Going Beyond Clinical Care to Reduce Health Care Spending: Findings From the J-CHiP Community-based Population Health Management Program Evaluation.

BACKGROUND: Addressing both clinical and nonclinical determinants of health is essential for improving population health outcomes. In 2012, the Johns Hopkins Community Health Partnership (J-CHiP) implemented innovative population health management programs across acute and community environments. The community-based program involved multidisciplinary teams [ie, physicians, care managers (CM), health behavior specialists (HBS), community health workers, neighborhood navigators] and collaboration with community-based organizations to address social determinants. OBJECTIVES: To report the impact of a community-based program on cost and utilization from 2011 to 2016. DESIGN: Difference-in-difference estimates were calculated for an inclusive cohort of J-CHiP participants and matched nonparticipants. The analysis was replicated for participants with a CM and/or HBS to estimate the differential impact with more intensive program services. SUBJECTS: A total of 3268 high-risk Medicaid and Medicare beneficiaries (1634 total J-CHiP participants, 1365 with CM and 678 with HBS). OUTCOME MEASURES: Paid costs and counts of emergency department visits, admissions, and readmissions per member per year. RESULTS: For Medicaid, costs were almost $1200 per member per year lower for participants as a whole, $2000 lower for those with an HBS, and $3000 lower for those with a CM; hospital admission and readmission rates were 9%-26% lower for those with a CM and/or HBS. For Medicare, costs were lower (-$476), but utilization was similar or higher than nonparticipants. None of the observed Medicaid or Medicare differences were statistically significant. CONCLUSIONS: Although not statistically significant, the results indicate a promising innovation for Medicaid beneficiaries. For Medicare, the impact was negligible, indicating the need for further program modification.

Applying JIT principles to resident education to reduce patient delays: a pilot study in an academic medical center pain clinic.

OBJECTIVES: This study investigated the effect on patient waiting times, patient/doctor contact times, flow times, and session completion times of having medical trainees and attending physicians review cases before the clinic session. The major hypothesis was that review of cases prior to clinic hours would reduce waiting times, flow times, and use of overtime, without reducing patient/doctor contact time. DESIGN: Prospective quality improvement. SETTING: Specialty pain clinic within Johns Hopkins Outpatient Center, Baltimore, MD, United States. PARTICIPANTS: Two attending physicians participated in the intervention. Processing times for 504 patient visits are involved over a total of 4 months. INTERVENTION: Trainees were assigned to cases the day before the patient visit. Trainees reviewed each case and discussed it with attending physicians before each clinic session. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary measures were activity times before and after the intervention. These were compared and also used as inputs to a discrete event simulation to eliminate differences in the arrival process as a confounding factor. RESULTS: The average time that attending physicians spent teaching trainees while the patient waited was reduced, but patient/doctor contact time was not significantly affected. These changes reduced patient waiting times, flow times, and clinic session times. CONCLUSIONS: Moving some educational activities ahead of clinic time improves patient flows through the clinic and decreases congestion without reducing the times that trainees or patients interact with physicians.

Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.

OBJECTIVES: Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy. METHODS: In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16. RESULTS: At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed. CONCLUSIONS: Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: NCT01172938.

Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus.

OBJECTIVE: To assess the effects of the B lymphocyte stimulator (BLyS)-specific inhibitor belimumab on immunologic biomarkers, including B cell and T cell populations, and maintenance of antibody titers to prior vaccines in autoantibody-positive systemic lupus erythematosus (SLE) patients. METHODS: Pooled data from 2 phase III trials, the Study of Belimumab in Subjects with SLE 52-week (BLISS-52) and 76-week (BLISS-76) trials, comparing belimumab 1 mg/kg or 10 mg/kg versus placebo (plus standard SLE therapy for each group) were analyzed for changes in autoantibody, immunoglobulin, and complement levels. BLISS-76 patients were also analyzed for changes in B cell and T cell populations and effects on prior vaccine-induced antibody levels. RESULTS: Belimumab-treated patients experienced significant sustained reductions in IgG and autoantibodies and improvement in C3/C4 levels, resulting in greater positive-to-negative conversion rates for IgG anti-double-stranded DNA (anti-dsDNA), anti-Sm, anticardiolipin, and anti-ribosomal P autoantibodies and normalization of hypergammaglobulinemia and low C3/C4 levels. Belimumab-treated patients experienced significant decreases in the numbers of naive and activated B cells, as well as plasma cells, whereas memory B cells and T cell populations did not decrease. Belimumab did not substantially affect preexisting antipneumococcal or anti-tetanus toxoid antibody levels. Post hoc analysis showed greater reductions in SLE disease activity and the risk of severe flares in patients treated with belimumab 10 mg/kg (P≤0.01) who were anti-dsDNA positive and had low C3/C4 levels at baseline. Normalization of the C3 or anti-dsDNA level by 8 weeks, irrespective of therapy, was predictive of a reduced risk of severe flare over 52 weeks. CONCLUSION: Belimumab appears to promote normalization of serologic activity and reduce BLyS-dependent B cell subsets in serologically and clinically active SLE. Greater serologic activity may predict a better treatment response to belimumab.

Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials.

OBJECTIVE: To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity. METHODS: Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores. RESULTS: At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains. CONCLUSIONS: Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.

Using process analysis to assess the impact of medical education on the delivery of pain services: a natural experiment.

BACKGROUND: The medical, social, and economic effects of the teaching mission on delivery of care at an academic medical center (AMC) are not fully understood. When a free-standing private practice ambulatory clinic with no teaching mission was merged into an AMC, a natural experiment was created. The authors compared process measures across the two settings to observe the differences in system performance introduced by the added steps and resources of the AMC's teaching mission. METHODS: After creating process maps based on activity times realized in both settings, the authors developed discrete-event simulations of the two environments. The two settings were comparable in the levels of key resources, but the AMC process flow included three residents/fellows. Simulation enabled the authors to consider an identical schedule across the two settings. RESULTS: Under identical schedules, the average accumulated processing time per patient was higher in the AMC. However, the use of residents allowed simultaneous processing of multiple patients. Consequently, the AMC had higher throughput (3.5 vs. 2.7 patients per hour), higher room utilization (82.2% vs. 75.5%), reduced utilization of the attending physician (79.0% vs. 93.4%), and a shorter average waiting time (30.0 vs. 83.9 min). In addition, the average completion time for the final patient scheduled was 97.9 min less, and the average number of patients treated before incurring overtime was 37.9% greater. CONCLUSIONS: Although the teaching mission of the AMC adds processing steps and costs, the use of trainees within the process serves to increase throughput while decreasing waiting times and the use of overtime.

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus.

OBJECTIVE: To assess the efficacy/safety of the B lymphocyte stimulator inhibitor belimumab plus standard therapy compared with placebo plus standard therapy in active systemic lupus erythematosus (SLE). METHODS: In a phase III, multicenter, randomized, placebo-controlled trial, 819 antinuclear antibody-positive or anti-double-stranded DNA-positive SLE patients with scores ≥6 on the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) were randomized in a 1:1:1 ratio to receive 1 mg/kg belimumab, 10 mg/kg belimumab, or placebo intravenously on days 0, 14, and 28 and then every 28 days for 72 weeks. The primary efficacy end point was the SLE Responder Index (SRI) response rate at week 52 (an SRI response was defined as a ≥4-point reduction in SELENA-SLEDAI score, no new British Isles Lupus Assessment Group [BILAG] A organ domain score and no more than 1 new BILAG B score, and no worsening in physician's global assessment score versus baseline). RESULTS: Belimumab at 10 mg/kg plus standard therapy met the primary efficacy end point, generating a significantly greater SRI response at week 52 compared with placebo (43.2% versus 33.5%; P = 0.017). The rate with 1 mg/kg belimumab was 40.6% (P = 0.089). Response rates at week 76 were 32.4%, 39.1%, and 38.5% with placebo, 1 mg/kg belimumab, and 10 mg/kg belimumab, respectively. In post hoc sensitivity analyses evaluating higher SELENA-SLEDAI score thresholds, 10 mg/kg belimumab achieved better discrimination at weeks 52 and 76. Risk of severe flares over 76 weeks (based on the modified SLE Flare Index) was reduced with 1 mg/kg belimumab (34%) (P = 0.023) and 10 mg/kg belimumab (23%) (P = 0.13). Serious and severe adverse events, including infections, laboratory abnormalities, malignancies, and deaths, were comparable across groups. CONCLUSION: Belimumab plus standard therapy significantly improved SRI response rate, reduced SLE disease activity and severe flares, and was generally well tolerated in SLE.

Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study.

OBJECTIVE: To evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of iberdomide in patients with SLE. Iberdomide is a high-affinity cereblon ligand that targets the hematopoietic transcription factors Ikaros and Aiolos for proteasomal degradation. METHODS: A 12-week, multicentre, double-blind, placebo-controlled, dose-escalation study in active SLE was followed by a 2-year, open-label active treatment extension phase (ATEP) (NCT02185040). In the dose-escalation phase, adults with active SLE were randomised to oral placebo or iberdomide (0.3 mg every other day, 0.3 mg once daily, 0.6 mg and 0.3 mg alternating once daily, or 0.6 mg once daily). Primary endpoints were safety and tolerability. RESULTS: The dose-escalation phase enrolled 42 patients, with 33 completing this phase and 17 patients enrolling into the ATEP. In the dose-escalation phase, the most common treatment-emergent adverse events (TEAEs; iberdomide/placebo groups) were nausea (20.6%/12.5%), diarrhoea (17.6%/12.5%) and upper respiratory tract infection (11.8%/12.5%). Most TEAEs were mild or moderate in severity and more common in the highest dose groups in both study phases. In the dose-escalation phase, Physician's Global Assessment and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity scores improved relative to baseline and placebo in all iberdomide groups, with a trend toward continued score improvements in the ATEP. In the dose-escalation phase, iberdomide treatment resulted in dose-dependent reductions in total B cells and plasmacytoid dendritic cells in blood. Improvements in CLASI activity scores correlated with plasmacytoid dendritic cell depletion. CONCLUSIONS: These proof-of-concept findings suggest a favourable benefit/risk ratio in SLE for iberdomide, a drug with a novel immunomodulatory mechanism of action, supporting further clinical investigation.

Spebrutinib (CC-292) Affects Markers of B Cell Activation, Chemotaxis, and Osteoclasts in Patients with Rheumatoid Arthritis: Results from a Mechanistic Study.

INTRODUCTION: Spebrutinib (CC-292) is an orally administered, covalent, small-molecule inhibitor of Bruton's tyrosine kinase (BTK), part of the B-cell and Fc receptor signaling pathways. This study evaluated spebrutinib pharmacology and mechanism of action over a 4-week treatment period in patients with active rheumatoid arthritis (RA). METHODS: Primary human B cells, T cells, natural killer cells, macrophages, dendritic cells, basophils, and osteoclasts were treated with spebrutinib in vitro. Clinical pharmacodynamics were studied in 47 patients with active RA on background methotrexate therapy randomized to oral spebrutinib 375 mg/day or placebo. RESULTS: In vitro, spebrutinib inhibited B-cell proliferation more potently than T-cell proliferation and reduced both lymphoid and myeloid cytokine production and degranulation, as well as osteoclastogenesis. Clinical efficacy trended higher in spebrutinib-treated RA patients, with 41.7% (10/24) achieving ≥ 20% improvement in ACR response criteria (ACR20) versus 21.7% (5/23) of placebo patients at week 4 (P = 0.25). Treatment-emergent adverse events were comparable between treatment groups. In spebrutinib-treated patients, median BTK occupancy in peripheral blood was 83%, and significant increases in total CD19+ and mature-naive CD27-CD38-IgD+ B cells and decreases in transitional CD27-CD38+ B cells were observed. Spebrutinib significantly reduced serum chemokines chemokine ligand 13 (CXCL13), macrophage inflammatory protein-1ß (MIP-1ß), and the bone resorption biomarker carboxy-terminal collagen cross-linking telopeptide (CTX-I) (P < 0.05). Clinical response to spebrutinib was associated with lower increases in CD19+ B cells and greater decreases in CXCL13 and MIP-1ß from baseline to week 4. High CD19+ B cells and low CTX-I at baseline were associated with better spebrutinib clinical response. CONCLUSIONS: Spebrutinib inhibited various leukocyte responses in vitro, including those of B cells and osteoclasts. In this small study in RA patients, spebrutinib was well tolerated, showed a downward trend for symptoms, significantly modulated B-cell populations, and reduced markers of chemotaxis and osteoclast activity. TRIAL REGISTRATION: NCT01975610.

Key Design Considerations When Calculating Cost Savings for Population Health Management Programs in an Observational Setting.

OBJECTIVE: To illustrate the impact of key quasi-experimental design elements on cost savings measurement for population health management (PHM) programs. DATA SOURCES: Population health management program records and Medicaid claims and enrollment data from December 2011 through March 2016. STUDY DESIGN: The study uses a difference-in-difference design to compare changes in cost and utilization outcomes between program participants and propensity score-matched nonparticipants. Comparisons of measured savings are made based on (1) stable versus dynamic population enrollment and (2) all eligible versus enrolled-only participant definitions. Options for the operationalization of time are also discussed. DATA COLLECTION/EXTRACTION METHODS: Individual-level Medicaid administrative and claims data and PHM program records are used to match study groups on baseline risk factors and assess changes in costs and utilization. PRINCIPAL FINDINGS: Savings estimates are statistically similar but smaller in magnitude when eliminating variability based on duration of population enrollment and when evaluating program impact on the entire target population. Measurement in calendar time, when possible, simplifies interpretability. CONCLUSION: Program evaluation design elements, including population stability and participant definitions, can influence the estimated magnitude of program savings for the payer and should be considered carefully. Time specifications can also affect interpretability and usefulness.

Pomalidomide in Patients with Interstitial Lung Disease due to Systemic Sclerosis: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study.

OBJECTIVE: To evaluate the safety and efficacy of pomalidomide (POM) on forced vital capacity (FVC), modified Rodnan skin score (mRSS), and gastrointestinal (GI) symptomatology over 52 weeks of treatment in patients with interstitial lung disease due to systemic sclerosis (SSc). METHODS: Twenty-three adult patients diagnosed with SSc were randomized 1:1 POM:placebo (PBO). RESULTS: Mean change at Week 52 from baseline in predicted FVC% -5.2 and -2.8; mRSS -2.7 and -3.7; and UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (SCTC GIT 2.0) score 0.1 and 0.0, with POM and PBO, respectively. Statistical significance was not achieved for any of these 3 primary endpoints at 52 weeks. CONCLUSION: Because of recruitment challenges, subject enrollment was discontinued early. In an interim analysis, the study did not meet its Week 52 primary endpoints. Therefore, a decision was made to terminate all study phases. POM was generally well tolerated, with an adverse event profile consistent with the known safety and tolerability profile of POM in other diseases. Study results were neither positive nor negative because too few subjects were enrolled to make meaningful conclusions. Clinical Trials number: NCT01559129.

Association of a Care Coordination Model With Health Care Costs and Utilization: The Johns Hopkins Community Health Partnership (J-CHiP).

Importance: The Johns Hopkins Community Health Partnership was created to improve care coordination across the continuum in East Baltimore, Maryland. Objective: To determine whether the Johns Hopkins Community Health Partnership (J-CHiP) was associated with improved outcomes and lower spending. Design, Setting, and Participants: Nonrandomized acute care intervention (ACI) and community intervention (CI) Medicare and Medicaid participants were analyzed in a quality improvement study using difference-in-differences designs with propensity score-weighted and matched comparison groups. The study spanned 2012 to 2016 and took place in acute care hospitals, primary care clinics, skilled nursing facilities, and community-based organizations. The ACI analysis compared outcomes of participants in Medicare and Medicaid during their 90-day postacute episode with those of a propensity score-weighted preintervention group at Johns Hopkins Community Health Partnership hospitals and a concurrent comparison group drawn from similar Maryland hospitals. The CI analysis compared changes in outcomes of Medicare and Medicaid participants with those of a propensity score-matched comparison group of local residents. Interventions: The ACI bundle aimed to improve transition planning following discharge. The CI included enhanced care coordination and integrated behavioral support from local primary care sites in collaboration with community-based organizations. Main Outcomes and Measures: Utilization measures of hospital admissions, 30-day readmissions, and emergency department visits; quality of care measures of potentially avoidable hospitalizations, practitioner follow-up visits; and total cost of care (TCOC) for Medicare and Medicaid participants. Results: The CI group had 2154 Medicare beneficiaries (1320 [61.3%] female; mean age, 69.3 years) and 2532 Medicaid beneficiaries (1483 [67.3%] female; mean age, 55.1 years). For the CI group's Medicaid participants, aggregate TCOC reduction was $24.4 million, and reductions of hospitalizations, emergency department visits, 30-day readmissions, and avoidable hospitalizations were 33, 51, 36, and 7 per 1000 beneficiaries, respectively. The ACI group had 26 144 beneficiary-episodes for Medicare (13 726 [52.5%] female patients; mean patient age, 68.4 years) and 13 921 beneficiary-episodes for Medicaid (7392 [53.1%] female patients; mean patient age, 52.2 years). For the ACI group's Medicare participants, there was a significant reduction in aggregate TCOC of $29.2 million with increases in 90-day hospitalizations and 30-day readmissions of 11 and 14 per 1000 beneficiary-episodes, respectively, and reduction in practitioner follow-up visits of 41 and 29 per 1000 beneficiary-episodes for 7-day and 30-day visits, respectively. For the ACI group's Medicaid participants, there was a significant reduction in aggregate TCOC of $59.8 million and the 90-day emergency department visit rate decreased by 133 per 1000 episodes, but hospitalizations increased by 49 per 1000 episodes and practitioner follow-up visits decreased by 70 and 182 per 1000 episodes for 7-day and 30-day visits, respectively. In total, the CI and ACI were associated with $113.3 million in cost savings. Conclusions and Relevance: A care coordination model consisting of complementary bundled interventions in an urban academic environment was associated with lower spending and improved health outcomes.

Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

OBJECTIVE: To study the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, compared with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). METHODS: Patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. Patients whose swollen and tender joint counts had not improved by ≥20% were considered nonresponders at week 16 and were required to enter the protocol-defined early escape. At week 24, patients were transitioned in a blinded manner to receive apremilast 20 mg twice a day if they were initially randomized to receive placebo. Patients who were not initially randomized to receive placebo continued to receive their target apremilast dose. Patients were required to take a stable dose of MTX (7.5-25 mg/week) throughout the study. Magnetic resonance imaging (MRI) was performed in a subset of patients. RESULTS: A total of 237 patients who were receiving MTX therapy were randomized and received ≥1 dose of study medication. At week 16, similar proportions of patients receiving placebo (35%), apremilast 20 mg twice a day (28%), and apremilast 30 mg twice a day (34%) met the American College of Rheumatology criteria for 20% improvement in disease activity (the primary efficacy end point). In the MRI substudy, mean change from baseline in total joint damage scores according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system was generally similar with either apremilast dose at week 16. At week 52, no trends were noted for clinical end points by treatment group. Both apremilast doses were generally well tolerated. CONCLUSION: Apremilast efficacy was not demonstrated in patients who had active RA despite stable MTX therapy.

Is bigger always better? The optimal size of a group practice.

The past decade saw several attempts to consolidate physician practices, but this sector remains one of the last cottage industries in the United States. This article develops a framework for analyzing the optimal size of a physician practice. The framework addresses technological factors (e.g., economies of scale and scope), behavioral factors (e.g., changing physician goals, costs of organizing and operating a practice), and market-driven factors (e.g., managed care contracting). Existing empirical research suggests three "optimal" sizes of practices: 5-10 physicians, based on economies of scale and decision-making; 20-30 physicians, based on economies of scope and initial development of a corporate structure; and 80+ (multi-specialty) physicians, which can create an system of referrals and utilization. The article concludes with observations about the challenges to physician practices as they grow.

Effect of belimumab on vaccine antigen antibodies to influenza, pneumococcal, and tetanus vaccines in patients with systemic lupus erythematosus in the BLISS-76 trial.

OBJECTIVE: In patients with systemic lupus erythematosus (SLE), evidence suggests that most vaccines (except live-virus vaccines) are safe, although antibody response may be reduced. This substudy from the phase III, randomized, double-blind, placebo-controlled BLISS-76 trial evaluated the effects of belimumab on preexisting antibody levels against pneumococcal, tetanus, and influenza antigens in patients with SLE. METHODS: In BLISS-76, patients with autoantibody-positive, active SLE were treated with placebo or belimumab 1 or 10 mg/kg every 2 weeks for 28 days and every 28 days thereafter, plus standard SLE therapy, for 76 weeks. This analysis included a subset of patients who had received pneumococcal or tetanus vaccine within 5 years or influenza vaccine within 1 year of study participation. Antibodies to vaccine antigens were tested at baseline and Week 52, and percentage changes in antibody levels from baseline and proportions of patients maintaining levels at Week 52 were assessed. Antibody titers were also assessed in a small number of patients vaccinated during the study. RESULTS: Consistent with preservation of the memory B cell compartment with belimumab treatment, the proportions of patients maintaining antibody responses to pneumococcal, tetanus, and influenza antigens were not reduced. In a small group receiving influenza vaccine on study, antibody responses were frequently lower with belimumab, although titer levels were > 1:10 in all patients treated with 10 mg/kg and in the majority treated with 1 mg/kg. CONCLUSION: Treatment with belimumab did not affect the ability of patients with SLE to maintain antibody titers to previous pneumococcal, tetanus, and influenza immunizations. [ClinicalTrials.gov registration number NCT 00410384].

Outcomes of a program in business education for physicians and other health care professionals.

BACKGROUND: We sought to determine the expectations that graduates of one business of medicine program had upon enrollment and to ascertain fulfillment of those expectations after completion, as well as the extent to which participating in the program improved business skills and led to advancement in office practice or career development. METHODS: A postal mail survey was conducted of graduates of The Johns Hopkins University's Business of Medicine Program, a year-long, four-course certificate program to educate midcareer academic and nonacademic physicians and other health care professionals about fundamental business practices and their application to health care. RESULTS: Surveys were sent to 285 graduates, and responses were received from 136 (48%) of them. Most respondents expected the program to expand their management skills, to enhance their knowledge of marketplace trends, and to advance their careers. These results were not correlated with respondents' age, sex, or profession (ie, physician, non-physician). More than 87% of respondents agreed that their overall expectations had been fulfilled by the time they completed the survey. Participants noted, however, that several expectations were unfulfilled upon replying to the survey. CONCLUSION: Programs designed to educate physicians and other health care professionals--in private practice, academia, or industry--about the business aspects of medicine can be effective but need to be designed carefully to integrate business theory and application to the medical setting.