Major Update 2: Antibody Response and Risk for Reinfection After SARS-CoV-2 Infection-Final Update of a Living, Rapid Review.

BACKGROUND: The durability of the antibody response after SARS-CoV-2 infection and the role of antibodies in protection against reinfection are unclear. PURPOSE: To synthesize evidence on the SARS-CoV-2 antibody response and reinfection risk with a focus on gaps identified in our prior reports. DATA SOURCES: MEDLINE (Ovid), EMBASE, CINAHL, World Health Organization Research Database, and reference lists from 16 December 2021 through 8 July 2022, with surveillance through 22 August 2022. STUDY SELECTION: English-language, cohort studies evaluating IgG antibody duration at least 12 months after SARS-CoV-2 infection, the antibody response among immunocompromised adults, predictors of nonseroconversion, and reinfection risk. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Most adults had IgG antibodies after SARS-CoV-2 infection at time points greater than 12 months (low strength of evidence [SoE]). Although most immunocompromised adults develop antibodies, the overall proportion with antibodies is lower compared with immunocompetent adults (moderate SoE for organ transplant patients and low SoE for patients with cancer or HIV). Prior infection provided substantial, sustained protection against symptomatic reinfection with the Delta variant (high SoE) and reduced the risk for severe disease due to Omicron variants (moderate SoE). Prior infection was less protective against reinfection with Omicron overall (moderate SoE), but protection from earlier variants waned rapidly (low SoE). LIMITATION: Single review for abstract screening and sequential review for study selection, data abstraction, and quality assessment. CONCLUSION: Evidence for a sustained antibody response to SARS-CoV-2 infection is considerable for both Delta and Omicron variants. Prior infection protected against reinfection with both variants, but, for Omicron, protection was weaker and waned rapidly. This information may have limited clinical applicability as new variants emerge. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

"I'm Clean and Sober, But Not Necessarily Free": Perceptions of Buprenorphine Among Patients in Long-Term Treatment.

BACKGROUND: Patients receiving buprenorphine for the treatment of opioid use disorder (OUD) experience a roughly 50% reduction in mortality risk relative to those not receiving medication. Longer periods of treatment are also associated with improved clinical outcomes. Despite this, patients often express desires to discontinue treatment and some view taper as treatment success. Little is known about the beliefs and medication perspectives of patients engaged in long-term buprenorphine treatment that may underlie motivations to discontinue. METHODS: This study was conducted at the VA Portland Health Care System (2019-2020). Qualitative interviews were conducted with participants prescribed buprenorphine for ≥2 years. Coding and analysis were guided by directed qualitative content analysis. RESULTS: Fourteen patients engaged in office-based buprenorphine treatment completed interviews. While patients expressed strong enthusiasm for buprenorphine as a medication, the majority expressed the desire to discontinue, including patients actively tapering. Motivations to discontinue fell into 4 categories. First, patients were troubled by perceived side effects of the medication, including effects on sleep, emotion, and memory. Second, patients expressed unhappiness with being "dependent" on buprenorphine, framed in opposition to personal strength/independence. Third, patients expressed stigmatized beliefs about buprenorphine, describing it as "illicit," and associated with past drug use. Finally, patients expressed fears about buprenorphine unknowns, including potential long-term health effects and interactions with medications required for surgery. CONCLUSIONS: Despite recognizing benefits, many patients engaged in long-term buprenorphine treatment express a desire to discontinue. Findings from this study may help clinicians anticipate patient concerns and can be used to inform shared decision-making conversations regarding buprenorphine treatment duration.

Perioperative Management of Buprenorphine/Naloxone in a Large, National Health Care System: a Retrospective Cohort Study.

BACKGROUND: Medication for opioid use disorder, including buprenorphine and methadone, is considered the gold standard treatment for opioid use disorder (OUD). As the number of patients receiving buprenorphine has grown, clinicians increasingly care for patients prescribed buprenorphine who present for surgery and require management of perioperative pain. OBJECTIVE: To describe practice patterns of perioperative and post-surgical use of buprenorphine among patients prescribed buprenorphine for OUD who experience major surgery. DESIGN: Retrospective cohort study utilizing data from the VA Corporate Data Warehouse (CDW), a national repository of patient-level data. Data not accessible in CDW, including clinical instructions to patients to modify buprenorphine dose, were accessed via chart review. PARTICIPANTS: National sample of patients receiving care through the Veterans Health Administration. MAIN MEASURES: We report descriptive statistics on the incidence of buprenorphine dose hold prior to, during, and immediately following surgery, as well as post-surgical outcomes. Multivariable logistic regression identified socio-demographic and clinical characteristics associated with perioperative hold. KEY RESULTS: Our final sample comprised 183 patients, the majority of whom were white and male. Most patients (66%) experienced a perioperative buprenorphine dose hold: during the pre-operative, day of surgery, and post-operative periods, 40%, 62%, and 55% of patients had buprenorphine held. Buprenorphine dose hold was less likely for patients who had experienced homelessness/housing insecurity in the year prior to surgery (aOR = 0.25; 95% CI 0.10-0.61) as well as patients residing in rural areas (aOR=0.29; 0.12-0.68). Within the 12-month period following surgery, 122 patients (67%) were retained on buprenorphine, 10 patients (5.5%) had experienced an overdose, and 15 (8.2%) had died. CONCLUSIONS: We identified high rates of perioperative buprenorphine dose holds. As holding buprenorphine perioperatively does not align with emerging clinical recommendations and carries significant risks, educational campaigns or other provider-targeted interventions may be needed to ensure patients with OUD receive recommended care.

Antibody Response After SARS-CoV-2 Infection and Implications for Immunity : A Rapid Living Review.

BACKGROUND: The clinical significance of the antibody response after SARS-CoV-2 infection remains unclear. PURPOSE: To synthesize evidence on the prevalence, levels, and durability of detectable antibodies after SARS-CoV-2 infection and whether antibodies to SARS-CoV-2 confer natural immunity. DATA SOURCES: MEDLINE (Ovid), Embase, CINAHL, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, World Health Organization global literature database, and Covid19reviews.org from 1 January through 15 December 2020, limited to peer-reviewed publications available in English. STUDY SELECTION: Primary studies characterizing the prevalence, levels, and duration of antibodies in adults with SARS-CoV-2 infection confirmed by reverse transcriptase polymerase chain reaction (RT-PCR); reinfection incidence; and unintended consequences of antibody testing. DATA EXTRACTION: Two investigators sequentially extracted study data and rated quality. DATA SYNTHESIS: Moderate-strength evidence suggests that most adults develop detectable levels of IgM and IgG antibodies after infection with SARS-CoV-2 and that IgG levels peak approximately 25 days after symptom onset and may remain detectable for at least 120 days. Moderate-strength evidence suggests that IgM levels peak at approximately 20 days and then decline. Low-strength evidence suggests that most adults generate neutralizing antibodies, which may persist for several months like IgG. Low-strength evidence also suggests that older age, greater disease severity, and presence of symptoms may be associated with higher antibody levels. Some adults do not develop antibodies after SARS-CoV-2 infection for reasons that are unclear. LIMITATIONS: Most studies were small and had methodological limitations; studies used immunoassays of variable accuracy. CONCLUSION: Most adults with SARS-CoV-2 infection confirmed by RT-PCR develop antibodies. Levels of IgM peak early in the disease course and then decline, whereas IgG peaks later and may remain detectable for at least 120 days. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42020207098).

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review.

BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in coronavirus disease 2019 (COVID-19) susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).

Antithrombotic Therapies in COVID-19 Disease: a Systematic Review.

BACKGROUND: Infection with coronavirus SARS-CoV-2, causing COVID-19 disease, leads to inflammation and a prothrombotic state. OBJECTIVE: This rapid systematic review aims to synthesize evidence on thromboembolism incidence and outcomes with antithrombotic therapies in COVID-19. DATA SOURCES: We searched MEDLINE (Ovid), Cochrane Rapid Reviews, PROSPERO, and the WHO COVID-19 Database from January 1, 2003, to April 22, 2020, for studies meeting pre-specified inclusion criteria. STUDY SELECTION, DATA EXTRACTION, AND SYNTHESIS: One investigator identified articles for inclusion, abstracted data, and performed quality assessment, with second reviewer checking. RESULTS: Incidence of thromboembolism among hospitalized patients with COVID-19 ranged from 25 to 53% in 4 retrospective series. We identified 3 studies (1 retrospective cohort study, 1 prospective uncontrolled observational study, and 1 case series) examining outcomes among COVID-19 patients who received antithrombotic therapies. These studies all included different interventions (thromboprophylaxis with unfractionated heparin (UFH) or low molecular-weight heparin (LMWH); an intensive thromboprophylaxis protocol with LMWH, antithrombin, and clopidogrel; and salvage therapy with tissue plasminogen activator and heparin). These studies are overall poor quality due to methodological limitations including unclear patient selection protocols, lack of reporting or adjustment for patient baseline characteristics, inadequate duration of follow-up, and partial reporting of outcomes. CONCLUSIONS: New evidence on thromboembolism in COVID-19 does not warrant a change in current guidance on thromboprophylaxis among hospitalized patients. Prospective trials of antithrombotic treatment strategies among patients with COVID-19 are urgently needed.

Barriers and Facilitators to the Use of Medications for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment. METHODS: We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second. RESULTS: We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged-stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies. DISCUSSION: Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use. PROTOCOL REGISTRATION: PROSPERO; CRD42019133394.

Managing Acute Pain in Patients Taking Medication for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Managing acute pain in patients with opioid use disorder (OUD) on medication (methadone, buprenorphine, or naltrexone) can be complicated by patients' higher baseline pain sensitivity and need for higher opioid doses to achieve pain relief. This review aims to evaluate the benefits and harms of acute pain management strategies for patients taking OUD medications and whether strategies vary by OUD medication type or cause of acute pain. METHODS: We systematically searched multiple bibliographic sources until April 2020. One reviewer used prespecified criteria to assess articles for inclusion, extract data, rate study quality, and grade our confidence in the body of evidence, all with second reviewer checking. RESULTS: We identified 12 observational studies-3 with control groups and 9 without. Two of the studies with control groups suggest that continuing buprenorphine and methadone in OUD patients after surgery may reduce the need for additional opioids and that ineffective pain management in patients taking methadone can result in disengagement in care. A third controlled study found that patients taking OUD medications may need higher doses of additional opioids for pain control, but provided insufficient detail to apply results to clinic practice. The only case study examining naltrexone reported that postoperative pain was managed using tramadol. We have low confidence in these findings as no studies directly addressed our question by comparing pain management strategies and few provided adequate descriptions of the dosage, timing, or rationale for clinical decisions. DISCUSSION: We lack rigorous evidence on acute pain management in patients taking medication for OUD; however, evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes. Well-described, prospective studies of adjuvant pain management strategies when OUD medications are continued would add to the existing literature base. Studies on nonopioid treatments are also needed for patients taking naltrexone. PROTOCOL REGISTRATION: PROSPERO; CRD42019132924.

Benefits and Harms of Long-term Opioid Dose Reduction or Discontinuation in Patients with Chronic Pain: a Rapid Review.

BACKGROUND: Many clinicians are reevaluating the use of long-term opioid therapy (LTOT) for chronic pain in response to the opioid crisis and calls from organizations including the Centers for Disease Control & Prevention to limit prescribing of high-dose opioids. However, this practice change is occurring largely in the absence of data regarding patient outcomes. A 2017 systematic review found inconclusive evidence on the impact of LTOT dose reduction and discontinuation on pain severity and function, quality of life, withdrawal symptoms, substance abuse, and adverse effects. This rapid systematic review provides an updated evidence synthesis of patient outcomes following LTOT dose reduction including serious harms such as overdose and suicide. METHODS: We systematically searched numerous bibliographic databases from January 2017 (the end search date of the 2017 systematic review) through May 2020. One reviewer used prespecified criteria to assess articles for inclusion, evaluate study quality, abstract data, and grade strength of evidence, with a second reviewer checking. RESULTS: We included 49 studies-1 systematic review, 34 studies included in that systematic review, and 14 new studies. We prioritized evidence synthesis of 19 studies with the most applicability to the Veteran population and outpatient settings. Among these studies, improvements in mean pain scores were common among patients tapering opioids while participating in intensive multimodal pain interventions and mostly unchanged with less intensive or nonspecific co-interventions. Our confidence in these findings is low due to methodological limitations of the studies. Observational data suggests that serious harms such as opioid overdose and suicidal ideation can occur following opioid dose reduction or discontinuation, but the incidence of these harms at the population level is unknown. DISCUSSION: The net balance of benefits and harms of LTOT dose reduction for patients with chronic pain is unclear. Clinicians should closely monitor patients during the tapering process given the potential for harm.

Effectiveness of Models Used to Deliver Multimodal Care for Chronic Musculoskeletal Pain: a Rapid Evidence Review.

BACKGROUND: Primary care providers (PCPs) face many system- and patient-level challenges in providing multimodal care for patients with complex chronic pain as recommended in some pain management guidelines. Several models have been developed to improve the delivery of multimodal chronic pain care. These models vary in their key components, and work is needed to identify which have the strongest evidence of clinically-important improvements in pain and function. Our objective was to determine which primary care-based multimodal chronic pain care models provide clinically relevant benefits, define key elements of these models, and identify patients who are most likely to benefit. METHODS: To identify studies, we searched MEDLINE® (1996 to October 2016), CINAHL, reference lists, and numerous other sources and consulted with experts. We used predefined criteria for study selection, data abstraction, internal validity assessment, and strength of evidence grading. RESULTS: We identified nine models, evaluated in mostly randomized controlled trials (RCTs). The RCTs included 3816 individuals primarily from the USA. The most common pain location was the back. Five models primarily coupling a decision-support component-most commonly algorithm-guided treatment and/or stepped care-with proactive ongoing treatment monitoring have the best evidence of providing clinically relevant improvement in pain intensity and pain-related function over 9 to 12 months (NNT range, 4 to 13) and variable improvement in quality of life, depression, anxiety, and sleep. The strength of the evidence was generally low, as each model was only supported by a single RCT with imprecise findings. DISCUSSION: Multimodal chronic pain care delivery models coupling decision support with proactive treatment monitoring consistently provide clinically relevant improvement in pain and function. Wider implementation of these models should be accompanied by further evaluation of clinical and implementation effectiveness.

Sources of Distress in Primary Care Opioid Management and the Role of a Controlled Substance Review Group: A Qualitative Study.

Objective: The objective of the study was to explore provider perspectives surrounding opioid prescribing in the context of the early implementation of a multidisciplinary group, called the Controlled Substance Review Group, that provided structured opioid case discussion and consultation to primary care providers. Setting: A Veterans Health Administration primary care clinic in Portland, Oregon. Participants: 12 members of primary care clinic staff representing multiple disciplines with recent participation in the Controlled Substance Review Group. Methods: Six semistructured interviews with primary care providers, one focus group discussion with six Nurse Care Managers, and 28 structured observations of CSRG meetings were conducted. In an iterative process using applied thematic analysis, a trained qualitative researcher reviewed textual data for themes. Results: Four broad domains with associated themes emerged from the analysis: 1) challenges of pain management-objective pain measures, changing guidelines, lack of coordinated approach; 2) patient attachment to opioids-threats, entitlement, abandonment; 3) provider frustration-confrontation in clinic visits, lack of mental health engagement, complex social situation; and 4) role of the Controlled Substance Review Group-communication techniques, supporting mental health engagement, structured backing. Conclusions: Primary care providers experience stress associated with opioid prescribing, including the provision of appropriate pain management using opioid analgesics and difficult patient-provider communication. The Controlled Substance Review Group functions to support providers through assistance with decision-making and shared responsibility for decision outcomes.

Divergent responses of Atlantic coastal and oceanic Synechococcus to iron limitation.

Marine Synechococcus are some of the most diverse and ubiquitous phytoplankton, and iron (Fe) is an essential micronutrient that limits productivity in many parts of the ocean. To investigate how coastal and oceanic Atlantic Synechococcus strains acclimate to Fe availability, we compared the growth, photophysiology, and quantitative proteomics of two Synechococcus strains from different Fe regimes. Synechococcus strain WH8102, from a region in the southern Sargasso Sea that receives substantial dust deposition, showed impaired growth and photophysiology as Fe declined, yet used few acclimation responses. Coastal WH8020, from the dynamic, seasonally variable New England shelf, displayed a multitiered, hierarchical cascade of acclimation responses with different Fe thresholds. The multitiered response included changes in Fe acquisition, storage, and photosynthetic proteins, substitution of flavodoxin for ferredoxin, and modified photophysiology, all while maintaining remarkably stable growth rates over a range of Fe concentrations. Modulation of two distinct ferric uptake regulator (Fur) proteins that coincided with the multitiered proteome response was found, implying the coastal strain has different regulatory threshold responses to low Fe availability. Low nitrogen (N) and phosphorus (P) availability in the open ocean may favor the loss of Fe response genes when Fe availability is consistent over time, whereas these genes are retained in dynamic environments where Fe availability fluctuates and N and P are more abundant.

Physiological and proteomic characterization of light adaptations in marine Synechococcus.

Marine Synechococcus thrive over a range of light regimes in the ocean. We examined the proteomic, genomic and physiological responses of seven Synechococcus isolates to moderate irradiances (5-80 µE m-2 s-1 ), and show that Synechococcus spans a continuum of light responses ranging from low light optimized (LLO) to high light optimized (HLO). These light responses are linked to phylogeny and pigmentation. Marine sub-cluster 5.1A isolates with higher phycouribilin: phycoerythrobilin ratios fell toward the LLO end of the continuum, while sub-cluster 5.1B, 5.2 and estuarine Synechococcus with less phycouribilin fell toward the HLO end of the continuum. Global proteomes were highly responsive to light, with > 50% of abundant proteins varying more than twofold between the lowest and highest irradiance. All strains downregulated phycobilisome proteins with increasing irradiance. Regulation of proteins involved in photosynthetic electron transport, carbon fixation, oxidative stress protection (superoxide dismutases) and iron and nitrogen metabolism varied among strains, as did the number of high light inducible protein (Hlip) and DNA photolyase genes in their genomes. All but one LLO strain possessed the photoprotective orange carotenoid protein (OCP). The unique combinations of light responses in each strain gives rise to distinct photophysiological phenotypes that may affect Synechococcus distributions in the ocean.

Screening for Celiac Disease: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Silent or subclinical celiac disease may result in potentially avoidable adverse health consequences. Objective: To review the evidence on benefits and harms of screening for celiac disease in asymptomatic adults, adolescents, and children 3 years and older for the US Preventive Services Task Force. Data Sources: Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews, searched to June 14, 2016. Study Selection: Randomized clinical trials and cohort or case-control studies on clinical benefits and harms of screening vs no screening for celiac disease or treatment vs no treatment for screen-detected celiac disease; studies on diagnostic accuracy of serologic tests for celiac disease. Data Extraction and Synthesis: One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. Main Outcomes and Measures: Cancer incidence, gastrointestinal outcomes, psychological outcomes, child growth outcomes, health outcomes resulting from nutritional deficiencies, quality of life, mortality, and harms of screening. No meta-analytic pooling was done. Results: One systematic review and 3 primary studies met inclusion criteria. No trials of screening for celiac disease were identified. One recent, good-quality systematic review of 56 original studies and 12 previous systematic reviews (sample sizes of primary studies ranging from 62 to more than 12 000 participants) found IgA tissue transglutaminase was associated with high accuracy (sensitivity and specificity both >90%) for diagnosing celiac disease. IgA endomysial antibodies tests were associated with high specificity. Only 2 studies of serologic tests for celiac disease involving 62 and 158 patients were conducted in asymptomatic populations and reported lower sensitivity (57% and 71%). One fair-quality, small (n = 40) Finnish treatment trial of asymptomatic adults with screen-detected celiac disease based on positive serologic findings found initiation of a gluten-free diet associated with small improvement in gastrointestinal symptoms compared with no gluten-free diet (difference less than 1 point on a scale of 1 to 7) at 1 year, with no differences on most measures of quality of life. No withdrawals due to adverse events occurred during the trial; no other harms were reported. No studies were identified that addressed the other outcomes. Conclusions and Relevance: Although some evidence was found regarding diagnostic accuracy of tests for celiac disease, little or no evidence was identified to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals. More research is needed to understand the effectiveness of screening and treatment for celiac disease, accuracy of screening tests in asymptomatic persons, and optimal screening strategies.