The Utility of Ultrasound in Evaluating Joint Pain in Systemic Lupus Erythematosus: Looking beyond Fibromyalgia.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune condition with varied clinical presentations, and musculoskeletal pain is one of the most commonly associated symptoms. However, fibromyalgia (FM) is a prevalent co-existing condition in SLE patients that can also cause widespread pain, and in patients with both conditions, it is often difficult to distinguish the underlying cause of musculoskeletal pain and provide optimal therapy. METHODS: A retrospective cohort study was conducted including all adult SLE patients who received musculoskeletal ultrasound (US) examinations for joint pain at the Ohio State University Wexner Medical Center between 1 July 2012, and 30 June 2022. Binary and multiple logistic regression analyses were performed to determine predictors of US-detected inflammatory arthritis as well as improved musculoskeletal pain. RESULTS: A total of 31 of 72 SLE patients (43.1%) had a co-existing diagnosis of FM. In binary logistic regression, a co-existing diagnosis of FM was not significantly associated with US-detected inflammatory arthritis. In multiple logistic regression analysis, clinically detected synovitis was significantly associated with US-detected inflammatory arthritis (aOR, 142.35, p < 0.01), and there was also a weak association with erythrocyte sedimentation rate (ESR) (aOR 1.04, p = 0.05). In separate multiple logistic regression analysis, US-guided intra-articular steroid injection was the only predictor of improved joint pain at follow-up visit (aOR 18.43, p < 0.001). CONCLUSIONS: Musculoskeletal US can be an effective modality to detect inflammatory arthritis as well as to guide targeted intra-articular steroid injection to alleviate joint pain in SLE patients with or without FM.

A Narrative Review of the Design of Ultrasound Indices for Detecting Enthesitis.

With the increased utilization of musculoskeletal ultrasound in clinical practice, there has been rapid proliferation of publications on sonographic evaluation of enthesitis. This has led to the development of multiple new approaches to scoring sonographic findings in the detection of enthesitis, with variations including entheseal sites and sonographic features that limit cross-study comparisons. Furthermore, despite efforts to standardize the definition of enthesitis, there is still heterogeneity in the sonographic features included in existing ultrasound scores, and additional adjustments are required to distinguish active inflammatory changes from non-inflammatory conditions and to adjust for demographic features associated with increased prevalence of abnormal sonographic findings. This review provides an update on the current landscape of ultrasound scoring systems for enthesitis and emphasizes the importance of future data-based ultrasound scoring systems to improve the distinction between inflammatory and non-inflammatory or degenerative changes of the enthesis.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.

BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V. METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype. RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis. CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.

A diagnosis of discernment: Identifying a novel ATRX mutation in myelodysplastic syndrome with acquired α-thalassemia.

Myelodysplastic syndromes (MDS) are a heterogeneous category of myeloid neoplasms that represent the most common class of acquired bone marrow failure syndromes in adults. MDS is typically associated with a hypoproliferative macrocytic anemia, but atypical findings on initial diagnostic evaluations can raise concern for a distinct pathophysiological process and lead to the investigation of alternative etiologies. Here, we report a case of MDS with a concomitant hypoproliferative microcytic and hypochromic anemia that led to the identification of acquired hemoglobin H due to a novel somatic ATRX mutation.

FLT3 mutational status is an independent risk factor for adverse outcomes after allogeneic transplantation in AML.

Allogeneic hematopoietic cell transplantation (HCT) has been increasingly used in the setting of FMS-like tyrosine kinase-3 (FLT3)-mutated AML. However, its role in conferring durable relapse-free intervals remains in question. Herein we sought to investigate FLT3 mutational status on transplant outcomes. We conducted a retrospective cohort study of 262 consecutive AML patients who underwent first-time allogeneic HCT (2008-2014), of whom 171 had undergone FLT3-ITD (internal tandem duplication) mutational testing. FLT3-mutated AML was associated with nearly twice the relapse risk (RR) compared with those without FLT3 mutation 3 years post-HCT (63% vs 37%, P<0.001) and with a shorter median time to relapse (100 vs 121 days). FLT3 mutational status remained significantly associated with this outcome after controlling for patient, disease and transplant-related risk factors (P<0.05). Multivariate analysis showed a significant association of FLT3 mutation with increased 3-year RR (hazard ratio (HR) 3.63, 95% confidence interval (CI): 2.13, 6.19, P<0.001) and inferior disease-free survival (HR 2.05, 95% CI: 1.29, 3.27, P<0.01) and overall survival (HR 1.92, 95% CI: 1.14, 3.24, P<0.05). These data demonstrate high risk of early relapse after allogeneic HCT for FLT3-mutated AML that translates into adverse disease-free and overall survival outcomes. Additional targeted and coordinated interventions are needed to maintain durable remission after allogeneic HCT in this high-risk population.

Histone deacetylase inhibition regulates inflammation and enhances Tregs after allogeneic hematopoietic cell transplantation in humans.

We examined immunological responses in patients receiving histone deacetylase (HDAC) inhibition (vorinostat) for graft-versus-host disease prophylaxis after allogeneic hematopoietic cell transplant. Vorinostat treatment increased histone acetylation in peripheral blood mononuclear cells (PBMCs) from treated patients, confirming target HDAC inhibition. HDAC inhibition reduced proinflammatory cytokine levels in plasma and from PBMCs and decreased ex vivo responses of PBMCs to proinflammatory TLR-4 stimuli, but did not alter the number or response of conventional T cells to nonspecific stimuli. However, the numbers of regulatory T cells (Tregs) were increased, which revealed greater demethylation of the Foxp3 T regulatory-specific demethylation region. Vorinostat-treated patients showed increased expression of CD45RA and CD31 on Tregs, and these Tregs demonstrated greater suppression on a per cell basis. Consistent with preclinical findings, HDAC inhibition also increased signal transducer and activator of transcription 3 acetylation and induced indoleamine-2,3-dioxygenase. Our data demonstrate that HDAC inhibition reduces inflammatory responses of PBMC but enhances Tregs after allo-HCT.

Combining prostate-specific antigen nadir and time to nadir allows for early identification of patients at highest risk for development of metastasis and death following salvage radiation therapy.

PURPOSE: Little is known regarding the prognostic capability of prostate-specific antigen (PSA) nadir (nPSA) and time to nPSA (TnPSA) following salvage radiation therapy (SRT) for biochemical failure (BF) postradical prostatectomy (RP). We sought to assess their prognostic significance in this setting. METHODS AND MATERIALS: A total of 448 patients who received SRT without androgen deprivation therapy at a single academic institution were included in this retrospective analysis. Univariate analysis and multivariate Cox proportional hazards models were used to assess BF, distant metastasis (DM), prostate cancer-specific death (PCSD), and overall survival (OS). A prognostic nomogram incorporating nPSA and TnPSA was developed and validated in randomly allocated training and validation cohorts. RESULTS: Median follow-up post-SRT was 64 months. Median nPSA and TnPSA were undetectable and 6.7 months, respectively. On univariate analysis, a detectable nPSA (P < .01) and TnPSA <6 months (P < .01) were predictive of all outcomes. In a training cohort, a 14-point nomogram incorporating detectable nPSA, TnPSA, Gleason score, pre-radiation therapy PSA, and seminal vesicle invasion predicted BF (hazard ratio[HR], 1.4; P < .0001), DM (HR, 1.3; P < .0001), PCSD (HR, 1.3; P < .0001), and decreased OS (HR, 1.2; P < .0001). Adding nPSA and TnPSA improved the prognostic value of the nomogram compared to using clinical predictors only. The nomogram was evaluated in a validation cohort where it was predictive of BF (c-index = 0.77), DM (0.73), and PCSD (0.69). CONCLUSIONS: Patients with a detectable nPSA also having a TnPSA <6 months post-SRT are at high-risk for DM, PCSD, and decreased OS. These patients are unlikely to have clinically localized disease and should be considered for initiation of systemic therapies.

The Challenge of t (6;9) and FLT3-Positive Acute Myelogenous Leukemia in a Young Adult.

Translocation t(6;9) is a rare cytogenetic abnormality found in fewer than 5% of pediatric and adult cases of acute myelogenous leukemia (AML). The outcomes of t(6;9) AML are generally poor, with low five-year overall survival and increased risk for relapse. Furthermore, FLT3-ITD is one of the most common molecular abnormalities found in AML that is associated with increased risk of treatment failure and mortality. Allogeneic hematopoietic cell transplantation (HCT) with the best available donor is a standard treatment option for these cases once remission is achieved. We report a challenging case of t(6;9) and FLT3-positive AML in a young adult male. After failing multiple standard induction regimens, morphologic remission was eventually achieved with a FLT3 inhibitor (sorafenib) and a hypomethylating agent (azacytidine). However, despite allogeneic HCT and re-initiation of sorafenib in the post-HCT setting, he experienced early relapse with the original [FLT3-ITD and t(6;9)] and new (FLT3-D835 and +8) molecular and cytogenetic markers, respectively. This case highlights the need for improved strategies in the post-HCT setting for high-risk AML.

A prostate-specific antigen doubling time of <6 months is prognostic for metastasis and prostate cancer-specific death for patients receiving salvage radiation therapy post radical prostatectomy.

BACKGROUND: The ideal prostate-specific antigen (PSA) doubling time (PSADT) threshold for identifying patients at high-risk for poor clinical outcome following salvage radiation therapy (SRT) has not been well established. We sought to assess what PSADT threshold is most clinically prognostic in this setting. METHODS: 575 patients who received SRT at a single institution for biochemical recurrence after radical prostatectomy were retrospectively reviewed. We assessed the impact of pre-SRT PSADT on biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). Kaplan-Meier methods, hazard ratio (HR) assessment, and Cox Proportional Hazard models were used to assess the discriminatory ability of various PSADT thresholds. RESULTS: Sufficient data to calculate PSADTs were available for 277 patients. PSADT was prognostic for BF, DM, PCSM, and OM on univariate analysis regardless of threshold. HR assessment identified 6 months as a strong threshold. No statistically significant difference was observed in BF, DM, PCSM, or OM between patients with PSADT <3 (n=40) and 3-6 months (n=61) or between 6-10 (n=62) and >10 months (n=114). However significant differences were seen in BF (HR:2.2, [95%CI: 1.4-3.5], p<0.01) and DM (HR:2.2, [95%CI: 1.2-4.3], p=0.02) between a PSADT of 3-6 and 6-10 months. On multivariate analysis a PSADT <6 months predicted BF (HR:2.0, [95%CI: 1.4-2.9], p=0.0001), DM (HR:2.0, [95%CI: 1.2-3.4], p=0.01), and PCSM (HR:2.6, [95%CI: 1.1-5.9], p=0.02). CONCLUSIONS: A pre-SRT PSADT <6 months was a strong predictor of outcomes in our data set, including PCSM. The most common nomogram for SRT uses a 10-month PSADT threshold for assigning points used to assess BF following SRT. If validated, our findings suggest that a PSADT threshold of <6 months should be considered for stratification of patients in future clinical trials in this setting.

Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy.

BACKGROUND: The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level. METHODS: A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models. RESULTS: On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). CONCLUSION: In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP.

Larger maximum tumor diameter at radical prostatectomy is associated with increased biochemical failure, metastasis, and death from prostate cancer after salvage radiation for prostate cancer.

PURPOSE: To investigate the maximum tumor diameter (MTD) of the dominant prostate cancer nodule in the radical prostatectomy specimen as a prognostic factor for outcome in patients treated with salvage external beam radiation therapy (SRT) for a rising prostate-specific antigen (PSA) value after radical prostatectomy. METHODS AND MATERIALS: From an institutional cohort of 575 patients treated with SRT, data on MTD were retrospectively collected. The impact of MTD on biochemical failure (BF), metastasis, and prostate cancer-specific mortality (PCSM) was assessed on univariate and multivariate analysis using Kaplan-Meier and Cox proportional hazards models. RESULTS: In the 173 patients with MTD data available, median follow-up was 77 months (interquartile range, 47-104 months) after SRT, and median MTD was 18 mm (interquartile range, 13-22 mm). Increasing MTD correlated with increasing pT stage, Gleason score, presence of seminal vesicle invasion, and lymph node invasion. Receiver operating characteristic curve analysis identified MTD of >14 mm to be the optimal cut-point. On univariate analysis, MTD >14 mm was associated with an increased risk of BF (P=.02, hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.8), metastasis (P=.002, HR 4.0, 95% CI 2.1-7.5), and PCSM (P=.02, HR 8.0, 95% CI 2.9-21.8). On multivariate analysis MTD >14 mm remained associated with increased BF (P=.02, HR 1.9, 95% CI 1.1-3.2), metastasis (P=.02, HR 3.4, 95% CI 1.2-9.2), and PCSM (P=.05, HR 9.7, 95% CI 1.0-92.4), independent of extracapsular extension, seminal vesicle invasion, positive surgical margins, pre-RT PSA value, Gleason score, and pre-RT PSA doubling time. CONCLUSIONS: For patients treated with SRT for a rising PSA value after prostatectomy, MTD at time of radical prostatectomy is independently associated with BF, metastasis, and PCSM. Maximum tumor diameter should be incorporated into clinical decision making and future clinical risk assessment tools for those patients receiving SRT.

Modeling the regional spread and control of vancomycin-resistant enterococci.

BACKGROUND: Because patients can remain colonized with vancomycin-resistant enterococci (VRE) for long periods of time, VRE may spread from one health care facility to another. METHODS: Using the Regional Healthcare Ecosystem Analyst, an agent-based model of patient flow among all Orange County, California, hospitals and communities, we quantified the degree and speed at which changes in VRE colonization prevalence in a hospital may affect prevalence in other Orange County hospitals. RESULTS: A sustained 10% increase in VRE colonization prevalence in any 1 hospital caused a 2.8% (none to 62%) average relative increase in VRE prevalence in all other hospitals. Effects took from 1.5 to >10 years to fully manifest. Larger hospitals tended to have greater affect on other hospitals. CONCLUSIONS: When monitoring and controlling VRE, decision makers may want to account for regional effects. Knowing a hospital's connections with other health care facilities via patient sharing can help determine which hospitals to include in a surveillance or control program.

The interval to biochemical failure is prognostic for metastasis, prostate cancer-specific mortality, and overall mortality after salvage radiation therapy for prostate cancer.

PURPOSE: To investigate the utility of the interval to biochemical failure (IBF) after salvage radiation therapy (SRT) after radical prostatectomy (RP) for prostate cancer as a surrogate endpoint for distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). METHODS AND MATERIALS: A retrospective analysis of 575 patients treated with SRT after RP from a single institution. Of those, 250 patients experienced biochemical failure (BF), with the IBF defined as the time from commencement of SRT to BF. The IBF was evaluated by Kaplan-Meier and Cox proportional hazards models for its association with DM, PCSM, and OM. RESULTS: The median follow-up time was 85 (interquartile range [IQR] 49.8-121.1) months, with a median IBF of 16.8 (IQR, 8.5-37.1) months. With a cutoff time of 18 months, as previously used, 129 (52%) of patients had IBF ≤18 months. There were no differences among any clinical or pathologic features between those with IBF ≤ and those with IBF >18 months. On log-rank analysis, IBF ≤18 months was prognostic for increased DM (P<.0001, HR 4.9, 95% CI 3.2-7.4), PCSM (P<.0001, HR 4.1, 95% CI 2.4-7.1), and OM (P<.0001, HR 2.7, 95% CI 1.7-4.1). Cox proportional hazards models with adjustment for other clinical variables demonstrated that IBF was independently prognostic for DM (P<.001, HR 4.9), PCSM (P<.0001, HR 4.0), and OM (P<.0001, HR 2.7). IBF showed minimal change in performance regardless of androgen deprivation therapy (ADT) use. CONCLUSION: After SRT, a short IBF can be used for early identification of patients who are most likely to experience progression to DM, PCSM, and OM. IBF ≤18 months may be useful in clinical practice or as an endpoint for clinical trials.

The Regional Healthcare Ecosystem Analyst (RHEA): a simulation modeling tool to assist infectious disease control in a health system.

OBJECTIVE: As healthcare systems continue to expand and interconnect with each other through patient sharing, administrators, policy makers, infection control specialists, and other decision makers may have to take account of the entire healthcare 'ecosystem' in infection control. MATERIALS AND METHODS: We developed a software tool, the Regional Healthcare Ecosystem Analyst (RHEA), that can accept user-inputted data to rapidly create a detailed agent-based simulation model (ABM) of the healthcare ecosystem (ie, all healthcare facilities, their adjoining community, and patient flow among the facilities) of any region to better understand the spread and control of infectious diseases. RESULTS: To demonstrate RHEA's capabilities, we fed extensive data from Orange County, California, USA, into RHEA to create an ABM of a healthcare ecosystem and simulate the spread and control of methicillin-resistant Staphylococcus aureus. Various experiments explored the effects of changing different parameters (eg, degree of transmission, length of stay, and bed capacity). DISCUSSION: Our model emphasizes how individual healthcare facilities are components of integrated and dynamic networks connected via patient movement and how occurrences in one healthcare facility may affect many other healthcare facilities. CONCLUSIONS: A decision maker can utilize RHEA to generate a detailed ABM of any healthcare system of interest, which in turn can serve as a virtual laboratory to test different policies and interventions.

Perioperative characteristics, complications, and outcomes of single-level versus multilevel thoracic corpectomies via modified costotransversectomy approach.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To compare perioperative end points and outcomes of single-level versus multilevel corpectomy performed using a modified costotransversectomy approach. SUMMARY OF BACKGROUND DATA: Single-level corpectomy via posterolateral approach has been shown to be an effective alternative to the traditional anterior thoracotomy approach. However, there is a paucity of studies that have examined multilevel thoracic corpectomy via posterolateral approach. METHODS: Using electronic medical records, we identified a consecutive population of adult patients who underwent modified costotransversectomy corpectomy in the thoracic region between 2006 and 2009. Patients were stratified by number of corpectomies performed into either a single-level or multilevel group. With the use of baseline descriptive statistics and multivariate analysis, perioperative parameters and follow-up outcomes were assessed between the 2 groups. RESULTS: A total of 40 patients were included in the final analysis, with 25 patients in the single-level group and 15 patients in the multilevel group. Mean follow-up was 16.1 months. Overall complication rate was 37.5%. Between the 2 groups, there were no significant differences in operative time, blood loss, transfusion rate, quantity of blood transfused, length of hospital stay, or complication rates. Also, there were no significant differences in repeat surgery rate, Medical Research Council strength, Nurick score, or pain at most recent follow-up, and all groups gained a comparable magnitude of benefit from surgery. CONCLUSION: Multilevel corpectomy via modified costotransversectomy approach in the thoracic region is a feasible and effective option that does not seem to be associated with significantly increased morbidity. The degree of clinical improvement also seems comparable with single-level corpectomy.

Radiological outcomes of static vs expandable titanium cages after corpectomy: a retrospective cohort analysis of subsidence.

BACKGROUND: Mesh cages have commonly been used for reconstruction after corpectomy. Recently, expandable cages have become a popular alternative. Regardless of cage type, subsidence is a concern following cage placement. OBJECTIVE: To assess whether subsidence rates differ between static and expandable cages, and identify independent risk factors for subsidence and extent of subsidence when present. METHODS: A consecutive population of patients who underwent corpectomy between 2006 and 2009 was identified. Subsidence was assessed via x-ray at 1-month and 1-year follow-ups. In addition to cage type, demographic, medical, and cage-related covariates were recorded. Multivariate models were used to assess independent associations with rate, odds, and extent of subsidence. RESULTS: Of 91 patients, 44.0% had expandable cages and 56.0% had static cages. One-month subsidence rate was 36.3%, and the 1-year subsidence rate was 51.6%. Expandable cages were independently associated with higher rates and odds of subsidence in comparison with static cages. Infection, trauma, and footplate-to-vertebral body endplate ratio of less than 0.5 were independent risk factors for subsidence. The presence of prongs on cages and posterior fusion 2 or more levels above and below corpectomy level had lower rates and odds of subsidence. Infection and cage placement in the thoracic or lumbar region had greater extent of subsidence when subsidence was present. CONCLUSION: Expandable cages had higher rates and risk of subsidence in comparison with static cages. When subsidence was present, expandable cages had greater magnitudes of subsidence. Other factors including footplate-to-vertebral body endplate ratio, prongs, extent of supplemental posterior fusion, spinal region, and diagnosis also impacted subsidence.

Simulation shows hospitals that cooperate on infection control obtain better results than hospitals acting alone.

Efforts to control life-threatening infections, such as with methicillin-resistant Staphylococcus aureus (MRSA), can be complicated when patients are transferred from one hospital to another. Using a detailed computer simulation model of all hospitals in Orange County, California, we explored the effects when combinations of hospitals tested all patients at admission for MRSA and adopted procedures to limit transmission among patients who tested positive. Called "contact isolation," these procedures specify precautions for health care workers interacting with an infected patient, such as wearing gloves and gowns. Our simulation demonstrated that each hospital's decision to test for MRSA and implement contact isolation procedures could affect the MRSA prevalence in all other hospitals. Thus, our study makes the case that further cooperation among hospitals--which is already reflected in a few limited collaborative infection control efforts under way--could help individual hospitals achieve better infection control than they could achieve on their own.

The potential economic value of a Staphylococcus aureus vaccine among hemodialysis patients.

Staphylococcus aureus infections are a substantial problem for hemodialysis patients. Several vaccine candidates are currently under development, with hemodialysis patients being one possible target population. To determine the potential economic value of an S. aureus vaccine among hemodialysis patients, we developed a Markov decision analytic computer simulation model. When S. aureus colonization prevalence was 1%, the incremental cost-effectiveness ratio (ICER) of vaccination was ≤$25,217/quality-adjusted life year (QALY). Vaccination became more cost-effective as colonization prevalence, vaccine efficacy, or vaccine protection duration increased or vaccine cost decreased. Even at 10% colonization prevalence, a 25% efficacious vaccine costing $100 prevented 29 infections, 21 infection-related hospitalizations, and 9 inpatient deaths per 1000 vaccinated HD patients. Our results suggest that an S. aureus vaccine would be cost-effective (i.e., ICERs ≤ $50,000/QALY) among hemodialysis patients over a wide range of S. aureus prevalence, vaccine costs and efficacies, and vaccine protection durations and delineate potential target parameters for such a vaccine.

Routine pre-cesarean Staphylococcus aureus screening and decolonization: a cost-effectiveness analysis.

OBJECTIVES: To estimate the economic value of screening pregnant women for Staphylococcus aureus carriage before cesarean delivery. STUDY DESIGN: Computer simulation model. METHODS: We used computer simulation to assess the cost-effectiveness, from the third-party payer perspective, of routine screening for S aureus (and subsequent decolonization of carriers) before planned cesarean delivery. Sensitivity analyses explored the effects of varying S aureus colonization prevalence, decolonization treatment success rate (for the extent of the puerperal period), and the laboratory technique (agar culture vs polymerase chain reaction [PCR]) utilized for screening and pathogen identification from wound isolates. RESULTS: Pre-cesarean screening and decolonization were only cost-effective when agar was used for both screening and wound cultures when the probability of decolonization success was ≥ 50% and colonization prevalence was ≥ 40%, or decolonization was ≥ 75% successful and colonization prevalence was ≥ 20%. The intervention was never cost-effective using PCR-based laboratory methods. The cost of agar versus PCR and their respective sensitivities and specificities, as well as the probability of successful decolonization, were important drivers of the economic and health impacts of preoperative screening and decolonization of pregnant women. The number needed to screen ranged from 21 to 2294, depending on colonization prevalence, laboratory techniques used, and the probability of successful decolonization. CONCLUSIONS: Despite high rates of cesarean delivery, presurgical screening of pregnant women for S aureus and decolonization of carriers is unlikely to be cost-effective under prevailing epidemiologic circumstances.

Modeling the spread of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks throughout the hospitals in Orange County, California.

BACKGROUND: Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals. METHODS: Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (ß), MRSA loss rate, probability of patient transfer or readmission, and time to readmission. RESULTS: Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%). CONCLUSION: MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.