Predictors Of Fatality Research Articles

P1040 Clinical and laboratory features of Crimean-Congo haemorrhagic fever: predictors of fatality

Outbreaks of flaviviruses such as dengue (DV), yellow fever (YFV), Japanese encephalitis (JEV), tick-borne encephalitis (TBEV) and West Nile (WNV) affect numerous countries around the world. The fast spread of these viruses is the result of increases in the human population, rapid urbanisation and globalisation. While vector control is an important preventive measure against vector-borne diseases, it has failed to prevent the spread of these diseases, particularly in developing countries where the implementation of control measures is intermittent. As antiviral drugs against flaviviruses are not yet available, vaccination remains the most important tool for prevention. Although human vaccines for YFV, TBEV and JEV are available, on-going vaccination efforts are insufficient to prevent infection. No vaccines against DENV and WNV are available. Research advances have provided important tools for flavivirus vaccine development, such as the use of plants as a recombinant antigen production platform. This review summarises the research efforts in this area and highlights why a plant system is considered a necessary alternative production platform for high-tech subunit vaccines.

Predictors of Fatality in Hemolytic Uremic Syndrome Lack Numbers: In Reply

We appreciate the thoughtful comments of Drs Harrington, Hawkes, and Al-Odayani regarding our study of risk factors for death among children with hemolytic uremic syndrome.1 Harrington correctly highlights the limitations of a study that included patients over a 33-year period and included small numbers of deaths, variations in data collection, and changes in medical practice. We agree that great care should be used before generalizing from a retrospective study in one region to current practice. Nonetheless, the factors we identified may generate hypotheses for future studies and may help identify patients whose conditions warrant early …

Predictors of Fatality in Hemolytic Uremic Syndrome Lack Numbers

To the Editor.—As an exercise in evidence-based medicine, fellows in the clinical training program at our institution dissect a current article at a monthly journal-club meeting. We recently reviewed the case-control study on predictors of death in hemolytic uremic syndrome by Oakes et al.1 We have the following concerns regarding a conceptual error in the statistical analysis.Oakes et al described the causes of death in children who presented with hemolytic uremic syndrome over a 30-year period in Utah. Using information from a registry of 358 patients, they used a case-control design to determine the effect of prognostic variables, both clinical (bloody diarrhea, oliguria, anuria, fever, seizures, coma, edema, vomiting, dehydration, and lethargy) and laboratory parameters (hematocrit, white blood cell count), on the outcome of interest: death. They used both univariate and multivariate analyses to identify key prognostic variables. They presented the results of the univariate analysis as a “relative risk”; for example, fatal cases were associated with a relative risk of elevated hematocrit of 7.58 (P = .00045). Given the study design, this analysis is backward: the risk of the prognostic factor (elevated hematocrit) is given as a function of the outcome (death)! A more conventional approach for a case-control study, which provides more intuitive and useful information, would be to use an odds ratio, which approximates the relative risk of the outcome (death) given the presence or absence of the prognostic variable (elevated hematocrit). Using the data presented, the odds ratio of death for a patient with an elevated hematocrit is 16.8 (P = .00002, Fisher's exact test), meaning that the odds of dying are ∼17-fold higher in a patient with an elevated hematocrit. We view this as a fundamental, conceptual error, highlighting the importance of a clear distinction between outcome variables and prognostic variables and the utility of the odds ratio in approaching the analysis of a case-control study on prognosis. The error provided an excellent platform for discussion at our educational journal club!Second, the authors used conditional logistic regression to determine which variables were independently associated with death. Only an elevated white blood cell count and an elevated hematocrit were independent predictors, yet the authors' conclusions include oligoanuria and dehydration as important prognostic variables. We feel that the analysis supports only the elevated white blood cell count and the elevated hematocrit as significant prognostic variables.We also noted incidental discrepancies between the text and Table 3 and request clarification from the authors: P value for edema (text: P = .035; table: P = 0.35); percent lethargy among nonfatal cases (text: 49.1%; table: 66.1%); P value for lethargy (text: P = .016; table: P = 0.3); and seizures listed in the table as significant (P < .05) variable but not in text.

Predictors of Fatality in Hemolytic Uremic Syndrome Lack Numbers

To the Editor.—I congratulate Oakes et al1 for attempting to identify possible risk factors for mortality in pediatric patients with postdiarrheal hemolytic uremic syndrome. Obviously, performing a retrospective review of charts over a 33-year period can have its limitations, not the least of which is uniformity of data. Even with multivariate analysis, it might be somewhat speculative to make some type of predictive model with only 12 comparative cases. Understandably, a physician in the intermountain west area may not have the same access to a tertiary care facility as a physician located on one of the coasts, and this type of predictive model may prove to be extremely useful.However, I do have some concerns with their Table 3. It seems there are several typographical mistakes, where the text does not match up with the table. For example, “lethargy” had a P value in the text of .016, but in the table it is listed as 0.3. In addition, the P value in the text for “edema” is listed as .035 and in the table as 0.35. However, when I performed the actual calculations on a straightforward 2-by-2 contingency table, the relative risk and P value were 1.6 and .48, respectively. Several of the other parameters of clinical illnesses in the table were also intuitively, and statistically, not correlating with the numbers found in the manuscript. Because I consider myself a very weak statistician, at best, I think a reanalysis of your numbers with a statistician might help solidify your conclusions.

Predictors of Fatality in Postdiarrheal Hemolytic Uremic Syndrome

Describe the cause of deaths among patients with postdiarrheal hemolytic uremic syndrome (HUS) and identify predictors of death at the time of hospital admission. Case-control study of 17 deaths among patients with HUS identified from the Intermountain HUS Patient Registry (1970-2003) compared against all nonfatal cases. Of the 17 total deaths, 15 died during the acute phase of disease. Two died because treatment was withdrawn based on their preexisting conditions, and 1 died because of iatrogenic cardiac tamponade; they were excluded from analysis. Brain involvement was the most common cause of death (8 of 12); congestive heart failure, pulmonary hemorrhage, and hyperkalemia were infrequent causes. Presence of prodromal lethargy, oligoanuria, or seizures and white blood cell count (WBC) >20 x 10(9)/L or hematocrit >23% on admission were predictive of death. In multivariate analysis, elevated WBC and elevated hematocrit were independent predictors. The combination of prodromal dehydration, oliguria, and lethargy and admission WBC values >20 x 10(9)/L and hematocrit >23% appeared in 7 of the 12 acute-phase deaths. Diarrheal HUS patients presenting with oligoanuria, dehydration, WBC >20 x 10(9)/L, and hematocrit >23% are at substantial risk for fatal hemolytic uremic syndrome. Such individuals should be referred to pediatric tertiary care centers.

Evaluation of WHO Classification of Hypothermia in Sick Extramural Neonates as Predictor of Fatality

The objective of this study is to correlate the severity of hypothermia in sick extramural neonates with fatality and physiological derangements. This is a prospective observational study carried out at the referral neonatal unit of a teaching hospital admitting extramural neonates. The subjects comprised of 100 extramural hypothermic neonates transported to the Referral neonatal unit. Neonates weighing more than 1000 g, with abdominal skin temperature less than 36.5 degrees C at admission were included in the study. Hypothermia was classified as per WHO recommendations. Clinical features including age, weight, gestational age, clinical diagnosis, vitals, place of delivery, details of transportation and capillary filling time were recorded at the time of admission. Oxygen saturation was recorded by a pulse oximeter. Samples for sepsis screen, blood culture and blood glucose were taken at admission. During the study it was observed that fatality was 39.3% in mildly hypothermic babies, 51.6% in moderately hypothermic babies and 80% in severely hypothermic babies. However, the presence of associated illness (birth asphyxia, neonatal sepsis and respiratory distress), physiological derangements (hypoxia, hypoglycemia and shock) and weight less than 2000 g were associated with more than 50% fatality even in mildly hypothermic babies. When moderate hypothermia was associated with hypoxia or shock, the fatality was 83.3% and 90.9% respectively. Similarly, mild hypothermia with hypoglycemia was associated with 71.4% fatality. The conclusion drawn from this study is that the WHO classification of severity of hypothermia correlates with the risk of fatality. However, it considers only body temperature to classify severity of hypothermia. The presence of associated illness (birth asphyxia, neonatal sepsis and respiratory distress), physiological derangements (hypoxia, hypoglycemia and shock) and weight less than 2000 g should be considered adverse factors in hypothermic neonates. Their presence should classify hypothermia in the next higher category of severity in WHO classification.

Lupus in the 1980s: III. Influence of clinical variables, biopsy,and treatment on the outcome in 150 patients with lupus nephritis seen at a single center

Of 500 patients with systemic lupus erythematosus observed at our center, 150 fulfilled criteria for lupus nephritis. Of these 150 patients, 91% were female, and 67% were white. The mean age of onset was 26.2 years, and the mean follow-up duration was 11.7 years. Biopsies (n = 142) performed on 107 patients showed the following World Health Organization (WHO) class distribution: class I, n = 1; class II, n = 13; class III, n = 19; class IV, n = 69; class V, n = 17; class VI, n = 8; and class not determinable, n = 15. Ninety-five patients were nephrotic. Therapeutic intervention courses given to all patients (n = 356) included parenteral (IV) cyclophosphamide (n = 58), high-dose oral steroids (n = 126), pulse steroids (n = 49), apheresis (n = 39), azathioprine (n = 43), oral cyclophosphamide (n = 5), nitrogen mustard (n = 27), and chlorambucil (n = 6). In addition to examining the course of disease for various subsets, various predictors for fatality and end-stage renal disease (ESRD) were analyzed. Descriptive data for the short-term response to five therapies are provided for the complete patient sample, proliferative disease, and nephrotic syndrome. Twenty patients died, primarily from cardiovascular complications and sepsis, with 97% and 92% 5-and 10-year survival rates, respectively. Twenty-nine were dialyzed, and 11 were transplanted. Risk of ESRD by WHO class at 5 years was as follows: class III, 0%; IV, 9%; V, 16% ( P = .04 for class V v other patterns). Blacks had a higher risk of death and ESRD. Class III was clearly associated with a lower risk of death and ESRD than class IV or V. Ten-year probabilities of ESRD are 25% for nephrotic patients versus 4% for nonnephrotic patients. IV cyclophosphamide and high-dose oral steroids both appeared to be beneficial for proliferative disease and nephrosis. Treatment with pulse steroids (given with cytotoxic drugs 85% of the time) was associated with nephritis improvement.

The Clinical and Renal Biopsy Predictors of Long-term Outcome in Lupus Nephritis: A Study of 87 Patients and Review of the Literature

The prognostic markers in 87 consecutive patients with lupus nephritis who underwent renal biopsy are reported for five clinically relevant long-term outcomes--renal insufficiency, renal failure, death due to renal systemic lupus erythematosus, death due to non-renal SLE and death due to SLE, both renal and non-renal. We have demonstrated that a number of previously neglected or rarely studied predictors were important prognostic markers. These included the duration of renal disease before biopsy, overall severity of SLE, as well as the presence of vasculitis, hypertension or a comorbid ailment. Furthermore, the study confirms the predictive importance of serum creatinine, 24-h urinary excretion of protein, C3, and of the activity and chronicity indices on biopsy. However, overall a simple measure of tubulointerstitial disease was the best predictor obtained from biopsy. Prognostic models based on clinical data alone were developed for each of the five outcomes. The models amplify our clinical understanding of lupus nephritis. Markers of renal severity were most important in predicting renal outcomes such as renal insufficiency and renal failure. Prognostic factors less directly related to renal disease (comorbidity and vasculitis) were important predictors of fatality. A marker of immunologic disease activity (C3) was a valuable predictor for many of the outcomes. Thus markers of disease severity reflecting organ damage due to SLE and other comorbid conditions could be combined with markers of immunologic activity to predict a variety of outcomes of relevance to a clinician. When biopsy data obtained by light or electron microscopy were evaluated for their ability to add new predictive information to the clinical models, only a limited value for biopsy was noted. It is likely that this reflected the close correlational relationships between clinical and biopsy variables, the strong clinical models generated, and the inclusion in the clinical models of the previously neglected clinical variables, duration of renal disease before biopsy and the presence of vasculitis or comorbid disease.

Electrophysiologic profile of asymptomatic Wolff-Parkinson-White pattern

Electrophysiologic testing in patients with asymptomatic Wolff-Parkinson-White syndrome (WPW) may be useful in defining arrhythmic substrates and predictors of fatality. Forty-two patients with asymptomatic WPW, mean age 36 years, underwent electrophysiologic studies and were followed prospectively. They were compared with a matched control group of patients studied within the same period for documented tachycardia associated with the WPW syndrome. Asymptomatic patients had longer anterograde effective refractory periods of the accessory pathway, longer minimum cycle lengths maintaining 1:1 conduction over the accessory pathway, longer minimum RR intervals between consecutive preexcited beats during atrial fibrillation (AF) and longer mean RR intervals during AF than their symptomatic counterparts. Sustained reciprocating tachycardia could not be induced in most patients and induction of AF required rapid atrial pacing in all patients. Nine patients had an anterograde effective refractory period of less than 270 ms and 17% had minimum cycle length less than 250 ms during induced AF. Over a follow-up of 29 ± 18 months, 1 patient died of noncardiac causes and the rest remained asymptomatic. Thus, patients with asymptomatic WPW have deficient electrophysiologic substrates to maintain orthodromic reciprocating tachycardia under baseline conditions and do not have atrial vulnerability. Seventeen percent of patients had potentially lethal ventricular rates during induced AF.