Intraoperative Anesthetic Strategies to Mitigate Early Allograft Dysfunction After Orthotopic Liver Transplantation: A Narrative Review.

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease (ESLD). Hepatic insufficiency within a week of OLT, termed early allograft dysfunction (EAD), occurs in 20% to 25% of deceased donor OLT recipients and is associated with morbidity and mortality. Primary nonfunction (PNF), the most severe form of EAD, leads to death or retransplantation within 7 days. The etiology of EAD is multifactorial, including donor, recipient, and surgery-related factors, and largely driven by ischemia-reperfusion injury (IRI). IRI is an immunologic phenomenon characterized by dysregulation of cellular oxygen homeostasis and innate immune defenses in the allograft after temporary cessation (ischemia) and later restoration (reperfusion) of oxygen-rich blood flow. The rising global demand for OLT may lead to the use of marginal allografts, which are more susceptible to IRI, and thus lead to an increased incidence of EAD. It is thus imperative the anesthesiologist is knowledgeable about EAD, namely its pathophysiology and intraoperative strategies to mitigate its impact. Intraoperative strategies can be classified by 3 phases, specifically donor allograft procurement, storage, and recipient reperfusion. During procurement, the anesthesiologist can use pharmacologic preconditioning with volatile anesthetics, consider preharvest hyperoxemia, and attenuate the use of norepinephrine as able. The anesthesiologist can advocate for normothermic regional perfusion (NRP) and machine perfusion during allograft storage at their institution. During recipient reperfusion, the anesthesiologist can optimize oxygen exposure, consider adjunct anesthetics with antioxidant-like properties, and administer supplemental magnesium. Unfortunately, there is either mixed, little, or no data to support the routine use of many free radical scavengers. Given the sparse, limited, or at times conflicting evidence supporting some of these strategies, there are ample opportunities for more research to find intraoperative anesthetic strategies to mitigate the impact of EAD and improve postoperative outcomes in OLT recipients.

Ascertaining Design and Implementation Requirements for a Perioperative Neurocognitive Training Intervention for the Prevention of Persistent Pain After Surgery.

BACKGROUND: Persistent postsurgical pain (PPSP) is a common complication that impacts quality of life, often necessitating long-term opioid treatment. Certain neurocognitive factors, including reduced performance on cognitive flexibility tasks, are associated with increased risk of PPSP. We examine the perceptions of surgical patients and clinicians with regard to perioperative pain management activities and needs; patient acceptance and use of a perioperative neurocognitive training intervention; and implementation feasibility. METHODS: We conducted both individual and focus group interviews with patients undergoing thoracic surgery and clinicians in an academic medical center. The Consolidated Framework for Intervention Research guided the development of interview questions related to the adoption and implementation of a neurocognitive intervention to mitigate PPSP. A thematic analysis was used to analyze the responses. RESULTS: Forty patients and 15 clinicians participated. Interviews revealed that there is minimal discussion between clinicians and patients about PPSP. Most participants were receptive to a neurocognitive intervention to prevent PPSP, if evidence demonstrating its effectiveness were available. Potential barriers to neurocognitive training program adoption included fatigue, cognitive overload, lack of familiarity with the technology used for delivering the intervention, and immediate postoperative pain and stress. Implementation facilitators would include patient education about the intervention, incentives for its use, and daily reminders. CONCLUSION: The study identified several guiding principles for addressing patients' and clinicians' barriers to effectively implementing a neurocognitive training intervention to mitigate PPSP after surgery. To ensure the sustainability of neurocognitive interventions for preventing PPSP, such interventions would need to be adapted to meet patients' and clinicians' needs within the perioperative context.

CDC14A phosphatase is essential for hearing and male fertility in mouse and human.

The Cell Division-Cycle-14 gene encodes a dual-specificity phosphatase necessary in yeast for exit from mitosis. Numerous disparate roles of vertebrate Cell Division-Cycle-14 (CDC14A) have been proposed largely based on studies of cultured cancer cells in vitro. The in vivo functions of vertebrate CDC14A are largely unknown. We generated and analyzed mutations of zebrafish and mouse CDC14A, developed a computational structural model of human CDC14A protein and report four novel truncating and three missense alleles of CDC14A in human families segregating progressive, moderate-to-profound deafness. In five of these families segregating pathogenic variants of CDC14A, deaf males are infertile, while deaf females are fertile. Several recessive mutations of mouse Cdc14a, including a CRISPR/Cas9-edited phosphatase-dead p.C278S substitution, result in substantial perinatal lethality, but survivors recapitulate the human phenotype of deafness and male infertility. CDC14A protein localizes to inner ear hair cell kinocilia, basal bodies and sound-transducing stereocilia. Auditory hair cells of postnatal Cdc14a mutants develop normally, but subsequently degenerate causing deafness. Kinocilia of germ-line mutants of mouse and zebrafish have normal lengths, which does not recapitulate the published cdc14aa knockdown morphant phenotype of short kinocilia. In mutant male mice, degeneration of seminiferous tubules and spermiation defects result in low sperm count, and abnormal sperm motility and morphology. These findings for the first time define a new monogenic syndrome of deafness and male infertility revealing an absolute requirement in vivo of vertebrate CDC14A phosphatase activity for hearing and male fertility.

Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents.

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of targeted chemotherapeutic agents while maintaining their hydrophilicity and small size will represent a significant advance toward effective and safe cancer treatment. Here, we present a new approach for enhancing the safety and efficacy of targeted chemotherapeutic agents. By endowing hydrophobic chemotherapeutic agents with a targeting moiety and a hydrophilic small molecule that binds reversibly to the serum protein transthyretin, we generated small hydrophilic drug conjugates that displayed enhanced circulation half-life in rodents and selectivity to cancer cells. To the best of our knowledge, this is the first demonstration of a successful approach that maintains the small size and hydrophilicity of targeted anticancer agents containing hydrophobic payloads while at the same time extending their circulation half-life. This was demonstrated by the superior in vivo efficacy and lower toxicity of our conjugates in xenograft mouse models of metastatic prostate cancer.

Preliminary in vitro and in vivo investigation of a potent platelet derived growth factor receptor (PDGFR) family kinase inhibitor.

Aberrant expression of wild-type and mutant forms of the platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases has been implicated in various oncologic indications such as leukemias, gliomas, and soft tissue sarcomas. Clinically used kinase inhibitors imatinib and sunitinib are potent inhibitors of wild-type PDGFR family members, but show reduced binding to mutant forms. Here we describe compound 5 which binds to both wild-type and oncogenic mutant forms of PDGFR family members, and demonstrates both cellular and in vivo activity.

A Comparison of Recruitment Methods for an mHealth Intervention Targeting Mothers: Lessons from the Growing Healthy Program.

BACKGROUND: Mobile health (mHealth) programs hold great promise for increasing the reach of public health interventions. However, mHealth is a relatively new field of research, presenting unique challenges for researchers. A key challenge is understanding the relative effectiveness and cost of various methods of recruitment to mHealth programs. OBJECTIVE: The objectives of this study were to (1) compare the effectiveness of various methods of recruitment to an mHealth intervention targeting healthy infant feeding practices, and (2) explore factors influencing practitioner referral to the intervention. METHODS: The Growing healthy study used a quasi-experimental design with an mHealth intervention group and a concurrent nonrandomized comparison group. Eligibility criteria included: expectant parents (>30 weeks of gestation) or parents with an infant <3 months old, ability to read and understand English, own a mobile phone, ≥18 years old, and living in Australia. Recruitment to the mHealth program consisted of: (1) practitioner-led recruitment through Maternal and Child Health nurses, midwives, and nurses in general practice; (2) face-to-face recruitment by researchers; and (3) online recruitment. Participants' baseline surveys provided information regarding how participants heard about the study, and their sociodemographic details. Costs per participant recruited were calculated by taking into account direct advertising costs and researcher time/travel costs. Practitioner feedback relating to the recruitment process was obtained through a follow-up survey and qualitative interviews. RESULTS: A total of 300 participants were recruited to the mHealth intervention. The cost per participant recruited was lowest for online recruitment (AUD $14) and highest for practice nurse recruitment (AUD $586). Just over half of the intervention group (50.3%, 151/300) were recruited online over a 22-week period compared to practitioner recruitment (29.3%, 88/300 over 46 weeks) and face-to-face recruitment by researchers (7.3%, 22/300 over 18 weeks). No significant differences were observed in participant sociodemographic characteristics between recruitment methods, with the exception that practitioner/face-to-face recruitment resulted in a higher proportion of first-time parents (68% versus 48%, P=.002). Less than half of the practitioners surveyed reported referring to the program often or most of the time. Key barriers to practitioner referral included lack of time, difficulty remembering to refer, staff changes, lack of parental engagement, and practitioner difficulty in accessing the app. CONCLUSIONS: Online recruitment using parenting-related Facebook pages was the most cost effective and timely method of recruitment to an mHealth intervention targeting parents of young infants. Consideration needs to be given to addressing practitioner barriers to referral, to further explore if this can be a viable method of recruitment.

Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence.

BACKGROUND: Lyme disease is diagnosed by 2-tiered serologic testing in patients with a compatible clinical illness, but the significance of positive test results in low-prevalence regions has not been investigated. METHODS: We reviewed the medical records of patients who tested positive for Lyme disease with standardized 2-tiered serologic testing between 2005 and 2010 at a single hospital system in a region with little endemic Lyme disease. Based on clinical findings, we calculated the positive predictive value of Lyme disease serology. Next, we reviewed the outcome of serologic testing in patients with select clinical syndromes compatible with disseminated Lyme disease (arthritis, cranial neuropathy, or meningitis). RESULTS: During the 6-year study period 4723 patients were tested for Lyme disease, but only 76 (1.6%) had positive results by established laboratory criteria. Among 70 seropositive patients whose medical records were available for review, 12 (17%; 95% confidence interval, 9%-28%) were found to have Lyme disease (6 with documented travel to endemic regions). During the same time period, 297 patients with a clinical illness compatible with disseminated Lyme disease underwent 2-tiered serologic testing. Six of them (2%; 95% confidence interval, 0.7%-4.3%) were seropositive, 3 with documented travel and 1 who had an alternative diagnosis that explained the clinical findings. CONCLUSIONS: In this low-prevalence cohort, fewer than 20% of positive Lyme disease tests are obtained from patients with clinically likely Lyme disease. Positive Lyme disease test results may have little diagnostic value in this setting.

Detection of Multiple Respiratory Viruses Associated With Mortality and Severity of Illness in Children.

OBJECTIVE: Respiratory viral infection is a common source of morbidity and mortality in children. Coinfection with multiple viruses occurs frequently; however, the clinical significance of concomitant viral pathogens is unclear. We hypothesized that presence of more than one respiratory virus is associated with increased morbidity and mortality when compared with children with a single respiratory virus. DESIGN: Retrospective cohort study. SETTING: A tertiary care hospital. PATIENTS: All children at Duke Children's Hospital over a 2-year period with isolation of a virus on an extended viral respiratory panel result. Demographic data, comorbidities, and details of hospital encounter were recorded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred thirty-five hospital encounters demonstrated positive extended viral respiratory panels. Immunocompromised status (37%) and respiratory comorbidities (23%) were common. Twenty-eight patients (12%) tested positive for multiple viruses, with adenovirus (23/28) and respiratory syncytial virus (15/28) most prevalent in patients with multiple viruses. Viral codetection was associated with increased use of noninvasive ventilation (p = 0.02), extracorporeal membrane oxygenation (p = 0.02), increased likelihood of moderate or severe illness (p = 0.005), and increased mortality (p = 0.01). Subgroup analysis demonstrated that this mortality association persisted for children with normal immune function (p = 0.003) and children with no comorbidities (p = 0.007). CONCLUSIONS: Children with multiple respiratory viruses may be at increased risk of moderate or severe illness and mortality, with previously healthy children potentially being at greatest risk. Further studies are indicated to determine the significance and generalizability of this finding and to better understand the pathophysiology of viral coinfection.

Development and validation of the comprehensive health activities scale: a new approach to health literacy measurement.

Current health literacy measures have been criticized for solely measuring reading and numeracy skills when a broader set of skills is necessary for making informed health decisions, especially when information is often conveyed verbally and through multimedia video. The authors devised 9 health tasks and a corresponding 190-item assessment to more comprehensively measure health literacy skills. A sample of 826 participants between the ages of 55 and 74 years who were recruited from an academic general internal medicine practice and three federally qualified health centers in Chicago, Illinois, completed the assessment. Items were reduced using hierarchical factor analysis and item response theory resulting in the 45-item Comprehensive Health Activities Scale. All 45 items loaded on 1 general latent trait, and the resulting scale demonstrated high reliability and strong construct validity using measures of health literacy and global cognitive functioning. The predictive validity of the Comprehensive Health Activities Scale using self-reported general, physical, and mental health status was comparable to or better than widely used measures of health literacy, depending on the outcome. Despite comprehensively measuring health literacy skills, items in the Comprehensive Health Activities Scale supported 1 primary construct. With similar psychometric properties, current measures may be adequate, depending on the purpose of the assessment.

OXIDATIVE study: A pilot prospective observational cohort study protocol examining the influence of peri-reperfusion hyperoxemia and immune dysregulation on early allograft dysfunction after orthotopic liver transplantation.

Early allograft dysfunction (EAD) is a functional hepatic insufficiency within a week of orthotopic liver transplantation (OLT) and is associated with morbidity and mortality. The etiology of EAD is multifactorial and largely driven by ischemia reperfusion injury (IRI), a phenomenon characterized by oxygen scarcity followed by paradoxical oxidative stress and inflammation. With the expanded use of marginal allografts more susceptible to IRI, the incidence of EAD may be increasing. This necessitates an in-depth understanding of the innate molecular mechanisms underlying EAD and interventions to mitigate its impact. Our central hypothesis is peri-reperfusion hyperoxemia and immune dysregulation exacerbate IRI and increase the risk of EAD. We will perform a pilot prospective single-center observational cohort study of 40 patients. The aims are to determine (1) the association between peri-reperfusion hyperoxemia and EAD and (2) whether peri-reperfusion perturbed cytokine, protein, and hypoxia inducible factor-1 alpha (HIF-1α) levels correlate with EAD after OLT. Inclusion criteria include age ≥ 18 years, liver failure, and donation after brain or circulatory death. Exclusion criteria include living donor donation, repeat OLT within a week of transplantation, multiple organ transplantation, and pregnancy. Partial pressure of arterial oxygen (PaO2) as the study measure allows for the examination of oxygen exposure within the confines of existing variability in anesthesiologist-administered fraction of inspired oxygen (FiO2) and the inclusion of patients with intrapulmonary shunting. The Olthoff et al. definition of EAD is the primary outcome. Secondary outcomes include postoperative acute kidney injury, pulmonary and biliary complications, surgical wound dehiscence and infection, and mortality. The goal of this study protocol is to identify EAD contributors that could be targeted to attenuate its impact and improve OLT outcomes. If validated, peri-reperfusion hyperoxemia and immune perturbations could be targeted via FiO2 titration to a goal PaO2 and/or administration of an immunomodulatory agent by the anesthesiologist intraoperatively.

Cognitive flexibility training for chronic pain: a randomized clinical study.

Introduction: Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain. Objectives: This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain. Methods: We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend 35 minutes daily completing a program with tasks on cognitive flexibility, memory, attention, and speed. The primary outcome was performance on the neurocognitive performance test (NCPT). Secondary outcomes included levels of pain interference and severity. Results: At 5 weeks, the treatment group showed greater improvements on NCPT compared with the control group (d = 0.37); effect size was smaller at 3 months (d = 0.18). The treatment group reported lower pain severity at 5 weeks (d = 0.16) and 3 months (d = 0.39) than the control group, but pain interference was only lower at 3 months (d = 0.20). Conclusions: Outcomes suggest that using neurocognitive training to modify cognitive flexibility in patients with chronic pain may improve pain severity. This study provided effect size estimates to inform sample size calculations for randomized controlled trials to test the effectiveness of neurocognitive interventions for the prevention and treatment of chronic pain.

Asthma beliefs are associated with medication adherence in older asthmatics.

BACKGROUND: Empirical research and health policies on asthma have focused on children and young adults, even though asthma morbidity and mortality are higher among older asthmatics. OBJECTIVE: To explore the relationship of asthma-related beliefs and self-reported controller medication adherence in older asthmatics. DESIGN: An observational study of asthma beliefs and self-management among older adults. PARTICIPANTS: Asthmatics ages ≥ 60 years (N = 324, mean age 67.4 ± 6.8, 28 % white, 32 % black, 30 % Hispanic) were recruited from primary care practices in New York City and Chicago. MAIN MEASURES: Self-reported controller medication adherence was assessed using the Medication Adherence Report Scale. Based on the Common Sense Model of Self-Regulation, patients were asked if they believe they only have asthma with symptoms, their physician can cure their asthma, and if their asthma will persist. Beliefs on the benefit, necessity and concerns of treatment use were also assessed. Multivariate logistic regression was used to examine the association of beliefs with self-reported medication adherence. KEY RESULTS: The majority (57.0 %) of patients reported poor adherence. Poor self-reported adherence was more common among those with erroneous beliefs about asthma illness and treatments, including the "no symptoms, no asthma" belief (58.7 % vs. 31.7 %, respectively, p < 0.001), "will not always have asthma" belief (34.8 % vs. 12.5 %, p < 0.001), and the "MD can cure asthma" belief (21.7 % vs. 9.6 %, p = 0.01). Adjusting for illness beliefs, treatment beliefs and demographics, patients with a "no symptoms, no asthma" belief had lower odds of having good self-reported adherence (odds ratio [OR] 0.45, 95 % confidence interval [CI] 0.23-0.86), as did those with negative beliefs about the benefits (OR 0.73, 95 % CI 0.57-0.94) and necessity (OR 0.89, 95 % CI 0.83-0.96) of treatment. CONCLUSIONS: Illness and treatment beliefs have a strong influence on self-reported medication adherence in older asthmatics. Interventions to improve medication adherence in older asthmatics by modifying illness and treatment beliefs warrant study.

Depressive symptoms, low adherence, and poor asthma outcomes in the elderly.

OBJECTIVE: To examine the impact of depressive symptoms on asthma outcomes and medication adherence in inner-city elderly patients with asthma. METHODS: Cohort study of elderly asthmatics receiving primary care at three clinics in New York City and Chicago from 1 January 2010 to 1 January 2012. Depressive symptoms were ascertained with the Patient Health Questionnaire (PHQ-9). Outcomes included asthma control (Asthma Control Questionnaire, ACQ), asthma-related quality of life (Asthma Quality of Life Questionnaire, AQLQ), and acute resource utilization (inpatient and outpatient visits). Asthma medication adherence was evaluated using the Medication Adherence Reporting Scale (MARS). RESULTS: Three hundred and seventeen participants ≥60 years were included in the study (83% women, 30% Hispanic, and 31% Black). In unadjusted analyses, participants with depressive symptoms were more likely to report poor asthma control (p < .001), worse AQLQ scores (p < .001), and higher rates of inpatient asthma-related visits (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.04-3.99). Those with depressive symptoms also reported lower medication adherence (OR: 0.23, 95%CI: 0.10-0.54). Similar results were obtained in analyses adjusting for age, sex, race/ethnicity, income, asthma medication prescription, years with asthma, intubation history, comorbidities, and health literacy. CONCLUSION: In this cohort of elderly inner-city participants, depressive symptoms were associated with poorer asthma control and quality of life, as well as with lower rates of adherence to controller medications. Future work exploring possible mediators, including adherence, might elucidate the relationship between depression and poorer asthma outcomes in this population.

Photocatalytic cyclohexane oxidation and epoxidation using hedgehog particles.

Inorganic particles are effective photocatalysts for the liquid-state production of organic precursors and monomers at ambient conditions. However, poor colloidal stability of inorganic micro- and nanoparticles in low-polarity solvents limits their utilization as heterogeneous catalysts and coating them with surfactants drastically reduces their catalytic activity. Here we show that effective photo-oxidation of liquid cyclohexane (CH) is possible using spiky particles from metal oxides with hierarchical structure combining micro- and nanoscale structural features engineered for enhanced dispersibility in CH. Nanoscale ZnO spikes are assembled radially on α-Fe2O3 microcube cores to produce complex 'hedgehog' particles (HPs). The 'halo' of stiff spikes reduces van der Waals attraction, preventing aggregation of the catalytic particles. Photocatalysis in Pickering emulsions formed by HPs with hydrogen peroxide provides a viable pathway to energy-efficient alkane oxidation in the liquid state. Additionally, HPs enable a direct chemical pathway from alkanes to epoxides at ambient conditions, specifically to cyclohexene oxide, indicating that the structure of HPs has a direct effect on the recombination of ion-radicals during the hydrocarbon oxidation. These findings demonstrate the potential of inorganic photocatalysts with complex architecture for 'green' catalysis.

Use of Intramuscular Ephedrine Sulfate During Kidney Transplantation.

Hypotension during kidney transplantation can be common. Vasopressor use during these procedures is often avoided, with a fear of decreasing renal perfusion in the transplanted kidney. However, adequate perfusion for the rest of the body is also necessary, and given that these patients often have underlying hypertension or other comorbid conditions, an appropriate mean arterial pressure (MAP) has to be maintained. Intramuscular injections of ephedrine have been studied in the anesthesiology literature in a variety of case types, and it is seen as a safe and effective method to boost MAP. We present a case series of three patients who underwent renal transplantation and who received an intramuscular injection of ephedrine for hypotension control. The medication worked well for increasing blood pressures without apparent side effects. All three patients were followed for more than one year, and all patients had good graft function at the end of that time period. This series shows that while further research is necessary in this arena, intramuscular ephedrine may have a place in the management of persistent hypotension in the operating room during kidney transplantation.

Establishing the Reliability, Validity, and Prognostic Utility of the Momentary Pain Catastrophizing Scale for Use in Ecological Momentary Assessment Research.

Despite the marked increase in ecological momentary assessment research, few reliable and valid measures of momentary experiences have been established. The goal of this preregistered study was to establish the reliability, validity, and prognostic utility of the momentary Pain Catastrophizing Scale (mPCS), a 3-item measure developed to assess situational pain catastrophizing. Participants in 2 studies of postsurgical pain outcomes completed the mPCS 3 to 5 times per day prior to surgery (N = 494, T = 20,271 total assessments). The mPCS showed good psychometric properties, including multilevel reliability and factor invariance across time. Participant-level average mPCS was strongly positively correlated with dispositional pain catastrophizing as assessed by the Pain Catastrophizing Scale (r = .55 and .69 in study 1 and study 2, respectively). To establish prognostic utility, we then examined whether the mPCS improved prediction of postsurgical pain outcomes above and beyond one-time assessment of dispositional pain catastrophizing. Indeed, greater variability in momentary pain catastrophizing prior to surgery was uniquely associated with increased pain immediately after surgery (b = .58, P = .005), after controlling for preoperative pain levels and dispositional pain catastrophizing. Greater average mPCS score prior to surgery was also uniquely associated with lesser day-to-day improvement in postsurgical pain (b = .01, P = .003), whereas dispositional pain catastrophizing was not (b = -.007, P = .099). These results show that the mPCS is a reliable and valid tool for ecological momentary assessment research and highlight its potential utility over and above retrospective measures of pain catastrophizing. PERSPECTIVE: This article presents the psychometric properties and prognostic utility of a new measure to assess momentary pain catastrophizing. This brief, 3-item measure will allow researchers and clinicians to assess fluctuations in pain catastrophizing during individuals' daily lives, as well as dynamic relationships between catastrophizing, pain, and related factors.

Usability of FDA-approved medication guides.

BACKGROUND: Medication guides are required documents to be distributed to patients in order to convey serious risks associated with certain prescribed medicines. Little is known about the effectiveness of this information to adequately inform patients on safe use. OBJECTIVE: To examine the readability, suitability, and comprehensibility of medication guides, particularly for those with limited literacy. DESIGN: Assessments of suitability and readability of 185 medication guides, and a sub-study examining change in suitability and readability from 2006 to 2010 among 32 of the medication guides (Study 1); 'open book' comprehension assessment of medication guides (Study 2). SETTING: Two general internal medicine clinics in Chicago, IL. PATIENTS: Four hundred and forty-nine adults seeking primary care services, ages 18-85. MEASUREMENTS: For Study 1, the Suitability Assessment of Materials (SAM) and Lexile score for readability. For Study 2, a tailored comprehension assessment of content found in three representative medication guides. RESULTS: The 185 analyzed medication guides were on average 1923 words (SD = 1022), with a mean reading level of 10-11th grade. Only one medication guide was deemed suitable in SAM analyses. None provided summaries or reviews, or framed the context first, while very few were rated as having made the purpose evident (8 %), or limited the scope of content (22 %). For Study 2, participants' comprehension of medication guides was poor (M = 52.7 % correct responses, SD = 22.6). In multivariable analysis, low and marginal literacy were independently associated with poorer understanding (ß = -14.3, 95 % CI -18.0 - -10.6, p < 0.001; low: ß = -23.7, 95 % CI -28.3 - -19.0, p < 0.001). CONCLUSION: Current medication guides are of little value to patients, as they are too complex and difficult to understand especially for individuals with limited literacy. Explicit guidance is offered for improving these print materials.

Literacy, cognitive function, and health: results of the LitCog study.

BACKGROUND: Emerging evidence suggests the relationship between health literacy and health outcomes could be explained by cognitive abilities. OBJECTIVE: To investigate to what degree cognitive skills explain associations between health literacy, performance on common health tasks, and functional health status. DESIGN: Two face-to-face, structured interviews spaced a week apart with three health literacy assessments and a comprehensive cognitive battery measuring 'fluid' abilities necessary to learn and apply new information, and 'crystallized' abilities such as background knowledge. SETTING: An academic general internal medicine practice and three federally qualified health centers in Chicago, Illinois. PATIENTS: Eight hundred and eighty-two English-speaking adults ages 55 to 74. MEASUREMENTS: Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine (REALM), Test of Functional Health Literacy in Adults (TOFHLA), and Newest Vital Sign (NVS). Performance on common health tasks were globally assessed and categorized as 1) comprehending print information, 2) recalling spoken information, 3) recalling multimedia information, 4) dosing and organizing medication, and 5) healthcare problem-solving. RESULTS: Health literacy measures were strongly correlated with fluid and crystallized cognitive abilities (range: r=0.57 to 0.77, all p<0.001). Lower health literacy and weaker fluid and crystallized abilities were associated with poorer performance on healthcare tasks. In multivariable analyses, the association between health literacy and task performance was substantially reduced once fluid and crystallized cognitive abilities were entered into models (without cognitive abilities: ß= -28.9, 95 % Confidence Interval (CI) -31.4 to -26.4, p; with cognitive abilities: ß= -8.5, 95 % CI -10.9 to -6.0). LIMITATIONS: Cross-sectional analyses, English-speaking, older adults only. CONCLUSIONS: The most common measures used in health literacy studies are detecting individual differences in cognitive abilities, which may predict one's capacity to engage in self-care and achieve desirable health outcomes. Future interventions should respond to all of the cognitive demands patients face in managing health, beyond reading and numeracy.

The influence of health literacy on comprehension of a colonoscopy preparation information leaflet.

BACKGROUND: Successful bowel preparation is important for safe, efficacious, cost-effective colonoscopy procedures; however, poor preparation is common. OBJECTIVE: We sought to determine whether there was an association between health literacy and comprehension of typical written instructions on how to prepare for a colonoscopy to enable more targeted interventions in this area. DESIGN: This is a cross-sectional observational study. SETTING: This study was performed at primary care clinics and federally qualified health centers in Chicago, Illinois. PATIENTS: Seven hundred sixty-four participants (mean age, 63 years; SD, 5.42) were recruited. The sample was from a mixed sociodemographic background, and 71.9% of the participants were classified as having adequate health literacy scores. INTERVENTION: Seven hundred sixty-four participants were presented with an information leaflet outlining the bowel preparatory instructions for colonoscopy. MAIN OUTCOME MEASURES: Five questions were used to assess participants' comprehension of the instructions in an "open book" test. RESULTS: Comprehension scores on the bowel preparation items were low. The mean number of items correctly answered was 3.2 (SD, 1.2) of a possible 5. Comprehension scores overall and for each individual item differed significantly by health literacy level (all p < 0.001). After controlling for sex, age, race, socioeconomic status, and previous colonoscopy experience in a multivariable model, health literacy was a significant predictor of comprehension (inadequate vs adequate: ß = -0.2; p < 0.001; marginal vs adequate: ß = -0.2; p < 0.001). LIMITATIONS: The outcome represents a simulated task and not actual comprehension of preparation instructions for participants' own recommended behavior. CONCLUSIONS: Comprehension of a written colonoscopy preparation leaflet was generally low and significantly lower among people with low health literacy. Poor comprehension has implications for the safety and economic impact of gastroenterological procedures such as colonoscopy. Therefore, future interventions should aim to improve comprehension of complex medical information by reducing literacy-related barriers.