long-term opioid use. Several factors were mostly associated (>75% agreement) with long-term opioid use, including benzodiazepine use, comorbidity scores, (generally undefined) substance misuse, tobacco use, and low income. However, studies were mostly consistent that alcohol abuse and healthcare utilization were not associated with long-term opioid use. Gender, age among older adults, Black race, dementia, rural/nonurban residence, prescription of long-acting opioids, unmarried status, and use of muscle relaxants were variably associated (<75% agreement) with long-term opioid use. Six studies examined factors associated with opioid-related disorders, although only one study evaluated factors associated with opioid use disorder. Alcohol misuse and gender were variably associated with opioid misuse (examined by three studies each). All other evaluations of specific pairs of associated factors and outcomes of interest were evaluated by only one or two studies each. These included analyses of factors associated with multiple opioid prescribers, mental health outcomes, physical health outcomes, all-cause hospitalization, opioid-related hospitalization, nonopioid-specific hospitalization, emergency department visits, opioid overdose, all-cause death, opioid-related death, and nonopioid-related death. The evidence on interventions directed at older adults is sparse. Of the 16 studies of opioid- related interventions in older adults, six examined screening tools to predict opioid-related harms, but none of these tools was tested in clinical practice to assess real-world results. Two studies found that prescription drug monitoring programs are associated with less opioid use in communities. Other studied interventions include multidisciplinary pain education for patients, an educational pamphlet for patients, implementation of an opioid safety initiative, provision of patient information and pain management training for clinicians, a bundle of educational modalities for clinicians, free prescription acetaminophen, a nationally mandated tamper- resistant opioid formulation, and motivational interview training for nursing students. Few intervention studies evaluated pain or other patient-centered outcomes such as disability and functioning. Conclusions. The evidence base that is directly applicable to older adults who are prescribed opioids or have opioid-related disorders is limited. Fundamental research is necessary to determine which factors may predict clinically important, patient-centered, opioid-related outcomes. Studies to date have identified numerous possible factors associated with long-term opioid use (whether appropriate or not), but analyses of other opioid-related outcomes in older adults are relatively sparse. Research is also needed to identify interventions to reduce opioid prescribing where harms outweigh benefits (including screening tools), reduce opioid-related harms and disorders, and treat existing misuse or opioid use disorder among older adults.