Screening for asymptomatic carotid artery stenosis: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Approximately 10% of ischemic strokes are caused by carotid artery stenosis (CAS). Estimated prevalence of asymptomatic CAS is 1%. PURPOSE: To evaluate evidence on screening and treating asymptomatic adults for CAS. DATA SOURCES: MEDLINE, the Cochrane Library, EMBASE, and trial registries through September 2013; MEDLINE through March 2014 for trials. STUDY SELECTION: Good- or fair-quality trials of screening, carotid endarterectomy (CEA), or stenting compared with medical therapy or of intensification of medical therapy; systematic reviews; multi-institution studies reporting harms; and externally validated risk-stratification tools. DATA EXTRACTION: Dual extraction and quality assessment. DATA SYNTHESIS: No trials compared screening with no screening or stenting with medical therapy or assessed intensification of medical therapy, and no externally validated, reliable risk-stratification tools were found. Given the specificity of ultrasonography (range, 88% to 94% for CAS ≥ 50% to ≥ 70%), its use in low-prevalence populations would yield many false-positive results. Absolute reduction of nonperioperative strokes was 5.5% (95% CI, 3.9% to 7.0%; 3 trials; 5223 participants) over approximately 5 years for CEA compared with medical therapy. The 30-day rates of stroke or death after CEA in trials and cohort studies were 2.4% (CI, 1.7% to 3.1%; 6 trials; 3435 participants) and 3.3% (CI, 2.7% to 3.9%; 7 studies; 17474 participants), respectively. Other harms of interventions included myocardial infarction, nerve injury, and hematoma. LIMITATIONS: Trials may have overestimated benefits and used highly selected surgeons. Medical therapy used in trials was outdated, and stroke rates have declined in recent decades. Harms may have been underreported. CONCLUSION: Current evidence does not establish incremental overall benefit of CEA, stenting, or intensification of medical therapy. Potential for overall benefit is limited by low prevalence and harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Marsh migration and beyond: A scalable framework to assess tidal wetland resilience and support strategic management.

Tidal wetlands are critical but highly threatened ecosystems that provide vital services. Efficient stewardship of tidal wetlands requires robust comparative assessments of different marshes to understand their resilience to stressors, particularly in the face of relative sea level rise. Existing assessment frameworks aim to address tidal marsh resilience, but many are either too localized or too general, and few directly translate resilience evaluations to recommendations for management strategies. In response to the deficiencies in existing frameworks, we identified a set of metrics that influence overall marsh resilience that can be assessed at any spatial scale. We then developed a new comprehensive assessment framework to rank relative marsh resilience using these metrics, which are nested within three categories. We represent resilience as the sum of results across the three metric categories: current condition, adaptive capacity, and vulnerability. Users of this framework can add scores from each category to generate a total resilience score to compare across marshes or take the score from each category and refer to recommended management actions we developed based on expert elicitation for each combination of category results. We then applied the framework across the contiguous United States using publicly available data, and summarized results at multiple spatial scales, from regions to coastal states to National Estuarine Research Reserves to finer scale marsh units, to demonstrate the framework's value across these scales. Our national analysis allowed for comparison of tidal marsh resilience across geographies, which is valuable for determining where to prioritize management actions for desired future marsh conditions. In combination, the assessment framework and recommended management actions function as a broadly applicable decision-support tool that will enable resource managers to evaluate tidal marshes and select appropriate strategies for conservation, restoration, and other stewardship goals.

Evaluation of serum and rapid serum separator collection tubes for therapeutic drug assays.

Appropriate specimen collection and storage is essential to preserve sample integrity and ensure accurate test results. The default collection containers for blood drug concentrations are tubes without gel separators to avoid possible drug adsorption. However, routine chemistry tests are generally collected in gel separator tubes due to their convenient transport and processing; collection of an additional gel-free tube is often required for drug measurements. Citrated whole blood was pooled, spiked with drug, and transferred to three tubes (red, SST gold, RST orange) containing calcium chloride. Blood was allowed to clot, centrifuged and stored at ambient temperature (24 h) or refrigerated (7 days). At defined times, serum drug concentrations were determined (Roche cobas c502). Based on these results, specimen collection requirements were updated to allow serum separator tubes for 17 assays. Of the 21 assays evaluated, 18 displayed acceptable stability in both gel-containing tubes (acetaminophen, amikacin, carbamazepine, digoxin, ethanol, gentamicin, lamotrigine, levetiracetam, lithium, methotrexate, phenobarbital, phenytoin, salicylate, theophylline, tobramycin, valproic acid, vancomycin, voriconazole). Three drugs displayed strong decreases in measured concentrations after storage in one or both gel-containing tubes (total tricyclics, lidocaine, and free phenytoin). Following adoption of gel-containing tubes, 94% of the five most frequently ordered drug monitoring tests in the Emergency Department were collected in serum separator tubes. Evaluation of the stability and accuracy of commonly monitored drugs revealed that the majority were not affected by exposure to gel separator material under conditions similar to outpatient clinic storage, courier transport, and laboratory storage. Expanding the collection requirements for appropriate drugs to include gel separator tubes decreases the number of specimens drawn and the complexity of laboratory workflows.

Low barrier medication for opioid use disorder at a federally qualified health center: a retrospective cohort study.

BACKGROUND: Medication for opioid use disorder (MOUD) reduces mortality, but few patients access MOUD. At a Federally Qualified Health Center (FQHC), we implemented a low barrier model of MOUD, including same-day MOUD initiation and a harm reduction philosophy. OBJECTIVE: To investigate whether low barrier MOUD improved retention in care compared to traditional treatment. DESIGN AND PARTICIPANTS: Retrospective cohort study of patients with at least one visit seeking MOUD at the FQHC during a historical control period (3/1/2018-3/31/2019) and a low barrier intervention period (11/1/2019-7/31/2020). MAIN MEASURES: Primary outcomes were any MOUD prescription within 6 months of the index visit and 3- and 6-month retention in treatment without care gap, with care gap defined as 60 consecutive days without a visit or prescription. Secondary outcomes were all-cause hospitalization and emergency department visit within 6 months of the index visit. KEY RESULTS: Baseline characteristics were similar between the intervention (n = 113) and control (n = 90) groups, except the intervention group had higher rates of uninsured, public insurance and diabetes. Any MOUD prescription within 6 months of index visit was higher in the intervention group (97.3% vs 70%), with higher adjusted odds of MOUD prescription (OR = 4.01, 95% CI 2.08-7.71). Retention in care was similar between groups at 3 months (61.9% vs 60%, aOR = 1.06, 95% CI 0.78-1.44). At 6 months, a higher proportion of the intervention group was retained in care, but the difference was not statistically significant (53.1% vs 45.6%, aOR 1.27, 95% CI 0.93-1.73). There was no significant difference in adjusted odds of 6-month hospitalization or ED visit between groups. CONCLUSIONS: Low barrier MOUD engaged a higher risk population and did not result in any statistically significant difference in retention in care compared with a historical control. Future research should determine what interventions improve retention of patients engaged through low barrier care. Primary care clinics can implement low barrier treatment to make MOUD accessible to a broader population.

Low barrier buprenorphine treatment for persons experiencing homelessness and injecting heroin in San Francisco.

BACKGROUND: Opioid overdose is a leading cause of death in persons experiencing homelessness (PEH), despite effective medications for opioid use disorder (OUD). In 2016, the San Francisco Street Medicine Team piloted a low barrier buprenorphine program with the primary goal of engaging and retaining PEH with OUD in care as a first step toward reducing opioid use and improving overall health. OBJECTIVE: To characterize the patients; assess treatment retention, retention on buprenorphine, and opioid use; and to describe adverse events. METHODS: Retrospective chart review of patients receiving at least one buprenorphine prescription from Street Medicine (November 2016-October 2017). We abstracted demographic, medical, substance use, prescription, and health care utilization data from medical records. We assessed retention in care at 1, 3, 6, 9 and 12 months, defined as a provider visit 1 week prior to or any time after each time point. We considered patients to be retained on buprenorphine if they had active buprenorphine prescriptions for more than 2 weeks of the month. We estimated opioid use by the percentage of patients with any opioid-negative, buprenorphine-positive urine toxicology test. We reviewed emergency department and hospital records for adverse events, including deaths and nonfatal opioid overdoses. RESULTS: Among the 95 persons eligible for analysis, mean age was 39.2, and 100% reported injecting heroin and homelessness. Medical and psychiatric comorbidities and co-occurring substance use were common. The percentages of patients retained in care at 1, 3, 6, 9 and 12 months were 63%, 53%, 44%, 38%, and 26%, respectively. The percentages of patients retained on buprenorphine at 1, 3, 6, 9 and 12 months were 37%, 27%, 27%, 26%, and 18%, respectively. Twenty-three percent of patients had at least one opioid-negative, buprenorphine-positive test result. One patient died from fentanyl overdose, and four patients presented on six occasions for non-fatal overdoses requiring naloxone. CONCLUSIONS: This program engaged and retained a subset of PEH with OUD in care and on buprenorphine over 12 months. While uninterrupted treatment and abstinence are reasonable outcomes for conventional treatment programs, intermittent treatment with buprenorphine and decreased opioid use were more common in this pilot and may confer important reductions in opioid and injection-related harms.

Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment.

Objective. The study goals were to evaluate performance of SLE classification criteria, to define patients with incomplete lupus erythematosus (ILE), and to probe for features in these patients that might be useful as indicators of disease status and hydroxychloroquine response. Methods. Patients with ILE (N = 70) and SLE (N = 32) defined by the 1997 American College of Rheumatology criteria were reclassified using the 2012 Systemic Lupus International Collaborating Clinics criteria. Disease activity, patient reported outcomes, and levels of Type I interferon- (IFN-) inducible genes, autoantibodies, and cytokines were measured. Subgroups treated with hydroxychloroquine (HCQ) were compared to patients not on this drug. Results. The classification sets were correlated (R2 = 0.87). ILE patients were older (P = 0.0043) with lower disease activity scores (P < 0.001) and greater dissatisfaction with health status (P = 0.034) than SLE patients. ILE was associated with lower levels of macrophage-derived cytokines and levels of expressed Type I IFN-inducible genes. Treatment of ILE with HCQ was associated with better self-reported health status scores and lower expression levels of Type I IFN-inducible genes than ILE patients not on HCQ. Conclusion. The 2012 SLICC SLE classification criteria will be useful to define ILE in trials. Patients with ILE have better health status and immune profiles when treated with HCQ.

Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods.

OBJECTIVE: To determine the optimal method for quantifying and monitoring overdiagnosis in cancer screening over time. DESIGN: Systematic review of primary research studies of any design that quantified overdiagnosis from screening for nine types of cancer. We used explicit criteria to critically appraise individual studies and assess strength of the body of evidence for each study design (double blinded review), and assessed the potential for each study design to accurately quantify and monitor overdiagnosis over time. DATA SOURCES: PubMed and Embase up to 28 February 2014; hand searching of systematic reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: English language studies of any design that quantified overdiagnosis for any of nine common cancers (prostate, breast, lung, colorectal, melanoma, bladder, renal, thyroid, and uterine); excluded case series, case reports, and reviews that only reported results of other studies. RESULTS: 52 studies met the inclusion criteria. We grouped studies into four methodological categories: (1) follow-up of a well designed randomized controlled trial (n=3), which has low risk of bias but may not be generalizable and is not suitable for monitoring; (2) pathological or imaging studies (n=8), drawing conclusions about overdiagnosis by examining biological characteristics of cancers, a simple design limited by the uncertain assumption that the measured characteristics are highly correlated with disease progression; (3) modeling studies (n=21), which can be done in a shorter time frame but require complex mathematical equations simulating the natural course of screen detected cancer, the fundamental unknown question; and (4) ecological and cohort studies (n=20), which are suitable for monitoring over time but are limited by a lack of agreed standards, by variable data quality, by inadequate follow-up time, and by the potential for population level confounders. Some ecological and cohort studies, however, have addressed these potential weaknesses in reasonable ways. CONCLUSIONS: Well conducted ecological and cohort studies in multiple settings are the most appropriate approach for quantifying and monitoring overdiagnosis in cancer screening programs. To support this work, we need internationally agreed standards for ecological and cohort studies and a multinational team of unbiased researchers to perform ongoing analysis.

Neutrophil elastase increases airway epithelial nonheme iron levels.

Alpha-1-antitrypsin (A1AT) deficiency is characterized by increased neutrophil elastase (NE) activity and oxidative stress in the lung. We hypothesized that NE exposure generates reactive oxygen species by increasing lung non-heme iron. To test this hypothesis, we measured bronchoalveolar lavage (BAL) iron and ferritin levels, using inductively coupled plasma (ICP) optical emission spectroscopy and an ELISA respectively, in A1AT-deficient patients and healthy subjects. To confirm the role of NE in regulating lung iron homeostasis, we administered intratracheally NE or control buffer to rats and measured BAL and lung iron and ferritin. Our results demonstrated that A1AT-deficient patients and rats post-elastase exposure have elevated levels of iron and ferritin in the BAL. To investigate the mechanism of NE-induced increased iron levels, we exposed normal human airway epithelial cells to either NE or control vehicle in the presence or absence of ferritin, and quantified intracellular iron uptake using calcein fluorescence and ICP mass spectroscopy. We also tested whether NE degraded ferritin in vitro using ELISA and western analysis. We demonstrated in vitro that NE increased intracellular non-heme iron levels and degraded ferritin. Our results suggest that NE digests ferritin increasing the extracellular iron pool available for cellular uptake.