Preventing metastatic recurrence in low-risk ER/PR + breast cancer patients-a retrospective clinical study exploring the evolving challenge of persistence with adjuvant endocrine therapy.

PURPOSE: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed. METHODS: Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. RESULTS: We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p < 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028). CONCLUSION: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Applying the Peter Parker Principle to Healthcare.

The role of power in healthcare can raise many ethical challenges. Power is ownership, whether given, ceded, or taken of another person's autonomy. When a person has power over someone else, they can control or strongly influence the decision-making freedom of that person. From the principalist perspective1,2 of healthcare ethics, denying a person their freedom to choose should only occur when justifying conditions related to beneficence and nonmaleficence are sufficiently satisfied. In healthcare, it is rare to be able to identify situations where paternalism is justified. However, experience suggests that abusive power in healthcare is used too frequently without justifying criteria.

Decreasing patient length of stay via new flexible exam room allocation policies in ambulatory care clinics.

To address prolonged lengths of stay (LOS) in ambulatory care clinics, we analyze the impact of implementing flexible and dynamic policies for assigning exam rooms to providers. In contrast to the traditional approaches of assigning specific rooms to each provider or pooling rooms among all practitioners, we characterize the impact of alternate compromise policies that have not been explored in previous studies. Since ambulatory care patients may encounter multiple different providers in a single visit, room allocation can be determined separately for each encounter accordingly. For the first phase of the visit, conducted by the medical assistant, we define a dynamic room allocation policy that adjusts room assignments based on the current state of the clinic. For the second phase of the visit, conducted by physicians, we define a series of room sharing policies which vary based on two dimensions, the number of shared rooms and the number of physicians sharing each room. Using a discrete event simulation model of an outpatient cardiovascular clinic, we analyze the benefits and costs associated with the proposed room allocation policies. Our findings show that it is not necessary to fully share rooms among providers in order to reduce patient LOS and physician idle time. Instead, most of the benefit of pooling can be achieved by implementation of a compromise room allocation approach, limiting the need for significant organizational changes within the clinic. Also, in order to achieve most of the benefits of room allocation policies, it is necessary to increase flexibility in the two dimensions simultaneously. These findings are shown to be consistent in settings with alternate patient scheduling and distinctions between physicians.

Implementation of a Workflow Initiative for Integrating Transitional Care Management Codes in a Geriatric Primary Care Practice.

We implemented a transitional care management service led by a nurse care manager. An interdisciplinary team developed a workflow using a Plan-Do-Study-Act cycle for contacting patients. Of the 146 (97.9%) eligible patients, 143 (97.9%) had a phone call within 48 hours. There were 84 of 120 (70.0%) and 117 of 120 (97.5%) attendance rates of those attending visits within 7 and 14 days. A care manager-led workflow was successfully and easily implemented within a primary care practice.

Telemedicine and primary care obesity management in rural areas - innovative approach for older adults?

BACKGROUND: The growing prevalence of obesity is paralleling a rise in the older adult population creating an increased risk of functional impairment, nursing home placement and early mortality. The Centers for Medicare and Medicaid recognized the importance of treating obesity and instituted a benefit in primary care settings to encourage intensive behavioral therapy in beneficiaries by primary care clinicians. This benefit covers frequent, brief, clinic visits designed to address older adult obesity. DISCUSSION: We describe the challenges in the implementation and delivery into real-world settings. The challenges in rural settings that have the fastest growing elderly population, high obesity rates, but also workforce shortages and lack of specialized services are emphasized. The use of Telemedicine has successfully been implemented in other specialties and could be a useful modality in delivering much needed intensive behavioral therapy, particularly in distant, under-resourced environments. This review outlines some of the challenges with the current benefit and proposed solutions in overcoming rural primary care barriers to implementation, including changes in staffing models. CONCLUSIONS: Recommendations to extend the benefit's coverage to be more inclusive of non-physician team members is needed but also for improvement in reimbursement for telemedicine services for older adults with obesity.

Simulation as an ethical imperative and epistemic responsibility for the implementation of medical guidelines in health care.

Guidelines orient best practices in medicine, yet, in health care, many real world constraints limit their optimal realization. Since guideline implementation problems are not systematically anticipated, they will be discovered only post facto, in a learning curve period, while the already implemented guideline is tweaked, debugged and adapted. This learning process comes with costs to human health and quality of life. Despite such predictable hazard, the study and modeling of medical guideline implementation is still seldom pursued. In this article we argue that to systematically identify, predict and prevent medical guideline implementation errors is both an epistemic responsibility and an ethical imperative in health care, in order to properly provide beneficence, minimize or avoid harm, show respect for persons, and administer justice. Furthermore, we suggest that implementation knowledge is best achieved technically by providing simulation modeling studies to anticipate the realization of medical guidelines, in multiple contexts, with system and scenario analysis, in its alignment with the emerging field of implementation science and in recognition of learning health systems. It follows from both claims that it is an ethical imperative and an epistemic responsibility to simulate medical guidelines in context to minimize (avoidable) harm in health care, before guideline implementation.

Murine Gammaherpesvirus 68 LANA and SOX Homologs Counteract ATM-Driven p53 Activity during Lytic Viral Replication.

UNLABELLED: Tumor suppressor p53 is activated in response to numerous cellular stresses, including viral infection. However, whether murine gammaherpesvirus 68 (MHV68) provokes p53 during the lytic replication cycle has not been extensively evaluated. Here, we demonstrate that MHV68 lytic infection induces p53 phosphorylation and stabilization in a manner that is dependent on the DNA damage response (DDR) kinase ataxia telangiectasia mutated (ATM). The induction of p53 during MHV68 infection occurred in multiple cell types, including splenocytes of infected mice. ATM and p53 activation required early viral gene expression but occurred independently of viral DNA replication. At early time points during infection, p53-responsive cellular genes were induced, coinciding with p53 stabilization and phosphorylation. However, p53-related gene expression subsided as infection progressed, even though p53 remained stable and phosphorylated. Infected cells also failed to initiate p53-dependent gene expression and undergo apoptosis in response to treatment with exogenous p53 agonists. The inhibition of p53 responses during infection required the expression of the MHV68 homologs of the shutoff and exonuclease protein (muSOX) and latency-associated nuclear antigen (mLANA). Interestingly, mLANA, but not muSOX, was necessary to prevent p53-mediated death in MHV68-infected cells under the conditions tested. This suggests that muSOX and mLANA are differentially required for inhibiting p53 in specific settings. These data reveal that DDR responses triggered by MHV68 infection promote p53 activation. However, MHV68 encodes at least two proteins capable of limiting the potential consequences of p53 function. IMPORTANCE: Gammaherpesviruses are oncogenic herpesviruses that establish lifelong chronic infections. Defining how gammaherpesviruses overcome host responses to infection is important for understanding how these viruses infect and cause disease. Here, we establish that murine gammaherpesvirus 68 induces the activation of tumor suppressor p53. p53 activation was dependent on the DNA damage response kinase ataxia telangiectasia mutated. Although active early after infection, p53 became dominantly inhibited as the infection cycle progressed. Viral inhibition of p53 was mediated by the murine gammaherpesvirus 68 homologs of muSOX and mLANA. The inhibition of the p53 pathway enabled infected cells to evade p53-mediated cell death responses. These data demonstrate that a gammaherpesvirus encodes multiple proteins to limit p53-mediated responses to productive viral infection, which likely benefits acute viral replication and the establishment of chronic infection.

Phosphoproteomic analyses reveal signaling pathways that facilitate lytic gammaherpesvirus replication.

Lytic gammaherpesvirus (GHV) replication facilitates the establishment of lifelong latent infection, which places the infected host at risk for numerous cancers. As obligate intracellular parasites, GHVs must control and usurp cellular signaling pathways in order to successfully replicate, disseminate to stable latency reservoirs in the host, and prevent immune-mediated clearance. To facilitate a systems-level understanding of phosphorylation-dependent signaling events directed by GHVs during lytic replication, we utilized label-free quantitative mass spectrometry to interrogate the lytic replication cycle of murine gammaherpesvirus-68 (MHV68). Compared to controls, MHV68 infection regulated by 2-fold or greater ca. 86% of identified phosphopeptides - a regulatory scale not previously observed in phosphoproteomic evaluations of discrete signal-inducing stimuli. Network analyses demonstrated that the infection-associated induction or repression of specific cellular proteins globally altered the flow of information through the host phosphoprotein network, yielding major changes to functional protein clusters and ontologically associated proteins. A series of orthogonal bioinformatics analyses revealed that MAPK and CDK-related signaling events were overrepresented in the infection-associated phosphoproteome and identified 155 host proteins, such as the transcription factor c-Jun, as putative downstream targets. Importantly, functional tests of bioinformatics-based predictions confirmed ERK1/2 and CDK1/2 as kinases that facilitate MHV68 replication and also demonstrated the importance of c-Jun. Finally, a transposon-mutant virus screen identified the MHV68 cyclin D ortholog as a viral protein that contributes to the prominent MAPK/CDK signature of the infection-associated phosphoproteome. Together, these analyses enhance an understanding of how GHVs reorganize and usurp intracellular signaling networks to facilitate infection and replication.

Patient-clinician concordance, face-time and access.

PURPOSE: People in socially disadvantageous positions may receive less time with their clinicians and consequently reduced access to healthcare resources, potentially magnifying health disparities. Socio-cultural characteristics of clinicians and patients may influence the time spent together. The purpose of this paper is to explore the relationship between clinician/patient time and clinician and patient characteristics using real-time location systems (RTLS). DESIGN/METHODOLOGY/APPROACH: In the MGH/MGPO Outpatient RFID (radio-frequency identification) project clinicians and patients wore RTLS tags during the workday to measure face-time (FT), the duration patients and clinicians are co-located, wait time (WT); i.e. from registration to clinical encounter and flow time (FLT) from registration to discharge. Demographic data were derived from the health system's electronic medical record (EMR). The RTLS and EMR data were synthesized and analyzed using standard structured-query language and statistical analytic methods. FINDINGS: From January 1, 2009 to January 1, 2011, 1,593 clinical encounters were associated with RTLS measured FTs, which differed with socioeconomic status and gender: women and lower income people received greater FT. WT was significantly longer for lower socioeconomic patients and for patients seeing trainee clinicians, women or majority ethnic group clinicians (Caucasian). FLT was shortest for men, higher socioeconomic status and for attending physician patients. Demographic concordance between patient and clinician did not significantly affect process times. RESEARCH LIMITATIONS/IMPLICATIONS: The study demonstrates the feasibility of using RTLS to capture clinically relevant process measures and suggests that the clinical delivery system surrounding a clinical encounter may more significantly influence access to clinician time than individual patient and clinician characteristics. ORIGINALITY/VALUE: Applying RTLS to healthcare is coming. We can now successfully install and run these systems in healthcare settings and extract useful information from them. Interactions with the clinical delivery system are at least as important as interactions with clinicians for providing access to care: measure FT, WT and FLT with RTLS; link clinical behavior, e.g. FT, with patient characteristics; explore how individual characteristics interact with system behavior.

Amplification of JNK signaling is necessary to complete the murine gammaherpesvirus 68 lytic replication cycle.

Several studies have previously defined host-derived signaling events capable of driving lytic gammaherpesvirus replication or enhancing immediate-early viral gene expression. Yet signaling pathways that regulate later stages of the productive gammaherpesvirus replication cycle are still poorly defined. In this study, we utilized a mass spectrometric approach to identify c-Jun as an abundant cellular phosphoprotein present in late stages of lytic murine gammaherpesvirus 68 (MHV68) infection. Kinetically, c-Jun phosphorylation was enhanced as infection progressed, and this correlated with enhanced phosphorylation of the c-Jun amino-terminal kinases JNK1 and JNK2 and activation of AP-1 transcription. These events were dependent on progression beyond viral immediate-early gene expression, but not dependent on viral DNA replication. Both pharmacologic and dominant-negative blockade of JNK1/2 activity inhibited viral replication, and this correlated with inhibition of viral DNA synthesis and reduced viral gene expression. These data suggest a model in which MHV68 by necessity amplifies and usurps JNK/c-Jun signaling as infection progresses in order to facilitate late stages of the MHV68 lytic infection cycle.

Nitrous oxide and methane emissions from a Ferralsol as affected by loblolly pine cultivation time in subtropical Brazil.

We hypothesized that the age of loblolly pine stands influences soil methane (CH4) and nitrous oxide (N2O) emissions. This is a relevant topic to be studied in subtropical Brazil, where the pine plantation area is increasing considerably. We evaluated N2O and CH4 emissions for two years in a Ferralsol under loblolly pine (Pinus taeda L.) stands of 1, 9 and 18 year-olds and a native forest (NF). We calculated the net CO2eq emission by considering the N2O and CH4 emissions from soil and the carbon (C) accumulation as litter in the forest floor. The soil N2O emission reduced gradually over the loblolly pine cultivation years, whereas CH4 uptake rates showed no clear pattern. Soil N2O emission showed a positive relationship with soil temperature in NF, and with soil ammonium and nitrate intensities in the pine stands. Soil CH4 uptake was inversely related to water-filled pore space in the pine stands, but this relationship was not observed in NF. The soil CH4 uptake rate was 4.6 times higher (p < 0.10) in NF than the average uptake in loblolly pine stands. On the other hand, soil N2O emissions in 9 and 18-year-old stands were similar (p > 0.10) to those in NF (1.3 kg N ha-1 yr-1). Our results suggest that cultivation with loblolly pine for 18 years can reduce soil N2O emission, and the uptake of CH4 in this system offsets 17 % of N2O emissions. Furthermore, the C accumulation as litter in the forest floor of the mature pine stands (9- and 18-year-old) generated a net emission of -1.6 Mg CO2eq ha-1 yr-1, showing to be an expressive offsetting mechanism. Therefore, we conclude that aged loblolly forests can reach N2O emissions levels comparable to those of NF, and the C sequestration in these forests floor can significantly contribute to offset N2O emissions and act as sink for net atmospheric CO2eq.

Modeling using discrete event simulation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force--4.

Discrete event simulation (DES) is a form of computer-based modeling that provides an intuitive and flexible approach to representing complex systems. It has been used in a wide range of health care applications. Most early applications involved analyses of systems with constrained resources, where the general aim was to improve the organization of delivered services. More recently, DES has increasingly been applied to evaluate specific technologies in the context of health technology assessment. The aim of this article was to provide consensus-based guidelines on the application of DES in a health care setting, covering the range of issues to which DES can be applied. The article works through the different stages of the modeling process: structural development, parameter estimation, model implementation, model analysis, and representation and reporting. For each stage, a brief description is provided, followed by consideration of issues that are of particular relevance to the application of DES in a health care setting. Each section contains a number of best practice recommendations that were iterated among the authors, as well as among the wider modeling task force.

IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses. METHODS: Eosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation. RESULTS: Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation. CONCLUSIONS: This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.

SMART-ly Managing Type 1 Diabetes - Modifying Glucose Metabolism With an Online Mind-Body Intervention: A Feasibility and Pilot Study.

Objective: Managing type 1 diabetes is stressful. Stress physiology influences glucose metabolism. Continuous glucose monitors allow us to track glucose variability in the real-world environment. Managing stress and cultivating resiliency should improve diabetes management and reduce glucose variability. Research Design and Methods: The study was designed as a randomized prospective cohort pre-post study with wait time control. Participants were adult type 1 diabetes patients who used a continuous glucose monitor and recruited from an academic endocrinology practice. The intervention was the Stress Management and Resiliency Training (SMART) program conducted over 8 sessions over web-based video conference software. The main outcome measures were Glucose variability, the Diabetes Self-Management questionnaire (DSMQ),Short-Form Six-Dimension (SF-6D), and the Connor-Davidson Resiliency (CD-RSIC) instrument. Results: There was statistically significant improvement in participants DSMQ and CD RISC scores though the SF-6D did not change. Participants under age 50 years-old showed a statistically significant reduction in average glucose (p = .03) and Glucose Management Index (GMI) (p = .02). Participants also had reduced percentage of time high and increased time in range though this did not reach statistical significance. The participants found doing the intervention online acceptable if not always ideal. Conclusions: An 8-session stress management and resiliency training program reduced diabetes related stress and improved resiliency and reduced average blood glucose and GMI in those under 50 years-old. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04944264.

Chemotherapy-related hospitalization among community cancer center patients.

PURPOSE: To describe the frequency, nature, trends, predictors, and outcomes of chemotherapy-related hospitalizations (CRHs) among a nonselected population of cancer patients treated at a community cancer center, and to explore the feasibility of implementing continuous quality improvement methodologies in routine oncology practice. METHODS: We conducted a prospective cohort study of consecutive adult cancer patients who received chemotherapy at a community cancer center January 2003 to December 2006. Demographic, comorbidity, diagnosis, treatment, and laboratory data were collected via medical record abstraction. Hospitalizations were classified as chemotherapy related or unrelated by a multidisciplinary panel. Patients who experienced CRHs were compared with those who did not. Using a randomly sampled subset of cases and controls, we built a logistic regression model to identify independent predictors of CRH. RESULTS: Of 2,068 chemotherapy recipients, 179 (8.7%) experienced 262 CRHs. Most hospitalizations were not chemotherapy related (73.7%). The mean monthly rate of CRH was 1.5%, the median length of stay was 5 days, the most common type of CRH was gastrointestinal (46.1%) followed by infectious (31.4%), and 0.9% of chemotherapy recipients had a fatal CRH. Significant predictors of CRH included having a comorbidity score of 3-4 versus 0 and having a higher creatinine level. CONCLUSIONS: Although the vast majority of chemotherapy recipients did not experience a CRH, these events were, unfortunately, not without serious consequences. Care should be taken when offering chemotherapy to patients with multiple comorbid conditions. Systematic efforts to monitor toxicity can lead directly to improvements in quality of care.

Informing the Management of Asymptomatic Nephrolithiasis: Markov Decision Analysis for the 1 cm Renal Stone.

INTRODUCTION: The management of an incidentally discovered, asymptomatic renal stone includes watchful waiting, shock wave lithotripsy, ureteroscopy with basket extraction of fragmented stones (URS-B) or ureteroscopy with laser "dusting" (URS-D). Each intervention has varying stone-free rates, requirements for ureteral stenting, and variable impact on a patient's quality of life. Decision analysis was used to assess the optimal quality adjusted life-years associated with each treatment option. METHODS: A Markov model was constructed to represent potential outcomes for a single 1 cm renal stone after treatment. The cohort was followed for 1-month cycles over 3 years and toll penalties for receiving a stent and undergoing surgery were standardized and incorporated into each subtree. Probabilities, utilities and toll penalties were derived from existing literature or clinical extrapolation when no published data were available. One-way sensitivity analyses were performed to determine threshold probabilities/utilities that may alter preferred options. RESULTS: Watchful waiting was the preferred intervention, preserving 2.82 quality adjusted life-years over 3 years. The remaining options had similar but decreasing quality adjusted life-years: URS-B provided 2.78 quality adjusted life-years; shock wave lithotripsy provided 2.72 quality adjusted life-years, and URS-D provided 2.67 quality adjusted life-years. One-way sensitivity analysis showed that URS-D was preferred when stone-free rates from URS-B dropped below 37%. Shock wave lithotripsy was preferred over URS-B when stone-free rates from URS-B dropped below 62%. As stents became progressively less bothersome, watchful waiting is preferred, followed by URS-B, shock wave lithotripsy and URS-D. CONCLUSIONS: Watchful waiting is the preferred management decision for asymptomatic renal stones. However, these results are sensitive to both actual stone-free rate and individual stent tolerance.

A global point prevalence survey of antimicrobial use in neonatal intensive care units: The no-more-antibiotics and resistance (NO-MAS-R) study.

BACKGROUND: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts. METHODS: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality. FINDINGS: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received ≥1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0·02). INTERPRETATION: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide. FUNDING: Merck & Co.; The Ohio State University College of Medicine Barnes Medical Student Research Scholarship.

Improving clinical access and continuity through physician panel redesign.

BACKGROUND: Population growth, an aging population and the increasing prevalence of chronic disease are projected to increase demand for primary care services in the United States. OBJECTIVE: Using systems engineering methods, to re-design physician patient panels targeting optimal access and continuity of care. DESIGN: We use computer simulation methods to design physician panels and model a practice's appointment system and capacity to provide clinical service. Baseline data were derived from a primary care group practice of 39 physicians with over 20,000 patients at the Mayo Clinic in Rochester, MN, for the years 2004-2006. Panel design specifically took into account panel size and case mix (based on age and gender). MEASURES: The primary outcome measures were patient waiting time and patient/clinician continuity. Continuity is defined as the inverse of the proportion of times patients are redirected to see a provider other than their primary care physician (PCP). RESULTS: The optimized panel design decreases waiting time by 44% and increases continuity by 40% over baseline. The new panel design provides shorter waiting time and higher continuity over a wide range of practice panel sizes. CONCLUSIONS: Redesigning primary care physician panels can improve access to and continuity of care for patients.

Initial development of the Temporary Utilities Index: a multiattribute system for classifying the functional health impact of diagnostic testing.

PURPOSE: The effects of testing and screening on quality of life may influence the future behavior of society, but have not been quantified. We derived a health classification and survey items for the morbidities of testing and screening, to be the foundation of a multiattribute utility instrument, the Temporary Utilities Index. METHODS: Seventy-six women ranked the importance of attributes of the testing process after breast biopsy. Seven survey items on the testing process were subsequently developed and assessed for clarity by a second group of 19 patients. The items cover attributes of mental and physical well-being before, during, and after testing. A survey panel of 164 subjects accessed online used the items to endorse expected and experienced effects of colon screening and mammography. They also endorsed items from a colorectal benefits and barriers scale, a risk perception scale, and EQ-5D, to utilize in the analyses of validity of the TUI items. RESULTS: Based on criteria from the literature and limited psychometric analysis, the items showed evidence of practicality, validity, and a strong association with barriers. CONCLUSIONS: The TUI health classification and survey items show evidence of validity, and may inform economic analysis, once combined with utility weights.

Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis.

CONTEXT: In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. OBJECTIVE: To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. DESIGN AND SETTING: Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. PATIENTS: Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). MAIN OUTCOME MEASURE: Quality-adjusted life expectancy (QALE). RESULTS: Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. CONCLUSIONS: Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.