Healthcare Resource Utilization Following Minimally Invasive Sacrocolpopexy: Impact of Concomitant Rectopexy.

INTRODUCTION AND HYPOTHESIS: Combined surgical procedures with sacrocolpopexy (SCP) and rectopexy (RP) are more commonly being performed for treatment of multicompartment pelvic organ prolapse. This study aimed to compare healthcare resource utilization (HRU) within 6 weeks following combined surgery (SCP-RP) versus SCP alone (SCP-only). We hypothesized that concomitant RP does not impact HRU. METHODS: A retrospective cohort study of patients who underwent minimally invasive SCP from 2017 to 2022 was conducted at a tertiary referral center. Patients were grouped based on the performance of concomitant RP. HRU was defined as a composite of unscheduled office visits, emergency department visits, and readmissions before the 6-week postoperative visit. HRU was compared in the SCP-RP and SCP-only groups. Multivariable regression analysis was performed to identify factors associated with HRU. RESULTS: There were 144 patients in the SCP-RP group and 405 patients in the SCP-only group. Patient characteristics were similar between the two groups, with the following exceptions: the SCP-RP group was older, more likely to have comorbid conditions, and live >60 miles from the hospital. Of the 549 patients, 183 (33.3%) had ≥1 HRU encounter within 6 weeks after surgery. However, there was no difference between the SCP-RP and SCP-only groups in composite HRU (34.0% vs 33.1%, p = 0.84). The most common reasons for HRU were pain, urinary tract infection symptoms, and wound issues. Concomitant mid-urethral sling was associated with a two-fold increased risk of HRU after surgery. CONCLUSIONS: One in 3 patients undergoing minimally invasive SCP had at least one unanticipated encounter within 6 weeks after surgery. Concomitant RP was not associated with increased postoperative HRU.

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater : A Cost-Effectiveness Analysis.

BACKGROUND: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. OBJECTIVE: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. DESIGN: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. DATA SOURCES: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. TARGET POPULATION: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Total knee replacement. OUTCOME MEASURES: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. RESULTS OF SENSITIVITY ANALYSIS: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. LIMITATION: Data are derived from several sources. CONCLUSION: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Hospital Length of Stay With a Proactive Psychiatric Consultation Model in the Medical Intensive Care Unit: A Prospective Cohort Analysis.

BACKGROUND: Previous studies have demonstrated that proactive psychiatric consultation reduces hospital length of stay (LOS) in the general medical setting; however this model has not been studied in the intensive care unit (ICU). OBJECTIVE: To compare outcomes between a conventional consultation model and a proactive psychiatric consultation model. METHODS: Two medical ICUs (MICUs) were randomized to proactive psychiatric consultation vs conventional consultation psychiatric models. Proactive consultation included embedding a psychiatrist into daily MICU team rounds on all patients. In the conventional consultation MICU, psychiatric consultations were activated when deemed necessary. Primary outcomes were hospital LOS and MICU LOS. Secondary outcomes included delirium-coma-free hours and ventilator-free hours. RESULTS: A total of 429 patients were admitted to the proactive consultation MICU; 393 patients were admitted to the conventional consultation MICU. The consultation rate for the intervention group was 24.2% vs 6.1% in the control group (p < 0.001). Time to psychiatric consultation was shorter in the intervention group. Median hospital LOS was 6.92 days, interquartile range 3.70-14.31 in the intervention group vs 7.69 days, interquartile range 3.95-16.21 in the control group (p = 0.113). MICU LOS, delirium-coma-free hours, and ventilator-free hours were not significantly different between the 2 groups. Among the respiratory failure subgroup, hospital LOS was shorter in the intervention vs control group (median 9.46 days, interquartile range 4.95-17.56 vs 12.29 days, interquartile range 6.58-21.10, p = 0.011). CONCLUSIONS: Proactive psychiatric consultation in a MICU was associated with decreased time to consultation among all patients and shorter hospital LOS among patients with respiratory failure.

Lipidomics Profiling of Human Adipose Tissue Identifies a Pattern of Lipids Associated with Fish Oil Supplementation.

To understand the interaction between diet and health, biomarkers that accurately reflect consumption of foods of perceived health relevance are needed. The aim of this investigation was to use direct infusion-mass spectrometry (DI-MS) lipidomics to determine the effects of fish oil supplementation on lipid profiles of human adipose tissue. Adipose tissue samples from an n-3 polyunsaturated fatty acid (PUFA) supplementation study (n = 66) were analyzed to compare the pattern following supplementation equivalent to zero or four portions of oily fish per week. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were incorporated into highly unsaturated (≥5 double bonds) triglycerides (TGs), phosphocholines, and phosphoethanolamines as well as being detected directly as the nonesterified fatty acid forms. Multivariate statistics demonstrated that phospholipids were the most accurate and sensitive lipids for the assessing EPA and DHA incorporation into adipose tissue. Potential confounding factors (adiposity, age, and sex of the subject) were also considered in the analysis, and adiposity was also associated with an increase in highly unsaturated TGs as a result of incorporation of the n-6 PUFA arachidonic acid. DI-MS provides a high-throughput analysis of fatty acid status that can monitor oily fish consumption, suitable for use in cohort studies.

Effectiveness of a Mobile Mammography Program.

OBJECTIVE: Mobile mammography units have increasingly been used to address patient health care disparities; however, there are limited data comparing mobile units to stationary sites. This study aims to evaluate the characteristics of women who underwent mammography screening in a mobile unit versus those who underwent mammography screening at a cancer center. MATERIALS AND METHODS: In this retrospective study, we analyzed all screening mammography examinations performed in a mobile unit in 2014 (n = 1433 examinations). For comparison, we randomized and reviewed an equivalent number of screening mammography examinations performed at our cancer center in 2014 (n = 1434 examinations). BI-RADS assessment, adherence to follow-up, biopsies performed, cancer detection rate, and sociodemographic variables were recorded. An independent-samples t test was conducted to identify potential differences in age between cancer center patients and mobile unit patients. Chi-square analyses were used to test for associations between location and factors such as health insurance, race, marital status, geographic area, adherence to screening guidelines, recall rate, adherence to follow-up, and cancer detection rates. RESULTS: Patients visiting our cancer center (mean = 57.74 years; SD = 10.55) were significantly older than those visiting the mobile unit (mean = 52.58 years; SD = 8.19; p < 0.001). There was a significant association between location and health insurance status (χ2 = 610.92; p < 0.001) with more uninsured patients undergoing screening in the mobile van (cancer center = 3.70%, mobile unit = 38.73%). There was a significant association between screening location and patient race (χ2 = 118.75, p < 0.001), with more white patients being screened at the cancer center (cancer center = 47.28%, mobile unit = 33.30%), more black patients being screened in the mobile van (cancer center = 49.30%, mobile unit = 54.15%), and more Hispanic patients being screened in the mobile van (cancer center = 1.05%, mobile unit = 6.77%). There was a significant association between location and patient marital status (χ2 = 135.61, p < 0.001), with more married patients screened at the cancer center (cancer center = 49.16%, mobile unit = 38.31%), more single patients screened in the mobile van (cancer center = 25.17%, mobile unit = 34.47%), and more widowed patients being screened at the cancer center (cancer center = 8.09%, mobile unit = 4.47%). There was a significant association between location and geographic area (χ2 = 33.33, p < 0.001), with both locations reaching more urban than rural patients (cancer center = 79.99%, mobile unit = 70.62%). There was a significant association between location and adherence to screening guidelines (χ2 = 179.60, p < 0.001), with patients screened at the cancer center being more compliant (cancer center = 56.90%, mobile unit = 34.47%). Finally, there was a significant association between location and recall rate (χ2 = 4.06, p < 0.001). The cancer center had a lower recall rate (13.32%) than the mobile van (15.98%). Of those patients with BI-RADS 0, there was a significant association between location and adherence to follow-up (χ2 = 22.75, p < 0.001) with patients using the mobile unit less likely to return for additional imaging (cancer center = 2.65%, mobile unit = 17.03%). CONCLUSION: Significant differences were found among patients visiting the cancer center versus the mobile mammography van. The cancer center's population is older and more adherent to guidelines, whereas the mobile mammography population exhibited greater racial and marital diversity, higher recall rate, and lack of adherence to follow-up recommendations. By identifying these characteristics, we can develop programs and materials that meet these populations' needs and behaviors, ultimately increasing mammography screening and follow-up rates among underserved populations.

Integration of metabolomics, lipidomics and clinical data using a machine learning method.

BACKGROUND: The recent pandemic of obesity and the metabolic syndrome (MetS) has led to the realisation that new drug targets are needed to either reduce obesity or the subsequent pathophysiological consequences associated with excess weight gain. Certain nuclear hormone receptors (NRs) play a pivotal role in lipid and carbohydrate metabolism and have been highlighted as potential treatments for obesity. This realisation started a search for NR agonists in order to understand and successfully treat MetS and associated conditions such as insulin resistance, dyslipidaemia, hypertension, hypertriglyceridemia, obesity and cardiovascular disease. The most studied NRs for treating metabolic diseases are the peroxisome proliferator-activated receptors (PPARs), PPAR-α, PPAR-γ, and PPAR-δ. However, prolonged PPAR treatment in animal models has led to adverse side effects including increased risk of a number of cancers, but how these receptors change metabolism long term in terms of pathology, despite many beneficial effects shorter term, is not fully understood. In the current study, changes in male Sprague Dawley rat liver caused by dietary treatment with a PPAR-pan (PPAR-α, -γ, and -δ) agonist were profiled by classical toxicology (clinical chemistry) and high throughput metabolomics and lipidomics approaches using mass spectrometry. RESULTS: In order to integrate an extensive set of nine different multivariate metabolic and lipidomics datasets with classical toxicological parameters we developed a hypotheses free, data driven machine learning approach. From the data analysis, we examined how the nine datasets were able to model dose and clinical chemistry results, with the different datasets having very different information content. CONCLUSIONS: We found lipidomics (Direct Infusion-Mass Spectrometry) data the most predictive for different dose responses. In addition, associations with the metabolic and lipidomic data with aspartate amino transaminase (AST), a hepatic leakage enzyme to assess organ damage, and albumin, indicative of altered liver synthetic function, were established. Furthermore, by establishing correlations and network connections between eicosanoids, phospholipids and triacylglycerols, we provide evidence that these lipids function as a key link between inflammatory processes and intermediary metabolism.

Are clinics not affiliated with a Menopause Society Certified Practitioner more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with a Menopause Society Certified Practitioner?

OBJECTIVE: To identify clinics in Ohio, Michigan, and Pennsylvania that advertise menopause treatment on their website and evaluate whether clinics not affiliated with a Menopause Society Certified Practitioner (MSCP) are more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with an MSCP. METHODS: We performed an Internet search to identify clinics advertising on their website menopause treatment in Ohio, Michigan, and Pennsylvania. We checked clinic personnel against The Menopause Society directory of practitioners to determine if the clinic was affiliated with an MSCP. RESULTS: We identified 174 clinics (41% in OH, 28% in PA, and 31% in MI). Thirteen percent of clinics were affiliated with an MSCP. Clinics with an MSCP are significantly less likely to advertise hormone testing (primary outcome; odds ratio [OR], 0.11; 95% confidence interval, 0.02-0.39), compounded hormone therapy (OR, 0.06; 95% confidence interval, 0.001-0.41), and bioidentical hormone therapy (OR, 0.07; 95% confidence interval, 0.001-0.26), compared to clinics without an MSCP-affiliated clinics that are also less likely to advertise that hormone therapy will help maintain youth or help with weight loss. CONCLUSIONS: Our pilot study has shown that in the states of Ohio, Michigan, and Pennsylvania, clinics with an MSCP were more likely to advertise on their website an adherence to The Menopause Society's guidelines and not advertise for compounded or bioidentical hormones, recommend hormone testing, or advertise hormones for a youthful appearance or weight loss.

Reliability of home-based remote and self-assessment of transfers using the Transfer Assessment Instrument among wheelchair users with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate the reliability of home-based remote and self-assessment of transfer quality using the Transfer Assessment Instrument (TAI) among wheelchair users with spinal cord injury (SCI). SETTING: Participant's home environment. METHODS: Eighteen wheelchair users with SCI transferred from their wheelchair to a surface of their choice (bed, sofa, or bench) in their homes. During a live video conference, the transfer was recorded and evaluated live using the TAI (rater 1). Participants completed a self-assessment of their transfer using the TAI- questionnaire (TAI-Q). Two additional raters (raters 2 & 3) completed asynchronous assessments by watching recorded videos. Interrater reliability was assessed using Intraclass Coefficient Correlations (ICC) to compare rater 1 with the average of raters 2 & 3 and TAI-Q. Intrarater reliability was assessed by rater 1 completing another TAI by watching the recorded videos after a 4-week delay. Assessments were compared using paired sample t-tests and level of agreement between TAI scores was evaluated using Bland-Altman plots. RESULTS: Moderate to good interrater and good intrarater reliability were found for the total TAI score with ICCs: 0.57-0.90 and 0.90, respectively. Moderate to good intrarater and interrater reliability were found for all TAI subscores (ICC: 0.60-0.94) except for interrater reliability of flight/landing which was poor (ICC: 0.20). Bland-Altman plots indicate no systematic bias related to the measurement of error. CONCLUSIONS: The TAI is a reliable outcome measure for assessing the wheelchair and body setup phases of home-based transfers remotely and through self-assessment among individuals with SCI.

Computational design of an α-gliadin peptidase.

The ability to rationally modify enzymes to perform novel chemical transformations is essential for the rapid production of next-generation protein therapeutics. Here we describe the use of chemical principles to identify a naturally occurring acid-active peptidase, and the subsequent use of computational protein design tools to reengineer its specificity toward immunogenic elements found in gluten that are the proposed cause of celiac disease. The engineered enzyme exhibits a k(cat)/K(M) of 568 M(-1) s(-1), representing a 116-fold greater proteolytic activity for a model gluten tetrapeptide than the native template enzyme, as well as an over 800-fold switch in substrate specificity toward immunogenic portions of gluten peptides. The computationally engineered enzyme is resistant to proteolysis by digestive proteases and degrades over 95% of an immunogenic peptide implicated in celiac disease in under an hour. Thus, through identification of a natural enzyme with the pre-existing qualities relevant to an ultimate goal and redefinition of its substrate specificity using computational modeling, we were able to generate an enzyme with potential as a therapeutic for celiac disease.

Characteristics of Female Sexual Health Programs and Providers in the United States.

BACKGROUND: Female sexual dysfunction is a prevalent condition affecting 12% of women, yet few academic centers in the US have female sexual medicine programs. AIM: To characterize female sexual health programs in the United States, services offered, and training of female sexual health providers. METHODS: We performed an internet search to identify female sexual health programs and clinics in the US. From each programs' website we abstracted the location, clinic setting (academic vs private), training of providers, and whether the clinic provided investigational services (ie, PRP injections, laser/radiofrequency therapy). We categorized clinics as specialized in sexual medicine, specialized with a focus on cancer patients, general, aesthetics-focused, general & aesthetic, or specialized & aesthetic. We used Chi-square and Fisher's exact test to evaluate association between practice setting and provision of investigational therapies with a Bonferroni-adjusted critical P-value of 0.017. OUTCOMES: Our outcomes were the number of clinics in each setting, in each category, and each state, as well as the number of providers by training type. RESULTS: We identified 235 female sexual medicine programs in the United States. Seventeen percent were in the academic setting. Clinics in the non-academic setting were significantly (α = 0.017) more likely to offer PRP injections (0% vs 47%, P < .001), laser/radiofrequency therapy (14% vs 56%, P < .0001), and shockwave therapy (0% vs 14%, P = .011). Among all clinics, 22% provided specialized care, 2% provided care for cancer patients, 29% were more general clinics that advertised female sexual healthcare, 23% were aesthetics-focused, 22% were general practices that provided aesthetics services, and 2% were specialized clinics that offered aesthetics services. 81% of aesthetics-focused clinics advertised PRP injections. Seven states had no clinics and 26 states lacked a clinic specializing in female sexual health. The most frequent providers were OB/Gyns (40%), nurse practitioners (22%), urologists (13%), and physicians assistants (10%). CLINICAL IMPLICATIONS: The geographic distribution of clinics and pervasiveness of clinics offering investigational services for female sexual dysfunction may be a barrier for patients seeking care. LIMITATIONS: As a result of our internet search methodology, we likely did not capture all clinics providing female sexual health services. Further, the accuracy of our data depends on the level of detail provided on each clinics' website. CONCLUSION: Online search identified few clinics providing female sexual healthcare in academic medicine: development of such clinics could benefit patients by improving access to evidence-based care and promoting training of future providers. Elizabeth E. Stanley and Rachel J. Pope, Characteristics of Female Sexual Health Programs and Providers in the United States. Sex Med 2022;10:100524.

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

OBJECTIVE: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the US use opioids on a prolonged basis. We aimed to characterize the societal economic burden of opioid use in this population. METHODS: We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the US SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with a mean ± SD age of 54 ± 14 years and Western Ontario and McMaster Universities Osteoarthritis Index pain score of 29 ± 17 (0-100, 100 = worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person, respectively. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. RESULTS: Assuming 5.1% prevalence of prolonged strong opioid use, the total lifetime opioid-related cost generated by the US SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. CONCLUSION: Lost productivity, diversion, and criminal justice costs comprise approximately half of opioid-related costs generated by the US SKOA population. Reducing prolonged opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

Leaders' Windows of Tolerance for Affect Arousal-and Their Effects on Political Decision-making During COVID-19.

The recent 'affect revolution' in strategic decision-making research has placed greater emphasis on the role of stress and emotions in decision-making, with new theorizing to highlight how leader decisions often differ from rational choice expectations. However, while existing theories add to our understanding of the interplay between affect and cognition, they have not yet explained why affect drives decisions in some situations and not others. Undertheorized connections between leaders' neurobiological windows of tolerance to affect arousal and their self-regulatory capacity-their capacity to regulate stress and emotions so that these phenomena do not drive resulting decisions-may hold the key to explaining this variation in affect's influence on decision-making. Furthermore, this article considers how leaders' windows of tolerance have unique ripple effects in their social environments, thereby affecting their groups' collective window of tolerance. While regulated leaders can convey a calming and creative influence in their organizations that helps the group access strategic decision-making, dysregulated leaders are likely to convey stress and emotion contagion-which may erode the group's ability to cooperate, adapt, and learn. It illustrates this argument using evidence from the upper echelons of governmental decision-making, comparing New Zealand Prime Minister Jacinda Ardern's and US President Donald Trump's responses to the coronavirus pandemic in their respective nations. It concludes by offering hypotheses for testing the argument in future empirical research.

Factors associated with use of antibiotic prophylaxis following dental procedures in total joint replacement recipients.

Background: Total joint replacement recipients (TJR) are at risk for prosthetic joint infection (PJI), particularly those with comorbidities such as diabetes mellitus (DM) and rheumatoid arthritis (RA). Methods: We mailed surveys to 1078 subjects undergoing primary TJR between 2011 and 2016 â€‹at an academic center. The survey asked about medical, dental, and orthopedic history and use of antibiotics prior to dental appointments. We generated adjusted relative risks (aRR) for using antibiotic prophylaxis less than always using Poisson regression, adjusting for demographic, clinical, and behavioral factors. Results: We received surveys from 639 subjects; 597 were eligible and formed the analytical sample. 66 â€‹% reported always using antibiotic prophylaxis. DM and RA were not associated with prophylaxis use. Factors associated with less frequent use included: BMI ≥30 (aRR â€‹= â€‹1.27, 95 â€‹% CI [1.01, 1.60]), dental cleanings <2 times/year (aRR â€‹= â€‹1.95, 95 â€‹% CI [1.56, 2.43]), and expressing little concern (compared to neutral) about getting PJI (aRR â€‹= â€‹1.23, 95 â€‹% CI [0.97, 1.55]), though this association was not statistically significant. Greater antibiotic use was reported in subjects who had ≥3 TJRs, (aRR â€‹= â€‹0.48, 95 â€‹% CI [0.29, 0.80]), underwent more invasive dental procedures (aRR â€‹= â€‹0.74, 95 â€‹% CI [0.59, 0.93]), and were concerned (vs. neutral) about PJI (aRR â€‹= â€‹0.53, 95 â€‹%CI [0.33, 0.84]). Conclusions: Two-thirds of TJR recipients in an academic center reported always using antibiotic prophylaxis prior to dental visits. Usage rates varied by demographics, BMI, number of TJRs, type of dental procedure, and behavioral factors -- but not by comorbidities associated with higher PJI risk.

Cardiovascular morbidity, heart rates and use of antimuscarinics in patients with overactive bladder.

OBJECTIVE: To determine if cardiovascular (CV) comorbidity and treatment-associated antimuscarinic effects differ between patients with and without overactive bladder (OAB), and between treated and untreated patients with OAB, as OAB, CV disorders and exposure to medications with antimuscarinic effects are common in older patients. PATIENTS AND METHODS: Adults from the HealthCore Integrated Research Database with a diagnosis of OAB (International Classification of Diseases-9 codes; from 1 January 2000 to 31 December 2006) or a pharmacy claim for an antimuscarinic OAB medication, formed the OAB cohort, further stratified as treated and untreated. A random sample of patients with neither a diagnosis for OAB nor any urinary bladder dysfunction, nor a pharmacy claim for antimuscarinics, formed the non-OAB cohort. CV comorbidities and use of medications with antimuscarinic effects were assessed for the 12 months before OAB diagnosis/treatment. Information on heart rate (HR) on the day of the first OAB drug prescription was obtained from the GE Healthcare dataset. HR was assessed for patients aged > or =18 years with a diagnosis of OAB who were prescribed antimuscarinics (oxybutynin or tolterodine) at any dose or oral formulation between January 1995 and November 2006. RESULTS: The 6607 patients with OAB, with a substantial proportion with elevated HR at baseline, were more likely to have CV comorbidities (39% vs 21%; P < 0.001) and previous exposure to medications with antimuscarinic effects (33% vs 17%; P < 0.001) than the non-OAB patients. Rate of CV comorbidities (40% vs 38%; P = 0.326) did not differ between treated and untreated patients with OAB. However, there was a difference in previous exposure to medications with antimuscarinic effects (37% vs 29%; P < 0.001); 39.1% of patients with OAB had a HR of >80 beats/min before starting antimuscarinic treatment. CONCLUSION: In this study, the prevalence of CV comorbidities was significantly higher in patients with than without OAB; previous exposure to medications with antimuscarinic effects was also higher in patients with OAB. There was no difference in pre-existing CV comorbidities between the treated and untreated patients with OAB, but the high use of medications with antimuscarinic effects among these patients suggests that the presence of CV comorbidity might not be considered before using antimuscarinic agents for OAB.

The economic impact of exacerbations of chronic obstructive pulmonary disease and exacerbation definition: a review.

Chronic obstructive pulmonary disease (COPD) poses a significant economic burden on society, and a substantial portion is related to exacerbations of COPD. A literature review of the direct and indirect costs of COPD exacerbations was performed. A systematic search of the MEDLINE database from 1998-2008 was conducted and supplemented with searches of conference abstracts and article bibliographies. Articles that contained cost data related to COPD exacerbations were selected for in-depth review. Eleven studies examining healthcare costs associated with COPD exacerbations were identified. The estimated costs of exacerbations vary widely across studies: $88 to $7,757 per exacerbation (2007 US dollars). The largest component of the total costs of COPD exacerbations was typically hospitalization. Costs were highly correlated with exacerbation severity. Indirect costs have rarely been measured. The wide variability in the cost estimates reflected cross-study differences in geographic locations, treatment patterns, and patient populations. Important methodological differences also existed across studies. Researchers have used different definitions of exacerbation (e.g., symptom- versus event-based definitions), different tools to identify and measure exacerbations, and different classification systems to define exacerbation severity. Unreported exacerbations are common and may influence the long-term costs of exacerbations. Measurement of indirect costs will provide a more comprehensive picture of the burden of exacerbations. Evaluation of pharmacoeconomic analyses would be aided by the use of more consistent and comprehensive approaches to defining and measuring COPD exacerbations.

Harnessing synthetic biology to enhance heterologous protein expression.

The ability to express heterologous proteins in microbial hosts is crucial for many areas of research and technology. In most cases, however, successful expression and purification of the desired protein require fusion to another protein. To date, all fusion partners have been chosen from natural sequences, which evolved for other purposes, and may not be optimal fusion partners. However, the rise of synthetic biology and protein design make it possible to design and optimize fusion proteins using novel sequences that did not arise in nature. Here, we describe a series of De novo Expression Enhancer Proteins (DEEPs) that facilitate high-level expression and facile purification of heterologous proteins and peptides. To test the DEEP system, a de novo protein was fused to several target proteins covering a range of sizes and solubilities. In all cases, fusions to DEEP outperformed fusions to SUMO, a commonly used natural fusion partner. The availability of novel proteins that can be engineered for specific fusion applications could be beneficial to enhance the expression of a wide range of heterologous proteins.

Cost-effectiveness of dental antibiotic prophylaxis in total knee arthroplasty recipients with type II diabetes mellitus.

Objective: Type II diabetes mellitus (T2DM) is prevalent in knee osteoarthritis (OA) patients undergoing total knee arthroplasty (TKA) and increases risk for prosthetic joint infection (PJI). We examined the cost-effectiveness of antibiotic prophylaxis (AP) before dental procedures to reduce PJI in TKA recipients with T2DM. Design: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare two strategies among TKA recipients with T2DM (mean age 68 years, mean BMI 35.4 kg/m2): 1) AP before dental procedures and 2) no AP. Outcomes included quality-adjusted life expectancy (QALE) and lifetime medical costs. We used published efficacy of AP. We report incremental cost-effectiveness ratios (ICERs) and considered strategies with ICERs below well-accepted willingness-to-pay (WTP) thresholds cost-effective. We conducted sensitivity analyses to examine the robustness of findings to uncertainty in model input parameters. We used a lifetime horizon and healthcare sector perspective. Results: We found that AP added 1.0 quality-adjusted life-year (QALY) and $66,000 for every 1000 TKA recipients with T2DM, resulting in an ICER of $66,000/QALY. In sensitivity analyses, reduction of the probability of PJI, T2DM-associated risk of infection, or attribution of infections to dental procedures by 50% resulted in ICERs exceeding $100,000/QALY. Probabilistic sensitivity analyses showed that AP was cost-effective in 32% and 58% of scenarios at WTP of $50,000/QALY and $100,000/QALY, respectively. Conclusions: AP prior to dental procedures is cost-effective for TKA recipients with T2DM. However, the cost-effectiveness of AP depends on the risk of PJI and efficacy of AP in this population.

Outcomes of Coronavirus Disease 2019 Drive-Through Screening at an Academic Military Medical Center.

Drive-through coronavirus disease 2019 screening can evaluate large numbers of patients while reducing healthcare exposures and personal protective equipment use. We describe the characteristics of screened individuals as well as drive-through process and outcome measures. Optimal drive-through screening involves rapid turnaround of test results and linkage to follow-up care.

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance.

Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1-/- mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1-/- only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.

PPAR-pan activation induces hepatic oxidative stress and lipidomic remodelling.

The peroxisome proliferator-activated receptors (PPARs) are ligand activated nuclear receptors that regulate cellular homoeostasis and metabolism. PPARs control the expression of genes involved in fatty-acid and lipid metabolism. Despite evidence showing beneficial effects of their activation in the treatment of metabolic diseases, particularly dyslipidaemias and type 2 diabetes, PPAR agonists have also been associated with a variety of side effects and adverse pathological changes. Agonists have been developed that simultaneously activate the three PPAR receptors (PPARα, γ and δ) in the hope that the beneficial effects can be harnessed while avoiding some of the negative side effects. In this study, the hepatic effects of a discontinued PPAR-pan agonist (a triple agonist of PPAR-α, -γ, and -δ), was investigated after dietary treatment of male Sprague-Dawley (SD) rats. The agonist induced liver enlargement in conjunction with metabolomic and lipidomic remodelling. Increased concentrations of several metabolites related to processes of oxidation, such as oxo-methionine, methyl-cytosine and adenosyl-methionine indicated increased stress and immune status. These changes are reflected in lipidomic changes, and increased energy demands as determined by free fatty acid (decreased 18:3 n-3, 20:5 n-3 and increased ratios of n-6/n-3 fatty acids) triacylglycerol, phospholipid (decreased and increased bulk changes respectively) and eicosanoid content (increases in PGB2 and 15-deoxy PGJ2). We conclude that the investigated PPAR agonist, GW625019, induces liver enlargement, accompanied by lipidomic remodelling, oxidative stress and increases in several pro-inflammatory eicosanoids. This suggests that such pathways should be monitored in the drug development process and also outline how PPAR agonists induce liver proliferation.