Timing of HIV Seroreversion Among HIV-Exposed, Breastfed Infants in Malawi: Type of HIV Rapid Test Matters.

Introduction Rapid HIV serological tests are a cost-effective, point-of-care test among HIV exposed infants but cannot distinguish between maternal and infant antibodies. The lack of data on the timing of decay of maternal antibodies in young infants hinders the potential use of rapid tests in exposed infants. We aimed to determine the time to seroreversion for two commonly used rapid tests in a prospective cohort of HIV-exposed breastfeeding infants ages 3-18 months of life. Methods We collected data on the performance of two commonly used rapid tests (Determine and Unigold) in Malawi between 2008 and 2012 or at the University of North Carolina between 2014 and 2015. Time to seroreversion was estimated for both rapid tests using the Kaplan-Meier product limit estimator which allows for interval censored data. Results At 3 months of age, 3 % of infants had seroreverted according to Determine and 7 % had seroreverted according to Unigold. About one in four infants had achieved seroreversion by 4 months using Unigold, but only about one in twelve infants by 4 months when using Determine. More than 95 % of all infants had seroverted by 7 months according to Unigold and by 12 months according to the Determine assay. Discussion We show that the time of seroreversion depends greatly on the type of test used. Our results highlight the need for recommendations to specify the timing and type of test used in the context of infant HIV detection in resource-poor settings, and base the interpretation of test result on knowledge of time to seroreversion of the selected test.

Clostridium difficile infection after allogeneic hematopoietic stem cell transplant: strain diversity and outcomes associated with NAP1/027.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at high risk for developing Clostridium difficile infection (CDI). We studied the incidence, risk factors, NAP1/027 prevalence, and clinical outcomes, including acute lower gastrointestinal graft-versus-host disease (GI GVHD), associated with early CDI in this population. A retrospective review was conducted of patients who underwent allogeneic HSCT at Memorial Sloan Kettering Cancer Center from January 1, 2005 to September 30, 2010. Early CDI was defined as infection occurring from day -10 to day +40 from stem cell infusion. Among 793 patients who received allogeneic HSCTs, early CDI occurred in 11.9%; 56% cases were between day -5 and day +5. Overall incidence was 25.2 cases/10,000 at-risk days. There was a high prevalence of NAP1/027 strains during peak incidence (61% in 2008). NAP1/027 was the most common strain in both adult and pediatric cases (24% and 23%, respectively). CDI was clinically mild, including those due to NAP1/027. Metronidazole was the primary treatment for 91 of 94 patients, 7 of 8 cases refractory to metronidazole had no response to vancomycin, and none was due to NAP1/027. Relapse of CDI was common (31%). The cumulative incidence of GI GVHD in patients with and without early CDI was 6.8% and 8%, respectively (P = .5). Most cases of CDI occurred during conditioning or immediately after transplant. Despite high prevalence of NAP1/027, we found only mild disease. Most patients were treated successfully with metronidazole, irrespective of NAP1/027 status. There was no significant association between early CDI and subsequent development of GI GVHD. This study demonstrates the high incidence of CDI early after allogeneic HSCT with wide diversity among infecting strains. Despite the high prevalence of NAP1/027, the disease is mild but relapses are common. No association was found between CDI and subsequent development of GI GVHD.

Opioid use surrounding diagnosis and follow-up in patients with ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis: Results from US claims databases.

OBJECTIVE: To describe patients' use of opioids in the year preceding and year following new diagnosis of ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), compared with patients without the/se diseases. METHODS: This study used US IBM® MarketScan® Commercial Claims and Encounters (CCAE) and Medicaid data and included three cohorts, comprised of incident cases of AS, PsA, or RA (2010-2017). Three matched comparator patients (without the incident disease) were selected for each patient within the disease cohort. Opioid use and appropriate treatment exposure (as defined by US guideline recommendations) in the 12-month baseline and follow-up periods were evaluated using descriptive analyses. RESULTS: Prevalence of claims for opioids was higher for disease cohorts vs. comparators in CCAE; 36.4% of patients with AS, 29.5% with PsA, and 44.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. Prevalence of claims for opioids was also higher for disease cohorts vs. comparators in Medicaid; 30.6% of patients with AS, 36.6% with PsA, and 65.4% with RA did not have any claim for guideline-appropriate therapy in follow-up. CONCLUSIONS: In patients with AS, PsA, or RA, there was high reliance on opioids at and around the time of diagnosis. Significant proportions of patients were not on appropriate treatment as defined by professional society post-diagnosis guidelines; this discordance between actual patient therapies and treatment recommendations may suggest a need for better awareness of appropriate pain management and treatment strategies in rheumatic diseases. Key Points • This study analysed opioid use among patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), or rheumatoid arthritis (RA), and adds to current knowledge by expanding beyond assessment of opioid use at diagnosis, to the year before and after diagnosis. • Opioid use was found to be highly prevalent in AS, PsA, and RA in the year prior to diagnosis and, interestingly, was still seen during the year after diagnosis. • Opioids are neither disease modifying, nor a targeted/recommended treatment for chronic autoimmune diseases. In addition to their association with significant economic costs, opioids are potentially hazardous and are not better than alternative treatments with superior safety profiles. • The reasons behind opioid prescribing patterns should be explored further to support movement to targeted therapies.

Evaluating the Cellular Roles of the Lysine Acetyltransferase Tip60 in Cancer: A Multi-Action Molecular Target for Precision Oncology.

Precision (individualized) medicine relies on the molecular profiling of tumors' dysregulated characteristics (genomic, epigenetic, transcriptomic) to identify the reliance on key pathways (including genome stability and epigenetic gene regulation) for viability or growth, and then utilises targeted therapeutics to disrupt these survival-dependent pathways. Non-mutational epigenetic changes alter cells' transcriptional profile and are a key feature found in many tumors. In contrast to genetic mutations, epigenetic changes are reversable, and restoring a normal epigenetic profile can inhibit tumor growth and progression. Lysine acetyltransferases (KATs or HATs) protect genome stability and integrity, and Tip60 is an essential acetyltransferase due to its roles as an epigenetic and transcriptional regulator, and as master regulator of the DNA double-strand break response. Tip60 is commonly downregulated and mislocalized in many cancers, and the roles that mislocalized Tip60 plays in cancer are not well understood. Here we categorize and discuss Tip60-regulated genes, evaluate Tip60-interacting proteins based on cellular localization, and explore the therapeutic potential of Tip60-targeting compounds as epigenetic inhibitors. Understanding the multiple roles Tip60 plays in tumorigenesis will improve our understanding of tumor progression and will inform therapeutic options, including informing potential combinatorial regimes with current chemotherapeutics, leading to improvements in patient outcomes.

A Benefit-Risk Conceptual Framework for Biologic Use During Pregnancy: A Mini-Review.

Recent reports related to in utero exposure of marketed immunosuppressive biologics led to clinical recommendations to delay live vaccinations for infants due to the concern of reduced vaccine effectiveness and/or increased risk of vaccine-related disease. These delays can increase the risk of children contracting vaccine preventable diseases, yet the alternative cessation of biologics during pregnancy may result in increased autoimmune disease activity for the pregnant person, raising complex benefit-risk (B-R) considerations and trade-offs. Our goal is to develop a conceptual framework for B-R assessment based on the key benefits and risks pregnant people would consider for themselves and their children when continuing (vs. discontinuing) a biologic during pregnancy. The proposed framework defines the decision contexts, key domains and attributes for potential benefits, and risks of biologic use during pregnancy, informed by a literature review of indications for biologics and refined with key clinical stakeholders. The framework includes both the pregnant person taking the biologic and the infant potentially exposed to the biologic in utero, with potential benefit and risk domains and attributes for each participant. To advance this conceptual framework, there are considerations of potential biases and uncertainty of available data that will be imperative to address when quantifying the B-R framework. For these reasons, we recommend the formation of a consortium to ensure development of a robust, validated framework that can be adopted in the healthcare setting.

Residual Disease Associated with Suboptimal Treatment Response in Patients with Psoriatic Arthritis: A Systematic Review of Real-World Evidence.

OBJECTIVE: This systematic literature review aimed to identify and summarise real-world observational studies reporting the type, prevalence and/or severity of residual symptoms and disease in adults with psoriatic arthritis (PsA) who have received treatment and been assessed against remission or low disease activity targets. METHODS: Patients had received treatment and been assessed with treat-to-target metrics, including minimal disease activity (MDA), Disease Activity Index in PsA (DAPSA) and others. MEDLINE, Embase® and the Cochrane Database of Systematic Reviews (CDSR) were searched using search terms for PsA, treatment targets and observational studies. Screening of search results was completed by two independent reviewers; studies were included if they reported relevant residual disease outcomes in adults with PsA who had received one or more pharmacological treatments for PsA in a real-world setting. Non-observational studies were excluded. Information from included studies was extracted into a prespecified grid by a single reviewer and checked by a second reviewer. RESULTS: Database searching yielded 2328 articles, of which 42 publications (27 unique studies) were included in this systematic literature review. Twenty-three studies reported outcomes for MDA-assessed patients, and 14 studies reported outcomes for DAPSA-assessed patients. Physician- and patient-reported residual disease was less frequent and/or severe in patients reaching targets, but often not absent, including when patients achieved very low disease activity (VLDA) or remission. For example, studies reported that 0-8% patients in remission according to DAPSA (or clinical DAPSA) had > 1 tender joint, 25-39% had Psoriasis Area and Severity Index (PASI) score > 1 and 0-10% had patient-reported pain > 15. Residual disease was usually less frequent and/or severe among patients achieving MDA-assessed targets versus DAPSA--assessed targets, especially for skin outcomes. CONCLUSION: The findings demonstrate a need for further optimisation of care for patients with PsA.

Occurrence of Possible Rheumatologic Immune-Related Adverse Events (rh-irAEs) Associated with Immune Checkpoint Inhibitor (ICI) Therapy.

INTRODUCTION: Current epidemiologic literature of rheumatologic immune-related adverse events (rh-irAEs) consists of clinical trials, case reports, or smaller, single-center series. We evaluate the occurrence of rh-irAEs during immune checkpoint inhibitor (ICI) therapy from US commercial claims data. METHODS: Patients newly initiating ICI therapy in commercial claims data were eligible for inclusion. Rh-irAEs were defined using ≥ 1 International Classification of Diseases (ICD)-9 or ICD-10-Clinical Modification (CM) claims for selected events, ranging from joint pain and myalgia to ankylosing spondylitis and psoriasis. The percentage of patients experiencing rh-irAEs after ICI initiation was determined. RESULTS: A total of 5722 patients initiating an ICI between January 1, 2012, and June 30, 2018, were included; 201 patients (3.5%) had a history of rheumatic disease. Among the 5521 patients without a history of rheumatic disease, 29.6% experienced ≥ 1 rh-irAE in follow-up, decreasing to 22.6% when assessing events for which there was no diagnostic history. Limiting to claims for rh-irAE with a rheumatologist provider, the proportion of patients experiencing an event decreased to 0.9%. Among patients with a history of rheumatic disease, 71.6% experienced ≥ 1 rh-irAE. Limiting to events for which the patient did not have a history during baseline, 35.3% experienced an event. CONCLUSIONS: Occurrence of rh-irAEs during ICI use is higher in patients with pre-existing rheumatic disease compared to those with no pre-existing rheumatic disease. However, the most common events were not definitive rheumatic diseases but rather symptoms, such as pain in joints. Occurrence of events associated with a rheumatologist provider was substantially lower, suggesting that either patients are not referred to a rheumatologist or referral does not result in confirmation of the diagnosis by the rheumatologist.

Epidemiology and Treatment of Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Psoriasis in Germany: A Real-World Evidence Study.

INTRODUCTION: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PSO) are chronic inflammatory diseases that have a substantial impact on patients' health. This retrospective database study aimed to assess the epidemiology, comorbidities, diagnosis and treatment patterns of RA, PsA and PSO in the German population. METHODS: Data were extracted from the Deutsche Forschungsdatenbank für Abrechnungsinformationen der Krankenversicherung database from 2012 to 2016 for patients aged ≥ 18 years holding full health coverage in the reporting year at least. Diagnoses were defined according to International Classification of Diseases (ICD)-10 codes. Reported outcomes included prevalence and incidence rates, pre-defined comorbidities, diagnosing and treating physicians, and treatment exposure. A subgroup analysis was performed for women of childbearing age (females aged 18-45 years). RESULTS: The prevalence rates of RA, PsA and PSO in Germany were consistent over the study period; by 2016 they were 0.4%, 0.3% and 2.1%, respectively, and in women of childbearing age they were 0.2%, 0.2% and 1.5%, respectively. RA, PsA and PSO were predominantly observed among patients aged > 45 years. RA and PsA were more prevalent in women, while PSO had an approximately equal gender distribution. Depressive episodes were the most frequently reported comorbidity in 2016 (RA: 25.7%; PsA: 25.1%; PSO: 17.8%), and this was similar in women of childbearing age (RA: 20.5%; PsA: 23.4%; PSO: 16.3%). Approximately 50% of patients with RA and PsA and 6% of patients with PSO were receiving systemic treatment in 2016, of which methotrexate (RA: 38.4%; PsA: 30.2%; PSO: 2.2%) was most common. Biologic therapies were the least frequently used treatment options (RA: 28.9%; PsA: 20.9%; PSO: 1.8%). CONCLUSIONS: This analysis provides key epidemiological information for patients with RA, PsA and PSO, including in women of childbearing age, in Germany and highlights common comorbidities and that patients were likely receiving insufficient treatment for these diagnoses.

The effect of HIV infection and exposure on cognitive development in the first two years of life in Malawi.

OBJECTIVES: To assess longitudinal patterns and determinants of cognitive development in infants living with HIV, infants exposed to maternal HIV infection, and HIV-unexposed infants. METHODS: Prospective, community-based cohort study of 555 Malawian infants aged 8 weeks to 24 months, using multivariable linear mixed-effects regression models with random intercepts to analyze repeated measures of cognitive function. RESULTS: At 3 months of age, cognitive scores on the Bayley Scales of Infant Development (BSID 3rd edition) were lower in the 96 HIV-infected infants (mean = 14.1 (SD:4.8)) compared to the 289 HIV-exposed (mean = 16.5 (SD:3.7)) and the 170 unexposed infants (mean = 17.5 (SD:3.3)). Over the first two years of life, the small deficit in cognitive development of infants living with HIV who survived and remained in care did not increase (mean score 52.9 among HIV-infected vs 55.6 among HIV unexposed). In multivariable analysis, malnutrition and a more advanced clinical infant HIV stage had a negative impact on cognition at age 3, while financial security, care by the biological mother, and ART for mother and child were associated with better cognitive status at this young age. The positive influence of maternal ART reversed with age. CONCLUSIONS: Malawian infants exposed to HIV had a cognitive development that was similar to their unexposed peers in the first two years of life, while that of HIV infected infants lagged behind from the start. Early initiation of effective ART in all HIV infected mothers and infants, and prevention of infant malnutrition are important to safeguard cognitive development of children affected by HIV.

Opioid Use in Patients with Ankylosing Spondylitis Is Common in the United States: Outcomes of a Retrospective Cohort Study.

OBJECTIVE: To assess the prevalence of chronic opioid use in patients with ankylosing spondylitis (AS), and to compare the characteristics of patients with and without chronic opioid use. METHODS: This was a retrospective cohort study of patients with AS identified in the Truven Health MarketScan Research database between January 1, 2012, and March 31, 2017. Commercial and Medicaid claims data were examined using both specific (720.0 and M45.x) and broader (720.x and M45.x) International Classification of Diseases (ICD) coding definitions. Patients were aged ≥ 18 years on the date of first qualifying ICD code occurrence (the index date). Demographics and clinical characteristics were assessed in the 12-month period preceding the index date. The 12-month followup period was used to assess prevalence and characteristics of chronic opioid use. RESULTS: Chronic opioid use was common among patients with commercial claims (23.5% of ICD 720.0 patients; 27.3% of ICD 720.x patients), and especially those with Medicaid claims (57.1% and 76.7%, respectively). The proportion of patients with claims for anti-tumor necrosis factor therapies during followup was often low, and for Medicaid patients was lower among those with chronic opioid use (29.6% of ICD 720.0 patients; 2.3% of ICD 720.x patients) than those without (47.1% and 7.1%, respectively). Among chronic opioid users in all cohorts, the cumulative supply of opioids was typically high (≥ 270 days in the followup period); most opioids prescribed were Schedule II. CONCLUSION: Patients with AS receive opioids with disturbing frequency. The infrequent prescription of recommended therapies to these patients reflects a need to optimize treatment further through education of patients and healthcare professionals alike.

Assessing Collaboration in a National Research Partnership in Quality Improvement in Indigenous Primary Health Care: A Network Approach.

Background: The ABCD National Research Partnership was formed in mid-2010 as a collaboration to harness the expertise, experiences and resources of Aboriginal and Torres Strait Islander community-controlled peak bodies, government and research organisations to improve the quality of Indigenous primary health care. The aim of this study was to apply social network methods to assess collaboration and functioning of the Partnership at two time-points. Methods: A social network analysis (SNA) survey was conducted in early 2013, with a follow-up survey in mid-2014. In the two survey rounds, online surveys were emailed to one senior person of the organisation participating in the Partnership (2013: 14 organisations; 2014: 11 organisations). The surveys collected data on respondent perceptions of the Partnership as well as social network relationship data. Social network methods were used to apply standardised metrics to assess how well the partnership was functioning as a collaborative three years into its operation, and in its fourth year. Results: Most respondents rated the Partnership as successful in progressing toward its goals. Network density and centrality scores show a well-connected partnership spanning different organisational types and states/territories (Northern Territory, Queensland, Western Australia, South Australia, and Far-West New South Wales). High centrality scores reflect high connectivity between key hubs in the network, contributing toward the shared goal of improved Indigenous primary health care. Network diagrams show key structural positions by organisational type, the frequency and intensity of interactions and the strengths and potential vulnerabilities in the partnership network, with comparisons at two time points for the partnership. Conclusions: The study found that the Partnership was effective in securing collaboration across its partners. Partners' contribution of resources reflected their active involvement. There was a high level of agreement on the achievement of the key goals of the Partnership, showing shared sense-making amongst partners. SNA tools assisted with monitoring the network over time to develop strategies supporting connections between partners for sustaining collaborative learning. Study findings identify successful approaches for a research partnership to improve quality of care in Indigenous primary health care and provide encouragement for wider applications for research partnerships and collaborations in Australia and internationally.

Early Antiretroviral Therapy Initiation and Mortality Among Infants Diagnosed With HIV in the First 12 Weeks of Life: Experiences From Kinshasa, DR Congo and Blantyre, Malawi.

BACKGROUND: Based on clinical trial results, the World Health Organization recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV-infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. METHODS: Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. RESULTS: One hundred and twenty-one infants were diagnosed at a median age of 7 weeks (interquartile range, 6-8). The cumulative incidence of ART initiation was 46% [95% confidence interval (CI), 36%, 55%] at 6 months and 70% (95% CI 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI 0.52, 0.91) for each week increase in age at DNA polymerase chain reaction test. The 12-month cumulative incidence of mortality was 20% (95% CI 13%, 28%). CONCLUSIONS: Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and World Health Organization's guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV-infected infants achieve optimal treatment outcomes under routine care settings.

Performance of HIV Rapid Tests Among Breastfeeding, Malawian Infants.

INTRODUCTION: Timely, accurate and affordable testing algorithms at point-of-care are critical for early infant HIV diagnosis and initiation of antiretroviral therapy in the postpartum period. We aimed to assess the utility of HIV rapid tests for young, breast-fed HIV-exposed infants in resource limited, high HIV burden settings. MATERIALS AND METHODS: We collected data on the performance of 2 commonly used rapid tests (Determine and Unigold) in Malawi between 2008 and 2012 or at the University of North Carolina between 2014 and 2015. For each 3-month interval between ages 3 and 18 months, we calculated the sensitivity, specificity, positive and negative predictive values of each test compared with the HIV DNA/RNA PCR gold standard. We also assessed the utility of each rapid test to diagnose incident HIV infection during the breastfeeding period. RESULTS: Among 121 HIV-exposed infants who were negative at age 6 weeks, 21 (17.2%) became infected by 18 months. At 3 months of age, both rapid tests had minimal clinical value with specificity values of 7.0% [95% confidence interval (CI): 2.3-15.7] for Determine and 19.4% (95% CI: 11.1-30.5) for Unigold. Starting at age 6 and 9 months, the Unigold test could be used as a screening tool in the follow-up of HIV-exposed infants with specificity values of 83.7% (95% CI: 74.4-89.9) and 97.7% (95% CI: 94.6-99.7), respectively. Starting at age 12 months, the type of test became less important as both tests performed well in identifying HIV-free children, although both tests failed to detect some incident HIV infections. CONCLUSIONS: Updated guidelines for the use of rapid tests in young HIV-exposed children that explicitly take type of test and infant age into account are urgently needed to ensure optimal care for the 1.5 million HIV-exposed infants born annually.

Norovirus in Transplantation.

Noroviruses are among the most common cause of diarrhea in transplant recipients. The clinical spectrum of norovirus infection after transplant is increasingly being recognized. As substantial morbidity is now associated with norovirus infections in this population; the quest for rapid diagnostic modalities and newer therapies has expanded. Transplant recipients with norovirus infection are at risk for several complications, including protracted illness with malnutrition, organ failure, and chronic viral shedding. This review summarizes the current knowledge on the epidemiology, complications, diagnosis, and treatment of norovirus infection in the transplant setting.

Transmission of Clostridium difficile During Hospitalization for Allogeneic Stem Cell Transplant.

OBJECTIVE To determine the role of unit-based transmission that accounts for cases of early Clostridium difficile infection (CDI) during hospitalization for allogeneic stem cell transplant. SETTING Stem cell transplant unit at a tertiary care cancer center. METHODS Serially collected stool from patients admitted for transplant was screened for toxigenic C. difficile through the hospital stay and genotyping was performed by multilocus sequence typing. In addition, isolates retrieved from cases of CDI that occurred in other patients hospitalized on the same unit were similarly characterized. Transmission links were established by time-space clustering of cases and carriers of shared toxigenic C. difficile strains. RESULTS During the 27-month period, 1,099 samples from 264 patients were screened, 69 of which had evidence of toxigenic C. difficile; 52 patients developed CDI and 17 were nonsymptomatic carriers. For the 52 cases, 41 had evidence of toxigenic C. difficile on the first study sample obtained within a week of admission, among which 22 were positive within the first 48 hours. A total of 24 sequence types were isolated from this group; 1 patient had infection with the NAP1 strain. A total of 11 patients had microbiologic evidence of acquisition; donor source could be established in half of these cases. CONCLUSIONS Most cases of CDI after stem cell transplant represent delayed onset disease in nonsymptomatic carriers. Transmission on stem cell transplant unit was confirmed in 19% of early CDI cases in our cohort with a probable donor source established in half of the cases.

Control of norovirus outbreak on a pediatric oncology unit.

BACKGROUND: Patients undergoing treatment for cancer with chemotherapy and hematopoietic stem cell recipients are at risk for severe morbidity caused by norovirus (NV). METHODS: We describe a NV outbreak on the Memorial Sloan Kettering Cancer Center's pediatric oncology unit. Stool testing for diagnosis of NV was performed by real-time polymerase chain reaction (PCR). RESULTS: Twelve NV cases occurred; 7 were hospital acquired. Twenty-five health care workers reported NV compatible illness. Patient-to-patient transmission occurred once. The practices of the Centers for Disease Control and Prevention were supplemented with electronic surveillance, surrogate screening for NV, and heightened cleaning. Two additional cases occurred after implementation of interventions. Long-term shedding was detected in 2 patients. CONCLUSION: We describe interventions for controlling NV on a pediatric oncology unit. High-risk chronic shedders pose ongoing transmission risks. PCR is a valuable diagnostic tool but may be overly sensitive. Surrogate markers to assess NV burden in stool and studies on NV screening are needed to develop guidelines for high-risk chronic shedders.

The impact of observation units on the rate of hospital-acquired infection.

Using Clostridium difficile as an example, we calculated the impact that reduced inpatient-day denominators resulting from implementation of hospital observation units would have on hospital-acquired infection rates. Using proposed scenarios of reduced inpatient-days, we estimated an increase in the hospital-acquired C. difficile infection rate of up to 12%.