TY - JOUR
T1 - Clinical outcomes associated with sickle cell trait
T2 - A systematic review
AU - Naik, Rakhi P.
AU - Smith-Whitley, Kim
AU - Hassell, Kathryn L.
AU - Umeh, Nkeiruka I.
AU - De Montalembert, Mariane
AU - Sahota, Puneet
AU - Haywood, Carlton
AU - Jenkins, Jean
AU - Lloyd-Puryear, Michele A.
AU - Joiner, Clinton H.
AU - Bonham, Vence L.
AU - Kato, Gregory J.
N1 - Funding Information:
The quality of each article was assessed using rubrics tailored for this review by Abt Associates with input from the EWG. These rubrics were modeled after the Agency for Healthcare Research and Quality's Evidence- based Practice Centers methodology (Supplement Table 2, available at Annals.org) (11). For study-level grading, each relevant outcome from included studies was assessed separately. Studies were rated as high quality if they involved a population-based observational cohort, included a direct measure of the relevant outcome and adjustment for relevant confounders, and had precise findings and no suspected bias. Studies rated as high quality were adjusted for age and sex (at a minimum) and for additional outcome-specific confounders that had been determined by discussion as necessary. Any study with suspected bias was automatically rated as very low quality. Two members of the EWG who were not authors on the included studies independently rated quality, and differences were resolved through discussion. Data Synthesis and Analysis We categorized the 24 outcomes into 6 areas (exertion-related injury; renal, vascular, pediatric, and surgery-or trauma-related outcomes; and overall mortality) and assessed the strength of evidence for each outcome. Strength of evidence was defined by using rubrics tailored for this review by Abt Associates with input from the EWG (Supplement Table 3, available at Annals .org). These rubrics were modeled after the Agency for Healthcare Research and Quality's Evidence-based Practice Centers methodology (12). By consensus agreement, the EWG determined strength of evidence separately for each outcome on the basis of the number, design, and rating of relevant studies and the consistency in direction and association estimate of their findings. Outcome data from studies rated as very low quality were not included in the strength-of-evidence assessment. Members with a potential conflict of interest for any given outcome did not participate in the grading. Role of the Funding Source This work was supported in part by the Intramural Research Program at the National Human Genome Research Institute of the National Institutes of Health. The funding source had no role in the design, conduct, interpretation, or reporting of the study or the decision to publish the manuscript.
Funding Information:
Disclosures: Dr. Naik reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr. de Montalembert reports grants and personal fees from No-vartis and grants and personal fees from Addmedica outside the submitted work. Dr. Joiner reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study and personal fees from Global Blood Therapeutics outside the submitted work. Dr. Kato reports consulting for several pharmaceutical companies and receiving research funding from one, all targeted at treatments for sickle cell disease; there is no actual conflict of interest with the present manuscript on sickle cell trait, which is not involved in any treatment development by any company. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/Conflict OfInterestForms.do?msNum=M18-1161.
Funding Information:
Grant Support: In part by grant ZIAHG200394 from the Division of Intramural Research at NHGRI (Mr. Bonham) and grant K08HL125100 from the National Heart, Lung, and Blood Institute (Dr. Naik).
Publisher Copyright:
© American College of Physicians. All rights reserved.
PY - 2018/11/6
Y1 - 2018/11/6
N2 - Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: Exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation: Publication bias was possible, and high-quality evidence was scant. Conclusion: Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT.
AB - Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: Exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation: Publication bias was possible, and high-quality evidence was scant. Conclusion: Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT.
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U2 - 10.7326/M18-1161
DO - 10.7326/M18-1161
M3 - Review article
C2 - 30383109
AN - SCOPUS:85056198341
VL - 169
SP - 619
EP - 627
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
SN - 0003-4819
IS - 9
ER -