Medication-assisted treatment and opioid use response to opioid overdose sentinel events

Introduction A nonfatal overdose due to opioids can be viewed as a failure to adequately treat addiction or as an opportunity to start or improve treatment for opioid use disorder (OUD). It is important to determine how patients are being treated before and after an overdose. Primary care providers are at the forefront of the opioid epidemic and have the potential to influence opioid prescribing habits and treatment of OUD. Evaluation of the opioid epidemic leading to potential solutions has significant public health relevance. Objective To determine treatment utilization before and after nonfatal overdoses. Methods We conducted a longitudinal retrospective cohort study of Pennsylvania Medicaid patients aged 12-64 with a nonfatal opioid or heroin overdose event between 2008-2013. We measured unduplicated patient-level univariate descriptive statistics for demographic and treatment utilization 6 months before and 6 months after an overdose. We identified inpatient, outpatient, and pharmacy claims data from Pennsylvania’s managed care and fee-for-service Medicaid programs. We excluded Non-Pennsylvania residents, those dually-eligible for Medicare, age 64, and non-opioid or non-heroin overdoses for a total of 7,690 enrollees. We evaluated the following demographic factors: age, gender, and race. The main outcome measure was OUD medication-assisted treatment (MAT) utilization: methadone, buprenorphine, and naltrexone. Secondary outcome measures included the length (days) supply of prescription opioids pre and post-overdose. Results Among 3,009 enrollees who had a heroin overdose and 4,989 who had a prescription opioid overdose, most were 90 days duration of opioids did not change in the heroin group pre- to post-overdose (9.4% to 9.0%, P =0.07) but decreased in the opioid group (32.2% to 28.3%,

Feasibility and Acceptability of a US National Telemedicine Curriculum for Medical Students and Residents: Multi-institutional Cross-sectional Study

BackgroundTelemedicine use increased as a response to health care delivery changes necessitated by the COVID-19 pandemic. However, lack of standardized curricular content creates gaps and inconsistencies in effectively integrating telemedicine training at both the undergraduate medical education and graduate medical education levels. ObjectiveThis study evaluated the feasibility and acceptability of a web-based national telemedicine curriculum developed by the Society of Teachers of Family Medicine for medical students and family medicine (FM) residents. Based on the Association of American Medical Colleges telehealth competencies, the asynchronous curriculum featured 5 self-paced modules; covered topics include evidence-based telehealth uses, best practices in communication and remote physical examinations, technology requirements and documentation, access and equity in telehealth delivery, and the promise and potential perils of emerging technologies. MethodsA total of 17 medical schools and 17 FM residency programs implemented the curriculum between September 1 and December 31, 2021. Participating sites represented 25 states in all 4 US census regions with balanced urban, suburban, and rural settings. A total of 1203 learners, including 844 (70%) medical students and 359 (30%) FM residents, participated. Outcomes were measured through self-reported 5-point Likert scale responses. ResultsA total of 92% (1101/1203) of learners completed the entire curriculum. Across the modules, 78% (SD 3%) of participants agreed or strongly agreed that they gained new knowledge, skills, or attitudes that will help them in their training or career; 87% (SD 4%) reported that the information presented was at the right level for them; 80% (SD 2%) reported that the structure of the modules was effective; and 78% (SD 3%) agreed or strongly agreed that they were satisfied. Overall experience using the national telemedicine curriculum did not differ significantly between medical students and FM residents on binary analysis. No consistent statistically significant relationships were found between participants’ responses and their institution’s geographic region, setting, or previous experience with a telemedicine curriculum. ConclusionsBoth undergraduate medical education and graduate medical education learners, represented by diverse geographic regions and institutions, indicated that the curriculum was broadly acceptable and effective

Genetic variability at the leptin receptor ( LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels

Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor ( LEPR) locus on the plasma levels of fibrinogen and CRP—two markers of inflammation and susceptibility to atherosclerosis. Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen ( p = 0.005), accounting for 3% of its variance ( r 2 = 0.030). The same block was also associated with CRP levels ( p = 0.049, r 2 = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes ( p = 0.015). At rs1805096, it was 5% higher ( p = 0.007) and CRP 32% higher ( p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis

Dietary Elimination for the Treatment of Atopic Dermatitis: A Systematic Review and Meta-Analysis

BACKGROUND: The influence of diet on atopic dermatitis (AD) is complex, and the use of dietary elimination as a treatment has conflicting views. OBJECTIVE: To systematically review the benefits and harms of dietary elimination for the treatment of AD. METHODS: We searched MEDLINE, Embase, AMED, PsycINFO, and the Cochrane Central Register of Controlled Trials from inception to January 18, 2022, without language restrictions, for randomized controlled trials (RCTs) and observational studies comparing dietary elimination and no dietary elimination for the treatment of AD. We conducted random-effects meta-analyses of eczema outcomes. We used the grading of recommendations, assessment, development, and evaluation approach to assess certainty of evidence (CRD42021237953). RESULTS: Ten RCT (n = 599; baseline median of study mean age, 1.5 years; median of study mean SCOring Atopic Dermatitis index, 20.7, range, 3.5-37.6) were included in the meta-analysis. Compared with no dietary elimination, low-certainty evidence showed that dietary elimination may slightly improve eczema severity (50% with vs 41% without dietary elimination improved the SCOring Atopic Dermatitis index by a minimally important difference of 8.7 points, risk difference of 9% [95% CI, 0-17]), pruritus (daytime itch score [range, 0-3] mean difference, -0.21 [95% CI, -0.57 to 0.15]), and sleeplessness (sleeplessness score [range, 0-3] mean difference, -0.47 [95% CI, -0.80 to -0.13]). There were no credible subgroup differences based on elimination strategy (empiric vs guided by testing) or food-specific sensitization. Insufficient data addressed harms of elimination diets among included RCTs, although indirect evidence suggests that elimination diets may increase the risk for developing IgE-mediated food allergy. CONCLUSIONS: Dietary elimination may lead to a slight, potentially unimportant improvement in eczema severity, pruritus, and sleeplessness in patients with mild to moderate AD. This must be balanced against potential risks for indiscriminate elimination diets including developing IgE-mediated food allergy and withholding more effective treatment options for AD

Bleach baths for atopic dermatitis: A systematic review and meta-analysis including unpublished data, Bayesian interpretation, and GRADE

BACKGROUND: Bleach bathing is frequently recommended to treat atopic dermatitis (AD), but its efficacy and safety are uncertain. OBJECTIVE: To systematically synthesize randomized controlled trials (RCTs) addressing bleach baths for AD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and GREAT from inception to December 29, 2021, for RCTs assigning patients with AD to bleach vs no bleach baths. Paired reviewers independently and in duplicate screened records, extracted data, and assessed risk of bias (Cochrane version 2) and GRADE quality of evidence. We obtained unpublished data, harmonized individual patient data and did Frequentist and Bayesian random-effects meta-analyses. RESULTS: There were 10 RCTs that enrolled 307 participants (median of mean age 7.2 years, Eczema Area Severity Index baseline mean of means 27.57 [median SD, 10.74]) for a median of 6 weeks (range, 4-10). We confirmed that other trials registered globally were terminated. Bleach baths probably improve AD severity (22% vs 32% improved Eczema Area Severity Index by 50% [ratio of means 0.78, 95% credible interval 0.59-0.99]; moderate certainty) and may slightly reduce skin Staphylococcal aureus colonization (risk ratio, 0.89 [95% confidence interval, 0.73-1.09]; low certainty). Adverse events, mostly dry skin and irritation, along with itch, patient-reported disease severity, sleep quality, quality of life, and risk of AD flares were not clearly different between groups and of low to very low certainty. CONCLUSION: In patients with moderate-to-severe AD, bleach baths probably improve clinician-reported severity by a relative 22%. One in 10 will likely improve severity by 50%. Changes in other patient-important outcomes are uncertain. These findings support optimal eczema care and the need for additional large clinical trials. TRIAL REGISTRATION: PROSPERO Identifier: CRD42021238486

Values and Preferences of Patients and Caregivers Regarding Treatment of Atopic Dermatitis (Eczema): A Systematic Review

IMPORTANCE: Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available. OBJECTIVE: To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters AD guideline development, patient and caregiver values and preferences in the management of AD were systematically synthesized. EVIDENCE REVIEW: Paired reviewers independently screened MEDLINE, Embase, PsycINFO, and CINAHL databases from inception until March 20, 2022, for studies of patients with AD or their caregivers, eliciting values and preferences about treatment, rated risk of bias, and extracted data. Thematic and inductive content analysis to qualitatively synthesize the findings was used. Patients, caregivers, and clinical experts provided triangulation. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) informed rating of the quality of evidence. FINDINGS: A total of 7780 studies were identified, of which 62 proved eligible (n = 19 442; median age across studies [range], 15 years [3-44]; 59% female participants). High certainty evidence showed that patients and caregivers preferred to start with nonmedical treatments and to step up therapy with increasing AD severity. Moderate certainty evidence showed that adverse effects from treatment were a substantial concern. Low certainty evidence showed that patients and caregivers preferred odorless treatments that are not visible and have a minimal effect on daily life. Patients valued treatments capable of relieving itching and burning skin and preferred to apply topical corticosteroids sparingly. Patients valued a strong patient-clinician relationship. Some studies presented varied perspectives and 18 were at high risk for industry sponsorship bias. CONCLUSIONS AND RELEVANCE: In the first systematic review to address patient values and preferences in management of AD to our knowledge, 6 key themes that may inform optimal clinical care, practice guidelines, and future research have been identified

Allergen Immunotherapy for Atopic Dermatitis: A Systematic Review and Meta-Analysis of Benefits and Harms

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli (eg. allergens, irritants, microbes). The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: Systematically synthesize evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 AAAAI/ACAAI JTFPP AD Guideline update, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, GREAT and Web of Science (all databases) to December 2021 for randomized controlled trials (RCTs) comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard of care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares and adverse events. Raters independently screened, extracted data and assessed risk of bias in duplicate. We synthesized intervention effects using Frequentist and Bayesian random-effects models. The GRADE approach determined quality of the evidence. RESULTS: 23 RCTs including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing AD (SCORAD; RR 1.53 [95%CI 1.31-1.78]; 26% to 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index (DLQI) by 4 points or more (RR 1.44 [1.03-2.01]; 39% to 56%, absolute difference 17%; both outcomes moderate-certainty). Both routes of AIT increased adverse events (RR 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high-certainty). AIT\u27s effect on sleep disturbance and eczema flares were very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared-decision making approach to optimally managing AD

Systemic treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We systematic synthesized the benefits and harms of AD systemic treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT, from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. OSF: https://osf.io/e5sna. RESULTS: 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty, high-dose upadacitinib was among the most effective for five of six patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for two outcomes. These JAK inhibitors were among the most harmful in increasing adverse events. With high-certainty, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest-modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. The efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes but also among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and favorable safety

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms

BackgroundAtopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. ObjectiveWe systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. MethodsAs part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel–defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. ResultsTwenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT’s effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. ConclusionsSCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD

Topical treatments for atopic dermatitis (eczema): systematic review and network meta-analysis of randomized trials

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVES: We systematically synthesized the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 AAAAI/ACAAI JTFPP AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT to September 5, 2022 for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-quality of life, flares, and harms. The GRADE approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using seven classes-group 1 being most potent. OSF: https://osf.io/q5m6s. RESULTS: 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty, pimecrolimus improved six of seven outcomes-among the best for two; high-dose tacrolimus (0.1%) improved five-among the best for two; low-dose tacrolimus (0.03%) improved five-among the best for one. With moderate-to-high certainty, group 5 TCS improved six-among the best for three; group 4 TCS and delgocitinib improved four-among the best for two; ruxolitinib improved four-among the best for one; group 1 TCS improved three-among the best for two. These interventions did not increase harms. Crisaborole and difamilast were intermediately effective, but uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective