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Systematic reviews aide the analysis and dissemination of evidence, using rigorous and transparent methods to generate empirically attained answers to focused research questions. Identifying all evidence relevant to the research questions is an essential component, and challenge, of systematic reviews. Gray literature, or evidence not published in commercial publications, can make important contributions to a systematic review. Gray literature can include academic papers, including theses and dissertations, research and committee reports, government reports, conference papers, and ongoing research, among others. It may provide data not found within commercially published literature, providing an important forum for disseminating studies with null or negative results that might not otherwise be disseminated. Gray literature may thusly reduce publication bias, increase reviews' comprehensiveness and timeliness, and foster a balanced picture of available evidence. Gray literature's diverse formats and audiences can present a significant challenge in a systematic search for evidence. However, the benefits of including gray literature may far outweigh the cost in time and resource needed to search for it, and it is important for it to be included in a systematic review or review of evidence. A carefully thought out gray literature search strategy may be an invaluable component of a systematic review. This narrative review provides guidance about the benefits of including gray literature in a systematic review, and sources for searching through gray literature. An illustrative example of a search for evidence within gray literature sources is presented to highlight the potential contributions of such a search to a systematic review. Benefits and challenges of gray literature search methods are discussed, and recommendations made.
The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established. We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.).
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