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To gain a complex understanding of willingness to participate in genomics research among African Americans, we developed a technique specifically suited to studying decision making in a relaxed social setting. The "Qualitative Story Deck," (QSD) is a gamified, structured elicitation technique that allows for the spontaneous creation of scenarios with variable attributes. We used the QSD to create research scenarios that varied on four details (race/ethnicity of the researcher; research goal; biospecimen requested; and institutional affiliation). Participants created scenarios by randomly choosing cards from these categories and provided: (1) a judgement about their willingness to participate in the research project represented; and (2) their thought process in reaching a decision. The QSD has applicability to topics involving decision making or in cases where it would be beneficial to provide vignettes with alternate attributes. Additional benefits include: rapid establishment of rapport and engagement and the facilitation of discussion of little known or sensitive topics.

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Importance: The risk of developing a surgical site infection after extremity fracture repair is nearly 5 times greater than in most elective orthopedic surgical procedures. For all surgical procedures, it is standard practice to prepare the operative site with an antiseptic solution; however, there is limited evidence to guide the choice of solution used for orthopedic fracture repair. Objective: To compare the effectiveness of iodophor vs chlorhexidine solutions to reduce surgical site infections and unplanned fracture-related reoperations for patients who underwent fracture repair. Design, Setting, and Participants: The PREP-IT (Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma) master protocol will be followed to conduct 2 multicenter pragmatic cluster randomized crossover trials, Aqueous-PREP (Pragmatic Randomized Trial Evaluating Pre-Operative Aqueous Antiseptic Skin Solution in Open Fractures) and PREPARE (Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities). The Aqueous-PREP trial will compare 4% aqueous chlorhexidine vs 10% povidone-iodine for patients with open extremity fractures. The PREPARE trial will compare 2% chlorhexidine in 70% isopropyl alcohol vs 0.7% iodine povacrylex in 74% isopropyl alcohol for patients with open extremity fractures and patients with closed lower extremity or pelvic fractures. Both trials will share key aspects of study design and trial infrastructure. The studies will follow a pragmatic cluster randomized crossover design with alternating treatment periods of approximately 2 months. The primary outcome will be surgical site infection and the secondary outcome will be unplanned fracture-related reoperations within 12 months. The Aqueous-PREP trial will enroll a minimum of 1540 patients with open extremity fractures from at least 12 hospitals; PREPARE will enroll a minimum of 1540 patients with open extremity fractures and 6280 patients with closed lower extremity and pelvic fractures from at least 18 hospitals. The primary analyses will adhere to the intention-to-treat principle and account for potential between-cluster and between-period variability. The patient-centered design, implementation, and dissemination of results are guided by a multidisciplinary team that includes 3 patients and other relevant stakeholders. Discussion: The PREP-IT master protocol increases efficiency through shared trial infrastructure and study design components. Because prophylactic skin antisepsis is used prior to all surgical procedures and the application, cost, and availability of all study solutions are similar, the results of the PREP-IT trials are poised to inform clinical guidelines and bring about an immediate change in clinical practice. Trial Registration: ClinicalTrials.gov Identifiers: NCT03385304 and NCT03523962.

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Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as "Seshat: Global History Databank." We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history.

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OBJECTIVES: To characterize psychotropic medication use before and after traumatic brain injury (TBI) hospitalization among older adults. A secondary objective is to determine how receipt of indicated pharmacologic treatment for anxiety and post-traumatic stress disorder (PTSD) differs following TBI. DESIGN: Retrospective cohort. SETTING: United States. PARTICIPANTS: Medicare beneficiaries aged ≥65 years hospitalized with TBI between 2006 and 2010 with continuous drug coverage for 12 months before and after TBI (N = 60,276). MEASUREMENTS: We obtained monthly psychotropic medication use by drug class and specific drugs from Medicare Part D drug event files.ICD-9 codes were used to define anxiety (300.0x) and PTSD (309.81). RESULTS: Average monthly prevalence of psychotropic medication use among all patients hospitalized for TBI was 44.8%; antidepressants constituted 73%. Prevalence of psychotropic medication use increased from 2006 to 2010. Following TBI, psychotropic medication use increased slightly (OR: 1.05; 95% CI: 1.03, 1.06.) Tricyclic antidepressant use decreased post-TBI (OR: 0.76; 95% CI: 0.73, 0.79) whereas use of the sedating antidepressants mirtazapine (OR: 1.31; 95% CI: 1.25, 1.37) and trazadone (OR: 1.11; 95% CI: 1.06, 1.17) increased. Antipsychotic (OR: 1.15; 95% CI: 1.12, 1.19) use also increased post-TBI. Beneficiaries newly diagnosed with anxiety (OR: 0.42; 95% CI: 0.36, 0.48) and/or PTSD (OR: 0.39; 95% CI: 0.18, 0.84) post-TBI were less likely to receive indicated pharmacologic treatment. CONCLUSIONS: Older adults hospitalized with TBI have a high prevalence of psychotropic medication use yet are less likely to receive indicated pharmacological treatment for newly diagnosed anxiety and PTSD following TBI.

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OBJECTIVES: To identify the pain instruments and study end points most commonly used in clinical trial settings and to provide insight into the extent to which outcome measures in clinical studies are meeting payer needs. METHODS: A literature review was conducted to identify published clinical studies and ongoing/recently completed registered trials in chronic pain. Inclusion criteria were interventional study, chronic pain in adults, and pain measured within the primary end point. RESULTS: Of 1256 PubMed citations and 3006 clinical trial registry entries, 356 reported large clinical studies in pain populations (e.g., malignant, neuropathic, functional, and musculoskeletal). Studies were designed for superiority in 28% of PubMed citations and 8% of registry entries. The primary end points of most studies were single-dimension pain instruments, such as the numerical rating scale (n = 131) and the visual analogue scale (n = 69). In cases in which multidimensional pain end points were used, this was most commonly the Brief Pain Inventory (n = 37). Payer-relevant end points were typically limited to secondary end points, and were limited and/or reported inconsistently in published studies and ongoing/recently completed studies: preference-weighted quality of life (36% and 42%), resource use (2% and 8%), physical function (28% and 39%), and psychological function (25% and 24%). CONCLUSIONS: Most pain trials were not designed to show superiority to an active comparator, and they used single-dimension pain scales as their primary end point in combination with a broader selection of secondary end points. The inclusion of payer-relevant end points among clinical trials was inconsistent.

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OBJECTIVE: To describe the characteristics, treatment, and health care expenditures of Medicare Supplemental-insured patients with painful diabetic peripheral neuropathy (pDPN), post-herpetic neuralgia (PHN), or fibromyalgia. DESIGN: Retrospective cohort study. SETTING: United States clinical practice, as reflected within a database comprising administrative claims from 2.3 million older adults participating in Medicare supplemental insurance programs. SUBJECTS: Selected patients were aged ≥65 years, continuously enrolled in medical and prescription benefits throughout years 2008 and 2009, and had ≥1 medical claim with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for DPN, PHN, or fibromyalgia, followed within 60 days by a medication or pain intervention procedure used in treating pDPN, PHN, or fibromyalgia during 2008-2009. OUTCOME MEASURES: Utilization of, and expenditures on, pain-related and all-cause pharmacotherapy and medical interventions in 2009. RESULTS: The study included 25,716 patients with pDPN (mean age 75.2 years, 51.2% female), 4,712 patients with PHN (mean age 77.7 years, 63.9% female), and 25,246 patients with fibromyalgia (mean age 74.4 years, 73.0% female). Patients typically had numerous comorbidities, and many were treated with polypharmacy. Mean annual expenditures on total pain-related health care and total all-cause health care, respectively, (in 2010 USD) were: $1,632, $24,740 for pDPN; $1,403, $16,579 for PHN; and $1,635, $18,320 for fibromyalgia. In age-stratified analyses, pain-related health care expenditures decreased as age increased. CONCLUSIONS: The numerous comorbidities, polypharmacy, and magnitude of expenditures in this sample of Medicare supplemental-insured patients with pDPN, PHN, or fibromyalgia underscore the complexity and importance of appropriate management of these chronic pain patients.

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BACKGROUND: Peritoneal dialysis catheter (PDC) dysfunction can often be treated fluoroscopically by manipulation with wire, balloon or stiff stylet, saving surgical intervention for refractory cases. We describe an enhanced percutaneous approach to PDC salvage that can lead to a more definitive intervention and salvage for cases refractory to fluoroscopic manipulation. METHODS: In five cases of PD catheter malfunction, the deep cuff was dissected free after a 0.035 hydrophilic wire was passed into the peritoneum through the PDC. Only the intraperitoneal portion of the PDC was explanted. The PDC was cleared of obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted over wire via a peel-away sheath and the deep cuff sutured. RESULTS: Omental entrapment was present in three of five patients and fibrin occlusion in four of the five cases. All catheters were repaired successfully by the described technique. Post procedure, 3-5 days of lower volume, recumbent PD exchanges were performed prior to full-dose PD. No perioperative complications or leaks were noted. All PDCs were patent at 6 months. One patient required laparoscopy for recurrent omental wrapping 3 months post intervention. CONCLUSIONS: PDC salvage in this manner is a cost-effective alternative to laparoscopic repair of PDCs failing catheter manipulation. The infection barrier afforded by the original superficial cuff and subcutaneous tunnel is maintained. PD can be resumed immediately. Only refractory cases need laparoscopy. This procedure allows for a more definitive correction of catheter migration and obstruction, avoids placement of a new PDC or temporary hemodialysis, is cost-effective and expands percutaneous options for dysfunctional PD catheters.

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BACKGROUND: Randomized controlled trials (RCTs) reflect priorities established by regulators. Recently, pragmatic clinical trials (PCTs) have begun to attract interest. Unlike RCTs, PCTs aim to better inform post-regulatory decision making by using head-to-head comparisons of alternative treatments, diverse patient populations, and outcomes meaningful to patients, prescribers, and payers. OBJECTIVES: To describe how U.S. insurers and public payers perceive the value of PCTs for assessment of new prescription drugs. STUDY DESIGN: Criterion-based sample of U.S. insurers and public payers. METHODS: We gathered qualitative evidence from intensive interviews with formulary decision makers at 15 payers, representing 10 major types of U.S. payers. Prior literature and exploratory interviews informed our question selection. RESULTS: Payers viewed PCTs favorably despite wariness of drug company-sponsored trials. Payers would accept results from PCTs as part of payers' synthesis of multiple sources of evidence. Payers were enthusiastic about 2 PCT features-a diverse population (compared with the more homogeneous populations typical of RCTs) and an active comparator drug (not placebo). Payers did not anticipate that PCTs would displace their own analyses of internal data. Pharmaceutical companies' financial interest in obtaining trial results that favor their own drugs reduces PCTs' perceived value and dampens their appeal to payers; nonetheless, payers would seek PCT results and review them carefully, as they do other evidence. CONCLUSIONS: Recommendations to trial designers based on payers' views include tailoring different types of PCTs to different disease conditions, building in head-to-head comparisons in phase IIIb PCTs, and designing phase IV PCTs to include broader populations.

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Significant growth inhibition and induction of apoptosis by IFN-beta in cancer cells including colorectal cancer cells have been observed. We and others have previously reported the Stat 1 induction of TRAIL is a crucial step in the IFN-beta induced apoptosis pathway. However, when evaluating the sensitivity of a panel of colorectal cancer cell lines, we found no clear correlation between activation of the Jak/Stat signaling pathway and response to interferon. In the present study, we have evaluated the interaction of the PI3k/Akt pathway and IFN-beta induced apoptosis in human colorectal cancer cells. The results demonstrate a correlation between Akt activity, phosphorylation of Bad and resistance to interferon-induced apoptosis in these cells. The association of activation of Akt, phosphorylation of Bad and resistance to IFN-beta-induced apoptosis was further supported by the observation that disruption of the pathway in a more resistant cell line led to sensitization, and expression of an activated Akt in a more sensitive cell line led to increased resistance. Taken together, this data indicates that the PI3/Akt kinase pathway may be an important contributor to IFN-beta sensitivity and resistance in colorectal cancer cells. This data demonstrates a potential pathway by which cells may develop resistance to IFN, and further elucidation of this process may allow us to better target IFN therapy.

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OBJECTIVE: To identify patient characteristics that are associated with the incidence of thiadolidinediones (TZDs) or metformin prescnbing in Medicaid managed care plans. RESEARCH DESIGN AND METHODS: We utilized a retrospective cohort study design. Two-and-one-half years of prescription claims of Medicaid managed care organizations (MCOs) patients who were new utilizers of metformin or TZDs were analyzed using univariate, bivariate and multivariate models. Multivariate logistic regression models were built to assess the combined effect of all variables on the likelihood of incident use of TZDs or metformin. RESULTS: Claims for 3,041 patients were analyzed for the period between January 15, 2000 and June 15, 2002. African Americans and urban residents were less likely to be started on TZDs (OR = 0.678, 95% C1 = 0.830-1.206; OR = 0.579, 95% CI = 0.479-0.699, respectively). Advanced age, preexisting comorbidities and diabetes complications, and prior use of other oral diabetes drugs or insulin were predictors of increased likelihood of TZD initiation. CONCLUSIONS: Race, age, residential setting, preexisting comorbidities and diabetes complications, other oral diabetes drug use, and insulin use are statistically significant predictors of initial prescribing of TZD or metformin in a Medicaid MCO population. Findings can potentially inform the management of diabetes in managed care so as to improve outcomes.

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