A cost-effectiveness analysis of identifying Fusobacterium necrophorum in throat swabs followed by antibiotic treatment to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses

The main purpose of this paper was to estimate the cost per quality-adjusted life year (QALY) saved by identifying Fusobacterium necrophorum in throat swabs followed by proper antibiotic treatment, to reduce the incidence of Lemierre’s syndrome and peritonsillar abscesses (PTA) originating from a pharyngitis. The second purpose was to estimate the population size required to indicate that antibiotic treatment has an effect. Data from publications and our laboratory were collected. Monte Carlo simulation and one-way sensitivity analysis were used to analyse cost-effectiveness. The cost-effectiveness analysis shows that examining throat swabs from 15- to 24-year-olds for F. necrophorum followed by antibiotic treatment will probably be less costly than most other life-saving medical interventions, with a median cost of US$8,795 per QALY saved. To indicate a reduced incidence of Lemierre’s syndrome and PTA in Denmark, the intervention probably has to be followed for up to 5 years. Identifying F. necrophorum in throat swabs from 15- to 24-year-olds followed by proper antibiotic treatment only requires a reduction of 20–25 % in the incidence of Lemierre’s syndrome and PTA to be cost-effective. This study warrants further examination of the effect of antibiotic treatment on the outcome of F. necrophorum acute and recurrent pharyngitis, as well as the effect on Lemierre’s syndrome and PTA.     

Association between condylar morphology and changes in bony microstructure and sub‐synovial inflammation in experimental temporomandibular joint arthritis

J Oral Pathol Med (2011) 40 : 111–120 Background: In juvenile idiopathic arthritis involvement of the temporomandibular joints (TMJs) is often associated with mandibular growth deviations. The relation between the growth deviations and severity of the inflammation, condylar shape, the micro‐architecture, and the quality of the bone has not previously been investigated. This paper studies the effect on the bony structures in mandibular condylar development in rabbits with antigen‐induced arthritis. Methods: Included were 42 juvenile rabbits with ovalbumin‐induced arthritis of the TMJs treated with intraarticular saline, intraarticular etanercept or subcutaneous etanercept. A TMJ from each animal was scanned using micro‐computed tomography and structural parameters were calculated. Three‐dimensional reconstructions of the mandibular condyle were scored blindly as normal or abnormal. TMJs were stratified for condylar morphology and were evaluated against data on trabecular structural parameters, inflammation, degree of mineralization, overall mandibular growth, and mineral apposition rate. Results: Abnormal morphology were seen in 15/32 animals available for data analysis. Erosions were an uncommon finding. Abnormal morphology was strongly related to the degree of inflammation. The trabecular separation was larger in group with abnormal morphology than in the group with normal morphology. Abnormal condylar morphology was not associated with overall mandibular growth. No differences were observed in mineral apposition rate. No differences in structural parameters were seen according to treatment modality. Conclusion: We showed that severe inflammation in the TMJs during mandibular development was associated with morphological changes in the mandibular condyle. These changes were predominantly seen at the macro‐morphological level and only very few differences were structural.     

Collection,verification, sharing and dissemination of data: the CONTRAST experience

The scientific community is charged with growing demands regarding the management of project data and outputs and the dissemination of key results to various stakeholders. We discuss experiences and lessons from CONTRAST, a multidisciplinary alliance that had been funded by the European Commission over a 4-year period, in order to optimize schistosomiasis control and transmission surveillance in sub-Saharan Africa. From the start, project partners from Europe and Africa set out an ambitious goal: to sample data following standard protocols at all field sites and then sharing the data in a way that would enable all project partners to have access through a password-protected Internet-based data portal. This required anonymous agreement on several common standardized sample forms, ranging from the mundane but important issue of using the same units of measurement to more complex challenges, for instance agreeing on the same protocols for double-treatment of praziquantel in different settings. With the experiences gained by the CONTRAST project, this paper discusses issues of data management and sharing in research projects in the light of the current donor demand, and offers advice and specific suggestions for similar interdisciplinary research projects.     

875 Cases of bacterial meningitis: Diagnostic procedures and the impact of preadmission antibiotic therapy Part III of a three-part series

Data on the bacteriological findings, diagnostic measures and clinical course of 875 patients with bacterial meningitis are presented. Findings from the medical records and from a follow-up questionnaire survey of 667 of these cases revealed no significant difference between patients treated with antibiotics before admission (pretreated) and those who were not treated before admission (non-pretreated) with respect to clinical condition on admission, mortality and late sequelae. Pretreatment was, however, associated with a longer duration of symptoms. Apart from cases due to Neisseria meningitidis, there were no significant differences in diagnostic findings between pretreated and non-pretreated cases. In the group of pretreated meningococcal patients, however, positive blood cultures, pleiocytosis in the cerebrospinal fluid (CSF) and positive cultures from sites other than blood and CSF were less frequent than in the non-pretreated cases.     

Characteristics of recovery of adrenocortical function after treatment for Cushing's syndrome due to pituitary or adrenal adenomas

OBJECTIVE: Surgical cure of Cushing's syndrome (CS) is followed by adrenocortical insufficiency, which may be long-lasting. The aim was to elucidate recovery of adrenocortical function, defined as a normal cortisol response to ACTH stimulation, and the relation to ACTH in patients cured for CS due to pituitary Cushing's disease (CD) or adrenal (AA) adenomas. DESIGN: A retrospective study including 32 patients considered surgically cured for CS (18 CD, 14 AA). RESULTS: Twelve (67%) patients with CD recovered within median 24 months (range 7 months-4(1)/(2) years) whereas six did not recover within 3-12 years. Plasma ACTH (p-ACTH) at time of recovery was not different from p-ACTH in patients not recovering (P = 0.9). Eleven (79%) patients with AA recovered within 24 months (10 months-4 years) whereas three did not recover within 4-10 years. p-ACTH at time of recovery was higher compared to patients not recovering (P < 0.04). No differences were observed comparing CD and AA patients concerning preoperative 24-h urinary free cortisol (UFC) excretion, postoperative unstimulated s-cortisol or recovery time. By contrast, p-ACTH measured at time of recovery was higher in AA compared to CD (median 12.3 vs. 4.6 pmol/l) (P < 0.001), whereas plasma dehydroepiandrosterone sulfate (p-DHEAS) was lower in AA compared to CD (median 300 vs. 1500 nmol/l) (P = 0.02). CONCLUSION: Recovery of secondary adrenal insufficiency is a slow process in both CD and AA. ACTH measured at time of recovery was significantly higher and DHEAS significantly lower in patients with AA compared to CD, which may suggest different mechanisms of the recovery process and different set points in the glucocorticoid feedback inhibition of ACTH secretion.     

Familial protein S deficiency with a variant protein S molecule in plasma and platelets

A protein S deficient family presenting a variant protein S molecule in plasma and platelets is described. The propositus, age 20, and two brothers suffered from venous thrombotic disease. The propositus, the only family member studied while taking oral anticoagulants, had a protein S antigen (ag) level of 17% and undetectable activity. As demonstrated by immunoblotting both the propositus and one clinically affected brother (42% ag, 7% activity) presented variant protein S molecules of 65,000 molecular weight (mol wt) while the other clinically affected brother (64% ag, 11% activity) had only protein S with normal electrophoretic mobility of 70,000 mol wt. The mother had normal protein S levels (93% ag, 100% activity) but had both normal and variant protein S molecules and based on her functional protein S data a normal anticoagulant activity of the variant molecule is suggested. One asymptomatic but protein S deficient sister (68% ag, 9% activity) as well as the asymptomatic protein S deficient father (59% ag, 10% activity) had only protein S molecules of 70,000 mol wt. The variant protein S bound to C4b-binding protein in plasma, and differed from normal protein S in carbohydrate content. Platelets of each family member contained the same immunoblotting pattern of normal and variant protein S forms as found in plasma, consistent with the hypothesis that protein S gene expression involves codominant expression of two alleles that is similar in cells that control the synthesis of both platelet and plasma forms of protein S.     

Granulocyte colony-stimulating factor administration to healthy volunteers: analysis of the immediate activating effects on circulating neutrophils

In four healthy volunteers, we analyzed in detail the immediate in vivo effects on circulating neutrophils of subcutaneous administration of 300 micrograms of granulocyte colony-stimulating factor (G-CSF). Neutrophil activation was assessed by measurement of degranulation. Mobilization of secretory vesicles was shown by a decrease in leukocyte alkaline phosphatase content of the circulating neutrophils. Furthermore, shortly postinjection, Fc gamma RIII was found to be upregulated from an intracellular pool that we identified by immunoelectron microscopy as secretory vesicles. Intravascular release of specific granules was shown by increased plasma levels of lactoferrin and by upregulation of the expression of CD66b and CD11b on circulating neutrophils. Moreover, measurement of fourfold elevated plasma levels of elastase, bound to its physiologic inhibitor alpha 1- antitrypsin, indicated mobilization of azurophil granules. However, no expression of CD63, a marker of azurophil granules, was observed on circulating neutrophils. G-CSF--induced mobilization of secretory vesicles and specific granules could be mimicked in whole blood cultures in vitro, in contrast to release of azurophil granules. Therefore, we postulate that the most activated neutrophils leave the circulation, as observed shortly postinjection, and undergo subsequent stimulation in the endothelial microenvironment, resulting in mobilization of azurophil granules. Our data demonstrate that G-CSF should be regarded as a potent immediate activator of neutrophils in vivo.     

Left ventricular dysfunction in Klinefelter syndrome is associated to insulin resistance, abdominal adiposity and hypogonadism

Objective Epidemiological data suggest there is an increased risk of dying from heart disease among patients with Klinefelter syndrome (KS). Due to high prevalence of hypogonadism and metabolic syndrome, we speculated that patients with KS may have subclinical changes in the left ventricular function. Therefore, the aim was to assess left ventricular long axis function by tissue Doppler echocardiography in patients with KS and relate these findings to the metabolic status and testosterone levels. Design Cross-sectional study. Out-patient clinic. Patients We investigated 25 unselected patients with KS, recruited from endocrine and fertility clinics. Twenty-five age-matched males served as controls. Measurements Left ventricular systolic long axis function (velocities and strain rate) assessed by tissue Doppler echocardiography related to free testosterone, fasting values of plasma glucose, insulin, homeostasis model assessment (HOMA)-index, cholesterol and triglycerides in addition to dual energy X-ray absorptiometry (DEXA) scan derived assessment of truncal body fat. Results The long axis function was significantly reduced in patients with KS (peak systolic velocities 4·4 ± 1·3 vs. 5·3 ± 1·0 cm/s, P < 0·01 and strain rate –1·3 ± 0·3 vs.–1·6 ± 0·3 s⁻¹, P < 0·01). However, the ventricular dysfunction was mainly attributed KS patients with metabolic syndrome. The peak systolic velocities were significantly correlated to truncal body fat (r = –0·72, P < 0·01) and free testosterone (r = 0·63, P < 0·01), but uncorrelated to plasma glucose, insulin and HOMA-index. Conclusion Systolic long axis function is decreased in patients with KS and metabolic syndrome. The decrease in myocardial systolic function was significantly related to truncal body fat and hypogonadism, but not correlated to insulin sensitivity.