Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. OBJECTIVES: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. METHODS: The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. MEASUREMENTS AND MAIN RESULTS: In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. CONCLUSIONS: Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.

Transformation to "high grade" neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma.

Several different acquired resistance mechanisms of EGFR mutant lung adenocarcinoma to EGFR-tyrosine kinase inhibitor (TKI) therapy have been described, most recently transformation to small cell lung carcinoma (SCLC). We describe the case of a 46-year-old female with relapsed EGFR exon 19 deletion lung adenocarcinoma treated with erlotinib, and on resistance, cisplatin-pemetrexed. Liver rebiopsy identified an afatinib-resistant combined SCLC and non-small cell carcinoma with neuroendocrine morphology, retaining the EGFR exon 19 deletion. This case highlights acquired EGFR-TKI resistance through transformation to the high-grade neuroendocrine carcinoma spectrum and that that such transformation may not be evident at time of progression on TKI therapy.

Using UAV acquired photography and structure from motion techniques for studying glacier landforms: application to the glacial flutes at Isfallsglaciären

Glacier and ice sheet retreat exposes freshly deglaciated terrain which often contains small-scale fragile geomorphological features which could provide insight into subglacial or submarginal processes. Subaerial exposure results in potentially rapid landscape modification or even disappearance of the minor–relief landforms as wind, weather, water and vegetation impacts on the newly exposed surface. Ongoing retreat of many ice masses means there is a growing opportunity to obtain high resolution geospatial data from glacier forelands to aid in the understanding of recent subglacial and submarginal processes. Here we used an unmanned aerial vehicle to capture close-range aerial photography of the foreland of Isfallsglaciären, a small polythermal glacier situated in Swedish Lapland. An orthophoto and a digital elevation model with ~2 cm horizontal resolution were created from this photography using structure from motion software. These geospatial data was used to create a geomorphological map of the foreland, documenting moraines, fans, channels and flutes. The unprecedented resolution of the data enabled us to derive morphological metrics (length, width and relief) of the smallest flutes, which is not possible with other data products normally used for glacial landform metrics mapping. The map and flute metrics compare well with previous studies, highlighting the potential of this technique for rapidly documenting glacier foreland geomorphology at an unprecedented scale and resolution. The vast majority of flutes were found to have an associated stoss-side boulder, with the remainder having a likely explanation for boulder absence (burial or erosion). Furthermore, the size of this boulder was found to strongly correlate with the width and relief of the lee-side flute. This is consistent with the lee-side cavity infill model of flute formation. Whether this model is applicable to all flutes, or multiple mechanisms are required, awaits further study.

Acquired Cold Urticaria: Clinical Features, Particular Phenotypes, and Disease Course in a Tertiary Care Center Cohort

BACKGROUND: Data about special phenotypes, natural course, and prognostic variables of patients with acquired cold urticaria (ACU) are scarce. OBJECTIVES: We sought to describe the clinical features and disease course of patients with ACU, with special attention paid to particular phenotypes, and to examine possible parameters that could predict the evolution of the disease. METHODS: This study was a retrospective chart review of 74 patients with ACU who visited a tertiary referral center of urticaria between 2005 and 2015. RESULTS: Fourteen patients (18.9%) presented with life-threatening reactions after cold exposure, and 21 (28.4%) showed negative results after cold stimulation tests (classified as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution at the end of the surveillance period and had no subsequent recurrences. Higher rates of atypical ACU along with a lower likelihood of achieving complete symptom resolution was observed in patients who had an onset of symptoms during childhood (P < .05). In patients with atypical ACU, shorter disease duration and lower doses of antihistamines required for achieving disease control were detected (P < .05). Age at disease onset, symptom severity, and cold urticaria threshold values were found to be related to disease evolution (P < .05). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The knowledge of the clinical predictors of the disease evolution along with the clinical features of ACU phenotypes would allow for the establishment of an early and proper therapeutic strategy.

CURB-65 and Other Markers of Illness Severity in Community-Acquired Pneumonia Among HIV-Positive Patients

As the relative burden of community-acquired bacterial pneumonia among HIV-positive patients increases, adequate prediction of case severity on presentation is crucial. We sought to determine what characteristics measurable on presentation are predictive of worse outcomes. We studied all admissions for community-acquired bacterial pneumonia over one year at a tertiary centre. Patient demographics, comorbidities, HIV-specific markers and CURB-65 scores on Emergency Department presentation were reviewed. Outcomes of interest included mortality, bacteraemia, intensive care unit admission and orotracheal intubation. A total of 396 patients were included: 49 HIV-positive and 347 HIV-negative. Mean CURB-65 score was 1.3 for HIV-positive and 2.2 for HIV-negative patients (p < 0.0001), its predictive value for mortality being maintained in both groups (p = 0.03 and p < 0.001, respectively). Adjusting for CURB-65 scores, HIV infection by itself was only associated with bacteraemia (adjusted odds ratio [AOR] 7.1, 95% CI [2.6-19.5]). Patients with < 200 CD4 cells/µL presented similar CURB-65 adjusted mortality (aOR 1.7, 95% CI [0.2-15.2]), but higher risk of intensive care unit admission (aOR 5.7, 95% CI [1.5-22.0]) and orotracheal intubation (aOR 9.1, 95% CI [2.2-37.1]), compared to HIV-negative patients. These two associations were not observed in the > 200 CD4 cells/µL subgroup (aOR 2.2, 95% CI [0.7-7.6] and aOR 0.8, 95% CI [0.1-6.5], respectively). Antiretroviral therapy and viral load suppression were not associated with different outcomes (p > 0.05). High CURB-65 scores and CD4 counts < 200 cells/µL were both associated with worse outcomes. Severity assessment scales and CD4 counts may both be helpful in predicting severity in HIV-positive patients presenting with community-acquired bacterial pneumonia.

Gastric and Peritoneal Involvement of Human Herpes Virus 8 Related Kaposi Sarcoma in a Patient with Acquired Immunodeficiency Syndrome

Kaposi's sarcoma (KS) is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV). The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8). The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.

Prasugrel and Acquired Thrombotic Thrombocytopenic Purpura Associated with ADAMTS13 Activity Deficiency

We report a case of a 64-year-old male who, 44 days after starting treatment with prasugrel, presented with severe thrombocytopenia, anemia, renal failure, and severe ADAMTS13 activity deficiency, along with a high titer of autoantibodies to this protease.

Focus on sulfur count rates along marine sediment cores acquired by XRF Core Scanner

The aim of this study is to investigate the information provided by sulfur count rates obtained by X-ray fluorescence core scanner (XRF-CS) along sedimentary records. The analysis of two marine sediment cores from the Niger Delta margin shows that XRF-CS sulfur count rates obtained at the surface of split core sections with XRF-CS correlate with both direct quantitative pyrite concentrations, as inferred from X-ray powder diffraction (XRD) and sulfur determination by wavelength dispersive X-ray fluorescence (WD-XRF) spectrometry, and total dissolved sulfide (TDS) contents in the sediment pore water. These findings demonstrate the potential of XRF-CS for providing continuous profiles of pyrite distribution along split sections of sediment cores. The potential of XRF-CS to detect TDS pore water enrichments in marine sediment records, even a long time after sediment recovery, will be further discussed.

‘Failure to maintain’: care rationing and the clinical and financial burden of nurse sensitive hospital-acquired complications in complex older patients

Background: The ageing population, with concomitant increase in chronic conditions, is increasing the presence of older people with complex needs in hospital. People with dementia are one of these complex populations and are particularly vulnerable to complications in hospital. Registered nurses can offer simultaneous assessment and intervention to prevent or mitigate hospital-acquired complications through their skilled brokerage between patient needs and hospital functions. A range of patient outcome measures that are sensitive to nursing care has been tested in nursing work environments across the world. However, none of these measures have focused on hospitalised older patients. Method: This thesis explores nursing-sensitive complications for older patients with and without dementia using an internationally recognised, risk-adjusted patient outcome approach. Specifically explored are: the differences between rates of complications; the costs of complications; and cost comparisons of patient complexity. A retrospective cohort study of an Australian state’s 2006–07 public hospital discharge data was utilised to identify patient episodes for people over age 50 (N=222,440) where dementia was identified as a primary or secondary diagnosis (N=44,422). Extra costs for patient episodes were estimated based on length of stay (LOS) above the average for each patient’s Diagnosis Related Group (DRG) (N=157,178) and were modelled using linear regression analysis to establish the strongest patient complexity predictors of cost. Results: Hospitalised patients with a primary or secondary diagnosis of dementia had higher rates of complications than did their same-age peers. The highest rates and relative risk for people with dementia were found in four key complications: urinary tract infections; pressure injuries; pneumonia, and delirium. While 21.9% of dementia patients (9,751/44,488, p<0.0001) suffered a complication, only 8.8% of non-dementia patients did so (33,501/381,788, p<0.0001), giving dementia patients a 2.5 relative risk of acquiring a complication (p<0.0001). These four key complications in patients over 50 both with and without dementia were associated with an eightfold increase in length of stay (813%, or 3.6 days/0.4 days) and double the increased estimated mean episode cost (199%, or A$16,403/ A$8,240). These four complications were associated with 24.7% of the estimated cost of additional days spent in hospital in 2006–07 in NSW (A$226million/A$914million). Dementia patients accounted for 22.0% of these costs (A$49million/A$226million) even though they were only 10.4% of the population (44,488/426,276 episodes). Hospital-acquired complications, particularly for people with a comorbidity of dementia, cost more than other kinds of inpatient complexity but admission severity was a better predictor of excess cost. Discussion: Four key complications occur more often in older patients with dementia and the high rate of these complications makes them expensive. These complications are potentially preventable. However, the care that can prevent them (such as mobility, hydration, nutrition and communication) is known to be rationed or left unfinished by nurses. Older hospitalised people who have complex needs, such as those with dementia, are more likely to experience care rationing as their care tends to take longer, be less predictable and less curative in nature. This thesis offers the theoretical proposition that evidence-based nursing practices are rationed for complex older patients and that this rationed care contributes to functional and cognitive decline during hospitalisation. This, in turn, contributes to the high rates of complications observed. Thus four key complications can be seen as a ‘Failure to Maintain’ complex older people in hospital. ‘Failure to Maintain’ is the inadequate delivery of essential functional and cognitive care for a complex older person in hospital resulting in a complication, and is recommended as a useful indicator for hospital quality. Conclusions: When examining extra length of stay in hospital, complications and comorbid dementia are costly. Complications are potentially preventable, and dementia care in hospitals can be improved. Hospitals and governments looking to decrease costs can engage in risk-reduction strategies for common nurse sensitive complications such as healthy nursing work environments that minimise nurses’ rationing of functional and cognitive care. The conceptualisation of complex older patients as ‘business as usual’ rather than a ‘burden’ is likely necessary for sustainable health care services of the future. The use of the ‘Failure to Maintain’ indicators at institution and state levels may aid in embedding this approach for complex older patients into health organisations. Ongoing investigation is warranted into the relationships between the largest health services expense (hospitals), the largest hospital population (complex older patients), and the largest hospital expense (nurses). The ‘Failure to Maintain’ quality indicator makes a useful and substantive contribution to further clinical, administrative and research developments.