Pseudogestational Sac Delaying Diagnosis of Ectopic Pregnancy: A Case Report.

BACKGROUND: Diagnosis of ectopic pregnancy can be complicated by nonspecific laboratory and radiographic findings. The multiple alternative diagnoses must be weighed against each other based on the entire clinical presentation. CASE REPORT: We present a case of a 20-year-old woman who arrived to the Emergency Department (ED) with abdominal pain and ended up being transferred for an Obstetrics evaluation of a possible heterotopic pregnancy. Her radiology-performed ultrasound had revealed an "intrauterine gestational sac" along with an adnexal mass near the right ovary. The patient was not undergoing assisted-reproductive fertilization, nor did she have meaningful risk factors for heterotopic pregnancy. The patient was managed expectantly over the ensuing week to see whether the intrauterine fluid was a true gestational sac. After multiple repeat ED visits, the diagnosis of ectopic pregnancy was made. Ultimately, the patient elected for surgical management of her ectopic pregnancy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case offers a reminder of the subtleties of radiographic identification of intrauterine pregnancies and the ever-present need to "clinically correlate."

Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to cardiovascular diseases. Epigenetic regulation is emerging as a key regulatory mechanism, with the methylcytosine dioxygenase TET2 acting as a master regulator of smooth muscle cell phenotype. The histone acetyl-transferases p300 and CREB-binding protein (CBP) are highly homologous and often considered to be interchangeable, and their roles in smooth muscle cell phenotypic regulation are not known. METHODS: We assessed the roles of p300 and CBP in human VSMC with knockdown, in inducible smooth muscle-specific knockout mice (inducible knockout [iKO]; p300iKO or CBPiKO), and in samples of human intimal hyperplasia. RESULTS: P300, CBP, and histone acetylation were differently regulated in VSMCs undergoing phenotypic switching and in vessel remodeling after vascular injury. Medial p300 expression and activity were repressed by injury, but CBP and histone acetylation were induced in neointima. Knockdown experiments revealed opposing effects of p300 and CBP in the VSMC phenotype: p300 promoted contractile protein expression and inhibited migration, but CBP inhibited contractile genes and enhanced migration. p300iKO mice exhibited severe intimal hyperplasia after arterial injury compared with controls, whereas CBPiKO mice were entirely protected. In normal aorta, p300iKO reduced, but CBPiKO enhanced, contractile protein expression and contractility compared with controls. Mechanistically, we found that these histone acetyl-transferases oppositely regulate histone acetylation, DNA hydroxymethylation, and PolII (RNA polymerase II) binding to promoters of differentiation-specific contractile genes. Our data indicate that p300 and TET2 function together, because p300 was required for TET2-dependent hydroxymethylation of contractile promoters, and TET2 was required for p300-dependent acetylation of these loci. TET2 coimmunoprecipitated with p300, and this interaction was enhanced by rapamycin but repressed by platelet-derived growth factor (PDGF) treatment, with p300 promoting TET2 protein stability. CBP did not associate with TET2, but instead facilitated recruitment of histone deacetylases (HDAC2, HDAC5) to contractile protein promoters. Furthermore, CBP inhibited TET2 mRNA levels. Immunostaining of cardiac allograft vasculopathy samples revealed that p300 expression is repressed but CBP is induced in human intimal hyperplasia. CONCLUSIONS: This work reveals that p300 and CBP serve nonredundant and opposing functions in VSMC phenotypic switching and coordinately regulate chromatin modifications through distinct functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.

Use of a Victorian statewide surveillance programme to evaluate the burden of healthcare-associated Staphylococcus aureus bacteraemia and Clostridioides difficile infection in patients with cancer.

BACKGROUND: Patients with cancer are at high risk for infection, but the epidemiology of healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB) and Clostridioides difficile infection (HA-CDI) in Australian cancer patients has not previously been reported. AIMS: To compare the cumulative aggregate incidence and time trends of HA-SAB and HA-CDI in a predefined cancer cohort with a mixed statewide patient population in Victoria, Australia. METHODS: All SAB and CDI events in patients admitted to Victorian healthcare facilities between 1 July 2010 and 31 December 2018 were submitted to the Victorian Healthcare Associated Infection Surveillance System Coordinating Centre. Descriptive analyses and multilevel mixed-effects Poisson regression modelling were applied to a standardised data extract. RESULTS: In total, 10 608 and 13 118 SAB and CDI events were reported across 139 Victorian healthcare facilities, respectively. Of these, 89 (85%) and 279 (88%) were healthcare-associated in the cancer cohort compared with 34% (3561/10 503) and 66% (8403/12 802) in the statewide cohort. The aggregate incidence was more than twofold higher in the cancer cohort compared with the statewide cohort for HA-SAB (2.25 (95% confidence interval (CI): 1.74-2.77) vs 1.11 (95% CI: 1.07-1.15) HA-SAB/10 000 occupied bed-days) and threefold higher for HA-CDI (6.26 (95% CI: 5.12-7.41) vs 2.31 (95% CI: 2.21-2.42) HA-CDI/10 000 occupied bed-days). Higher quarterly diminishing rates were observed in the cancer cohort than the statewide data for both infections. CONCLUSIONS: Our findings demonstrate a higher burden of HA-SAB and HA-CDI in a cancer cohort when compared with state data and highlight the need for cancer-specific targets and benchmarks to meaningfully support quality improvement.

Problem representation and diagnostic accuracy during an OSCE.

PURPOSE: The National Academy of Medicine has called for "identifying opportunities to improve the diagnostic process". We studied the association between problem representation and diagnostic accuracy during an objective structured clinical exam (OSCE). MATERIALS AND METHODS: We conducted a non-randomized controlled trial during a ten-case OSCE. We measured whether a summary statement prompt increased the likelihood that the student listed the correct diagnosis and whether better summary statements were correlated with diagnostic accuracy. RESULTS: 114 students provided 1135 responses. The non-prompted control group yielded 631 responses, listing the correct diagnosis first 73% of the time and within the top three slots 85% of the time. The intervention group exposed to the prompt yielded 453 responses listing the correct diagnosis first 72% of the time (P = 0.617) and within the top three slots 84% of the time (P = 0.760). Summary statements were scored on a 0, 0.5, or 1 rubric. When grouped according to summary statement score, students listed the correct diagnosis first 74%, 70%, and 72% of the time respectively (P = 0.666). The correct diagnosis was included within the top three slots 88%, 82%, and 83% of the time (P = 0.238). CONCLUSIONS: Prompting students to form a summary statement did not improve diagnostic accuracy. Better summary statements were not correlated with diagnostic accuracy.

Burden and clinical outcomes of hospital-coded infections in patients with cancer: an 11-year longitudinal cohort study at an Australian cancer centre.

PURPOSE: Patients with cancer are at increased risk for infection, but the relative morbidity and mortality of all infections is not well understood. The objectives of this study were to determine the prevalence, incidence, time-trends and risk of mortality of infections associated with hospital admissions in patients with haematological- and solid-tumour malignancies over 11 years. METHODS: A retrospective, longitudinal cohort study of inpatient admissions between 1 January 2007 and 31 December 2017 at the Peter MacCallum Cancer Centre was conducted using administratively coded and patient demographics data. Descriptive analyses, autoregressive integrated moving average, Kaplan-Meier and Cox regression modelling were applied. RESULTS: Of 45,116 inpatient hospitalisations consisting of 3033 haematological malignancy (HM), 18,372 solid tumour neoplasm (STN) patients and 953 autologous haematopoietic stem cell transplantation recipients, 67%, 29% and 88% were coded with ≥ 1 infection, respectively. Gastrointestinal tract and bloodstream infections were observed with the highest incidence, and bloodstream infection rates increased significantly over time in both HM- and STN-cohorts. Inpatient length of stay was significantly higher in exposed patients with coded infection compared to unexposed in HM- and STN-cohorts (22 versus 4 days [p < 0.001] and 15 versus 4 days [p < 0.001], respectively). Risk of in-hospital mortality was higher in exposed than unexposed patients in the STN-cohort (adjusted hazard ratio [aHR] 1.61 [95% CI 1.41-1.83]; p < 0.001)) and HM-cohort (aHR 1.30 [95% CI 0.90-1.90]; p = 0.166). CONCLUSION: Infection burden among cancer patients is substantial and findings reflect the need for targeted surveillance in high-risk patient groups (e.g. haematological malignancy), in whom enhanced monitoring may be required to support infection prevention strategies.

A population-based analysis of attributable hospitalisation costs of invasive fungal diseases in haematological malignancy patients using data linkage of state-wide registry and costing databases: 2009-2015.

BACKGROUND: Invasive fungal diseases (IFD) are associated with significant treatment-related costs in patients with haematological malignancies (HM). OBJECTIVES: The objectives of this study were to characterise the gross and attributable hospitalisation costs of a variety of IFD in patients with HM by linking state-wide hospital administrative and costing datasets. PATIENTS/METHODS: We linked the Victorian Admitted Episodes Dataset, Victorian Cancer Registry and the Victorian Cost Data Collection from 1 July 2009 to 30 June 2015. IFD cases and uninfected controls were matched 1:1 based on age within ten years, same underlying HM and length of stay prior to IFD diagnosis. The cost difference between surviving cases and controls, indexed to 2019 Australian dollars (AUD) calculated twelve months from IFD diagnosis, was determined using Poisson and negative binomial regression (NBR). RESULTS: From 334 matched pairs, the gross hospitalisation cost of cases was AUD$67 277 compared to AUD$51 158 among uninfected controls, associated with an excess median hospitalisation cost of AUD$16 119 (P < .001) attributable to IFD, approximating to USD$11 362 and €10 154 at purchasing power parity. Median attributable costs were highest for patients with invasive aspergillosis (AUD$55 642; P < .001) and mucormycosis (AUD$51 272; P = .043) followed by invasive candidiasis AUD$24 572 (P < .001). No change in median excess attributable costs was observed over the study period (P = .90) Analyses by NBR revealed a 1.36-fold increase (P < .001) in total hospitalisation costs among cases as compared to controls twelve months from IFD diagnosis. CONCLUSION: Invasive aspergillosis and mucormycosis have high attributable hospitalisation costs but the overall excess IFD cost of AUD$16 119 is modest, potentially reflecting missed or miscoded fungal episodes arguing for better quality surveillance data at hospital level.

A population-based analysis of invasive fungal disease in haematology-oncology patients using data linkage of state-wide registries and administrative databases: 2005 - 2016.

BACKGROUND: Little is known about the morbidity and mortality of invasive fungal disease (IFD) at a population level. The aim of this study was to determine the incidence, trends and outcomes of IFD in all haematology-oncology patients by linking Victorian hospital data to state-based registries. METHODS: Episodes of IFD complicating adult haematological malignancy (HM) and haematopoietic stem cell transplantation (HSCT) patients admitted to Victorian hospitals from 1st July 2005 to 30th June 2016 were extracted from the Victorian Admitted Episodes Dataset and linked to the date of HM diagnosis from the Victorian Cancer Registry and mortality from the Victorian Death Index. Descriptive analyses and regression modelling were used. RESULTS: There were 619,702 inpatient-episodes among 32,815 HM and 1,765 HSCT-patients. IFD occurring twelve-months from HM-diagnosis was detected in 669 (2.04%) HM-patients and 111 (6.29%) HSCT-recipients, respectively. Median time to IFD-diagnosis was 3, 5, 15 and 22 months in acute myeloid leukaemia, acute lymphoblastic leukaemia, Hodgkin lymphoma and multiple myeloma, respectively. Median survival from IFD-diagnosis was 7, 7 and 3 months for invasive aspergillosis, invasive candidiasis and mucormycosis, respectively. From 2005-2016, IFD incidence decreased 0.28% per 1,000 bed-days. Fungal incidence coincided with spring peaks on time-series analysis. CONCLUSIONS: Data linkage is an efficient means of evaluating the epidemiology of a rare disease, however the burden of IFD is likely underestimated, arguing for better quality hospital level surveillance data to improve management strategies.

Spontaneous Coronary Artery Dissection: A Case Series Reviewing Typical Presentations of an Atypical Pathology.

Introduction: Spontaneous coronary artery dissection (SCAD) is a rare cause of myocardial infarction. Patients suffering SCAD are often young women without typical risk factors for atherosclerotic heart disease. Clinicians should maintain a high index of suspicion for SCAD. Case series: We report three cases of patients with SCAD from a single physician in a six-month period. Each case is unique and highlights the varied presentations and epidemiological risk factors associated with this condition. Discussion: We believe these cases are unique in that they provide insights into the variable presentations and conditions frequently associated with SCAD and will help clinicians maintain a high index of suspicion for this difficult to diagnose and rare cause of type 2 myocardial infarction. We discuss differences in interventional techniques and medical management.

Disease and economic burden of infections in hospitalised children in New South Wales, Australia.

Objectives To describe the burden of disease and hospitalisation costs in children with common infections using statewide administrative data. Methods We analysed hospitalisation prevalence and costs for 10 infections: appendicitis, cellulitis, cervical lymphadenitis, meningitis, osteomyelitis, pneumonia, pyelonephritis, sepsis, septic arthritis, and urinary tract infections in children aged <18 years admitted to hospital within New South Wales, Australia, using an activity-based management administrative dataset over three financial years (1 July 2016-30 June 2019). Results Among 339 077 admissions, 28 748 (8.48%) were coded with one of the 10 infections, associated with a total hospitalisation cost of AUD230 905 190 and a per episode median length-of-stay of 3 bed-days. Pneumonia was the most prevalent coded infection (3.1% [n = 10 524] of all admissions), followed by appendicitis (1.61%; n = 5460), cellulitis (1.22%; n = 4126) and urinary tract infections (0.94%; n = 3193). Eighty per cent of children (n = 22 529) were admitted to a non-paediatric hospital. Mean costs were increased 1.18-fold per additional bed-day, 2.14-fold with paediatric hospital admissions, and 5.49-fold with intensive care unit admissions, which were both also associated with greater total bed-day occupancy. Indigenous children comprised 9.7% of children admitted with these infections, and mean per episode costs, and median bed-days were reduced compared with non-Indigenous children (0.84 [95% CI 0.78, 0.89] and 3 (IQR: 2,5) vs 2 (IQR: 2,4), respectively. Conclusions Infections in children requiring hospitalisation contributea substantial burden of disease and cost to the community. This varies by infection, facility type, and patient demographics, and this information should be used to inform and prioritise programs to improve care for children.

Performance of ICD-10-AM codes for quality improvement monitoring of hospital-acquired pneumonia in a haematology-oncology casemix in Victoria, Australia.

BACKGROUND: The Australian hospital-acquired complication (HAC) policy was introduced to facilitate negative funding adjustments in Australian hospitals using ICD-10-AM codes. OBJECTIVE: The aim of this study was to determine the positive predictive value (PPV) of the ICD-10-AM codes in the HAC framework to detect hospital-acquired pneumonia in patients with cancer and to describe any change in PPV before and after implementation of an electronic medical record (EMR) at our centre. METHOD: A retrospective case review of all coded pneumonia episodes at the Peter MacCallum Cancer Centre in Melbourne, Australia spanning two time periods (01 July 2015 to 30 June 2017 [pre-EMR period] and 01 September 2020 to 28 February 2021 [EMR period]) was performed to determine the proportion of events satisfying standardised surveillance definitions. RESULTS: HAC-coded pneumonia occurred in 3.66% (n = 151) of 41,260 separations during the study period. Of the 151 coded pneumonia separations, 27 satisfied consensus surveillance criteria, corresponding to an overall PPV of 0.18 (95% CI: 0.12, 0.25). The PPV was approximately three times higher following EMR implementation (0.34 [95% CI: 0.19, 0.53] versus 0.13 [95% CI: 0.08, 0.21]; p = .013). CONCLUSION: The current HAC definition is a poor-to-moderate classifier for hospital-acquired pneumonia in patients with cancer and, therefore, may not accurately reflect hospital-level quality improvement. Implementation of an EMR did enhance case detection, and future refinements to administratively coded data in support of robust monitoring frameworks should focus on EMR systems. IMPLICATIONS: Although ICD-10-AM data are readily available in Australian healthcare settings, these data are not sufficient for monitoring and reporting of hospital-acquired pneumonia in haematology-oncology patients.

Classification performance of administrative coding data for detection of invasive fungal infection in paediatric cancer patients.

BACKGROUND: Invasive fungal infection (IFI) detection requires application of complex case definitions by trained staff. Administrative coding data (ICD-10-AM) may provide a simplified method for IFI surveillance, but accuracy of case ascertainment in children with cancer is unknown. OBJECTIVE: To determine the classification performance of ICD-10-AM codes for detecting IFI using a gold-standard dataset (r-TERIFIC) of confirmed IFIs in paediatric cancer patients at a quaternary referral centre (Royal Children's Hospital) in Victoria, Australia from 1st April 2004 to 31st December 2013. METHODS: ICD-10-AM codes denoting IFI in paediatric patients (<18-years) with haematologic or solid tumour malignancies were extracted from the Victorian Admitted Episodes Dataset and linked to the r-TERIFIC dataset. Sensitivity, positive predictive value (PPV) and the F1 scores of the ICD-10-AM codes were calculated. RESULTS: Of 1,671 evaluable patients, 113 (6.76%) had confirmed IFI diagnoses according to gold-standard criteria, while 114 (6.82%) cases were identified using the codes. Of the clinical IFI cases, 68 were in receipt of ≥1 ICD-10-AM code(s) for IFI, corresponding to an overall sensitivity, PPV and F1 score of 60%, respectively. Sensitivity was highest for proven IFI (77% [95% CI: 58-90]; F1 = 47%) and invasive candidiasis (83% [95% CI: 61-95]; F1 = 76%) and lowest for other/unspecified IFI (20% [95% CI: 5.05-72%]; F1 = 5.00%). The most frequent misclassification was coding of invasive aspergillosis as invasive candidiasis. CONCLUSION: ICD-10-AM codes demonstrate moderate sensitivity and PPV to detect IFI in children with cancer. However, specific subsets of proven IFI and invasive candidiasis (codes B37.x) are more accurately coded.

Large Iatrogenic Tracheal Injury From Attempted Endotracheal Cuff Leak Remedy: A Case Report.

Continuous insufflation of oxygen into the pilot balloon of an endotracheal tube has been documented as a viable method to fix an incompetent endotracheal tube cuff. We present a case of a large iatrogenic tracheal injury resulting from an improvised cuff leak management device. Valuable lessons are discussed to prevent similar incidents.

The current scope of healthcare-associated infection surveillance activities in hospitalized immunocompromised patients: a systematic review.

BACKGROUND: Immunocompromised patients are at increased risk of acquiring healthcare-associated infections (HAIs) and often require specialized models of care. Surveillance of HAIs is essential for effective infection-prevention programmes. However, little is known regarding standardized or specific surveillance methods currently employed for high-risk hospitalized patients. METHODS: A systematic review adopting a narrative synthesis approach of published material between 1 January 2000 and 31 March 2018 was conducted. Publications describing the application of traditional and/or electronic surveillance of HAIs in immunocompromised patient settings were identified from the Ovid MEDLINE®, Ovid Embase® and Elsevier Scopus® search engines [PROSPERO international prospective register of systematic reviews (registration ID: CRD42018093651)]. RESULTS: In total, 2708 studies were screened, of whom 17 fulfilled inclusion criteria. Inpatients diagnosed with haematological malignancies were the most-represented immunosuppressed population. The majority of studies described manual HAI surveillance utilizing internationally accepted definitions for infection. Chart review of diagnostic and pathology reports was most commonly employed for case ascertainment. Data linkage of disparate datasets was performed in two studies. The most frequently monitored infections were bloodstream infections and invasive fungal disease. No surveillance programmes applied risk adjustment for reporting surveillance outcomes. CONCLUSIONS: Targeted, tailored monitoring of HAIs in high-risk immunocompromised settings is infrequently reported in current hospital surveillance programmes. Standardized surveillance frameworks, including risk adjustment and timely data dissemination, are required to adequately support infection-prevention programmes in these populations.