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Can scribes boost FPs' efficiency and job satisfaction

Fri, 06/23/2017 - 10:25am

Purpose: Research in other medical specialties has shown that the addition of medical scribes to the clinical team enhances physicians' practice experience and increases productivity. To date, literature on the implementation of scribes in primary care is limited. To determine the feasibility and benefits of implementing scribes in family medicine, we undertook a pilot mixed- method quality improvement (QI) study.

Methods: In 2014, we incorporated 4 part-time scribes into an academic family medicine practice consisting of 7 physicians. We then measured, via survey and time-tracking data, the impact the scribes had on physician office hours and productivity, time spent on documentation, perceptions of work-life balance, and physician and patient satisfaction.

Results: Six of the 7 faculty physicians participated. This study demonstrated that the use of scribes in a busy academic primary care practice substantially reduced the amount of time that family physicians spent on charting, improved work-life balance, and had good patient acceptance. Specifically, the physicians spent an average of 5.1 fewer hours/week (hrs/wk) on documentation, while various measures of productivity revealed increases ranging from 9.2% to 28.8%. Perhaps most important of all, when the results of the pilot study were annualized, they were projected to generate $168,600 per year--more than twice the $79,500 annual cost of 2 full-time equivalent scribes. Surveys assessing work-life balance demonstrated improvement in the physicians' perception of the administrative burden/paperwork related to practice and a decrease in their perception of the extent to which work encroached on their personal lives. In addition, survey data from 313 patients at the time of their ambulatory visit with a scribe present revealed a high level of comfort. Likewise, surveys completed by physicians after 55 clinical sessions (ie, blocks of consecutive, uninterrupted patient appointments; there are usually 2 sessions per day) revealed good to excellent ratings more than 90% of the time.

Conclusion: In an outpatient family medicine clinic, the use of scribes substantially improved physicians' efficiency, job satisfaction, and productivity without negatively impacting the patient experience.

Infusion-related reactions with pegloticase, a recombinant uricase for the treatment of chronic gout refractory to conventional therapy

Fri, 06/23/2017 - 10:24am

BACKGROUND: In clinical trials of pegloticase, a PEGylated uricase developed for treatment of gout refractory to conventional therapy, infusion-related reactions (IRs) were the second most frequent adverse event reported.

OBJECTIVE: The objective of this study was to provide a detailed account of IRs with pegloticase therapy.

METHODS: Data from 2 replicate, 6-month randomized trials and an open-label extension study were pooled. Infusions of pegloticase (8 mg) were administered biweekly or monthly; all patients received prophylaxis (antihistamine, acetaminophen, and corticosteroid) and were tested for urate levels prior to each infusion. An IR was defined by protocol as any otherwise unexplained adverse event or cluster of temporally related events occurring during or within 2 hours of infusion.

RESULTS: Infusion-related reactions occurred in 94 (45%) of 208 patients receiving pegloticase; 10 patients reported IRs at first infusion and 84 during subsequent infusions. Chest discomfort (15%), flushing (12%), and dyspnea (11%) were the most common symptoms. Most IRs were rated mild or moderate; 7% were rated severe. All IRs resolved with slowing, interrupting, or stopping the infusion. No patient required blood pressure or ventilatory support. Infusion-related reactions were associated with loss of pegloticase urate-lowering efficacy: 91% of all IRs occurred in patients with preinfusion serum uric acid concentrations (sUA) greater than 6 mg/dL. For patients sustaining preinfusion sUA of less than 6 mg/dL, IRs occurred in fewer than 1 per 100 infusions.

CONCLUSIONS: Phase 3 trial data combined with post hoc analyses demonstrated that knowledge of sUA preceding each pegloticase infusion and cessation of therapy when urate-lowering efficacy is lost provide a means to optimize the safety of pegloticase in clinical practice.

The Association of Baseline Suicidality With Treatment Outcome in Psychotic Depression

Fri, 06/23/2017 - 10:24am

OBJECTIVE: To examine the association between baseline suicidality and outcome of major depression in a randomized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality, randomized treatment assignment, and depression outcome.

METHODS: This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo (the Study of the Pharmacotherapy of Psychotic Depression [STOP-PD], which ran from 2002 to 2007). The independent variable was baseline suicidality, defined by 4 groups (suicide attempt in the current episode, active suicidal ideation, passive suicidal ideation, and no suicidality). The outcome variables were change in 16-item Hamilton Depression Rating Scale (HDRS(1)(6)) total score (excluding the suicide item) over time and remission of psychotic depression over time.

RESULTS: Suicidality groups did not significantly differ on baseline HDRS(1)(6) total score. Baseline suicidality group was significantly associated with change in HDRS(1)(6) score over time in the sample as a whole (F(3),(1)(3)(9)(4) = 8.17; P < .0001), but was not significantly associated with probability of remission over time. Among participants assigned to olanzapine and placebo, persons with no suicidality had a significantly greater reduction in HDRS(1)(6) total score compared to those with passive suicidal ideation (7.5-point difference in change scores between the 2 groups; 95% CI, 4.3-10.7 t(1)(3)(9)(4) = 4.61, P < .0001), active suicidal ideation (4.4 points; 95% CI, 1.4-7.4; t(1)(3)(9)(4) = 2.85, P = .0176), or suicide attempts (6.1 points; 95% CI, 2.8-9.4; t(1)(3)(9)(4) = 3.66, P = .0015). The 12-week change from baseline in HDRS(1)(6) score for patients with no suicidality was not significantly different between the 2 treatment arms. However, the 12-week HDRS(1)(6) improvement was significantly greater in the olanzapine plus sertraline arm, compared with the olanzapine plus placebo arm, for patients with suicide attempts (8.7-point difference in change scores between the 2 groups; 95% CI, 5.1-12.4; t(1)(3)(9)(4) = 4.75, P < .0001), active suicidal ideation (8.1 points; 95% CI, 4.5-11.7; t(1)(3)(9)(4) = 4.38, P < .0001), or passive suicidal ideation (5.7 points; 95% CI, 2.2-9.2; t(1)(3)(9)(4) = 3.23, P = .0012), respectively.

CONCLUSIONS: Baseline suicidality predicted worse acute treatment outcome of psychotic depression. However, participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00056472.

Interdependence of Inhibitor Recognition in HIV-1 Protease

Fri, 06/23/2017 - 10:24am

Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites. Co-crystal structures of these analogs with HIV-1 protease provide the ideal opportunity to probe subsite interdependency. All-atom molecular dynamics simulations starting from these structures were performed and systematically analyzed in terms of atomic fluctuations, intermolecular interactions, and water structure. These analyses reveal that the S1' subsite highly influences other subsites: the extension of the hydrophobic P1' moiety results in 1) reduced van der Waals contacts in the P2' subsite, 2) more variability in the hydrogen bond frequencies with catalytic residues and the flap water, and 3) changes in the occupancy of conserved water sites both proximal and distal to the active site. In addition, one of the monomers in this homodimeric enzyme has atomic fluctuations more highly correlated with DRV than the other monomer. These relationships intricately link the HIV-1 protease subsites and are critical to understanding molecular recognition and inhibitor binding. More broadly, the interdependency of subsite recognition within an active site requires consideration in the selection of chemical moieties in drug design; this strategy is in contrast to what is traditionally done with independent optimization of chemical moieties of an inhibitor.

Dietary Inflammatory Index, Bone Mineral Density, and Risk of Fracture in Postmenopausal Women: Results From the Women's Health Initiative

Fri, 06/23/2017 - 10:24am

Previous studies suggest that bone loss and fracture risk are associated with higher inflammatory milieu, potentially modifiable by diet. The primary objective of this analysis was to evaluate the association of the dietary inflammatory index (DII), a measure of the inflammatory potential of diet, with risk of hip, lower-arm, and total fracture using longitudinal data from the Women's Health Initiative Observational Study and Clinical Trials. Secondarily, we evaluated changes in bone mineral density (BMD) and DII scores. DII scores were calculated from baseline food frequency questionnaires (FFQs) completed by 160,191 participants (mean age 63 years) without history of hip fracture at enrollment. Year 3 FFQs were used to calculate a DII change score. Fractures were reported at least annually; hip fractures were confirmed by medical records. Hazard ratios for fractures were computed using multivariable-adjusted Cox proportional hazard models, further stratified by age and race/ethnicity. Pairwise comparisons of changes in hip BMD, measured by dual-energy X-ray absorptiometry from baseline, year 3, and year 6 were analyzed by quartile (Q1 = least inflammatory diet) of baseline DII scores in a subgroup of women (n = 10,290). Mean DII score improved significantly over 3 years (p < 0.01), but change was not associated with fracture risk. Baseline DII score was only associated with hip fracture risk in younger white women (HR Q4,1.48; 95% CI, 1.09 to 2.01; p = 0.01). There were no significant associations among white women older than 63 years or other races/ethnicities. Women with the least inflammatory DII scores had less loss of hip BMD (p = 0.01) by year 6, despite lower baseline hip BMD, versus women with the most inflammatory DII scores. In conclusion, a less inflammatory dietary pattern was associated with less BMD loss in postmenopausal women. A more inflammatory diet was associated with increased hip fracture risk only in white women younger than 63 years.

Optimism, Cynical Hostility, Falls, and Fractures: The Women's Health Initiative Observational Study (WHI-OS)

Fri, 06/23/2017 - 10:24am

Traits of optimism and cynical hostility are features of personality that could influence the risk of falls and fractures by influencing risk-taking behaviors, health behaviors, or inflammation. To test the hypothesis that personality influences falls and fracture risk, we studied 87,342 women enrolled in WHI-OS. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility, the cynicism subscale of the Cook-Medley questionnaire. Higher scores indicate greater optimism and hostility. Optimism and hostility were correlated at r = -0. 31, p < 0.001. Annual self-report of falling > /=2 times in the past year was modeled using repeated measures logistic regression. Cox proportional hazards models were used for the fracture outcomes. We examined the risk of falls and fractures across the quartiles (Q) of optimism and hostility with tests for trends; Q1 formed the referent group. The average follow-up for fractures was 11.4 years and for falls was 7.6 years. In multivariable (MV)-adjusted models, women with the highest optimism scores (Q4) were 11% less likely to report > /=2 falls in the past year (odds ratio [OR] = 0.89; 95% confidence intervals [CI] 0.85-0.90). Women in Q4 for hostility had a 12% higher risk of > /=2 falls (OR = 1.12; 95% CI 1.07-1.17). Higher optimism scores were also associated with a 10% lower risk of fractures, but this association was attenuated in MV models. Women with the greatest hostility (Q4) had a modest increased risk of any fracture (MV-adjusted hazard ratio = 1. 05; 95% CI 1.01-1.09), but there was no association with specific fracture sites. In conclusion, optimism was independently associated with a decreased risk of > /=2 falls, and hostility with an increased risk of > /=2 falls, independent of traditional risk factors. The magnitude of the association was similar to aging 5 years. Whether interventions aimed at attitudes could reduce fall risks remains to be determined.

Exploring the need for interventions to manage weight and stress during interconception

Fri, 06/23/2017 - 10:24am

Interventions to manage weight and stress during the interconception period (i.e., time immediately following childbirth to subsequent pregnancy) are needed to promote optimal maternal and infant health outcomes. To address this gap, we summarize the current state of knowledge, critically evaluate the research focused on weight and stress management during the interconception period, and provide future recommendations for research in this area. Evidence supports the importance of weight and stress management during the reproductive years and the impact of weight on maternal and child health outcomes. However, evidence-based treatment models that address postpartum weight loss and manage maternal stress during the interconception period are lacking. This problem is further compounded by inconsistent definitions and measurements of stress. Recommendations for future research include interventions that address weight and stress tailored for women in the interconception period, interventions that address healthcare providers' understanding of the significance of weight and stress management during interconception, and long-term follow-up studies that focus on the public health implications of weight and stress management during interconception. Addressing obesity and stress during the interconception period via a reproductive lens will be a starting point for women and their families to live long and healthy lives.

Practical Care Support During the Early Recovery Period After Acute Coronary Syndrome

Fri, 06/23/2017 - 10:24am

OBJECTIVE: To describe the prevalence and predictors of receipt of practical support among acute coronary syndrome (ACS) survivors during the early post-discharge period.

METHOD: 406 ACS patients were interviewed about receipt of practical (instrumental and informational) support during the week after discharge. Demographic, clinical, functional, and psychosocial predictors of instrumental and informational practical support were examined.

RESULTS: 81% of participants reported receiving practical support during the early post-discharge period: 75% reported receipt of instrumental support and 51% reported receipt of informational support. Men were less likely to report receiving certain types of practical support, whereas married participants and those with higher education, impaired health literacy, impaired activities of daily living, and in-hospital complications were more likely to report receiving certain types of practical support.

CONCLUSION: Receipt of practical support is very common among ACS survivors during the early post-discharge period, and type of support received differs according to patient characteristics.

Retro-Orbital Venous Sinus Delivery of rAAV9 Mediates High-Level Transduction of Brain and Retina Compared with Temporal Vein Delivery in Neonatal Mouse Pups

Tue, 06/20/2017 - 2:38pm

In order to pursue a clinical gene therapy for a human neurologic disease, it is often necessary to perform proof-of-concept trials in mouse models of that disease. In order to demonstrate a potential clinical efficacy, one must be able to select an appropriate vector and route of delivery for the appropriate age group in the disease model. Since many diseases require correction early in life, investigators often need to deliver recombinant adeno-associated viral (rAAV) vectors to neonatal mice. Herein, general central nervous system expression patterns of nuclear GFP following delivery of rAAV by three different routes are reported.

An oral HemokineTM, alpha-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo

Tue, 06/20/2017 - 2:37pm

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained > 200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.

Evaluating Patient-Centered Outcomes in Clinical Trials of Procedural Sedation, Part 1 Efficacy: Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations

Tue, 06/20/2017 - 2:37pm

The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research, established by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the US Food and Drug Administration, convened a meeting of sedation experts from a variety of clinical specialties and research backgrounds with the objective of developing recommendations for procedural sedation research. Four core outcome domains were recommended for consideration in sedation clinical trials: (1) safety, (2) efficacy, (3) patient-centered and/or family-centered outcomes, and (4) efficiency. This meeting identified core outcome measures within the efficacy and patient-centered and/or family-centered domains. Safety will be addressed in a subsequent meeting, and efficiency will not be addressed at this time. These measures encompass depth and levels of sedation, proceduralist and patient satisfaction, patient recall, and degree of pain experienced. Consistent use of the recommended outcome measures will facilitate the comprehensive reporting across sedation trials, along with meaningful comparisons among studies and interventions in systematic reviews and meta-analyses.

Restrictive Lung Disease in the Cu/Zn Superoxide-Dismutase 1 G93A Amyotrophic Lateral Sclerosis Mouse Model

Tue, 06/20/2017 - 2:37pm

This study is the first to show progressive restrictive pulmonary disease in the most commonly used ALS mouse model—the SOD1G93A mouse.

Airway smooth muscle dysfunction in Pompe (Gaa-/-) mice

Tue, 06/20/2017 - 2:37pm

Pompe disease is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA) - an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi, and this lower airway pathology contributes to respiratory insufficiency in Pompe disease. Using an established mouse model of Pompe disease - the Gaa-/- mouse - we compared histology, pulmonary mechanics, airway smooth muscle function and calcium signaling between Gaa-/- and age matched wild type (WT) mice. Lysosomal glycogen accumulation was observed in the smooth muscle of both the bronchi and the trachea in Gaa-/- but not WT mice. Furthermore, Gaa-/- mice had hyporesponsive airway resistance and bronchial ring contraction to the bronchoconstrictive agents methacholine (Mch) and potassium chloride (KCl), and to a bronchodilator (albuterol). Finally, calcium signaling during bronchiolar smooth muscle contraction was impaired in Gaa-/- mice indicating impaired extracellular calcium influx. We conclude that GAA enzyme deficiency leads to glycogen accumulation in the trachea and bronchi, and impairs the ability of lower airway smooth muscle to regulate calcium and respond appropriately to bronchodilator or constrictors. Accordingly, airway smooth muscle dysfunction may contribute to respiratory impairments in Pompe disease.

Human Papillomavirus Vaccine Update

Tue, 06/20/2017 - 2:37pm

Rates of cancers attributable to human papillomavirus (HPV) are rising. A safe and extremely effective vaccine is available to prevent many of these cancers. Studies have shown that health care providers' recommendation to immunize is the most important factor in parents' decision. Parents of all adolescent boys and girls should receive a strong and unequivocal recommendation to vaccinate their child against HPV at the 11- or 12-year-old well child visit. Ideally, adolescents complete their HPV vaccine series by their 13th birthday, leading to greater immune response and protection before most adolescents are exposed to sexually transmitted HPV.

Adolescent Sexuality: Updates to the Sexually Transmitted Infection Guidelines

Tue, 06/20/2017 - 2:37pm

Adolescents are at high risk for acquisition and transmission of sexually transmitted infections (STI) secondary to both cognitive and biological susceptibility. The prevention, diagnosis, and treatment of STIs are a critical part of adolescent health care. This article discusses the most common bacterial, parasitic, and viral STIs encountered in this age group with an emphasis on new guidelines for screening and management.

Treating Youths in the Juvenile Justice System

Tue, 06/20/2017 - 2:37pm

Adolescents involved with the juvenile justice system have higher rates of risky sexual behaviors, resulting in high rates of sexually transmitted infections and increased risk of human immunodeficiency virus, early or complicated pregnancy, and parenting issues. Comorbid substance abuse, gang association, mental health issues, and history of having been abused as children result in further elevated rates. Girls and lesbian, gay, bisexual, and transgender youths represent growing subpopulations with special risks. Increasingly diverted to community-based alternatives, juvenile justice-involved teens obtain most of their medical care from community providers, who need to understand their risks to provide appropriate, optimal care.

A Primer for Primary Care Clinicians Caring for Sexually Active Adolescents

Tue, 06/20/2017 - 2:37pm

Issue preface: This slim issue of thirteen articles was specifically designed with the needs of the General Pediatrician in mind. The list of topics covers a broad scope of clinical issues that are common among adolescent patients, particularly adolescents who are sexually active. Many pediatricians feel poorly equipped to address sexual matters in teens either because they do not have updated knowledge about them or because the issues are complicated and take more time than usually scheduled in a busy practice. This issue will help pediatricians feel more confident caring for their adolescent patients. All the authors have made a concerted effort to provide a concise review of the topic assigned to them coupled with practical suggestions for the clinician to consider.

CAR T-Cell Therapy: Progress and Prospects

Tue, 06/20/2017 - 2:37pm

Lentivirus-mediated transduction of autologous T cells with a chimeric antigen receptor (CAR) to confer a desired epitope specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance antitumor immunity have been less specific and less effective. These have included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes, recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells with tumor antigens. Unlike any of those methods, the engineering of CAR T cells combine specific monoclonal antibody gene sequences to confer epitope specificity and other T-cell receptor and activation domains to create a self-contained single vector approach to produce a very specific antitumor response, as is seen with CD19-directed CAR T cells used to treat CD19-expressing B-cell malignancies. Recent success with these therapies is the culmination of a long step-wise iterative process of improvement in the design of CAR vectors. This review aims to summarize this long series of advances in the development of effective CAR vector since their initial development in the 1990s, and to describe emerging approaches to design that promise to enhance and widen the human gene therapy relevance of CAR T-cell therapy in the future.

The role of endoscopy in subepithelial lesions of the GI tract

Tue, 06/20/2017 - 2:37pm

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text.