Assessing Patient Values and Preferences to Inform the 2023 American College of Rheumatology/American College of Chest Physicians Interstitial Lung Disease Guidelines.

OBJECTIVE: Patient engagement is critical to clinical practice guideline (CPG) development. This work presents our approach to ascertaining patients' values and preferences to inform the American College of Rheumatology guidelines for screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We conducted a cross-sectional qualitative study of a purposefully sampled Patient Panel using a modified content analytic approach. The study team reviewed text transcripts from the Patient Panel discussion to identify themes and develop a clustered thematic schema. RESULTS: Twenty-one patients (75% women) participated, with a mean age of 53 years (range 33-73). Patients had one or more SARDs: systemic sclerosis (38%), Sjögren disease (38%), idiopathic inflammatory myopathy (33%), rheumatoid arthritis (24%), and mixed connective tissue disease (10%). We identified 10 themes in 4 thematic clusters: communication, screening and monitoring, treatment goals, and treatment adverse effects. Patients prioritized recognizing ILD symptoms, importance of ILD screening and close monitoring, goals of survival and improving quality of life, and willingness to accept treatment risks provided that there is close communication with providers. Patient representatives shared patients' priorities and insight at the Voting Panel meeting, influencing multiple guideline recommendations. CONCLUSION: Patient engagement fosters a holistic approach to CPG development, leading to recommendations aiming for the best clinical outcomes while prioritizing outcomes important for patients. The patient-identified themes played a critical role in ILD guideline development and provide core elements for shared decision-making as clinicians make management and therapeutic decisions with patients with SARD-associated ILD.

Effectiveness of Continuous Glucose Monitoring on Metrics of Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: To provide a systematic review and meta-analysis synthesizing the findings of randomized controlled trials (RCTs) of continuous glucose monitors (CGMs) in the management of adults with type 2 diabetes mellitus (T2DM) on glucose control and clinical outcomes. METHODS: MEDLINE, Embase, and Cochrane were searched for RCTs that assessed the effectiveness of real-time CGM (rt-CGM) or flash CGM (FGM) in adults (≥18 years) with T2DM that reported on at least 1 of the following outcomes: hemoglobin A1c (HbA1c), time in range, time in hyperglycemia, or time in hypoglycemia. The GRADE approach was used to assess certainty of evidence for primary outcomes. RESULTS: Fourteen RCTs assessing CGM were included, with 825 patients in 9 RCTs using rt-CGM and 822 in 5 RCTs using FGM. Moderate certainty of evidence indicated that use of CGM had a modest but statistically significant reduction in HbA1c levels of about 0.32%. Our analyses of each device type separately showed similar reductions in HbA1c (0.34% and 0.33%, respectively, for rt-CGM and FGM), with trends for improvement in other glucose metrics favoring rt-CGM over self-monitored blood glucose. CONCLUSION: Both rt-CGM and flash CGM led to modest but statistically significant declines in HbA1c among individuals with T2DM, with little heterogeneity in the results. However, the duration of the included RCTs was relatively short and few studies reported on important clinical outcomes, such as adverse events, emergency department use, or hospitalization. Longer term studies are needed to determine if the short-term improvements in glucose control leads to improvements in clinically important outcomes.

2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.

2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

OBJECTIVE: The objective is to update recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) for patients with rheumatic or nonrheumatic conditions receiving >3 months treatment with glucocorticoids (GCs) ≥2.5 mg daily. METHODS: An updated systematic literature review was performed for clinical questions on nonpharmacologic, pharmacologic treatments, discontinuation of medications, and sequential therapy. Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the certainty of evidence. A Voting Panel achieved ≥70% consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: For adults beginning or continuing >3 months of GC treatment, we strongly recommend as soon as possible after initiation of GCs, initial assessment of fracture risks with clinical fracture assessment, bone mineral density with vertebral fracture assessment or spinal x-ray, and Fracture Risk Assessment Tool if ≥40 years old. For adults at medium, high, or very high fracture risk, we strongly recommend pharmacologic treatment. Choice of oral or intravenous bisphosphonates, denosumab, or parathyroid hormone analogs should be made by shared decision-making. Anabolic agents are conditionally recommended as initial therapy for those with high and very high fracture risk. Recommendations are made for special populations, including children, people with organ transplants, people who may become pregnant, and people receiving very high-dose GC treatment. New recommendations for both discontinuation of osteoporosis therapy and sequential therapies are included. CONCLUSION: This guideline provides direction for clinicians and patients making treatment decisions for management of GIOP. These recommendations should not be used to limit or deny access to therapies.

Parent perceptions and decision making about treatments for epilepsy: a qualitative evidence synthesis.

OBJECTIVES: Epilepsy treatment decision making is complex and understanding what informs caregiver decision making about treatment for childhood epilepsy is crucial to better support caregivers and their children. We synthesised evidence on caregivers' perspectives and experiences of treatments for childhood epilepsy. DESIGN: Systematic review of qualitative studies using a best-fit framework and Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual) approach. DATA SOURCES: Searched Embase, PubMed, CINAHL, PsycINFO, SocINDEX and Web of Science from 1 January 1999 to 19 August 2021. ELIGIBILITY CRITERIA: We included qualitative studies examining caregiver's perspectives on antiseizure medication, diet or surgical treatments for childhood epilepsy. We excluded studies not reported in English. DATA EXTRACTION AND SYNTHESIS: We extracted qualitative evidence into 1 of 14 domains defined by the Theoretical Domains Framework (TDF). One reviewer extracted study data and methodological characteristics, and two reviewers extracted qualitative findings. The team verified all extractions. We identified themes within TDF domains and synthesised summary statements of these themes. We assessed our confidence in our summary statements using GRADE-CERQual. RESULTS: We identified five studies (in six reports) of good methodological quality focused on parent perceptions of neurosurgery; we found limited indirect evidence on parents' perceptions of medications or diet. We identified themes within 6 of the 14 TDF domains relevant to treatment decisions: knowledge, emotion; social/professional role and identity; social influence; beliefs about consequences; and environmental context and resources. CONCLUSIONS: Parents of children with epilepsy navigate a complex process to decide whether to have their child undergo surgery. Educational resources, peer support and patient navigators may help support parents through this process. More qualitative studies are needed on non-surgical treatments for epilepsy and among caregivers from different cultural and socioeconomic backgrounds to fully understand the diversity of perspectives that informs treatment decision making.

Interventions for malnutrition in hospitalized adults: A systematic review and meta-analysis.

BACKGROUND: Malnutrition is associated with poor outcomes in hospitalized adults. We aimed to assess the effectiveness of hospital-initiated interventions for patients with malnutrition. METHODS: Data sources included MEDLINE, Embase, Cochrane Library from January 1, 2000 to June 3, 2021. We included randomized controlled trials (RCTs) assessing interventions for hospitalized adults diagnosed or identified as at-risk for malnutrition using malnutrition screening and diagnostic assessment tools. Individual reviewers extracted study data and performed quality checks for accuracy. Meta-analysis was conducted using a random-effects model with variance correction. We assessed the overall strength of evidence at the outcome level. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. RESULTS: We found 11 RCTs that assessed two types of interventions: specialized nutrition care (8 RCTs) and increased protein provision (3 RCTs). The pooled findings of 11 RCTs found moderate strength of evidence that specialized nutrition care and increased protein provision reduced mortality by 21% (relative risk [RR]: 0.79, 95% confidence interval [CI]: 0.63-0.98; absolute risk reduction [ARR]: -0.02, 95% CI: -0.03 to -0.00). Pooled estimates indicated a nonsignificant decrease of 0.18 days in the length of stay (9 RCTs) and a 10% reduction in readmissions (7 RCTs). No eligible RCTs assessed parenteral or enteral nutrition. CONCLUSION: Certain malnutrition-focused hospital-initiated interventions (e.g., specialized nutrition care and increased protein provision) reduce mortality and may improve the quality of life among patients at risk for or diagnosed with malnutrition. Future trials are needed to assess the effectiveness of parenteral and enteral nutrition.

Telehealth for Substance Use Disorders: A Rapid Review for the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Management of Substance Use Disorders.

BACKGROUND: Approximately 20.4 million Americans met criteria for a substance use disorder (SUD) in 2019; however, only about 12.2% of persons with an SUD receive specialty care. Telehealth offers alternatives to traditional forms of substance use treatment. PURPOSE: To synthesize recent findings on the efficacy of telehealth for SUDs. DATA SOURCES: MEDLINE, Embase, PubMed, and the Cochrane Library from January 2015 through August 2021 (English language only). STUDY SELECTION: Randomized controlled trials (RCTs) of adults with a diagnosis of SUD based on the Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases. DATA EXTRACTION: One investigator abstracted data and assessed study quality, and a second checked for accuracy. DATA SYNTHESIS: This rapid review synthesized evidence from 17 RCTs. Evidence is very uncertain that telehealth provided as videoconference therapy (1 RCT) or web-based cognitive behavioral therapy (CBT) (3 RCTs) has similar effects to in-person therapy for improving abstinence from alcohol or cannabis. Low-strength evidence suggests that web-based CBT has similar effects for improving abstinence in multiple SUDs (2 RCTs). Low-strength evidence suggests that adding supportive text messaging to follow-up care improves abstinence and amount of alcohol per day (2 RCTs) but does not improve emergency department visits or frequency of consumption (2 RCTs). Enhanced telephone monitoring likely reduces readmissions for SUD detoxification compared with usual follow-up alone (1 RCT) but does not reduce days of substance use (low-strength evidence). LIMITATION: Narrative synthesis, heterogeneity of telehealth interventions, no assessment of publication bias, and study methodology. CONCLUSION: Evidence is very uncertain that telehealth is similar to in-person care for SUD outcomes. Limited evidence suggests some benefit of adding telehealth to usual SUD care. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs Veterans Health Administration.

Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation.

Background: Early rehabilitation after stroke is essential to help reduce disability. Purpose: To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke. Data Sources: English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors. Study Selection: 19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke. Data Extraction: One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator. Data Synthesis: Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind-body exercise, may reduce symptoms of depression and anxiety. Limitation: Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce. Conclusion: Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.

Treatments for the Prevention and Management of Suicide: A Systematic Review.

Background: Suicide is a growing public health problem, with the national rate in the United States increasing by 30% from 2000 to 2016. Purpose: To assess the benefits and harms of nonpharmacologic and pharmacologic interventions to prevent suicide and reduce suicide behaviors in at-risk adults. Data Sources: MEDLINE, EMBASE, PsycINFO, and other databases from November 2011 through May 2018. Study Selection: Systematic reviews (SRs) and randomized controlled trials (RCTs) that assessed nonpharmacologic or pharmacologic therapies for adults at risk for suicide. Data Extraction: One investigator abstracted data and assessed study quality, and a second investigator checked abstractions and assessments for accuracy. Data Synthesis: Eight SRs and 15 RCTs were included. The evidence for psychological interventions suggests that cognitive behavioral therapy (CBT) reduces suicide attempts, suicidal ideation, and hopelessness compared with treatment as usual (TAU). Limited evidence suggests that dialectical behavior therapy (DBT) reduces suicidal ideation compared with wait-list control or crisis planning. The evidence for pharmacologic treatments suggests that ketamine reduces suicidal ideation with minimal adverse events compared with placebo or midazolam. Lithium reduces rates of suicide among patients with unipolar or bipolar mood disorders compared with placebo. However, no differences were observed between lithium and other medications in reducing suicide. Limitation: Qualitative synthesis of new evidence with existing meta-analyses, methodological shortcomings of studies, heterogeneity of nonpharmacologic interventions, and limited evidence for pharmacologic treatments and harms. Conclusion: Both CBT and DBT showed modest benefit in reducing suicidal ideation compared with TAU or wait-list control, and CBT also reduced suicide attempts compared with TAU. Ketamine and lithium reduced the rate of suicide compared with placebo, but there was limited information on harms. Limited data are available to support the efficacy of other nonpharmacologic or pharmacologic interventions. Primary Funding Source: U.S. Department of Veterans Affairs Veterans Health Administration. (PROSPERO: CRD42018104978).

AHRQ series on complex intervention systematic reviews-paper 2: defining complexity, formulating scope, and questions.

BACKGROUND: The early stages of a systematic review set the scope and expectations. This can be particularly challenging for complex interventions given their multidimensional and dynamic nature. RATIONALE: This paper builds on concepts introduced in paper 1 of this series. It describes the methodological, practical, and philosophical challenges and potential approaches for formulating the questions and scope of systematic reviews of complex interventions. Furthermore, it discusses the use of theory to help organize reviews of complex interventions. DISCUSSION: Many interventions in medicine, public health, education, social services, behavioral health, and community programs are complex, and they may not fit neatly within the established paradigm for reviews of straightforward interventions. This paper provides conceptual and operational guidance for these early stages of scope formulation to assist authors of systematic reviews of complex interventions.

Assessing equivalence and noninferiority.

OBJECTIVE: For systematic reviews, no guidance exists for what review methods support valid conclusions of equivalence (EQ) and noninferiority (NI). To provide such guidance, we convened a workgroup of 13 experienced systematic reviewers from seven evidence-based practice centers (EPCs) and the Agency for Healthcare Research and Quality (AHRQ). STUDY DESIGN AND SETTING: The Lead EPC first performed two methods projects intended to assist the workgroup in clarifying the context, prioritizing the issues, targeting the scope, and summarizing the state of the art. RESULTS: Based on expert opinion, we devised guidance in four areas: 1) Unique risk of bias issues for trials self-identifying as EQ-NI trials; 2) Setting the reviewer's minimum important difference; 3) Analytic foundations for concluding EQ or NI; and 4) Language considerations when concluding EQ or NI. CONCLUSION: This article summarizes the main recommendations, and the full guidance chapter appears on the AHRQ Web site.

Autologous hematopoietic cell transplantation for multiple sclerosis: a systematic review.

BACKGROUND AND OBJECTIVES: The purpose of this systematic review was to evaluate the safety and efficacy of autologous hematopoietic cell transplantation in patients with progressive multiple sclerosis (MS) refractory to conventional medical treatment. METHODS: Eight case series met our a priori inclusion criteria for the primary outcome of progression-free survival. Individual study quality was rated using an 11-item scale for case series. The strength of the overall body of evidence for each outcome was rated using a system developed by the ECRI Institute. Data from different studies were statistically combined using meta-analysis. An additional six studies were included for a summary of mortality and morbidity. RESULTS: For secondary progressive MS, immunoablative therapy with autologous bone marrow/peripheral blood stem cell transplantation was associated with higher progression-free survival (up to 3 years following treatment) when using intermediate-intensity conditioning regimens compared with high-intensity conditioning regimens. The evidence was insufficient to determine whether the treatment was effective in patients with other types of MS. Treatment-related mortality was about 2.7%. CONCLUSIONS: Patients with secondary progressive MS refractory to conventional medical treatment have longer progression-free survival following autologous stem cell transplantation with intermediate-intensity conditioning regimens than with high-intensity conditioning regimens.

The relationship of case managers' expressed emotion to clients' outcomes.

BACKGROUND: Expressed emotion (EE) has been studied in families of a relative with schizophrenia as well as other psychiatric disorders; and high EE (hostile, critical, and overinvolved) families have been found to be strongly related to relapse among their relatives. EE has been assessed on a limited basis among non-familial care providers and determined that providers can also have high EE which results in poor quality of life and negative consequences for their clients. METHODS: The present study assessed 42 case managers serving clients with schizophrenia spectrum disorder regarding their EE for specific clients enrolled in a larger study examining the reliability and validity of two alliance measures. Case managers and clients were personally interviewed at baseline, 3, 6, 6 plus 2 weeks, and 9 months post-client entry into case management. The EE measure was inserted into the 6 months plus 2 week case manager interview. Generalized Estimating Equation analysis was employed to examine predicted outcomes of EE. RESULTS: High EE was found to be related to client attitudes toward medication compliance and social contact. CONCLUSIONS: Family psychoeducation interventions, an evidence-based practice, have been demonstrated to be effective in reducing relapse of relatives with serious mental illness. Given the clinical evidence that EE is modifiable, it is expected that such educational training for non-familial caregivers will have the same potential as for family caregivers. Providers dealing with challenging clients may also need support and skills to better handle difficult situations, especially direct support providers like case managers who are not clinically trained.

Computer-aided detection mammography for breast cancer screening: systematic review and meta-analysis.

CONTEXT: Mammography is generally accepted as the best available breast cancer screening method; however, some cancers detectable on mammography images are missed. Computer-aided detection (CAD) systems for mammography are intended to reduce false negatives by marking suspicious areas of the mammograms for reviewers to consider. Although the prospect of improving the sensitivity of screening mammograms has led to the diffusion of CAD for mammography, little is known about its diagnostic accuracy. OBJECTIVE: To assess the diagnostic performance of CAD for screening mammography in terms of sensitivity and specificity and incremental recall, biopsy, and cancer diagnosis rates. DATA SOURCES: Published literature identified by systematic literature searches of 17 databases, including MEDLINE, EMBASE, and the Cochrane Library, searched through 25 September 2008. STUDY SELECTION: A reviewer and an information specialist selected full-length English-language articles that enrolled asymptomatic women for routine breast cancer screening and provided data needed for our analyses using criteria established a priori. We identified 75 potentially relevant publications, of which 7 (9%) were included. DATA EXTRACTION: Data were extracted and internal validity was assessed by a single review author, and forms were approved by the co-authors. RESULTS: Three studies (n = 347,324) reported sensitivity and specificity, or data to calculate them, and five studies (n = 51,162) reported data to calculate incremental rates of cancer diagnoses and recall and biopsy of women who did not have breast cancer. The pooled sensitivity was 86.0% (95% CI 84.2-87.6%) and specificity was 88.2% (95% CI 88.1-88.3%). Of the 100,000 women screened, CAD yielded an additional 50 (95% CI 30-80) correct breast cancer diagnoses, 1,190 (95% CI 1,090-1,290) recalls of healthy women, and 80 (95% CI 60-100) biopsies of healthy women. A total of 96% (95% CI 93.9-97.3%) of women recalled based upon CAD and 65.1% (95% CI 52.3-76.0%) of women biopsied based upon CAD were healthy. No studies reported patient-oriented clinical outcomes.