Screening and Interventions for Social Risk Factors: Technical Brief to Support the US Preventive Services Task Force.

Importance: Evidence-based guidance is limited on how clinicians should screen for social risk factors and which interventions related to these risk factors improve health outcomes. Objective: To describe research on screening and interventions for social risk factors to inform US Preventive Services Task Force considerations of the implications for its portfolio of recommendations. Data Sources: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Sociological Abstracts, and Social Services Abstracts (through 2018); Social Interventions Research and Evaluation Network evidence library (January 2019 through May 2021); surveillance through May 21, 2021; interviews with 17 key informants. Study Selection: Individual-level and health care system-level interventions with a link to the health care system that addressed at least 1 of 7 social risk domains: housing instability, food insecurity, transportation difficulties, utility needs, interpersonal safety, education, and financial strain. Data Extraction and Synthesis: One investigator abstracted data from studies and a second investigator evaluated data abstractions for completeness and accuracy; key informant interviews were recorded, transcribed, summarized, and integrated with evidence from the literature; narrative synthesis with supporting tables and figures. Main Outcomes and Measures: Validity of multidomain social risk screening tools; all outcomes reported for social risk-related interventions; challenges or unintended consequences of screening and interventions. Results: Many multidomain social risk screening tools have been developed, but they vary widely in their assessment of social risk and few have been validated. This technical brief identified 106 social risk intervention studies (N = 5 978 596). Of the interventions studied, 73 (69%; n = 127 598) addressed multiple social risk domains. The most frequently addressed domains were food insecurity (67/106 studies [63%], n = 141 797), financial strain (52/106 studies [49%], n = 111 962), and housing instability (63/106 studies [59%], n = 5 881 222). Food insecurity, housing instability, and transportation difficulties were identified by key informants as the most important social risk factors to identify in health care. Thirty-eight studies (36%, n = 5 850 669) used an observational design with no comparator, and 19 studies (18%, n = 15 205) were randomized clinical trials. Health care utilization measures were the most commonly reported outcomes in the 68 studies with a comparator (38 studies [56%], n = 111 102). The literature and key informants described many perceived or potential challenges to implementation of social risk screening and interventions in health care. Conclusions and Relevance: Many interventions to address food insecurity, financial strain, and housing instability have been studied, but more randomized clinical trials that report health outcomes from social risk screening and intervention are needed to guide widespread implementation in health care.

Screening for Syphilis Infection in Pregnant Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: The incidence of syphilis and congenital syphilis in the United States has increased after reaching historic lows in the early 2000s. Objective: To systematically review literature on the effectiveness and harms of screening for syphilis in pregnancy and the harms of penicillin treatment in pregnancy to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language literature, published from January 1, 2008, to June 2, 2017. Ongoing surveillance was conducted through November 22, 2017. Study Selection: Studies conducted in countries categorized as "high" or "very high" on the Human Development Index that explicitly addressed 1 of 3 a priori-defined key questions. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Data from included studies were narratively synthesized without pooling data. Main Outcomes and Measures: Incidence of congenital syphilis; any harms of screening or penicillin treatment in pregnancy. Results: Seven studies in 8 publications were included. One observational study evaluated the implementation of syphilis screening in pregnancy in 2 441 237 women in China. From 2002 to 2012, screening for syphilis in all pregnant women increased from 89.8% to 97.2%, and the incidence of congenital syphilis decreased from 109.3 to 9.4 cases per 100 000 live births. Five studies (n = 21 795) evaluated the false-positive findings of treponemal tests and 1 study (n = 318) evaluated the false-negative findings of nontreponemal tests. These studies found that false-positives with treponemal-specific enzyme or chemiluminescent immunoassays were common (46.5%-88.2%), therefore warranting reflexive (automatic confirmatory) testing for all positive test findings. One study (n = 318) found no false-negatives with treponemal tests, and 1 study (n = 139) demonstrated the prozone phenomenon (false-negative response from high antibody titer) with rapid plasma reagin screening using undiluted samples (2.9%). No studies were identified for harms of penicillin in pregnancy. Conclusions and Relevance: Screening for syphilis infection in pregnant women is associated with reduced incidence of congenital syphilis, and available evidence supports the need for reflexive testing for positive test results.

Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. OBJECTIVE: To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016. STUDY SELECTION: English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin. MAIN OUTCOMES AND MEASURES: Weight or excess weight (eg, body mass index [BMI]; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms. RESULTS: There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: -0.86 (95% CI, -1.44 to -0.29; 6 studies; I2 = 0%) for metformin and -0.50 to -0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: -6.4 mm Hg (95% CI, -8.6 to -4.2; 6 studies; I2 = 51%) for systolic blood pressure and -4.0 mm Hg (95% CI, -5.6 to -2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%. CONCLUSIONS AND RELEVANCE: Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Evaluating Intensity, Complexity, and Potential for Causal Inference in Social Needs Interventions: A Review of a Scoping Review.

Importance: Interventions that address needs such as low income, housing instability, and safety are increasingly appearing in the health care sector as part of multifaceted efforts to improve health and health equity, but evidence relevant to scaling these social needs interventions is limited. Objective: To summarize the intensity and complexity of social needs interventions included in randomized clinical trials (RCTs) and assess whether these RCTs were designed to measure the causal effects of intervention components on behavioral, health, or health care utilization outcomes. Evidence Review: This review of a scoping review was based on a Patient-Centered Outcomes Research Institute-funded evidence map of English-language US-based RCTs of social needs interventions published between January 1, 1995, and April 6, 2023. Studies were assessed for features related to intensity (defined using modal values as providing as-needed interaction, 8 participant contacts or more, contacts occurring every 2 weeks or more often, encounters of 30 minutes or longer, contacts over 6 months or longer, or home visits), complexity (defined as addressing multiple social needs, having dedicated staff, involving multiple intervention components or practitioners, aiming to change multiple participant behaviors [knowledge, action, or practice], requiring or providing resources or active assistance with resources, and permitting tailoring), and the ability to assess causal inferences of components (assessing interventions, comparators, and context). Findings: This review of a scoping review of social needs interventions identified 77 RCTs in 93 publications with a total of 135 690 participants. Most articles (68 RCTs [88%]) reported 1 or more features of high intensity. All studies reported 1 or more features indicative of high complexity. Because most studies compared usual care with multicomponent interventions that were moderately or highly dependent on context and individual factors, their designs permitted causal inferences about overall effectiveness but not about individual components. Conclusions and Relevance: Social needs interventions are complex, intense, and include multiple components. Our findings suggest that RCTs of these interventions address overall intervention effectiveness but are rarely designed to distinguish the causal effects of specific components despite being resource intensive. Future studies with hybrid effectiveness-implementation and sequential designs, and more standardized reporting of intervention intensity and complexity could help stakeholders assess the return on investment of these interventions.

The ABC transporter family efflux pump PvdRT-OpmQ of Pseudomonas putida KT2440: purification and initial characterization.

Tripartite efflux systems of the ABC-type family transport a variety of substrates and contribute to the antimicrobial resistance of Gram-negative bacteria. PvdRT-OpmQ, a member of this family, is thought to be involved in the secretion of the newly synthesized and recycled siderophore pyoverdine in Pseudomonas species. Here, we purified and characterized the inner membrane component PvdT and the periplasmic adapter protein PvdR of the plant growth-promoting soil bacterium Pseudomonas putida KT2440. We show that PvdT possesses an ATPase activity that is stimulated by the addition of PvdR. In addition, we provide the first biochemical evidence for direct interactions between pyoverdine and PvdRT.

The RND efflux system ParXY affects siderophore secretion in Pseudomonas putida KT2440.

IMPORTANCE: Gram-negative bacteria from the Pseudomonas group are survivors in various environmental niches. For example, the bacteria secrete siderophores to capture ferric ions under deficiency conditions. Tripartite efflux systems are involved in the secretion of siderophores, which are also important for antibiotic resistance. For one of these efflux systems, the resistance-nodulation-cell division transporter ParXY from the model organism Pseudomonas putida KT2440, we show that it influences the secretion of the siderophore pyoverdine in addition to its already known involvement in antibiotic resistance. Phenotypically, its role in pyoverdine secretion is only apparent when other pyoverdine secretion systems are inactive. The results confirm that the different tripartite efflux systems have overlapping substrate specificities and can at least partially functionally substitute for each other, especially in important physiological activities such as supplying the cell with iron ions. This fact must be taken into account when developing specific inhibitors for tripartite efflux systems.

Contribution of Uncharacterized Target Genes of MxtR/ErdR to Carbon Source Utilization by Pseudomonas putida KT2440.

MxtR/ErdR is a two-component system that has been previously described as a regulator of the utilization of acetate in Vibrio cholerae and in some Pseudomonas species. Regulation is achieved by controlling the expression of the acs gene (acetyl-coenzyme A [CoA] synthetase). However, the physiological significance of other identified target genes is not fully understood. Here, we investigated the role of pp_0154 (scpC) and pp_0354/pp_0353 in the soil bacterium Pseudomonas putida KT2440. To this end, the genes were individually deleted and complemented in trans. Then, the growth of the resulting strains on different carbon sources was analyzed. To obtain information on protein function, a bioinformatic analysis was performed, and ScpC was purified and characterized in vitro. Our results indicated that scpC is important for P. putida KT2440 to cope with high concentrations of acetate. The encoded enzyme catalyzes the transfer of coenzyme A between acetate and succinate. On the contrary, pp_0353 and pp_0354 proved to be unimportant for the growth of the strain on acetate under our conditions. Extending the phenotypic analysis to other carbon sources led to the discovery that mxtR, erdR, and pp_0353 are important for the utilization of pyruvate as a carbon source. Taken together, the findings of this study expand the knowledge about the role of the MxtR/ErdR two-component system in carbon source utilization and about the specific functions of its target genes. IMPORTANCE MxtR/ErdR and homologous two-component systems play important roles in the regulatory networks that control cell metabolism and influence bacterial-host interactions. Using the MxtR/ErdR two-component system of the plant growth-promoting soil bacterium Pseudomonas putida KT2440 as a model, this work elucidates the function of previously uncharacterized target genes of MxtR/ErdR and extends the knowledge of the physiological significance of the two-component system. Our results suggest that the target gene scpC encodes an acetate:succinate CoA transferase that is involved in the detoxification of acetate when it is present in large amounts. Furthermore, it is shown that MxtR/ErdR controls the metabolism of not only acetate but also pyruvate. This control involves the target gene pp_0353 (putative exonuclease). These findings may facilitate the optimization of P. putida KT2440 as a chassis for biotechnological applications and may contribute to a better understanding of the regulatory network of pathogens like Pseudomonas aeruginosa.

Behavioral counseling to prevent skin cancer: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: More than 2 million cases of skin cancer are diagnosed annually in the United States, and melanoma incidence is increasing. PURPOSE: To assist the U.S. Preventive Services Task Force in updating its 2003 recommendation on behavioral counseling to prevent skin cancer. DATA SOURCES: Existing systematic reviews, database searches through February 2010, and outside experts. STUDY SELECTION: English-language, primary care-relevant counseling trials to promote sun-protective behaviors and studies examining the association between sun-protective behaviors and skin cancer outcomes or potential adverse effects were included. DATA EXTRACTION: Each study was appraised by using design-specific quality criteria. Important study details were abstracted into evidence tables. DATA SYNTHESIS: 11 fair- or good-quality, randomized, controlled trials examined the counseling interventions' effect on sun-protective behaviors. In young women, appearance-focused behavioral interventions decrease indoor tanning and ultraviolet exposure. In young adolescents, computer support can decrease midday sun exposure and increase sunscreen use. Thirty-five mainly fair-quality observational studies examined the relationship between ultraviolet exposure or sunscreen use and skin cancer. Increasing intermittent sun exposure in childhood is associated with an increased risk for squamous cell carcinoma, basal cell carcinoma, and melanoma. Evidence suggests that regular or early use of indoor tanning may increase melanoma risk. On the basis of 1 fair-quality trial, regular sunscreen use can prevent squamous cell carcinoma, but it is yet unclear if it can prevent basal cell carcinoma or melanoma. LIMITATIONS: There are limited rigorous counseling trials. Observational studies are limited by the complexity of measuring ultraviolet exposure and sunscreen use, and inadequate adjustment for important confounders. CONCLUSION: Randomized, controlled trials suggest that primary care-relevant counseling can increase sun-protective behaviors and decrease indoor tanning.

Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force.

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.

Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. PURPOSE: To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. STUDY SELECTION: Two independent reviewers selected fair- to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. DATA EXTRACTION: At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. DATA SYNTHESIS: On the basis of 4 fair- to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. LIMITATION: Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U.S. practice. CONCLUSION: Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older.

Supporting Communication of Shared Decision-Making Principles in US Preventive Services Task Force Recommendations.

Aims. This methods project was conducted to support the US Preventive Services Task Force's (USPSTF) consideration of how information pertinent to shared decision making (SDM) can be best communicated in its recommendations. Methods. The project included a literature scan to identify SDM frameworks, audit of six USPSTF recommendations to judge the completeness of SDM communication, input from eight SDM experts on the most helpful SDM guidance to provide in USPSTF recommendations, and review of USPSTF recommendations and evidence reports to establish criteria for identifying topics that would most benefit from additional communication resources. Results. We identified eight SDM frameworks and selected one to guide the audit of USPSTF recommendations. All six recommendations include SDM elements related to the patient's role in decision making, preventive service being considered, pros and cons of options, uncertainties about benefits and harms, and importance of patient preferences. Two SDM elements are not routinely communicated in the recommendations-identification of not screening or initiating preventive medication as an alternative and the importance of patient understanding of options. Experts offered suggestions for essential SDM elements to address, such as assessing decisional conflict to measure patient uncertainty in choosing an option and highlighting uncertainty in estimates of benefit and harm, credibility of the evidence base, precision of estimates, and applicability to the individual patient. We developed six criteria for selection of USPSTF recommendations to supplement with a communication resource. Conclusions. The findings of this project can assist the USPSTF and other clinical guideline developers in incorporating SDM information in recommendations and determining which topics would most benefit from additional communication resources to support clinicians in engaging patients in SDM.

HutT functions as the major L-histidine transporter in Pseudomonas putida KT2440.

Histidine is an important carbon and nitrogen source of γ-proteobacteria and can affect bacteria-host interactions. The mechanisms of histidine uptake are only partly understood. Here, we analyze functional properties of the putative histidine transporter HutT of the soil bacterium Pseudomonas putida. The hutT gene is part of the histidine utilization operon, and the gene product belongs to the amino acid-polyamine-organocation (APC) family of secondary transporters. Deletion of hutT severely impairs growth of P. putida on histidine, suggesting that the encoded transporter is the major histidine uptake system of P. putida. Transport experiments with cells and purified and reconstituted protein indicate that HutT functions as a high-affinity histidine : proton symporter with high specificity for the amino acid. Substitution analyses identified amino acids crucial for HutT function.

A feasibility trial of a video intervention to improve informed consent for parents of children with leukemia.

BACKGROUND: Research on parental understanding of informed consent for pediatric randomized clinical trials (RCTs) has highlighted weaknesses in understanding of key aspects of informed consent. The goals of the current study were to assess the feasibility of and parental satisfaction with a video intervention to improve informed consent for pediatric leukemia RCTs and to compare parental question asking during informed consent conferences (ICCs) for parents in the current study with historical control data. PROCEDURE: A 20-min video was produced. Utilizing the principles of anticipatory guidance, it included information delivered by nurses and physicians about leukemia and key aspects of informed consent. Parents were encouraged to be active participants in ICCs. Participants included 12 parents of children newly diagnosed with pediatric leukemia. The video was viewed by local pediatric oncologists prior to utilization with families. RESULTS: Ninety-two percent of parents reported that the video made it easier to understand information that their child's physician later provided; 83% of parents reported that it helped them to think of questions to ask the physician; and 67% of parents indicated that the video made them feel more comfortable with asking questions of the physician. Results of a t-test comparing question asking during ICCs revealed that parents who participated in the intervention asked a higher rate of questions than parents from a historical control sample (t = 1.95, P = 0.05). DISCUSSION: Our study supports the feasibility and potential efficacy of a brief video intervention employing anticipatory guidance to prepare parents for future discussions about RCTs.

Transport and kinase activities of CbrA of Pseudomonas putida KT2440.

The CbrA/CbrB system is a two-component signal transduction system known to participate in the regulation of the cellular carbon/nitrogen balance and to play a central role in carbon catabolite repression in Pseudomonas species. CbrA is composed of a domain with similarity to proteins of the solute/sodium symporter family (SLC5) and domains typically found in bacterial sensor kinases. Here, the functional properties of the sensor kinase CbrA and its domains are analyzed at the molecular level using the system of the soil bacterium P. putida KT2440 as a model. It is demonstrated that CbrA can bind and transport L-histidine. Transport is specific for L-histidine and probably driven by an electrochemical proton gradient. The kinase domain is not required for L-histidine uptake by the SLC5 domain of CbrA, and has no significant impact on transport kinetics. Furthermore, it is shown that the histidine kinase can autophosphorylate and transfer the phosphoryl group to the response regulator CbrB. The SLC5 domain is not essential for these activities but appears to modulate the autokinase activity. A phosphatase activity of CbrA is not detected. None of the activities is significantly affected by L-histidine. The results demonstrate that CbrA functions as a L-histidine transporter and sensor kinase.

The Use of Rapid Review Methods for the U.S. Preventive Services Task Force.

Rapid review products are intended to synthesize available evidence in a timely fashion while still meeting the needs of healthcare decision makers. Various methods and products have been applied for rapid evidence syntheses, but no single approach has been uniformly adopted. Methods to gain efficiency and compress the review time period include focusing on a narrow clinical topic and key questions; limiting the literature search; performing single (versus dual) screening of abstracts and full-text articles for relevance; and limiting the analysis and synthesis. In order to maintain the scientific integrity, including transparency, of rapid evidence syntheses, it is imperative that procedures used to streamline standard systematic review methods are prespecified, based on sound review principles and empiric evidence when possible, and provide the end user with an accurate and comprehensive synthesis. The collection of clinical preventive service recommendations maintained by the U.S. Preventive Services Task Force, along with its commitment to rigorous methods development, provide a unique opportunity to refine, implement, and evaluate rapid evidence synthesis methods and add to an emerging evidence base on rapid review methods. This paper summarizes the U.S. Preventive Services Task Force's use of rapid review methodology, its criteria for selecting topics for rapid evidence syntheses, and proposed methods to streamline the review process.

An approach to addressing subpopulation considerations in systematic reviews: the experience of reviewers supporting the U.S. Preventive Services Task Force.

BACKGROUND: Guideline developers and other users of systematic reviews need information about whether a medical or preventive intervention is likely to benefit or harm some patients more (or less) than the average in order to make clinical practice recommendations tailored to these populations. However, guidance is lacking on how to include patient subpopulation considerations into the systematic reviews upon which guidelines are often based. In this article, we describe methods developed to consistently consider the evidence for relevant subpopulations in systematic reviews conducted to support primary care clinical preventive service recommendations made by the U.S. Preventive Services Task Force (USPSTF). PROPOSED APPROACH: Our approach is grounded in our experience conducting systematic reviews for the USPSTF and informed by a review of existing guidance on subgroup analysis and subpopulation issues. We developed and refined our approach based on feedback from the Subpopulation Workgroup of the USPSTF and pilot testing on reviews being conducted for the USPSTF. This paper provides processes and tools for incorporating evidence-based identification of important sources of potential heterogeneity of intervention effects into all phases of systematic reviews. Key components of our proposed approach include targeted literature searches and key informant interviews to identify the most important subpopulations a priori during topic scoping, a framework for assessing the credibility of subgroup analyses reported in studies, and structured investigation of sources of heterogeneity of intervention effects. CONCLUSIONS: Further testing and evaluation are necessary to refine this proposed approach and demonstrate its utility to the producers and users of systematic reviews beyond the context of the USPSTF. Gaps in the evidence on important subpopulations identified by routinely applying this process in systematic reviews will also inform future research needs.

Altruistic discourse in the informed consent process for childhood cancer clinical trials.

Scholars have debated the role that altruistic considerations play--and should play--in recruitment and decision-making processes for clinical trials. Little empirical data are available to support their various perspectives. We analyzed 140 audiotaped pediatric informed consent sessions, of which 95 (68%) included at least one discussion of how participation in a cancer clinical trial might benefit: 1) the pursuit of scientific knowledge generally; 2) other children with cancer specifically; and 3) "the future" and other vaguely defined recipients. Clinicians initiated most (80%) of these discussions of altruism. The enrollment rate of children in the clinical trial was high (83%) overall, but not higher among children whose parents were involved in an altruism-oriented discussion. These findings suggest that: (1) clinicians invoke a spectrum of altruistic considerations rather than a single monothematic notion of altruism, and (2) the effect of altruistic considerations on subsequent enrollment decisions is marginal. While further research on this topic is warranted, bioethical debate should strive to reflect the diversity of altruistic discourse in clinical research encounters and to place this discourse in the context of other, including nonaltruistic, considerations.

Groups potentially at risk for making poorly informed decisions about entry into clinical trials for childhood cancer.

PURPOSE: Some patients may be at greater risk than others of enrolling on a randomized clinical trial (RCT) without fully understanding the implications. To investigate this possibility, this study poses the question, Do non-English-speaking Latino parents of children with leukemia show differences in their discussion of and understanding of an RCT when compared with English-speaking minority parents and with English-speaking majority (ie, white) parents? This research hypothesizes that factors such as social and educational status and the role of language interpreters may account for significant differences in the discussion and understanding of an RCT among the three groups. PATIENTS AND METHODS: A total of 108 parents are reported on, all of whom were observed, interviewed, and audiotaped during informed-consent discussions about participation in an RCT with their child's oncologist. Comparisons among the groups were performed using chi2 tests and a one-way analysis of variance. RESULTS: Problems of consent-related communication and understanding were more frequent among parents of low social status who spoke little or no English than they were in the two other groups. Several factors may have contributed to this disparity, including language interpretation, social status, and prevailing cultural norms. CONCLUSION: Some patients may be at greater risk than others of enrolling on an RCT without fully understanding the implications of their decision to do so. Numerous factors may contribute to this disparity, including language interpretation, social status, and prevailing cultural norms. Some specific strategies are suggested to help address this disparity.

Communication of randomization in childhood leukemia trials.

CONTEXT: Most children diagnosed as having leukemia become research subjects in randomized clinical trials (RCTs), but little is known about how randomization is explained to or understood by parents. OBJECTIVE: To investigate physicians' explanation and parental understanding of randomization in childhood leukemia RCTs. DESIGN AND SETTING: A multisite study of the informed consent communication process for RCTs of childhood leukemia. Consecutive cases were recruited from pediatric oncology inpatient wards at 6 US children's hospitals associated with major academic medical centers from July 1, 1999, until December 31, 2001. The informed consent conferences were observed and audiotaped, and the information obtained was coded and analyzed. Parents were interviewed shortly after the conference to ascertain their understanding. PARTICIPANTS: Parents and members of the health care team who participated in 137 informed consent conferences for children with newly diagnosed acute leukemia. MAIN OUTCOME MEASURES: Observed explanations of randomization and parental understanding of randomization after the consent conference. RESULTS: Randomization was explained by physicians in 83% of cases and a consent document was presented during the conference in 95% of cases. Interviews after the conference demonstrated that 68 (50%) of 137 parents did not understand randomization. Parents of racial minority and lower socioeconomic status were less likely to understand randomization (P<.001 for each). Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with understanding. Eighty-four percent of children were enrolled in a leukemia trial. CONCLUSIONS: Despite oral and written explanation, half of the parents in this study did not understand randomization for childhood leukemia trials. To make informed consent more effective, future research must seek to improve communication during this critical interchange.

AHRQ series paper 3: identifying, selecting, and refining topics for comparative effectiveness systematic reviews: AHRQ and the effective health-care program.

OBJECTIVE: This article discusses the identification, selection, and refinement of topics for comparative effectiveness systematic reviews within the Agency for Healthcare Research and Quality's Effective Health Care (EHC) program. STUDY DESIGN AND SETTING: The EHC program seeks to align its research topic selection with the overall goals of the program, impartially and consistently apply predefined criteria to potential topics, involve stakeholders to identify high-priority topics, be transparent and accountable, and continually evaluate and improve processes. RESULTS: A topic prioritization group representing stakeholder and scientific perspectives evaluates topic nominations that fit within the EHC program (are "appropriate") to determine how "important" topics are as considered against seven criteria. The group then judges whether a new comparative effectiveness systematic review would be a duplication of existing research syntheses, and if not duplicative, if there is adequate type and volume of research to conduct a new systematic review. Finally, the group considers the "potential value and impact" of a comparative effectiveness systematic review. CONCLUSION: As the EHC program develops, ongoing challenges include ensuring the program addresses truly unmet needs for synthesized research because national and international efforts in this arena are uncoordinated, as well as engaging a range of stakeholders in program decisions while also achieving efficiency and timeliness.