Recently Published Projects

Objectives: Part of a suite of systematic reviews during the Tear Film and Ocular Surface Society (TFOS) Workshop on OCULAR SURFACE DISEASES: A LIFESTYLE EPIDEMIC

Objectives: Purpose: To systematically review the evidence on screening and treating asymptomatic adults with obstructive sleep apnea (OSA) or those with unrecognized symptoms for OSA. Data Sources: PubMed/MEDLINE, the Cochrane Library, Embase, and trial registries through August 23, 2021; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through September 23, 2022. Study Selection: Two investigators independently selected English-language studies using a priori criteria. Eligible studies included randomized, controlled trials (RCTs) of screening for or treatment of OSA reporting on health outcomes, studies evaluating accuracy of screening questionnaires or clinical prediction tools in asymptomatic adults with OSA or persons with unrecognized symptoms of OSA, and systematic reviews of treatment reporting on changes in blood pressure (BP) and apnea-hypopnea index (AHI) scores. Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated data quality for all included studies using predefined criteria. Data Synthesis: No reviewed RCT directly compared screening with no screening. In two studies (702 total participants), the screening accuracy measured as AUC of the Multivariable Apnea Prediction (MVAP) score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) was 0.80 (95% confidence interval [CI], 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively. Studies evaluating the Snoring, Tiredness, Observed apnea, blood Pressure, Body mass index, Age, Neck circumference, Gender (STOP-BANG) Questionnaire (k=4) and the Berlin Questionnaire (BQ) (k=2) enrolled different populations and used different criteria for a positive screening test. Recent systematic reviews of positive airway pressure (PAP) and mandibular advancement devices (MADs) show an association between PAP and MAD and reduction in BP and AHI, however reduction in BP outcomes versus inactive control is relatively small (2 to 3 mm Hg). Meta-analysis found that PAP compared with any control was associated with a significantly larger reduction in ESS score change (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials, 7,024 participants), modest improvement in sleep-related quality of life (QOL) (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 18 trials, 3,083 participants), and improved general health-related QOL measured by the SF-36 mental health component summary score change (2.20 [95% CI, 0.95 to 3.44]; 15 trials, 2,345 participants) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials, 2,031 participants). Meta-analysis also found that use of MADs was associated with a significantly larger ESS score change than controls (pooled mean difference, -1.67 [95% CI, -2.09 to -1.25]; 10 trials, 1,540 participants). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with PAP or MAD on mortality, cardiovascular outcomes, stroke, or motor vehicle accidents. Common adverse effects of PAP and MADs included oral or nasal dryness, irritation, and pain, among others. Limitations: Two studies assessing the accuracy of the MVAP score oversampled participants at high risk of OSA and those with OSA syndrome. No study prospectively evaluated screening Screening for Obstructive Sleep Apnea in Adults v RTI–UNC EPC tools to report calibration or clinical utility for improving health outcomes. Three studies assessing the accuracy of the STOP-BANG and two assessing the BQ enrolled different populations and used different criteria for positive screening tests. Most included trials assessing the benefit of PAP and MADs reported outcomes over a relatively short duration (12 weeks or less), and most pooled estimates showing improvement in excessive sleepiness or QOL (except benefit of PAP for improving ESS scores) fell short of the range considered to be a minimal clinically important difference. Populations enrolled in trials of treatment were referred for treatment; no trial enrolled populations who were identified by screening in primary care. Conclusions: The accuracy and clinical utility of potential screening tools for OSA that could be used in primary care settings are uncertain. PAP and MADs reduce AHI, BP and ESS score. Trials of PAP have not established whether treatment reduces mortality or improves most other health outcomes, except for its modest improvement in sleep-related QOL and general health–related QOL.

Objectives: Purpose: To review the evidence on benefits and harms of screening for and treatment of latent tuberculosis infection (LTBI) for adult populations and settings relevant to primary care in the United States. Data Sources: PubMed/MEDLINE, the Cochrane Library, and trial registries through December 3, 2021; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through January 20, 2023. Study Selection: English-language controlled studies evaluating (1) screening for LTBI with the tuberculin skin test (TST) using the Mantoux method or commercial interferon-gamma release assays (IGRAs) or (2) treatment of LTBI with pharmacotherapy regimens that are currently recommended by the Centers for Disease Control and Prevention. We excluded studies of close contacts of persons with active tuberculosis (TB) because testing and treatment of such populations is considered part of contact tracing for public health as opposed to a primary care function. We excluded studies of persons with underlying immunosuppression and for whom LTBI testing is considered part of standard disease management (e.g., persons with the human immunodeficiency virus, planned or active use of targeted immune modulators). Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria. Data Synthesis: This review included 113 publications (69,009 participants); 101 of those assessed screening test accuracy or reliability. No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at the 5-mm and 10-mm induration thresholds for positivity were 0.80 (95% confidence interval [CI], 0.74 to 0.87) and 0.81 (95% CI, 0.76 to 0.87), respectively. The pooled estimate at the 15-mm threshold was 0.60 (95% CI, 0.46 to 0.74). Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79 to 0.84) for the QuantiFERON-TB Gold-In-Tube® test (3rd-generation test) to 0.90 (95% CI, 0.87 to 0.92) for T-SPOT.TB. Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (N=27,830) good-quality randomized, controlled trial (RCT) found a relative risk (RR) for progression to active TB at 5 years of 0.35 (95% CI, 0.24 to 0.52) for 24 weeks of isoniazid compared with placebo (N=13,955; number needed to treat, 112). Our sensitivity analyses adding four RCTs that did not meet all of our eligibility criteria (e.g., using a longer duration of treatment than currently recommended) found an RR of 0.31 (95% CI, 0.24 to 0.41; 5 RCTs; N=36,823). A previously published network meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment, including isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval [CrI], 0.50 to 0.83] vs. placebo) or longer, rifampin plus isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78] vs. placebo), and weekly rifapentine plus isoniazid regimens (OR, 0.36 [CrI, 0.18 to 0.73] vs. no treatment). For harms, a large (N=27,830) good-quality RCT reported an RR for hepatotoxicity of 4.59 (95% CI, 2.03 to 10.39; number needed to harm, 279) for 24 weeks of isoniazid compared with placebo. Our sensitivity analyses adding three RCTs that did not meet all of our eligibility criteria (e.g., longer duration of isoniazid) yielded a similar result (pooled RR, 5.04 [95% CI, 2.50 to 10.15]; 4 RCTs; N=35,161). Our meta-analyses found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21 to 8.06], N=7,339). Limitations: Tests for the direct diagnosis of LTBI are not available. Thus, studies estimated accuracy using patients with confirmed active TB to establish sensitivity and healthy, low-risk persons to establish specificity. The applicability to other populations is somewhat uncertain. The single placebo-controlled trial meeting all eligibility criteria that established the effectiveness of isoniazid for preventing active TB was published more than 40 years ago and was conducted among subjects with pulmonary fibrotic lesions; it may overestimate the benefits of treatment for populations with lower risk for progression. Contemporary treatment studies have not included placebo arms; benefits and harms of newer treatments were estimated from comparative studies. Conclusions: No studies evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs are moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduces the risk of progression to active TB. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.

Objectives: Purpose: To review the evidence on benefits and harms of screening for and treatment of latent tuberculosis infection (LTBI) for adult populations and settings relevant to primary care in the United States. Data Sources: PubMed/MEDLINE, the Cochrane Library, and trial registries through December 3, 2021; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through January 20, 2023. Study Selection: English-language controlled studies evaluating (1) screening for LTBI with the tuberculin skin test (TST) using the Mantoux method or commercial interferon-gamma release assays (IGRAs) or (2) treatment of LTBI with pharmacotherapy regimens that are currently recommended by the Centers for Disease Control and Prevention. We excluded studies of close contacts of persons with active tuberculosis (TB) because testing and treatment of such populations is considered part of contact tracing for public health as opposed to a primary care function. We excluded studies of persons with underlying immunosuppression and for whom LTBI testing is considered part of standard disease management (e.g., persons with the human immunodeficiency virus, planned or active use of targeted immune modulators). Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria. Data Synthesis: This review included 113 publications (69,009 participants); 101 of those assessed screening test accuracy or reliability. No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at the 5-mm and 10-mm induration thresholds for positivity were 0.80 (95% confidence interval [CI], 0.74 to 0.87) and 0.81 (95% CI, 0.76 to 0.87), respectively. The pooled estimate at the 15-mm threshold was 0.60 (95% CI, 0.46 to 0.74). Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79 to 0.84) for the QuantiFERON-TB Gold-In-Tube® test (3rd-generation test) to 0.90 (95% CI, 0.87 to 0.92) for T-SPOT.TB. Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (N=27,830) good-quality randomized, controlled trial (RCT) found a relative risk (RR) for progression to active TB at 5 years of 0.35 (95% CI, 0.24 to 0.52) for 24 weeks of isoniazid compared with placebo (N=13,955; number needed to treat, 112). Our sensitivity analyses adding four RCTs that did not meet all of our eligibility criteria (e.g., using a longer duration of treatment than currently recommended) found an RR of 0.31 (95% CI, 0.24 to 0.41; 5 RCTs; N=36,823). A previously published network meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment, including isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval [CrI], 0.50 to 0.83] vs. placebo) or longer, rifampin plus isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78] vs. placebo), and weekly rifapentine plus isoniazid regimens (OR, 0.36 [CrI, 0.18 to 0.73] vs. no treatment). For harms, a large (N=27,830) good-quality RCT reported an RR for hepatotoxicity of 4.59 (95% CI, 2.03 to 10.39; number needed to harm, 279) for 24 weeks of isoniazid compared with placebo. Our sensitivity analyses adding three RCTs that did not meet all of our eligibility criteria (e.g., longer duration of isoniazid) yielded a similar result (pooled RR, 5.04 [95% CI, 2.50 to 10.15]; 4 RCTs; N=35,161). Our meta-analyses found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21 to 8.06], N=7,339). Limitations: Tests for the direct diagnosis of LTBI are not available. Thus, studies estimated accuracy using patients with confirmed active TB to establish sensitivity and healthy, low-risk persons to establish specificity. The applicability to other populations is somewhat uncertain. The single placebo-controlled trial meeting all eligibility criteria that established the effectiveness of isoniazid for preventing active TB was published more than 40 years ago and was conducted among subjects with pulmonary fibrotic lesions; it may overestimate the benefits of treatment for populations with lower risk for progression. Contemporary treatment studies have not included placebo arms; benefits and harms of newer treatments were estimated from comparative studies. Conclusions: No studies evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs are moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduces the risk of progression to active TB. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.

Objectives: Purpose: To review the evidence on benefits and harms of screening for and treatment of latent tuberculosis infection (LTBI) for adult populations and settings relevant to primary care in the United States. Data Sources: PubMed/MEDLINE, the Cochrane Library, and trial registries through December 3, 2021; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through January 20, 2023. Study Selection: English-language controlled studies evaluating (1) screening for LTBI with the tuberculin skin test (TST) using the Mantoux method or commercial interferon-gamma release assays (IGRAs) or (2) treatment of LTBI with pharmacotherapy regimens that are currently recommended by the Centers for Disease Control and Prevention. We excluded studies of close contacts of persons with active tuberculosis (TB) because testing and treatment of such populations is considered part of contact tracing for public health as opposed to a primary care function. We excluded studies of persons with underlying immunosuppression and for whom LTBI testing is considered part of standard disease management (e.g., persons with the human immunodeficiency virus, planned or active use of targeted immune modulators). Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria. Data Synthesis: This review included 113 publications (69,009 participants); 101 of those assessed screening test accuracy or reliability. No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at the 5-mm and 10-mm induration thresholds for positivity were 0.80 (95% confidence interval [CI], 0.74 to 0.87) and 0.81 (95% CI, 0.76 to 0.87), respectively. The pooled estimate at the 15-mm threshold was 0.60 (95% CI, 0.46 to 0.74). Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79 to 0.84) for the QuantiFERON-TB Gold-In-Tube® test (3rd-generation test) to 0.90 (95% CI, 0.87 to 0.92) for T-SPOT.TB. Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (N=27,830) good-quality randomized, controlled trial (RCT) found a relative risk (RR) for progression to active TB at 5 years of 0.35 (95% CI, 0.24 to 0.52) for 24 weeks of isoniazid compared with placebo (N=13,955; number needed to treat, 112). Our sensitivity analyses adding four RCTs that did not meet all of our eligibility criteria (e.g., using a longer duration of treatment than currently recommended) found an RR of 0.31 (95% CI, 0.24 to 0.41; 5 RCTs; N=36,823). A previously published network meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment, including isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval [CrI], 0.50 to 0.83] vs. placebo) or longer, rifampin plus isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78] vs. placebo), and weekly rifapentine plus isoniazid regimens (OR, 0.36 [CrI, 0.18 to 0.73] vs. no treatment). For harms, a large (N=27,830) good-quality RCT reported an RR for hepatotoxicity of 4.59 (95% CI, 2.03 to 10.39; number needed to harm, 279) for 24 weeks of isoniazid compared with placebo. Our sensitivity analyses adding three RCTs that did not meet all of our eligibility criteria (e.g., longer duration of isoniazid) yielded a similar result (pooled RR, 5.04 [95% CI, 2.50 to 10.15]; 4 RCTs; N=35,161). Our meta-analyses found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21 to 8.06], N=7,339). Limitations: Tests for the direct diagnosis of LTBI are not available. Thus, studies estimated accuracy using patients with confirmed active TB to establish sensitivity and healthy, low-risk persons to establish specificity. The applicability to other populations is somewhat uncertain. The single placebo-controlled trial meeting all eligibility criteria that established the effectiveness of isoniazid for preventing active TB was published more than 40 years ago and was conducted among subjects with pulmonary fibrotic lesions; it may overestimate the benefits of treatment for populations with lower risk for progression. Contemporary treatment studies have not included placebo arms; benefits and harms of newer treatments were estimated from comparative studies. Conclusions: No studies evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs are moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduces the risk of progression to active TB. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.