Clearance kinetics of parasites and pigment-containing leukocytes in severe malaria

In tropical areas, where unsupervised use of antimalarial drugs is common, patients with an illness consistent clinically with severe malaria but with negative blood smears pose a management dilemma. Malaria pigment is evident in peripheral blood leukocytes in greater than 90% of patients with severe malaria. To characterize the clearance kinetics of parasitized erythrocytes and malaria pigment-containing leukocytes, sequential peripheral blood and intradermal smears were assessed in 27 adult Vietnamese patients with severe falciparum malaria. The clearance of parasitized erythrocytes and pigment- containing monocytes (PCMs) followed first order kinetics. The elimination of pigment-containing neutrophils (PCNs) was first order initially, but deviated from this when counts were low. Clearance of peripheral blood PCMs (median clearance time, 216 hours; range, 84 to 492 hours) was significantly slower than that of parasitized erythrocytes (median, 96 hours; range, 36 to 168 hours) or PCNs (median, 72 hours; range, 0 to 168 hours; P < .0001). Intradermal PCM clearance times were the longest of all (median, 12 days; range, 6 to 23 days; significantly longer than peripheral blood PCM clearance, P < .001). Twenty-one (88%) patients still had signs, symptoms, or laboratory features of severe malaria after parasite clearance but before phagocyte pigment clearance. Sixteen of the 23 surviving patients (70%; 95% confidence interval, 50% to 87%) still had intraleukocytic malaria pigment on peripheral blood films 72 hours after parasite clearance. Thus, by determining the distribution of malaria pigment in peripheral blood and intradermal phagocytes, the time since effective antimalarial treatment started can be estimated. Microscopy for intraleukocytic pigment is valuable in the differential diagnosis of severe febrile illnesses in malarious areas where uncontrolled use of antimalarial drugs is widespread.     

46The feasibility of duodenum electrical stimulation to produce gastrointestinal symptoms in a clinical trial

Introduction:  Gastric Electrical Stimulation (GES) is available as a Humanitarian Use Device for patients with the symptoms of gastroparesis and is effective in reducing gastrointestinal symptoms. We have previously shown that patients with gastric motor disorders often have co-existing abnormalities of the genitourinary system (Gastroenterol 112: A737, 1997), which may now be treated with sacral electrical stimulation (SES), resulting in similar improvements in genitourinary symptoms.
Patients:  We compared the results of therapy with GES and SES in 13 patients who were implanted with both devices. Patients were 11 f, 2 m, mean age of 41 years, who had documented gastroparesis as well as bladder or other pelvic floor dysfunction. All 13 patients had received their GES before the SES.
Methods:  Patients were evaluated at baseline and latest follow up (median 4 years for GES and 2 years for SES), according to previously standardized scores of GI (GI: 0–4, TSS max 20) and GU (GU: 0–3, UTSS, max 12) function. Results were compared by paired t-tests and reported as mean ± SE.
Results:  All 13 patients improved both GI and GU symptoms and the improvement in all parameters as nausea, vomiting, anorexia, bloating, abdominal pain and gastric total symptom score (TSS), leakage, urgency, voiding difficulty, number of pads used and urinary total symptom score (UTSS) were statistically significant (see table below).
Conclusions:  The combination of GES and SES appears to be both safe and effective for patients with con-comitant gastroparesis and bladder dysfunction and the existence of a stimulator for one disorder does not preclude another stimulator.
 

     

Psychological profile of Taiwanese interstitial cystitis patients

Objectives:   The correlation between anxiety and interstitial cystitis has, as best we know, not yet been reported on. The present study investigated the psychological profile, including anxiety and depression, of patients suffering from interstitial cystitis (IC).
Methods:   A total of 47 IC patients, all of whom met National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIDDK) criteria, plus a group of 31 age-matched, asymptomatic women received a structured interview on depression (Hamilton Rating Scale for Depression) and also on anxiety symptoms (Hamilton Rating Scale for Anxiety). IC patients also completed questionnaires relating to IC symptom severity, including urgency and frequency (visual analog scale) and O'Leary Sant index.
Results:   A total of 85% of our IC patients featured significant affective symptoms. The average depression scores were 16.6. Fifteen patients (31.9%) featured mild depressive symptoms, five (10.6%) had mild to moderate and 20 (42.6%) had moderate to severe depression symptoms. The mean anxiety score was 21.0, with 21 (44.7%), nine (19.1%) and 17 (36.2%) patients revealing mild, mild to moderate, and moderate to severe anxiety symptoms, respectively. Further, IC patients reported a significantly greater extent of depression and anxiety than was the case for controls. Pain scale and O'Leary Sant index were significantly correlated to anxiety and depression score.
Conclusions:   Most of our IC patients feature significant depression and anxiety. The extent of affective symptoms would appear to correlate well with IC symptom severity.     

CC4 Cost-Benefit Analysis of Recombinant Erythropoietin in Premature Neonates

Assessing the economic impact of medication side effects is critical for the accurate determination of the cost-effectiveness of pharmaceuticals. It is often necessary to employ modeling techniques that utilize incidence rates that are based on the literature.
OBJECTIVE: To present a calculation of the cost of steroid-induced side effects in renal transplantation as an example of a literature-based model and to discuss the assumptions, techniques, and difficulties inherent in the methodology.
METHODS: We estimated the incidence of adverse events associated with steroids using evidence-based literature analyses. This evidence was used to construct a Markov cost model for each side effect. Side effects included in the analysis were hypertension (and its complications), post-transplant diabetes mellitus (PTDM), peripheral bone fractures, osteonecrosis of the hip, and cataracts.
RESULTS: The side effect incidences reported in the literature vary, in part due to different definitions and followup periods. Furthermore, data from randomized controlled trials can be handicapped by low statistical power to detect side effects and patient crossover or dropouts. Confounding and bias are concerns in case-control and cohort studies, and can complicate the determination of attributable risk from cohort studies. Utilizing the incidence data from the literature, the total 10-year discounted cost for a 50-patient cohort was $266,000.
CONCLUSIONS: Extracting side effect incidence data from the literature is a challenging but essential step in modeling side effect costs. The variability in reported results should be ascertained, and assumptions requiring clinical expertise are often required. We have demonstrated the methodology and estimated the financial cost of adverse events associated with steroids in renal transplantation.