Outcomes of an Asynchronous Care Model for Chronic Conditions in a Diverse Population: 12-Month Retrospective Chart Review Study.

BACKGROUND: Diabetes and hypertension are some of the most prevalent and costly chronic conditions in the United States. However, outcomes continue to lag behind targets, creating further risk of long-term complications, morbidity, and mortality for people living with these conditions. Furthermore, racial and ethnic disparities in glycemic and hypertension control persist. Flexible telehealth programs leveraging asynchronous care allow for increased provider access and more convenient follow-up, ultimately improving critical health outcomes across demographic groups. OBJECTIVE: We aim to evaluate the 12-month clinical outcomes of participants in the 9amHealth web-based clinic for diabetes and hypertension. We hypothesized that participation in the 9amHealth program would be associated with significant improvements in glycemic and blood pressure (BP) control across a diverse group of individuals. METHODS: We enrolled 95 patients in a completely web-based care clinic for diabetes and hypertension who received nutrition counseling, health coaching, and asynchronous physician consultations for medication prescribing. Patients received standard or cellular-connected glucose meters and BP cuffs in order to share data. Laboratory tests were completed either with at-home phlebotomy draws or a self-administered test kit. Patients' first and last hemoglobin A1c (HbA1c) and BP results over the 12-month period were compared, and analyses were repeated across race and ethnicity groups. RESULTS: Among all 95 patients, the average HbA1c decreased by -1.0 (from 8.2% to 7.2%; P<.001) over 12 months of program participation. In those with a baseline HbA1c >8%, the average HbA1c decreased by -2.1 (from 10.2% to 8.1%; P<.001), and in those with a baseline HbA1c >9%, the average HbA1c decreased by -2.8 (from 11% to 8.2%; P<.001). Among participants who identified as a race or ethnicity other than White, the HbA1c decreased by -1.2 (from 8.6% to 7.4%, P=.001). Further examination of subgroups confirmed HbA1c lowering within each race or ethnicity group. In the overall population, the average systolic BP decreased by 17.7 mm Hg (P=.006) and the average diastolic BP decreased by 14.3 mm Hg (P=.002). Among participants self-identifying as a race or ethnicity other than White, the results similarly showed a decrease in BP (average reduction in systolic BP of 10 mm Hg and in diastolic BP of 9 mm Hg). CONCLUSIONS: A fully web-based model leveraging all-asynchronous physician review and prescribing, combined with synchronous and asynchronous coaching and nutrition support, was associated with clinically meaningful improvement in HbA1c and BP control over a 12-month period among a diverse group of individuals. Further studies should prospectively evaluate the effectiveness of such models among larger populations, assess the longer-term sustainability of these outcomes, and explore financial models to make these types of programs broadly accessible.

"We're already doing this work": ethical research with community-based organizations.

BACKGROUND: Public health research frequently relies on collaborations with community-based organizations, and these partnerships can be essential to the success of a project. However, while public health ethics and oversight policies have historically focused on ensuring that individual subjects are protected from unethical or unfair practices, there are few guidelines to protect the organizations which facilitate relationships with - and are frequently composed of - these same vulnerable populations. As universities, governments, and donors place a renewed emphasis on the need for community engaged research to address systematic drivers of health inequity, it is vital that the ways in which research is conducted does not uphold the same intersecting systems of gender, race, and class oppression which led to the very same health inequities of interest. METHODS: To understand how traditional notions of public health research ethics might be expanded to encompass partnerships with organizations as well as individuals, we conducted qualitative interviews with 39 staff members (executive directors and frontline) at community-based organizations that primarily serve people who use drugs, Black men who have sex with men, and sex workers across the United States from January 2016 - August 2017. We also conducted 11 in-depth interviews with professional academic researchers with experience partnering with CBOs that serve similar populations. Transcripts were analyzed thematically using emergent codes and a priori codes derived from the Belmont Report. RESULTS: The concepts of respect, beneficence, and justice are a starting point for collaboration with CBOs, but participants deepened them beyond traditional regulatory concepts to consider the ethics of relationships, care, and solidarity. These concepts could and should apply to the treatment of organizations that participate in research just as they apply to individual human subjects, although their implementation will differ when applied to CBOs vs individual human subjects. CONCLUSIONS: Academic-CBO partnerships are likely to be more successful for both academics and CBOs if academic researchers work to center individual-level relationship building that is mutually respectful and grounded in cultural humility. More support from academic institutions and ethical oversight entities can enable more ethically grounded relationships between academic researchers, academic institutions, and community based organizations.

A randomized, cross-over trial of metoprolol succinate formulations to evaluate PK and PD end points for therapeutic equivalence.

There are limited comparison data throughout the dosing interval for generic versus brand metoprolol extended-release (ER) tablets. We compared the pharmacokinetics (PKs) and pharmacodynamics of brand name versus two generic formulations (drugs 1 and 2) of metoprolol ER tablets with different time to maximum concentration (Tmax ) in adults with hypertension. Participants were randomized to equal drug doses (50-150 mg/day) administered in one of two sequences (brand-drug1-brand-drug2 or brand-drug2-brand-drug1) and completed 24-h PK, digital heart rate (HR), ambulatory blood pressure (BP), and HR studies after taking each formulation for greater than or equal to 7 days. Metoprolol concentrations were determined by liquid chromatography tandem mass spectrometry, with noncompartmental analysis performed to obtain PK parameters in Phoenix WinNonlin. Heart rate variability (HRV) low-to-high frequency ratio was determined per quartile over the 24-h period. Thirty-six participants completed studies with the brand name and at least one generic product. Among 30 participants on the 50 mg dose, the primary PK end points of area under the concentration-time curve and Cmax were similar between products; Tmax was 6.1 ± 3.6 for the brand versus 3.5 ± 4.9 for drug 1 (p = 0.019) and 9.6 ± 3.2 for drug 2 (p < 0.001). Among all 36 participants, 24-h BPs and HRs were similar between products. Mean 24-h HRV low-to-high ratio was also similar for drug 1 (2.04 ± 1.35), drug 2 (1.86 ± 1.35), and brand (2.04 ± 1.77), but was more sustained over time for the brand versus drug 1 (drug × quartile interaction p = 0.017). Differences in Tmax between metoprolol ER products following repeated doses may have implications for drug effects on autonomic balance over the dosing interval.

Minority Older Adults' Access to and Use of Programs of All-Inclusive Care for the Elderly.

Programs of All-Inclusive Care for the Elderly (PACE) are an effective approach to improve care quality and delay institutional admissions especially for Black and Hispanic older adults who have seen a disproportionate rise in nursing home use. Guided by Andersen's Behavioral Model of Health Services Use and employing focus groups and one-on-one interviews, we qualitatively examined factors influencing access to and use of PACE by Black and Hispanic older adults. The study sample consisted of thirty-two PACE enrollees, six marketing-team members, and four family-caregivers from three PACE sites in a northeast urban city. Informed knowledge, cultural beliefs, and attitudes toward PACE were found to affect access. Community resources, available services, and care quality facilitated enrollment/participation. Barriers identified included poor dissemination of information and inadequate emphasis on staff's sensitivity to enrollees' cultural and disability differences. Findings will help healthcare leaders capitalize on facilitators and address barriers to enhance access and use of PACE by racial and ethnic minority older adults.

Ergonomic Risk Assessment of Dental Students-RULA Applied to Objective Kinematic Data.

Musculoskeletal disorder (MSD) is already prevalent in dental students despite their young age and the short duration of dental practice. The current findings state that the causes of MSD are related to posture during dental work. This study aims to investigate the ergonomic risk of dental students. In order to analyze the ergonomic risk of dental students, 3D motion analyses were performed with inertial sensors during the performance of standardized dental activities. For this purpose, 15 dental students and 15 dental assistant trainees (all right-handed) were measured in a team. Data were analyzed using the Rapid Upper Limb Assessment (RULA), which was modified to evaluate objective data. Ergonomic risk was found for the following body parts in descending order: left wrist, right wrist, neck, trunk, left lower arm, right lower arm, right upper arm, left upper arm. All relevant body parts, taken together, exhibited a posture with the highest RULA score that could be achieved (median Final Overall = 7), with body parts in the very highest RULA score of 7 for almost 80% of the treatment time. Dental students work with poor posture over a long period of time, exposing them to high ergonomic risk. Therefore, it seems necessary that more attention should be paid to theoretical and practical ergonomics in dental school.

Associations of Social Vulnerability Index With Pathologic Myocardial Findings at Autopsy.

Background: Social vulnerability is an important determinant of cardiovascular health. Prior investigations have shown strong associations of social determinants of health with cardiovascular risk factors, imaging findings, and clinical events. However, limited data exist regarding the potential role of social vulnerability and related physiologic stressors on tissue-level pathology. Methods: We analyzed clinical data and linked autopsy reports from 853 decedent individuals who underwent autopsy from 4/6/2002 to 4/1/2021 at a large urban medical center. The mean age at death was 62.9 (SD = 15.6) and 49% of decedent individuals were men. The primary exposure was census-tract level composite social vulnerability index based on the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Individuals were geocoded to census tracts and assigned SVI accordingly. Four myocardial tissue-level outcomes from autopsy were recorded as present or absent: any coronary atherosclerosis, severe/obstructive coronary atherosclerosis, myocardial fibrosis, and/or myopericardial inflammation. Multivariable-adjusted logistic regression models were constructed with SVI as the primary exposure and covariates including age, sex, race, body mass index (BMI), diabetes, and hypertension. Additional analyses were performed stratified by clinical diagnoses of heart failure (HF) and coronary artery disease (CAD). Results: In the overall cohort, SVI was not associated with outcomes on cardiac pathology in multivariable-adjusted models. However, in stratified multivariable-adjusted analyses, higher SVI (higher social vulnerability) was associated with a higher odds of myocardial fibrosis among individuals without clinical diagnoses of HF. Conclusions: Higher indices of social vulnerability are associated with a higher odds of myocardial fibrosis at autopsy among individuals without known clinical diagnoses of HF. Potential pathophysiological mechanisms and implications for prevention/treatment of myocardial dysfunction require further study.

Quantitative Benefit-Risk Assessment of P-gp-Mediated Drug-Drug Interactions of Dabigatran Coadministered With Pharmacokinetic Enhancers in Patients With Renal Impairment.

Drug-drug interactions (DDIs) between dabigatran and ritonavir/cobicistat are of major concern in people living with HIV, particularly in those with impaired renal function, because they can result in increased dabigatran exposure and thus an increased risk of major bleeding events. However, the extent of this interaction and subsequent need for dose adjustment in subjects with varying degrees of renal function is currently not yet fully understood. To close this knowledge gap, we conducted an integrated population physiologically-based pharmacokinetic/pharmacodynamic analysis linking changes in dabigatran exposure due to DDIs and varying degrees of renal function to the probability of experiencing an ischemic stroke or major bleeding event within 1 year. The results of our analysis suggest that coadministration of dabigatran etexilate (dabigatran prodrug) and ritonavir/cobicistat should be avoided in subjects with severe renal impairment. A 2-hour dose separation or dabigatran etexilate dose reduction to 110 mg b.i.d. (twice daily) should be considered in subjects with moderate renal impairment when coadministered with ritonavir, while the dabigatran etexilate dose should be further reduced to 75 mg b.i.d. when coadministered with cobicistat. No dabigatran etexilate dose adjustment is needed in subjects with normal renal function receiving ritonavir, but dabigatran etexilate dose reduction to 110 mg b.i.d. should be considered when coadministered with cobicistat.

User Characteristics of a Low-Acuity Emergency Department Alternative for Low-Income Patients.

INTRODUCTION: Emergency department (ED) use for healthcare that can be treated elsewhere is costly to the healthcare system. However, convenience settings such as urgent care centers (UCC) are generally inaccessible to low-income patients. Housing an UCC within a federally qualified health center (FQHC UCC) provides an accessible convenience setting for low-income patients. In 2014 a FQHC UCC opened two blocks from an ED in the same health system. Our goal was to compare characteristics, access to care, and utilization preferences for FQHC UCC and low-acuity ED patients through retrospective chart review and prospective surveying. METHODS: We completed a retrospective chart review of all patients from March 1, 2018-March 1, 2019, and compared characteristics of low-acuity ED patients (N = 3,911) and FQHC UCC patients (N = 12,571). We also surveyed FQHC UCC patients (N = 201) and low-acuity ED patients (N = 198) from January-July 2019. RESULTS: Half of FQHC UCC patients had private insurance. Of ED patients, 29% were aware of the FQHC UCC. Both groups had similar rates of primary care providers. The most common reason for choosing the ED was perceived severity, and for choosing a FQHC UCC was speed. CONCLUSION: These findings show similarities and differences between these two patient populations. Future research is needed to determine utilization patterns and in-depth reasons behind them. Interventions that help patients decide where to go for low-acuity care may create more utilization efficiency.

The burden of hyperkalemia in Germany - a real world evidence study assessing the treatment and costs of hyperkalemia.

BACKGROUND: Hyperkalemia (HK) can affect health outcomes and quality of life, as it is referred to as a potentially life-threatening condition caused by an increased serum potassium concentration in the blood. Patients suffering from heart failure or chronic kidney diseases are at a higher risk of HK, which can further be amplified by the treatment received. To date, data on HK prevalence is lacking for Germany and the aims of this study were to assess HK and compare health-relevant outcomes and healthcare costs between HK patients and non-HK patients. METHODS: The InGef research database containing healthcare claims of over 4 million individuals in Germany was utilized for this retrospective, matched cohort analysis. Patients with non-acute outpatient treated and a subgroup of patients with chronic HK, were identified in 2015 with an individual 1 year pre- and post-index period, taking the first observable HK diagnosis/treatment in 2015 into account as the index event. To identify non-acute outpatient treated HK patients, at least two ICD-10-GM diagnosis codes E87.5 "Hyperkalemia" and/or prescriptions of polystyrene sulfonate were required. Chronic HK patients had additional diagnoses and/or prescriptions in all quarters following the first observable HK diagnosis. Patients without HK were matched 1:1 to the respective HK cohorts. RESULTS: In the year 2015, 3333 patients with non-acute outpatient treated HK were identified of which 1693 were patients with chronic HK. After matching, 3191 and 1664 HK patients and controls were available for analysis. A significantly higher number of hospitalizations was observed for both HK cohorts in comparison to their matched controls. Dialysis initiation as well as the healthcare costs were higher for both HK cohorts when compared to their matched counterparts. CONCLUSIONS: The disease burden was higher for patients with HK, based on a higher proportion of patients with dialysis initiation and higher healthcare costs.

Predicting Cost-Effectiveness of Generic vs. Brand Dabigatran Using Pharmacometric Estimates Among Patients with Atrial Fibrillation in the United States.

Generic entry of newer anticoagulants is expected to decrease the costs of atrial fibrillation management. However, when making switches between brand and generic medications, bioequivalence concerns are possible. The objectives of this study were to predict and compare the lifetime cost-effectiveness of brand dabigatran with hypothetical future generics. Markov microsimulations were modified to predict the lifetime costs and quality-adjusted life years of patients on either brand or generic dabigatran from a US private payer perspective. Event rates for generics were predicted using previously developed pharmacokinetic-pharmacodynamic models. The analyses showed that generic dabigatran with lower-than-brand systemic exposure were dominant. Meanwhile, generic dabigatran with extremely high systemic exposure was not cost-effective compared with the brand reference. Cost-effectiveness of generic medications cannot always be assumed as shown in this example. Combined use of pharmacometric and pharmacoeconomic models can assist in decision making between brand and generic pharmacotherapies.

Assessment of poor functional status and post-acute care needs following primary ovarian cancer debulking surgery.

INTRODUCTION: Poor baseline functional status is associated with adverse surgical outcomes. Additionally, decline in the postoperative setting may result in the delay of additional treatments, impacting overall survival. This study assesses the incidence and risk factors for functional decline following primary ovarian cancer debulking surgery in previously independent women using discharge location as a surrogate. METHODS: All patients with a postoperative diagnosis of ovarian cancer who underwent surgical debulking and had documentation of discharge location were identified using the 2011-2012 American College of Surgeons National Surgical Quality Improvement Program database. Patients were excluded if their baseline functional status was dependent or partially dependent, or if they died before discharge. Discharge destination was dichotomized as home versus non-home. Descriptive data included demographics, comorbidities, and perioperative outcomes. Multivariable logistic regression was used to evaluate the association of clinical and surgical factors on discharge destination. RESULTS: 1786 patients met the criteria for analysis; 120 (6.7%) patients were discharged to non-home. Differences between home and non-home discharges included age (53.2% vs 83.3% ≥60), body mass index (26.5 vs 27.8 median), comorbidities (45.2% vs 64.2% with ≥1), and complications (8.6% vs 30.0% with ≥1, all p<0.05). In multivariable logistic regression analyses, only increasing age and complications were independently associated with discharge to non-home. Those age ≥70 had 9.0 times the risk (95% CI 3.5 to 23.4; p<0.001) as age <50. The presence of one or more postoperative complications carried 4.5 times (95% CI 2.9 to 7.0; p<0.001) the risk of those without complications. 30 day mortality was also increased in patients discharged to non-home. DISCUSSION: 6.7% of previously independent ovarian cancer patients were discharged to non-home following surgery. Major risk factors for non-home include older age, comorbidities, and postoperative complications. Efforts to optimize baseline functional status and minimize surgical complications may improve discharge rates to non-home and postoperative functional status.

[Primary Healthcare Provision and Introduction of New Models of Care in Hard to Serve Regions: A Population Survey]. / Hausärztliche Versorgungssituation und Einführung neuer Versorgungsformen in schwer zu versorgenden Regionen: Eine Befragung der Bevölkerung.

OBJECTIVE OF THE STUDY: One of the central challenges in health policy is to ensure nationwide provision of primary healthcare services. However, it is not clear how the general public rates the current primary healthcare provision in their region. Furthermore, there is very little information on whether people are willing to make use of new models of care that could contribute to ensuring a nationwide provision of healthcare services. Thus, the objective of this study was to analyse the general public's ratings of the local primary healthcare provision as well as their acceptance of selected new models of care. Furthermore, potential differences in the ratings of the population between hard to serve regions and normal regions will be analysed. METHODOLOGY: Focus group discussions and a literature review were conducted in order to develop a questionnaire to elicit the expectations of the population concerning the local provision of primary healthcare as well as their acceptance of new models of care. A postal questionnaire was sent to a random sample of 2,000 persons in 8 regions in Lower Saxony. RESULTS: The adjusted response rate of the postal survey was 51% (n=996). 97% of respondents saw a general practitioner regularly, with 5.4 visits per year on average. Patients could reach the practice in 13 min on average. Respondents predominantly rated the current healthcare provision as being good. However, the majority of respondents expected the local primary healthcare provision to deteriorate in the future. New models of care most preferred by the respondents were the delegation of medical tasks to non-medical professionals and mobility-oriented models. On the other hand, the provision of healthcare via telemedicine was rejected. DISCUSSION: According to the results of this study, respondents believe that new models of care can play an important role in ensuring the nationwide provision of healthcare services. Introducing, at an early stage, those new models of care that people accept could contribute to ensuring a sustainable provision of primary healthcare services. Furthermore, the introduction of these new models of care could reduce the public's concerns regarding a worsening provision of primary healthcare services in their regions. Additionally, pilot projects with those new models of care that are rather rejected might increase acceptance with these models of care if they prove to be successful.

Could Peer Support Programs Be a Good Resource for Managing the Unmet Needs of Cancer Patients?

The number of cancer patients has been rapidly increasing, and while there have been wide variations, cancer survival rates also improved globally. Despite the improved survival rates, supportive care needs of cancer patients have been unmet in various domains. The current study aimed to investigate unmet needs that had potential to be managed by peer supports according to cancer trajectories. We used the comprehensive needs assessment tool in cancer (CNAT) and a modified CNAT to evaluate the unmet needs and peer support needs of cancer patients at the tertiary hospital of South Korea. Of the 402 participants, 335 (83.3%) needed peer support. For patients who had been diagnosed with cancer for more than 5 years, the highest proportion of peer support needs to unmet supportive care was reported in information domain (92.9%). Patients with advanced cancer reported peer support needs in the social/religious/spiritual (84.4%) and practical domains (81.1%). Most of stomach cancer patients needed peer supports to receive information (96.6%). The need for peer supports in the information domain was reported highest according to longer survival period and also according to advanced cancer stages. The proportion of peer support needs in unmet supportive care varied by cancer type. Further interventional studies are needed to investigate satisfaction with peer support in specific domains.

Which strategies might improve local primary healthcare in Germany? An explorative study from a local government point of view.

BACKGROUND: Facing rising inequities and poorer accessibility of physicians in rural areas, new healthcare delivery structures are being considered to support local healthcare in German communities. To better understand perspectives on and attitudes towards different supplementary models, we examined attitudes among local politicians in the German federal state of Lower Saxony towards the suitability of supplementary care models. METHODS: As part of a cross-sectional study, we surveyed local politicians in Lower Saxony at the local authority and district levels (n = 449) by mail questionnaire. We asked for an assessment of four potential supplementary healthcare models at the local level: the use of trained medical assistants, patients' buses, mobile physicians' offices, and telemedicine. RESULTS: The response rate was 71.0% for mayors (n = 292) and 81.6% (n = 31) for county administrators. In summary, 72.4% of respondents supported the use of trained medical assistants, 48.9% voted for patients' buses, 22.0% for mobile physicians' offices, and 13.9% for telemedicine. Except for telemedicine, the politicians' approval of the supplementary models in rural areas was higher than in urban areas. The assessment regarding the suitability of each model was not significantly connected with indicators of a positively or negatively assessed local healthcare situation. The analyses showed that the use of trained medical assistants was associated with the positive effects of division of labor and potential to relieve physicians. In contrast, there was skepticism about technical support via telemedicine, mostly due to concerns about its unsuitability for elderly people and the potential lower quality of healthcare delivery. CONCLUSION: Local politicians widely accept the use of trained medical assistants, whereas the applicability of technical solutions such as telemedicine is perceived with skepticism. Therefore, the knowledge gap between evidence for and prejudices against telemedicine needs to be addressed more effectively. Reasons for the assessments of the presented models are more likely traceable to personal views than to assessments of the actual estimated local primary care situation.

Evaluation of the ASCO Value Framework for Anticancer Drugs at an Academic Medical Center.

BACKGROUND: Anticancer drug prices have increased by an average of 12% each year from 1996 to 2014. A major concern is that the increasing cost and responsibility of evaluating treatment options are being shifted to patients. This research compared 2 value-based pricing models that were being considered for use at the University of California, San Francisco (UCSF) Medical Center to address the growing burden of high-cost cancer drugs while improving patient-centered care. PROGRAM DESCRIPTION: The Medication Outcomes Center (MOC) in the Department of Clinical Pharmacy, University of California, San Francisco (UCSF), School of Pharmacy focuses on assessing the value of medication-related health care interventions and disseminating findings to the UCSF Medical Center. The High Cost Oncology Drug Initiative at the MOC aims to assess and adopt tools for the critical assessment and amelioration of high-cost cancer drugs. The American Society of Clinical Oncology (ASCO) Value Framework (2016 update) and a cost-effectiveness analysis (CEA) framework were identified as potential tools for adoption. To assess 1 prominent value framework, the study investigators (a) asked 8 clinicians to complete the ASCO Value Framework for 11 anticancer medications selected by the MOC; (b) reviewed CEAs assessing the drugs; (c) generated descriptive statistics; and (d) analyzed inter-rater reliability, convergence validity, and ranking consistency. OBSERVATIONS: On the scale of -20 to 180, the mean ASCO net health benefit (NHB) total score across 11 drugs ranged from 7.6 (SD = 7.8) to 53 (SD = 9.8). The Kappa coefficient (κ) for NHB scores across raters was 0.11, which is categorized as "slightly reliable." The combined κ score was 0.22, which is interpreted as low to fair inter-rater reliability. Convergent validity indicates that the correlation between NHB scores and CEA-based incremental cost-effectiveness ratios (ICERs) was low (-0.215). Ranking of ICERs, ASCO scores, and wholesale acquisition costs indicated different results between frameworks. IMPLICATIONS: The ASCO Value Framework requires further specificity before use in a clinical setting, since it currently results in low inter-rater reliability and validity. Furthermore, ASCO scores were unable to discriminate between drugs providing the most and least value. RECOMMENDATIONS: The evaluation provides specific areas of weakness that can be addressed in future updates of the ASCO framework to improve usability. Meanwhile, the UCSF Medical Center should rely on CEAs, which are highly accessible for the highlighted cancer drugs. The MOC role can include summarizing and disseminating available CEA studies for interpretation by clinicians and financial counselors around drug value. DISCLOSURES: Funding for this research was contributed by the University of California, San Francisco, Medical Center Campus Strategic Initiative Program. The authors have no conflicts of interest to disclose. Study concept and design were contributed primarily by Wilson, along with Wang and Patel. Kim, Dacey, and Yuen collected the data, and data interpretation was performed by Wilson and Lin. The manuscript was written by Wilson, Lin, Wang, and Tran and revised by Lin, Redondi, Brodowy, and Kroon.

Drugs to treat obesity: do they work?

Obesity is a disease that has historically eluded effective medical therapy. Prior to 2012, phentermine and orlistat were the only medications available to treat obesity in the USA, with phentermine approved only for short-term use. However, as of 2015, the repertoire of pharmacological agents available to treat obesity has greatly expanded to include four new drugs: lorcaserin, phentermine/topiramate extended release (ER), naltrexone ER/wellbutrin ER and liraglutide. Each has a unique mechanism of action and all are intended for long-term use. These newer medications share a common strategy to promote weight loss in that they are designed to manipulate the control of hunger and satiety in the central nervous system. Interestingly, the majority of these new agents are combinations of older medications that have been used for conditions other than obesity. The amount of weight loss seen with these agents beyond placebo varies but generally falls in the range of 3-10% of starting weight and requires continual use of the drug in order for weight loss to be sustained. In addition, each drug has a unique side effect profile that should be carefully considered when selecting the best agent for a given individual. This article provides a review of these recently approved medications focusing on efficacy, side effect profiles and appropriate application to the individual patient.

Reporting of quality measures in gynecologic oncology programs at Prospective Payment System (PPS)-Exempt Cancer Hospitals: an early glimpse into a challenging initiative.

OBJECTIVE: The Affordable Care Act mandates the Prospective Payment System (PPS)-Exempt Cancer Hospitals Quality Reporting program. These 11 hospitals (which are paid fee-for-service rather than on a DRG system) began reporting measures (2 general safety, 2 breast, 1 colon) in 2013. Given this reporting mandate, we set out to determine whether the PPS-exempt gynecologic oncology programs could identify quality measures specific to the care of our patients. METHODS: A list of 12 quality measures specific to gynecologic oncology was created (from sources including the National Quality Forum and the SGO). Measures already in use were not included. The list was ranked by the gynecologic oncology program directors at the PPS-exempt hospitals. Descriptive statistics (including mean and SD for rankings) were utilized. RESULTS: Despite mandatory reporting of quality measures for PPS-exempt cancer hospitals, little consensus exists regarding specific gynecologic cancer measures. Documentation of debulking status, cancer survival, and offering minimally invasive surgery (for endometrial cancer) and intraperitoneal chemotherapy (for ovarian cancer) are important, but with widely variable responses (when ranked 1-12, standard deviations are 2-3). General issues regarding adherence to guidelines for the use of GCSF, documentation of functional status, and tracking of patient satisfaction scores were ranked the lowest. Three of the directors reported that their compensation is partially linked to quality outcomes. CONCLUSIONS: There is wide variability in ranking of quality measures, and may relate to provider or institutional factors. Despite the mandatory reporting in PPS-exempt cancer hospitals, work remains to define gynecologic cancer quality measures.

Evaluation of patient-reported quality-of-life outcomes after renal surgery.

OBJECTIVE: To assess the feasibility of 2 patient-reported health-related quality of life (HRQOL) instruments, Convalescence and Recovery Evaluation (CARE), and SF-12, as tools for evaluating HRQOL outcome consequences after renal surgery, and to determine which domains of these HRQOL instruments are most sensitive to HRQOL outcome effects of renal surgery. METHODS: Patients completed CARE and SF-12 preoperatively (baseline) and at 2, 4, 12, and 24 weeks after surgery. Clinical data, patient response rate, HRQOL changes over time, and likelihood of patient return to baseline HRQOL were evaluated. RESULTS: Seventy-one patients were enrolled. Sixty patients completed the baseline and at least 1 follow-up set of questionnaires. The CARE pain, gastrointestinal (GI), and activity domain scores and the SF-12 physical composite score (PCS) were sensitive to changes in HRQOL (all P<.05), whereas other domain subscores of these instruments did not change from presurgical baseline to postsurgical follow-up. Postsurgical HRQOL effects detected by the CARE pain, GI, and activity domains, and SF-12 PCS were most evident at 2 weeks (all P<.001). The CARE composite score demonstrated that 74% and 50% of patients returned to within 90% of baseline 4 weeks after radical and partial nephrectomy, respectively. CONCLUSION: Evaluation of patient-reported HRQOL outcomes after renal surgery is feasible; our findings suggest that the activity, pain, and GI domains of CARE and PCS subscores of the SF-12 are sensitive measures of HRQOL outcome consequences of renal surgery and represent appropriate measures of either care quality or comparative effectiveness analyses of robotic, laparoscopic, and open renal surgery.

Assessment of general anaesthetic cytotoxicity in murine cortical neurones in dissociated culture.

General anaesthetics are proposed to cause unconsciousness by modulating neuronal excitability in the mammalian brain through mechanisms that include enhancement of inhibitory GABA(A) receptor currents and suppression of excitatory glutamate receptor responses. Both intravenous and volatile agents may produce neurotoxic effects during early postnatal rodent brain development through similar mechanisms. In the following study, we investigated anaesthetic cytotoxicity in primary cortical neurones and glia from postnatal day 2-8 mice. Cultures at 4-20 days in vitro were exposed to combinations of ketamine (100 µM to 3 mM), nitrous oxide (75%, v/v) and/or isoflurane (1.5-5%, v/v) for 6-12 h. Neuronal survival and cell death were measured via microtubule associated protein 2 immunoassay and lactate dehydrogenase release assays, respectively. Clinically relevant anaesthetic concentrations of ketamine, nitrous oxide and isoflurane had no significant neurotoxic effects individually or when given as anaesthetic cocktails, even with up to 12 h exposure. This lack of neurotoxicity was observed regardless of whether cultures were prepared from postnatal day 0-2 or day 8 mice, and was also unaffected by number of days in vitro (DIV 4-20). Significant neurotoxic effects were only observed at supraclinical concentrations (e.g. 1-3 mM ketamine). Our study suggests that neurotoxicity previously reported in vivo is not due to direct cytotoxicity of anaesthetic agents, but results from other impacts of the anaesthetised state during early brain development.

Invitro application of gold nanoprobes in live neurons for phenotypical classification, connectivity assessment, and electrophysiological recording.

Thermoregulatory neurons in the preoptic area of the anterior hypothalamus (POA) form synaptic networks, which affect responses that regulate body temperature. To characterize these pathways of activation, projections to effector control areas, like the dorsomedial hypothalamus (DMH), require labeling in live tissue slices. Traditional fluorescent dyes label axon terminals near an injection site, but unfortunately, also that of nearby fibers of passage. Here, we describe a novel methodology for retrograde labeling of neurons in vitro, which will allow for further electrophysiological recording. To determine if POA neurons project to the DMH, we have used nanometer-sized, gold nanoprobes, which provide for specific neuronal entry, via synapses in close proximity to the injection site. Upon neuronal entry, these nanoprobe complexes diffuse to the soma, where they are readily visualized and quantified. We found that conjugation of these gold nanoprobes with VGLUT-2 antibodies and polyethyleneimine (PEI) facilitates neuronal entry and a high level of labeling efficacy. This novel method, adapted from emerging cancer therapy technologies, is highly specific for determining axon terminal projections within particular neuronal populations, while maintaining neuronal viability for targeted live cell electrophysiological recording.