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Completed Systematic Reviews




Screening for Elevated Blood Lead Levels in Pregnancy [Entered Retrospectively]


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Statistics: 2 Studies, 6 Key Questions, 1 Extraction Form,
Date Published: Sep 20, 2019 09:42AM
Description: Structured Abstract Background: In 2006, the United States Preventive Services Task Force (USPSTF) recommended against routine screening for elevated blood lead levels in asymptomatic pregnant women (D recommendation). Purpose: To synthesize evidence on the effects of screening, testing, and treatment for elevated blood lead level in pregnant women, in order to update a 2006 USPSTF systematic review. Data Sources: Cochrane CENTRAL and Cochrane Database of Systematic Reviews (through June 2018), and Ovid MEDLINE (1946 to June 2018), reference lists, and surveillance through December 5, 2018. Study Selection: English-language trials and observational studies of screening effectiveness, test accuracy, benefits and harms of screening and interventions in asymptomatic pregnant women. Data Extraction: One investigator abstracted details about study design, patient population, setting, screening method, follow up, and results. Two investigators independently applied prespecified criteria to rate study quality using methods developed by the USPSTF. Discrepancies were resolved through consensus. Data Synthesis: No studies directly evaluated clinical benefits and harms of screening pregnant women for elevated lead levels versus no screening, or how effectiveness of screening varies according to the gestational age at which screening is performed. One fair quality study (N = 314) evaluated the diagnostic accuracy of using a version of the CDC screening questionnaire for lead exposure in children, modified for identifying pregnant women with elevated lead levels. The study used four out of five of the questions from the CDC questionnaire and found a sensitivity of 75.7 percent and specificity of 46.2 percent. The most predictive single item was living in a home built before 1960. One fair quality RCT from Mexico found calcium supplementation in healthy pregnant women (N = 670; mean baseline lead levels ~ 4 µg/dL) associated with a reduction in serum lead levels compared with placebo (difference 11%, p=0.004). No studies reported health outcomes or harms associated with interventions to reduce blood levels in asymptomatic pregnant women. Limitations: Limited to English-language articles; quality and applicability of studies were limited due to flawed study design, poor reporting of statistical outcomes, and loss to follow up. Two studies addressed the key questions, with no evidence on effects of screening or interventions for elevated lead levels in pregnant women on health outcomes. Conclusions: Evidence on the benefits and harms of screening pregnant women for elevated blood lead levels is extremely limited, with no evidence on effects of screening or interventions for lowering elevated blood lead levels in pregnant women on health outcomes.
Contributor(s): Amy G. Cantor, MD, MPH Marian S. McDonagh, PharmD Ian Blazina, MPH Jessica Griffin, MS Sara Grusing, BA Rob Hendrickson, MD
Funding Source: Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Prepared by the Pacific Northwest Evidence-based Practice Center under Contract No HHSA290201500009I Task Order No. 7)
Methodology Description: Study Selection: English-language trials and observational studies of screening effectiveness, test accuracy, benefits and harms of screening and interventions in asymptomatic pregnant women. Data Extraction: One investigator abstracted details about study design, patient population, setting, screening method, follow up, and results. Two investigators independently applied prespecified criteria to rate study quality using methods developed by the USPSTF. Discrepancies were resolved through consensus.

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Comparative Effectiveness of Analgesics to Reduce Acute Pain in the Prehospital Setting


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Statistics: 67 Studies, 4 Key Questions, 1 Extraction Form,
Date Published: Sep 20, 2019 09:42AM
Description: Objective. To assess comparative effectiveness and harms of opioid and nonopioid analgesics administered by emergency medical services for treatment of moderate to severe acute pain in the prehospital setting. Data sources. MEDLINE®, Embase® and Cochrane Central from earliest date through May 9, 2019; hand searches of references of relevant studies and study registries. Review methods. Two investigators screened abstracts, reviewed full-text files, abstracted data and assessed study level risk of bias. We performed meta-analyses when appropriate and graded the strength of evidence (SOE) upon which conclusions were made for a priori determined comparisons and outcomes. We defined the following as clinically important differences: 2 points on a 0 to 10 pain scale, time to analgesia of 5 minutes, 10% absolute risk difference for any adverse event, and 5% absolute risk difference for hypotension, respiratory depression and mental status changes. Results. We included 52 randomized controlled trials and 13 observational studies. Due to the absence or insufficiency of prehospital evidence we based conclusions for initial analgesia on indirect evidence from the emergency department (ED) setting. As initial analgesics, we found no evidence of a clinically important difference in the change of pain scores with opioids versus ketamine administered primarily intravenously (IV) (low SOE), IV acetaminophen (APAP) (low SOE), or nonsteroidal anti-inflammatory drugs (NSAIDs) administered primarily IV (moderate SOE). The combined use of an opioid and ketamine, administered primarily IV, may reduce pain more than an opioid alone at 15 and 30 minutes (low SOE) but we found no evidence of a clinically important difference at 60 minutes (low SOE). We found no evidence of a clinically important difference in time-to-analgesia with opioids compared with APAP, both administered IV. Opioids may cause fewer adverse events than ketamine (low SOE), primarily administered intranasally (IN). Opioids cause less dizziness than ketamine (low SOE) but may increase the risk of respiratory depression compared with ketamine (low SOE), primarily administered IV. Opioids cause more dizziness (moderate SOE) and may cause more adverse events than APAP (low SOE), both administered IV, but we found no evidence of a clinically important difference in hypotension (low SOE). Opioids may cause more adverse events and more drowsiness than NSAIDs (low SOE), administered primarily IV. Evidence on comparative effects of nitrous oxide and on harms of combined opioid and ketamine is insufficient. For patients whose pain is not adequately reduced by IV morphine initially, we found that giving IV ketamine may reduce pain more and may be quicker than giving additional IV morphine (low SOE, insufficient evidence to determine comparative harms). Conclusion. As initial analgesia administered primarily IV, opioids are no different than ketamine, APAP and NSAIDs in reducing acute pain in the prehospital setting. Opioids may cause fewer total side effects than ketamine, but more than APAP or NSAIDs. Differences in specific side effects vary between analgesics and can further inform treatment decisions. Combined administration of an opioid and ketamine may reduce acute pain more than an opioid alone but comparative harms are uncertain. When initial morphine is inadequate in reducing pain, giving ketamine may provide greater and quicker acute pain relief than giving additional morphine, although comparative harms are uncertain. Due to indirectness, strength of evidence is generally low, and future research in the prehospital setting is needed.
Contributor(s): UConn EPC
Funding Source: AHRQ
Methodology Description: None Provided

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Pre-Exposure Prophylaxis for the Prevention of HIV Infection [Entered Retrospectively]


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Statistics: 52 Studies, 5 Key Questions, 1 Extraction Form,
Date Published: Sep 20, 2019 09:42AM
Description: Background: Effective prevention strategies for HIV infection are an important public health priority. Pre-exposure prophylaxis (PrEP) involves use of antiretroviral therapy (ART) regularly (e.g., daily) or before and after HIV exposure events to decrease the risk of acquiring HIV infection. Purpose: To synthesize evidence for the U.S. Preventive Services Task Force (USPSTF) on effects of PrEP on risk of HIV acquisition, mortality, harms, and other clinical outcomes; effects of adherence on PrEP-associated outcomes; and accuracy of methods for identifying potential candidates for PrEP. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, and Embase from inception to June 2018 and manually reviewed reference lists; additional surveillance for new literature was conducted through January 25, 2019. Study Selection: Randomized, controlled trials on the benefits and harms of PrEP versus placebo or no PrEP in adults without HIV infection at high risk of becoming infected; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; studies on effects of adherence to PrEP on risk of HIV infection; and studies on rates of adherence to PrEP in U.S. populations. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): In populations at higher risk of acquiring HIV infection, PrEP was associated with decreased risk of HIV infection versus placebo or no PrEP (11 trials; relative risk [RR], 0.46 [95% confidence interval (CI), 0.33 to 0.66; I2=67%; absolute risk reduction, -2.0% [95% CI, -2.8% to -1.2%] after 4 months to 4 years). Effects were consistent across HIV risk categories and for PrEP with tenofovir disoproxil fumarate plus emtricitabine or tenofovir alone. There was a strong association between higher adherence and greater efficacy (adherence ≥70%: 6 trials; RR, 0.27 [95% CI, 0.19 to 0.39]; I2=0%; adherence >40% to <70%: 3 trials; RR, 0.51 [95% CI, 0.38 to 0.70]; I2=0%; and adherence ≤40%: 2 trials; RR, 0.93 [95% CI, 0.72 to 1.20]; I2=0%; p<0.00001 for interaction). No trial reported effects of nondaily dosing except for one trial of event-driven PrEP (RR, 0.14 [95% CI, 0.03 to 0.63]). There was no difference between PrEP and placebo or no PrEP in risk of serious adverse events (12 trials; RR, 0.93 [95% CI, 0.77 to 1.12]; I2=56%). PrEP was associated with increased risk of renal adverse events (12 trials; RR, 1.43 [95% CI, 1.18 to 1.75]; I2=0%; absolute risk difference, 0.56% [95% CI, 0.09% to 1.04%]) and gastrointestinal adverse events (12 trials; RR, 1.63 [95% CI, 1.26 to 2.11]; I2=43%; absolute risk difference, 1.95% [95% CI, 0.48% to 3.43%]); most adverse events were mild and resolved with discontinuation of PrEP or with longer therapy. The association between PrEP and fracture was not statistically significant (7 trials; RR, 1.23 [95% CI, 0.97 to 1.56]; I2=0%). There were no differences between PrEP and placebo in risk of sexually transmitted infections, but most trials were blinded. Among women who became pregnant in trials of PrEP, PrEP was not associated with increased risk of spontaneous abortion (3 trials; RR, 1.09 [95% CI, 0.79 to 1.50]; I2=0%) or other adverse pregnancy outcomes. Instruments for predicting risk of incident HIV infection had moderate discrimination and require further validation. Adherence to PrEP in U.S. populations of men who have sex with men varied from high to low. Limitations: Restricted to English language, statistical heterogeneity in some pooled analyses, most randomized trials were conducted in low-income settings, limited evidence on adherence in U.S. populations, and evidence lacking in adolescents and pregnant women. Conclusions: In adults at increased risk of HIV infection, oral PrEP with tenofovir or tenofovir disoproxil fumarate plus emtricitabine is associated with decreased risk of HIV infection compared with placebo or no PrEP, although effectiveness decreases with inadequate adherence. PrEP is associated with increased risk of renal and gastrointestinal adverse events. Evidence on the accuracy of instruments for identifying persons at high risk of HIV infection is limited, with further validation needed.
Contributor(s): Roger Chou, MD Christopher Evans, MD, MPH Adam Hoverman, DO, DTM&H Christina Sun, PhD Tracy Dana, MLS Christina Bougatsos, MPH Sara Grusing, BS P. Todd Korthuis, MD, MPH
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00009-I, Task Order No. 10)
Methodology Description: Study Selection: Randomized, controlled trials on the benefits and harms of PrEP versus placebo or no PrEP in adults without HIV infection at high risk of becoming infected; studies on the diagnostic accuracy of instruments for predicting incident HIV infection; studies on effects of adherence to PrEP on risk of HIV infection; and studies on rates of adherence to PrEP in U.S. populations. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

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Screening for HIV Infection in Pregnant Women [Entered Retrospectively]


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Statistics: 36 Studies, 5 Key Questions, 1 Extraction Form,
Date Published: Sep 20, 2019 09:42AM
Description: Structured Abstract Background: A 2012 systematic review on HIV screening for the U.S. Preventive Services Task Force (USPSTF) found strong evidence that antiretroviral therapy (ART) greatly decreases the risk of mother-to-child HIV transmission but that use of ART may be associated with increased risk of preterm delivery. The USPSTF previously found HIV screening tests to be highly accurate. Purpose: To systematically update the 2012 USPSTF review on HIV screening in pregnancy, focusing on research gaps identified in the prior review. Data Sources: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE (2012 to June 2018) and manually reviewed reference lists, with surveillance through January 25, 2019. Study Selection: We selected randomized, controlled trials (RCTs) and cohort studies of pregnant women that reported risk of mother-to-child transmission or maternal or infant harms associated with prenatal HIV screening or ART during pregnancy. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We identified no studies on the benefits or harms of prenatal HIV screening versus no screening, or on the yield of repeat versus one-time screening or screening at different intervals. One new RCT and five new cohort studies were consistent with the 2012 USPSTF review in finding combination ART highly effective at reducing the risk of mother-to-child transmission of HIV infection, especially if started early in pregnancy (rate of mother-to-child transmission <1%). As in the prior USPSTF review, one new RCT and several observational studies found certain ART regimens associated with increased risk of preterm delivery without increased risk of low birth weight. One RCT conducted in Africa found prenatal tenofovir-based ART associated with very preterm delivery and early infant death versus zidovudine-based ART, but the trial had methodological limitations. Prenatal exposure to most currently recommended ART drugs was not associated with increased risk of overall birth defects, but limited evidence found certain ART agents and regimens associated with increased risk of congenital abnormalities, cardiac anomalies, and echocardiographic changes, with no association with adverse neurodevelopmental outcomes. Evidence on long-term maternal harms associated with short-term exposure to ART during pregnancy remains limited, with some evidence of short-term harms. Limitations: Only English-language articles were included. Observational studies were included. Studies conducted in resource-poor settings were included, which might limit applicability to screening in the United States. Conclusions: Combination ART is highly effective at reducing risk of mother-to-child HIV transmission. The USPSTF previously determined that avoidance of breastfeeding and Caesarean delivery in women with HIV ribonucleic acid levels greater than 1,000 copies/mL near the time of delivery is also effective at reducing mother-to-child transmission, and that prenatal screening is accurate at diagnosing HIV infection. Use of certain ART regimens during pregnancy is associated with increased risk of preterm delivery and may be associated with other adverse pregnancy outcomes. Although more evidence is required to better understand short- and long-term maternal and infant harms, selection of ART regimens may help mitigate or reduce harms.
Contributor(s): Shelley S. Selph, MD, MPH Christina Bougatsos, MPH Tracy Dana, MLS Sara Grusing, BA Roger Chou, MD
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-209-2015-00009-I, Task Order No. 7)
Methodology Description: Study Selection: We selected randomized, controlled trials (RCTs) and cohort studies of pregnant women that reported risk of mother-to-child transmission or maternal or infant harms associated with prenatal HIV screening or ART during pregnancy. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

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Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults [Entered Retrospectively]


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Statistics: 29 Studies, 5 Key Questions, 1 Extraction Form,
Date Published: Sep 20, 2019 09:42AM
Description: Background: A 2012 systematic review on HIV screening for the U.S. Preventive Services Task Force (USPSTF) found strong evidence that antiretroviral therapy (ART) is associated with improved clinical outcomes in persons with CD4+ T helper cell (CD4) counts less than 500 cells/mm3 and substantially decreases risk of HIV transmission, with certain antiretroviral agents potentially associated with long-term cardiovascular harms. The USPSTF previously found HIV screening tests to be highly accurate. Purpose: To systematically update the 2012 USPSTF review on screening for HIV in adolescents and adults, focusing on research gaps identified in the prior review. Data Sources: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE (2012 to June 2018) and manually reviewed reference lists, with surveillance through January 2019. Study Selection: Randomized, controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening and on the yield of screening at different intervals; the effects of earlier versus later initiation of ART; and long-term (≥2 years) harms of ART. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We did not identify any studies on benefits or harms of HIV screening versus no screening, or on the yield of repeat versus one-time screening or of screening at different intervals. Two new RCTs conducted completely or partially in low-resource settings found initiation of ART in persons with CD4 counts greater than 500 cells/mm3 associated with lower risk of composite clinical outcomes (mortality, AIDS-defining events, or serious non-AIDS events) (relative risk [RR], 0.44 [95% confidence interval (CI), 0.31 to 0.63] and RR, 0.57 [95% CI, 0.35 to 0.95]); early initiation of ART was not associated with increased risk of cardiovascular events. A large observational study also found initiation of ART in persons in high-resource settings with CD4 counts greater than 500 cells/mm3 to be associated with reduced risk of mortality or AIDS events, although the magnitude of effect was smaller. New evidence regarding the association between abacavir use and increased risk of cardiovascular events was inconsistent, and certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. Limitations: Only English-language articles were included. Observational studies were included. Studies conducted in resource-poor settings were included, which might limit applicability to general screening in the United States. Conclusions: New evidence extends effectiveness of ART to asymptomatic persons with CD4 counts greater than 500 cells/mm3. Certain ART regimens may be associated with long-term cardiovascular, neuropsychiatric, hepatic, renal, or bone harms, but early initiation of ART is not associated with increased risk of cardiovascular events. Research is needed to inform optimal screening intervals.
Contributor(s): Roger Chou, MD Tracy Dana, MLS Sara Grusing, BA Christina Bougatsos, MPH
Funding Source: This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00009-I, Task Order No. 7)
Methodology Description: Study Selection: Randomized, controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening and on the yield of screening at different intervals; the effects of earlier versus later initiation of ART; and long-term (≥2 years) harms of ART. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.

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