Human antibodies to recombinant protein constructs of Plasmodium falciparum Apical Membrane Antigen 1 (AMA1) and their associations with protection from malaria

Serum antibodies from 1071 people in two Kenyan villages were assayed using eight different recombinant Apical Membrane Antigen 1 (AMA1) protein constructs to investigate their role in naturally acquired immunity. In both communities, antibodies against the full-length ectodomain (both FVO and 3D7 allele constructs) prior to a malaria transmission season were significantly associated with protection from malaria in the following 6 months, even after adjusting for age and antibody reactivity to whole parasite (schizont) extract. However, these protective associations of antibodies were only seen among subjects that were parasite slide positive at the time of pre-season serum sampling. Competition ELISAs with the FVO and 3D7 allele constructs showed that antibodies can recognise either conserved or allele-specific epitopes in AMA1. Results encourage the development of an AMA1 vaccine based on the full-length ectodomain, and indicate that the function of human antibodies to allele-specific and conserved epitopes in AMA1 should be studied further.     

Dependency issues in survival analyses of 55,782 primary hip replacements from 47,355 patients

Artificial hip joints are used in only one hip for about 85 per cent of the patients and in both hips (bilateral) for about 15 per cent of the patients. The occurrence of bilateral prostheses and the influence they have in survival analyses of joint arthroplasties are seldom considered. In this study we therefore focus on issues related to bilateral primary hip prostheses, time to revision surgery, and some commonly used statistical methods. We used information from 47,355 patients with 55,782 primary hip prostheses reported to the Norwegian Arthroplasty Register between 1987 and 2000. Due to the large number of diagnoses, fixation techniques for the prostheses, and combination of prostheses brands, we furthermore considered a 'homogeneous' subset of 8703 prostheses from 7930 patients with primary osteoarthritis, and Charnley prosthesis fixed with antibiotic-containing Palacos cement. Kaplan-Meier curves for all prostheses, ignoring that some patients have bilateral prostheses, were compared with Kaplan-Meier curves using only the first inserted prostheses, and with survival curves modified for patients with bilateral prostheses. Cox regression analyses were used to assess explanatory variables and to adjust for confounding factors. The results from the ordinary Cox regression analyses were compared with results from a marginal model, a shared gamma frailty model, and a model using a time dependent covariate to condition on failures in the opposite hip. We found no practical difference between the three calculated survival curves for the hip replacement data. The ordinary Cox-model and the marginal model gave equivalent results. In the shared gamma frailty model estimates for the risk factors were comparable with the former two approaches. The estimated frailty variance was higher when all data were used, even after adjustment for confounding factors. For the 'homogeneous' data the estimated frailty variance was negligible. Using a time dependent covariate to condition on previous revisions in the opposite hip, we found a higher risk of revision for the remaining primary hip prosthesis if the opposite hip had been revised (RR = 3.49, p < 0.0001). There was no difference in risk for revision between right and left hip prostheses. If the time interval between the two primary operations was more than two years, for the full data, the first hip prosthesis had an increased risk of revision compared to prostheses in patients with only one prosthesis (RR = 1.25, p = 0.01). For the 'homogeneous' data no statistically significant difference was found between unilateral and bilateral prostheses. A revision in one hip, for patients with bilateral prostheses, is a risk factor for revision of the other hip. Thus, in analyses of prostheses survival, dependencies between two hip prostheses from one patient should be considered. However, ignoring possible dependencies does not necessarily have an impact on the results on standard risk factors.     

Economic impact of respiratory syncytial virus-related illness in the US: an analysis of national databases

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) infection on healthcare resource use and costs in the US from the third-party payer perspective. DESIGN: The study retrospectively analysed cross-sectional medical encounter data from three federally funded databases that comprise nationally representative samples of hospital inpatient stays, physician office visits and visits to hospital outpatient departments and emergency rooms. METHODS: Identification of RSV infection-related medical encounters was based on the occurrence of RSV-specific International Classification of Diseases (9th Edition)-Clinical Modification diagnosis codes (079.6, 466.11, 480.1) as principal discharge diagnoses or the assumption that 10-15% of all otitis media visits were due to RSV infection. Outpatient drug costs were estimated based on average wholesale price, and physician fees and test/procedure costs were estimated based on prevailing national fees. Inpatient costs were estimated from total billed charges using a cost-to-charge ratio of 0.53. RESULTS: In 2000, nearly 98% of RSV infection-related hospitalisations occurred in children <5 years old. There were approximately 86,000 hospitalisations, 1.7 million office visits, 402 000 emergency room visits and 236,000 hospital outpatient visits for children <5 years old that were attributable to RSV infection. Total annual direct medical costs for all RSV infection-related hospitalisations ($US394 million) and other medical encounters ($US258 million) for children <5 years old were estimated at $US652 million in 2000. Otitis media was a major cost driver for physician visits. RSV infection-related hospitalisations increased from 1993 to 2000, but average costs per hospitalisation were relatively stable. CONCLUSION: Treatment of RSV infection-related illness represents a significant healthcare burden in the US. The economic impact of ambulatory care for RSV infection-related illness could be as important as that for RSV infection-related hospitalisation.     

Histology impacts the outcome of peripheral T-cell lymphomas after high dose chemotherapy and stem cell transplant

The role of high dose chemotherapy (HDC) and stem cell transplant (SCT) in peripheral T-cell lymphoma (PTCL) was studied in 28 patients, from 1988 to 2002. The aim was to determine if subsets recognized by the REAL/WHO classification have different prognoses. Outcome was compared to 86 patients with diffuse large B-cell lymphoma (DLBCL) transplanted during 1986-2000. The 3-year overall survival (OS) and event free survival (EFS) were 69% and 50%. Patients with anaplastic large cell lymphoma (ALCL) had a better 3-year OS compared to those with non-ALCL histology (86% vs. 47%, P=0.0122). Anaplastic lymphoma kinase (ALK)- positive ALCL patients had a superior EFS compared to ALK-negative ALCL (100% vs. 0; P=0.0228). Patients with cutaneous ALCL (ALK-negative) relapsed, but had an indolent course after SCT. Low International Prognostic Index score at relapse predicted for a better 3-year OS (85% vs. 34%, P=0.0238). When compared to DLBCL, patients with ALCL had a superior OS (86% vs. 36%, P=0.0034) and patients with non-ALCL had a comparable OS. ALCL histology confers better survival compared to non-ALCL and DLBCL histologies. ALK-positive ALCL is associated with the best EFS after relapse with HDC and SCT. The timing of SCT for non-ALCL histology remains to be determined.     

Pediatric septic shock: why has mortality decreased?-the utility of goal-directed therapy

Mortality from septic shock in children has decreased by 92 percent in the last 36 years. The contributions of goal-directed therapy, intensive care, and other forms of support are responsible for this decrease. A deeper and more specific understanding of innate immunity and the biomolecular processes that operate in septic shock has offered the scientific basis to implement goal-directed therapies. However, therapies that are aimed specifically at manipulating the inflammatory cascade have yet to prove safe and effective.     

Covariation of alternative measures of responding in rabbit (Oryctolagus cuniculus) eyeblink conditioning during acquisition training and tone generalization

The likelihood, size, and speed of eyelid movements are thought to covary during the acquisition and expression of conditioning in rabbits (Oryctolagus cuniculus) and are generally accepted as interchangeable measures of the associative strength activated by the conditioned stimulus (CS). To test this assumption, the authors examined the patterns of covariation in these eyelid movement measures in acquisition and stimulus generalization in the upper eyelid and nictitating membrane. Rather than the expected covariation among these measures, eyelid movement magnitudes during the CS were distributed in approximately a bimodal manner. That is, eyelid activity consisted largely of a mixture of very small (< 0.125 mm) baseline measurements and larger (> 1 mm) movements. The results are discussed with respect to their implications for real-time models of eyelid conditioning.     

Olfactory reference syndrome: diagnostic criteria and differential diagnosis

Olfactory reference syndrome (ORS) has been defined as a psychiatric condition characterized by persistent preoccupation about body odour accompanied by shame, embarrassment, significant distress, avoidance behaviour and social isolation. ORS has however not been included in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) and, given that its primary symptoms may be found in various other disorders, differential diagnosis can be problematic. Using an illustrative case of ORS, we propose diagnostic criteria for ORS. We also argue that ORS represents a unique cluster of symptoms that can be delineated as a separate diagnostic entity, and that ORS falls on a spectrum of social anxiety disorders that includes social anxiety disorder, taijin kyofusho, and body dysmorphic disorder.