Hypertensive nephrosclerosis: wider kidney biopsy indications may be needed to improve diagnostics.

BACKGROUND: Hypertensive nephrosclerosis is the presumed underlying cause in many end-stage kidney disease (ESKD) patients, but the diagnosis is disputed and based on clinical criteria with low diagnostic accuracy. OBJECTIVE: To evaluate and improve the diagnostic process for nephrosclerosis patients. METHODS: We included adults from the population-based HUNT study (n = 50 552), Norwegian CKD patients referred for kidney biopsy 1988-2012 (n = 7261), and unselected nephrology clinic patients (n = 193) used for matching. Decision tree analysis and ROC curve-based methods of optimal cut-offs were used to improve clinical nephrosclerosis criteria. RESULTS: Nephrosclerosis prevalence was 2.7% in the general population, and eGFR decline and risk for kidney-related hospital admissions and ESKD were comparable to patients with diabetic kidney disease. In the biopsy cohort, current clinical criteria had very low sensitivity (0.13) but high specificity (0.94) for biopsy-verified arterionephrosclerosis. A new optimized diagnostic algorithm based on proteinuria (<0.75 g d-1 ), systolic blood pressure (>155 mm Hg) and age (>75 years) only marginally improved diagnostic accuracy (sensitivity 0.19, specificity 0.96). Likewise, there were still false-positive cases with treatable diagnoses like glomerulonephritis, interstitial nephritis and others (40% of all test positive). Decision curve analysis showed that the new criteria can lead to higher clinical utility, especially for patients considering the potential harms to be close to the potential benefits, while the more risk-tolerant ones (harm:benefit ratio < 1:4) should consider kidney biopsy. CONCLUSION: Further improvements of the current clinical criteria seem difficult, so risks and benefits of kidney biopsy could be more actively discussed with selected patients to reduce misclassification and direct treatment.

Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer.

Oncolytic virotherapy-the use of viruses that specifically kill tumor cells-is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In this paper, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD8(+) T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.

Quality of life after cerebrovascular stroke: a systematic study of patients' preferences for different functional outcomes.

OBJECTIVES: To elicit valid quality of life estimates and the highest acceptable treatment risk of different outcomes after stroke. This is a prerequisite for rational medical decision-making, especially when considering treatments like thrombolysis. SUBJECTS: Healthy people, non-stroke medical patients and stroke survivors aged 20-84 years (n = 158) INTERVENTIONS: Subjects were interviewed by a physician using three different methods ('standard gamble', 'time trade-off' and 'direct scaling') supported by an interactive computer program. MAIN OUTCOME MEASURES: We measured utility, a numerical value ranging from 0.00 (death) to 1.00 (perfect health), representing the strength of the patient's preference for an outcome. When using the standard gamble method, risk is also introduced into the measurement. RESULTS: People's preferences for stroke outcomes varied widely, and the estimates were influenced by assessment method. We found that previous stroke, marital status and age were the only independent variables influencing the utility given. Subjects in our population over the age of 45 were very comparable to the real population at risk for acute stroke regarding these three variables, and they assigned a median utility of 0.91 (10th percentile, 0.65; 90th percentile, 0.99) to a minor stroke and 0.61 (10th percentile, 0.08; 90th percentile, 0.95) to a major stroke using the standard gamble method. CONCLUSIONS: Most people do not feel that suffering from stroke is an overwhelming catastrophe and they do not accept treatment options with very high risks.

A decision analysis of thrombolytic therapy compared with standard therapy in acute ischaemic stroke.

OBJECTIVES: Experts draw different conclusions on whether thrombolysis can be recommended or not for acute ischaemic stroke. A major problem is weighing the improvement in functional ability against the risk of increased mortality. We wanted to examine this uncertainty regarding thrombolysis using a systematic approach and with a strong emphasis on the patient's point of view. METHODS: We performed a decision analysis where the base case focused on an average stroke patient. We used published probabilities for different functional outcomes after standard supportive care and after adding tissue plasminogen activator (tPA), and we tried to estimate corresponding long-term survival. We interviewed 158 subjects with the standard gamble method to elicit their preference values (utility) for these outcomes. RESULTS: When using the baseline data for an average stroke patient, thrombolysis with tPA was the better choice, with 48 extra quality-adjusted living days; tPA was also superior in 117 individual decision analyses, giving from 10 to 173 extra days. However, sensitivity analysis showed that these results were highly susceptible to changes in utility for major disability, probability of early death, and long-term survival after thrombolysis. To increase the gain as well as the margin of safety regarding the treatment choice, thrombolysis should be restricted to patients who assign low utility values < 0.6-0.7 to major poststroke disability (death = 0.0, good health = 1.0). CONCLUSION: Evaluated by decision analysis, thrombolysis with tPA is on average superior to standard therapy for the few patients fulfilling the strict medical inclusion criteria. Individual incorporation of the patient's point of view narrows the indication even further.

The accuracy of C-reactive protein in diagnosing acute appendicitis--a meta-analysis.

The aim of the study was to review the literature on the accuracy of C-reactive protein (CRP) in diagnosing acute appendicitis. All the relevant articles found by searching Medline and the Science Citation Index were reviewed. We used summary receiver operating characteristic (SROC) curve analysis to describe the central tendency of the studies and to assess potential sources of variability. We included 22 articles with a total number of 3436 patients. The sensitivity ranged from 0.40 to 0.99, and the specificity from 0.27 to 0.90. The cut-off values for a positive test varied from 5 to 25 mg l-1. SROC curve analysis showed that CRP performed significantly better in acute abdomen populations (11 studies) than in populations already selected for appendectomy (11 studies). The diagnostic accuracy of CRP tended to be a little inferior to that of total leukocyte count (13 studies). CRP is a test of medium accuracy in diagnosing acute appendicitis. The formerly distractingly wide range of sensitivity and specificity is at least partly due to variations in cut-off values and to differences in study populations. However, definitive conclusions on the clinical usefulness of the test could not be drawn.

Additional value of biochemical tests in suspected acute appendicitis.

OBJECTIVE: To evaluate the efficacy of biochemical tests in diagnosing acute appendicitis. DESIGN: Open prospective study. SETTING: District hospital, Norway. SUBJECTS: 257 patients with suspected acute appendicitis. INTERVENTIONS: Initial diagnostic accuracy of a logistic regression model using available clinical data was compared with results of corresponding models that included an increasing number of inflammatory parameters. MAIN OUTCOME MEASURES: The estimated probabilities of appendicitis in different testing groups were analysed using receiver operating characteristic (ROC) curves. RESULTS: A model including only clinical variables had a mean area under the ROC curve of 0.854. When the total white blood cell count, C-reactive protein concentration, and neutrophil count were added, the model improved significantly to 0.920. CONCLUSION: Biochemical tests are of additional value in a computer model, and the tests should, if used rationally, also provide physicians with important information in the investigation of acute appendicitis.

Estimating the probability of acute appendicitis using clinical criteria of a structured record sheet: the physician against the computer.

OBJECTIVE: To evaluate physicians' probability estimates of acute appendicitis based on structured collection of clinical data. DESIGN: Open prospective study. SETTING: District hospital, Norway. SUBJECTS: 304 patients admitted with suspected acute appendicitis. INTERVENTIONS: Initial diagnostic accuracy of physicians was compared with corresponding results from a computer model. MAIN OUTCOME MEASURES: The estimated probabilities of appendicitis in different testing groups were analysed using receiver operating characteristic (ROC) curves. RESULTS: Physicians' estimates had a mean area under ROC-curve of 0.81 (95% CI 0.79 to 0.82), not significantly different from the computer model. Both correlated well with the actual rate of appendicitis, but the physicians tended to overestimate the probability by 10%. CONCLUSION: Physicians' probability estimates perform rather well. Further attempts to implement a probabilistic approach in the diagnostic process of acute appendicitis therefore seem justified.

[Bacteremia at a medium-sized Norwegian hospital]. / Bakteriemi ved et middels stort norsk sykehus.

This report, which is based on laboratory reports and patient records, covers the epidemiology, etiology and antibiotic susceptibility of all bacteremic episodes at a community hospital during 1988-90. The overall incidence was eight episodes per 1000 patient admissions, though this figure varied considerably between departments and between age groups. Most organisms were community acquired, and we had few Klebsiella spp., Pseudomonas spp., anaerobic bacteria, fungi and polymicrobial episodes. There were fewer antibiotic resistant strains than reported from outside Scandinavia. The combination of benzylpenicillin and aminoglycoside (plus metronidazole in surgical wards) has a broad enough spectrum of activity for 95% of our patients with sepsis of unknown origin. Thus, our rather "old-fashioned" prescribing policy, with the new and broadspectrum cephalosporins and betalactam drugs constituting only a minor part, is still good practice. The study also shows that cumulative reports issued by the local microbiological laboratory bring awareness to these issues and affect the prescribing pattern in a positive way.

Spectrum of disease in bacteraemic patients during a Streptococcus pyogenes serotype M-1 epidemic in Norway in 1988.

All 87 known cases of bacteraemia due to Streptococcus pyogenes (beta-haemolytic group A streptococci) occurring during the peak of a nationwide outbreak in Norway (population 4.2 million) between January and June 1988 were reviewed. Clinical features varied widely and appeared largely to be dependent on the patients' age. The case fatality rate ranged from 11% in the age group under 30 years to 44% in patients over 60 years. Clinical complications such as shock, severe renal or respiratory failure or serious local infection occurred particularly in 30-to 59-year old individuals. Shock was manifest in 32% of the patients and carried a 68% case fatality rate. Chronic heart disease in the elderly and pneumonia seemed to be associated with a fatal outcome. In the 25 patients (29%) who died the disease showed a fulminant course, 80% dying within 48 hours after admission. However, 56% of the patients had experienced symptoms for more than two days before admission, suggesting that early diagnosis and treatment might possibly have prevented the development of a serious disease. This study revealed a wide spectrum of clinical manifestations in bacteraemia cases in a unique epidemiological situation caused largely by a single serotype of Streptococcus pyogenes; 89% of the 27 preserved bacteraemia strains carried the M-1 antigen. The observations call attention to the ability of these organisms to cause fulminant clinical illness, indicating a probable increase in both invasiveness and toxicity of group A streptococci responsible for the epidemic.

[Causes and risk factors of intraoperative anesthesia complications. A prospective study of 14,735 anesthesias]. / Arsaker og risikofaktorer ved peroperative anestesiproblemer. En prospektiv studie av 14,735 anestesier.

Identification of risk factors is an essential part of our efforts to minimize problems during anesthesia. 14,735 patients were included in a prospective study in order to assess the magnitude of risk and identify risk factors. The rate of complications increased substantially after the age of 40, due mainly to a large number of patients with poor preoperative physical condition. High age in itself was not associated with increased risk of complications. Contrary to former belief, the maintenance period of anesthesia does represent a considerable risk of complications requiring emergency intervention by an anesthesiologist. The complications were related to the conduct of anaesthesia in 70% of the total number of cases and to poor physical status and the surgery in 30%. However, poor physical condition and the surgery were responsible for 50% of the very serious complications and for all the four deaths on the table. The results of the survey confirm that thorough preoperative preparation of the patient is extremely important in order to reduce intraoperative risk, especially in emergency surgery.

[Registration of problems during anesthesia. Analysis of risk factors and quality control]. / Registrering av problemer under anestesi. Risikoanalyse og kvalitetskontroll.

Society continues to increase its demands on the medical profession in regard to quality. We believe this situation should be met by a more systematic approach to risk evaluation and quality assessment of our work. We report an attempt to establish a routine system for recording complications during anesthesia. We included all 14,735 patients who were anesthetized during one year. Data on preoperative disease, type of anesthesia and operation, and problems encountered during anesthesia were recorded on the routine anesthesia chart. An arbitrary scale from 1-3 indicated the severity of the problem. Postoperatively, data from each patient were fed into a personal computer. The system is feasible in a busy clinical setting. Key problems are work discipline, exact criteria for complications, and quality control of anesthesia charts. 655 problems were recorded in 599 patients. 80 problems were very serious. Problems such as drop in blood pressure, intubation, laryngeal spasm and cardiac arrhythmias dominated. Such registration increases awareness for the safety of the patients, and enables us to assess the risk and evaluate the quality of our work. The system is now an integral part of the department's routine.

A study of risk evaluation and quality control in anaesthesia.

Because the community expects increasingly high standards of medical performance, there is every reason for meticulous recording of the problems which can arise during one's work. The aim must be to quantify risks, identify problem areas and create an instrument to facilitate quality control and the analysis of critical events. In the course of one calendar year, problems occurring in all 14,735 patients who underwent anaesthesia in a regional hospital were recorded systematically, classified as to their degree of severity, and entered alongside relevant patient data into individual anaesthesia records; following operation, the information was fed into a data base. The system proved to work well in a heavily committed anaesthesia unit. The main methodological difficulties lay in acquiring the necessary discipline, applying consistently the definitions of complications and controlling data. In all 655 problems were registered in 599 patients, 80 of these being severe; among the most prominent were hypotension, difficulties with intubation, cardiac arrhythmias and laryngeal spasm. Such a system of registration promotes increased alertness to questions of patient safety. Registration of problems is now integrated into the unit's permanent routines.