B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Evaluating cost-effectiveness in the management of neuroendocrine neoplasms.

The rapid evolution of novel, costly therapies for neuroendocrine neoplasia (NEN) warrants formal high-quality cost-effectiveness evaluation. Costs of individual investigations and therapies are high; and examples are presented. We aimed to review the last ten years of standalone health economic evaluations in NEN. Comparing to published standards, EMBASE, Cochrane library, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database and the Health Technology Assessment (HTA) Database were searched for health economic evaluations (HEEs) in NEN published between 2010 and October 2019. Of 12 economic evaluations, 11 considered exclusively pharmacological treatment (3 studies of SSAs, 7 studies of sunitinib, everolimus and/or 177Lu-DOTATATE and 1 study of telotristat ethyl) and 1 compared surgery with intraarterial therapy. 7 studies of pharmacological treatment had placebo or best supportive care as the only comparator. There remains a paucity of economic evaluations in NEN with the majority industry funded. Most HEEs reviewed did not meet published health economic criteria used to assess quality. Lack of cost data collected from patient populations remains a significant factor in HEEs where clinical expert opinion is still often substituted. Further research utilizing high-quality effectiveness data and rigorous applied health economic analysis is needed.

Facial allograft transplants: where's the catch?

Face transplantation--or, more properly, facial allograft transplantation (FAT)--generates much public interest and academic debate. In this paper, we suggest that it is up to opponents of FAT to make the case for its impermissibility. We allow that there is a number of apparently strong arguments that might be deployed against FAT. However, all but one of these turn out not to be compelling after examination. The remaining argument is not so easily dismissed--but its central point is fairly workaday and certainly does not tell us anything about FAT in particular. Therefore, qua argument about facial transplant surgery, it fails to hit its target. Overall, we conclude that a compelling case against FAT remains to be made.

Patients' understanding and use of advance directives.

The Patient Self-Determination Act was implemented in December 1991. Before and after its implementation, we used a structured interview of 302 randomly selected patients to determine their awareness, understanding, and use of advance directives. Implementation of the Act did not have a major effect on these. Although more than 90% of patients were aware of the living will, only about a third selected the correct definition or the correct circumstances in which it applied, and less than 20% of patients had completed one. About a third of patients were aware of a Durable Power of Attorney for Health Care and chose the correct definition, and about half identified the correct circumstances in which it applies; less than 10% had completed such a document. Surprisingly, patients who said they had completed advance directives did not demonstrate better understanding of these documents. Our results indicate that many patients, including some who have completed advance directives, do not fully understand them. It may be unwise to regard these documents as carefully considered, compelling statements of patients' preferences. Appropriate responses to our findings include increased public education, revising state statutes to bring them into congruence with public perception, and expanding the dialogue between physicians and patients.

The use of a game to promote arm reach in persons with traumatic brain injury.

This study tested a principle of occupational therapy and motor learning theory in the context of neurodevelopmental treatment techniques. Ten trials of occupationally embedded intervention (playing Simon, a computer-controlled game) were compared with 10 trials of rote arm-reach exercise. A counterbalanced design was structured so that each subject experienced each condition one week apart. Subjects were 17 men and 3 women with traumatic brain injury who exhibited mild to moderate spasticity in the upper extremity. Maximum distance from hip to wrist during active reach of the affected extremity was measured by digitization of videotape with the Motion Analysis EV-3D system. Results indicated that the use of the game elicited significantly more range of motion than the rote exercise (t (19) = 5.77, p < .001). These results support the use of an occupationally embedded intervention for persons with traumatic brain injury and add to the theoretical base of occupational therapy.