Staphylococcus aureus bacteremia in immunosuppressed patients: a multicenter, retrospective cohort study.

Staphylococcus aureus bacteremia (SAB) causes significant morbidity and mortality. We assessed the disease severity and clinical outcomes of SAB in patients with pre-existing immunosuppression, compared with immunocompetent patients. A retrospective cohort investigation studied consecutive patients with SAB hospitalized across six hospitals in Toronto, Canada from 2007 to 2010. Patients were divided into immunosuppressed (IS) and immunocompetent (IC) cohorts; the IS cohort was subdivided into presence of one and two or more immunosuppressive conditions. Clinical parameters were compared between cohorts and between IS subgroups. A competing risk model compared in-hospital mortality and time to discharge. A total of 907 patients were included, 716 (79%) were IC and 191 (21%) were IS. Within the IS cohort, 111 (58%) had one immunosuppressive condition and 80 (42%) had two or more conditions. The overall in-hospital mortality was 29%, with no differences between groups (IS 32%, IC 28%, p = 0.4211). There were no differences in in-hospital mortality (sub-distribution hazard ratio [sHR] 1.17, 95% confidence interval [CI] 0.88-1.56, p = 0.2827) or time to discharge (sHR 0.94, 95% CI 0.78-1.15, p = 0.5570). Independent mortality predictors for both cohorts included hypotension at 72 h (IS: p < 0.0001, IC: p < 0.0001) and early embolic stroke (IS: p < 0.0001, IC: p = 0.0272). Congestive heart failure was a mortality predictor in the IS cohort (p = 0.0089). Fever within 24 h (p = 0.0092) and early skin and soft tissue infections (p < 0.0001) were survival predictors in the IS cohort. SAB causes significant mortality regardless of pre-existing immune status, but immunosuppressed patients do not have an elevated risk of mortality relative to immunocompetent patients.

Clinical prediction rules in Staphylococcus aureus bacteremia demonstrate the usefulness of reporting likelihood ratios in infectious diseases.

Infectious diseases specialists often use diagnostic tests to assess the probability of a disease based on knowledge of the diagnostic properties. It has become standard for published studies on diagnostic tests to report sensitivity, specificity and predictive values. Likelihood ratios are often omitted. We compared published clinical prediction rules in Staphylococcus aureus bacteremia to illustrate the importance of likelihood ratios. We performed a narrative review comparing published clinical prediction rules used for excluding endocarditis in S. aureus bacteremia. Of nine published clinical prediction rules, only three studies reported likelihood ratios. Many studies concluded that the clinical prediction rule could safely exclude endocarditis based on high sensitivity and high negative predictive value. Of the studies with similar high sensitivity and high negative predictive value, calculated negative likelihood ratios were able to differentiate and identify the best clinical prediction rule for excluding endocarditis. Compared to sensitivity, specificity and predictive values, likelihood ratios can be more directly used to interpret diagnostic test results to assist in ruling in or ruling out a disease. Therefore, a new standard should be set to include likelihood ratios in reporting of diagnostic tests in infectious diseases research.

Histologic, Clinical, and Radiologic Findings of Alveolar Bone Expansion and Osteomyelitis of the Jaws in Cats.

The objective of this study was to characterize clinical, radiologic, and histologic patterns of alveolar bone expansion and osteomyelitis in cats. Based on case materials submitted as surgical biopsy specimens, alveolar bone pathology was diagnosed in 28 cats. These cats had a total of 37 oral lesions with clinical and radiologic changes that involved bone and/or teeth, including periodontitis, bone expansion, tooth resorption, and/or chronic osteomyelitis; 32 lesions were evaluated by histopathology. Canine teeth were affected in 19 cats (27 affected teeth), with bilateral lesions in 5 (26.3%) cats. The caudal premolar and/or molar regions were affected in 10 cats (10 affected sites). All biopsy sites evaluated by a review of clinical images and/or radiographs had evidence of periodontitis. Clinical photographs showed expansion of alveolar bone in 13 of 16 (81%) biopsy sites evaluated. Radiologically, rarifying osseous proliferation of alveolar bone was seen at 26 of 27 (96%) biopsy sites, and tooth resorption occurred at 15 of 18 (83%) sites. Histologically, the tissue samples from canine sites had compressed trabeculae of mature remodeled bone, loose fibrous stroma with paucicellular inflammation, and mild proliferation of woven bone. Tissue samples from the premolar/molar biopsy sites were often highly cellular with mixed lymphoplasmacytic and chronic suppurative inflammation, ulceration with granulation tissue, and robust proliferation of woven bone. Alveolar bone expansion and osteomyelitis in cats occurs in conjunction with periodontal inflammation and frequently with tooth resorption.

Linking live animals and products: traceability.

It is rarely possible to successfully contain an outbreak of an infectious animal disease, or to respond effectively to a chemical residue incident, without the use of a system for identifying and tracking animals. The linking of animals at the time they are slaughtered--through the use of identification devices or marks and accompanying movement documentation--with the meat produced from their carcasses, adds further value from the perspective of consumer safety. Over the past decade, animal identification technology has become more sophisticated and affordable. The development of the Internet and mobile communication tools, complemented bythe expanded capacity of computers and associated data management applications, has added a new dimension to the ability of Competent Authorities and industry to track animals and the food they produce for disease control, food safety and commercial purposes.

Diagnostic features of feline restrictive orbital myofibroblastic sarcoma.

A progressive debilitating disease of the orbit and adjacent connective tissues of cats has historically been called feline orbital pseudotumor. The authors reviewed clinical, histopathologic, and diagnostic imaging features of this disease in 12 cases from the Comparative Ocular Pathology Laboratory of Wisconsin. The cats' ages ranged from 7 to 16 years (mean, 10.8 years). All cats had a history of severely restricted mobility of the globe and eyelids with secondary corneal disease. Eleven cats (92%) had concurrent involvement of the contralateral eye and/or the oral cavity. Diffuse scleral or episcleral thickening was seen with computed tomography in all clinically affected eyes. Histologically, an insidious infiltration of neoplastic spindle cells in the orbit, eyelids, and periorbital skin and soft tissues, with collagen deposition and a few perivascular lymphocytes, led to entrapment and restricted mobility of the eyelids and orbital tissues. The tumor failed to form a discrete mass, and it spread along fascial planes to the contralateral orbit and eyelids and/or the lips and oral cavity. In all tested cases (n = 10), neoplastic cells were immunohistochemically positive for vimentin, S100 protein, and smooth muscle actin. The authors adopted the term feline restrictive orbital myofibroblastic sarcoma to reflect the restricted mobility of the eyelids and globe and the imaging and histologic features of an invasive yet low-grade myofibroblastic sarcoma.

Maxillary ameloblastic fibroma in a dog.

A 4-year-old spayed female Golden Retriever was presented for evaluation of a rostral maxillary gingival mass. An en bloc resection was performed after histologic diagnosis of ameloblastic fibroma from an incisional biopsy specimen. Histologically, the tumor was composed of (1) poorly differentiated vimentin-positive mesenchymal cells that surrounded islands and (2) thin anastomosing trabeculae of odontogenic epithelium that variably coexpressed pancytokeratin and vimentin. To the authors' knowledge, this is the first report of ameloblastic fibroma in a dog. The clinical, radiographic, and histologic findings in this case are compared to those in other domestic animals and humans.

A vascular subtraction method for improving the variability of evoked tympanic membrane displacement measurements.

OBJECTIVE: Evoked tympanic membrane displacement (TMD) measurements show a correlation with intracranial pressure (ICP). Attempts to use these measurements for non-invasive monitoring of ICP in patients have been limited by high measurement variability. Pulsing of the tympanic membrane at the cardiac frequency has been shown to be a significant source of the variability. In this study we describe a post processing method to remove the cardiac pulse waveform and assess the impact of this on the measurement and its repeatability. APPROACH: Three-hundred and sixteen healthy volunteers were recruited for evoked TMD measurements. The measurements were quantified by V m, defined as the mean displacement between the point of maximum inward displacement and the end of the stimulus. A sample of spontaneously pulsing TMDs was measured immediately before the evoked measurements. Simultaneous recording of the ECG allowed a heartbeat template to be extracted from the spontaneous data and subtracted from the evoked data. Intra-subject repeatability of V m was assessed from 20 repeats of the evoked measurement. Results with and without subtraction of the heartbeat template were compared. The difference was tested for significance using the Wilcoxon sign rank test. MAIN RESULTS: In left and right ears, both sitting and supine, application of the pulse correction significantly reduced the intra-subject variability of V m (p value range 4.0 × 10-27 to 2.0 × 10-31). The average improvement was from 98 ± 6 nl to 56 ± 4 nl. SIGNIFICANCE: The pulse subtraction technique substantially improves the repeatability of evoked TMD measurements. This justifies further investigations to assess the use of TMD measurements in clinical applications where non-invasive tracking of changes in ICP would be useful.

Effect of an antimicrobial stewardship programme on antimicrobial utilisation and costs in patients with leukaemia: a retrospective controlled study.

OBJECTIVES: To examine the effectiveness of an antimicrobial stewardship programme on utilization and cost of antimicrobials in leukaemia patients in Canada. METHODS: We conducted a multisite retrospective observational time series study from 2005 to 2013. We implemented academic detailing as the intervention of an antimicrobial stewardship programme in leukaemia units at a hospital, piloted February-July 2010, then fully implemented December 2010-March 2013, with no intervention in August-November 2010. Internal control was the same hospital's allogeneic haematopoietic stem-cell transplantation unit. External control was the combined leukaemia-haematopoietic stem-cell transplantation unit at another hospital. Primary outcome was antimicrobial utilization (antibiotics and antifungals) in defined daily dose per 100 patient-days (PD). Secondary outcomes were antimicrobial cost (Canadian dollars per PD); cost and utilization by drug class; length of stay; 30-day inpatient mortality; and nosocomial Clostridium difficile infection. We used autoregressive integrated moving average models to evaluate the impact of the intervention on outcomes. RESULTS: The intervention group included 1006 patients before implementation and 335 during full implementation. Correspondingly, internal control had 723 and 264 patients, external control 1395 and 864 patients. Antimicrobial utilization decreased significantly in the intervention group (p <0.01, 278 vs. 247 defined daily dose per 100 PD), increased in external control (p = 0.02, 237.4 vs. 268.9 defined daily dose per 100 PD) and remained stable in internal control (p = 0.66). Antimicrobial cost decreased in the intervention group (p = 0.03; $154.59 per PD vs. $128.93 per PD), increased in external control (p = 0.01; $109.4 per PD vs. $135.97 per PD) but was stable in internal control (p = 0.27). Mortality, length of stay and nosocomial C. difficile rate in intervention group remained stable. CONCLUSIONS: The antimicrobial stewardship programme reduced antimicrobial use in leukaemia patients without affecting inpatient mortality and length of stay.

Endotoxin removal from albumin and saline solutions.

Microporous membranes have been developed which can remove endotoxins selectively from electrolyte and albumin solutions by regioselective adsorption in the membrane matrix and outside surface of the membrane. The membranes were prepared in the form of hollow fibre membranes in a continuous process. By varying the membrane preparation parameters, different pore sizes and adsorption capacities could be realized, thus broadening applications for biological purification. Dynamic adsorption capacities for endotoxin from albumin and saline solution were determined and were found to be in the range of 0.2 and 0.1 microg endotoxin/g membrane, respectively, suggesting different adsorption mechanisms.

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Systematic overview of cost-utility assessments in oncology.

PURPOSE: Cost-utility analyses (CUAs) present the value of an intervention as the ratio of its incremental cost divided by its incremental survival benefit, with survival weighted by utilities to produce quality-adjusted life years (QALYs). We critically reviewed the CUA literature and its role in informing clinical oncology practice, research priorities, and policy. METHODS: The English-language literature was searched between 1975 and1997 for CUAs. Two readers abstracted from each article descriptions of the clinical situation and patients, the methods used, study perspective, the measures of effectiveness, costs included, discounting, and whether sensitivity analyses were performed. The readers then made subjective quality assessments. We also extracted utility values from the reviewed papers, along with information on how and from whom utilities were measured. RESULTS: Our search yielded 40 studies, which described 263 health states and presented 89 cost-utility ratios. Both the number and quality of studies increased over time. However, many studies are at variance with current standards. Only 20% of studies took a societal perspective, more than a third failed to discount both the costs and QALYs, and utilities were often simply estimates from the investigators or other physicians. CONCLUSION: The cost-utility literature in oncology is not large but is rapidly expanding. There remains much room for improvement in the methodological rigor with which utilities are measured. Considering quality-of-life effects by incorporating utilities into economic studies is particularly important in oncology, where many therapies obtain modest improvements in response or survival at the expense of nontrivial toxicity.

Charges for medical care at different hospitals.

BACKGROUND: The United States has a high proportion of people without health insurance (15%) and a low proportion of people without employment (5%), resulting in millions who lack insurance but have some ability to pay. We tested whether hospitals charge similar prices for well-specified elective services to individuals paying out-of-pocket for medical care. METHODS: We surveyed the 2 largest general hospitals from every large city (population >500 000) in the United States and Canada. At each hospital we evaluated 5 diagnostic, 7 therapeutic, and 3 nonclinical services to determine the total charge to patients who pay directly. RESULTS: Overall, 66 hospitals were included (average, 758 beds; not-for-profit, 97% [n = 64]; teaching, 80% [n = 53]). The range in charges was substantial; for example, a screening mammogram was $40 at one hospital in Los Angeles, Calif, and $346 at one hospital in Quebec City. Charges for a screening mammogram were relatively stable between 1996 and 1997 (r=0.79; 95% confidence interval, 0.68-0.87) and unrelated to the hospital's location or charges for other services. The relative amount of variation in charges was similar for high-priced and low-priced services, similar for diagnostic and therapeutic services, and similar for the United States and Canada. CONCLUSIONS: Charges for the same hospital service vary substantially. Greater visibility might reduce some variation by bringing outliers into closer scrutiny. Patients seeking care and paying out-of-pocket could save financially by comparison shopping.

Problems in the interpretation of the in vivo measurement of calcium by the argon-37 method: an investigation of inert-gas elimination in humans.

An investigation has been made of some physiological problems associated with the interpretation of in-vivo measurements of calcium by the argon-37 method. Inert-gas elimination in humans over a period of several days was studied using i.v. injections of Xe-133. The results imply that the exhalation rate of A-37 formed in bone will be affected by the individual's composition, in particular body fat. Comparison of calcium measurements between individuals and between laboratories is meaningful only if corrections are made for differing individual composition.

Radiation dose and second cancer risk in patients treated for cancer of the cervix.

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.

Are pharmaceuticals cost-effective? A review of the evidence.

The argument that prescription drugs are cost-effective has been made both by the pharmaceutical industry to support rising drug prices and expenditures, and by advocates of expanded drug coverage for elderly and low-income persons. A new database of 228 published cost-utility analyses sheds light on the issue. According to published data, some drugs do save money or are cost-effective, but the issue depends critically on the context in which the drug is used and the intervention with which it is compared. Cost-utility analyses funded by the drug industry tend to report more favorable results than do those funded by nonindustry sources. Cost-effectiveness analysis can help policymakers to determine whether drugs and other interventions offer value for money.

Aetiological factors in cutaneous malignant melanomas seen at a UK skin clinic.

A clinic-based case-control study was set up in 1961 to examine a variety of aetiological factors in malignant melanoma cases compared with controls with other non-malignant skin conditions. The 268 cases and 1577 controls showed odds ratios of 1.9 for red hair, 2.0 for skin that burns in the sun, and no difference between indoor and outdoor workers or between Celts and other Europeans, consistent with the results of more recent studies. Exposure to 16 specific chemicals was recorded in the study and, among these, men exposed to cutting oils were found to have a significantly raised odds ratio of 1.91. Other statistically significant findings were an elevated risk among women diabetics, particularly in the postmenopausal age group, and a reduced risk of 0.7 among cigarette smokers.

Abnormal pattern of erythrocyte ageing in hereditary spherocytosis as shown by Percoll density gradient centrifugation.

Erythrocytes from individuals with Hereditary Spherocytosis (HS) were fractionated on Percoll density gradients. The osmotic fragility, mean cell volume, mean cell haemoglobin concentration, reticulocyte count and cell morphology of the fractions showed that the gradients separate the erythrocytes according to age, the older small spherocytes appearing in the dense fractions. Comparison of the well established parameters of erythrocyte ageing, pyruvate kinase activity, acetylcholinesterase activity and cell potassium content in normal and HS erythrocyte fractions of similar age revealed abnormalities in the senescence of HS erythrocytes both before and after splenectomy.

Methodological issues in the use of guidelines and audit to improve clinical effectiveness in breast cancer in one United Kingdom health region.

AIMS: To develop a system to improve and monitor clinical performance in the management of breast cancer patients in one United Kingdom health region. DESIGN: An observational study of the changes brought about by the introduction of new structures to influence clinical practice and monitor change. SETTING: North Thames (East) Health region, comprising seven purchasing health authorities and 21 acute hospitals treating breast cancer. SUBJECTS: The multi-disciplinary breast teams in 21 hospitals and an audit sample of 419 (28%) of the breast cancer patients diagnosed in 1992 in the region. INTERVENTIONS: Evidence-based interventions for changing clinical practice: regional guidelines, senior clinicians acting as <>, audit of quality rather than cost of services, ownership of data by clinicians, confidential feed-back to participants and education. OUTCOME MEASURES: Qualitative measures of organizational and behavioural change. Quantitative measures of clinical outcomes compared to guideline targets and to results from previous studies within this population. RESULTS: Organizational changes included the involvement, participation of and feedback to 16 specialist surgeons and their multidisciplinary teams in 21 hospitals. Regional clinical guidelines were developed in 6 months and the dataset piloted within 9 months. The audit cycle was completed within 2 years. The pilot study led to prospective audit at the end of 2 years for all breast cancers in the region and a 15-fold increase in high quality clinical information for these patients. Changes in clinical practice between 1990 and 1992 were observed in the use of chemotherapy (up from 17-23%) and axillary surgery (up from 46-76%). CONCLUSIONS: The approach used facilitated rapid change and found a balance between local involvement (essential for sustainability within a hospital setting) and regional standardization (essential for comparability across hospitals). The principles of the approach are generalized to other cancers and to other parts of the UK and abroad.