Evaluating the impact of human papillomavirus vaccines

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines’ effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.     

Performance measures for evaluating services for people with a first episode of psychosis

Aim: The purpose of this project was to operationalize and apply a previously identified set of performance measures designed to evaluate services for those experiencing a first episode of a schizophrenia spectrum disorder. Methods: Operational definitions were developed for previously identified measures through an iterative process of discussions between clinical experts and health‐care evaluators. Data were collected from existing sources including corporate databases, clinical databases and chart review. Results: Definitions were developed for 44 measures covering seven of eight domains recommended for service level evaluation by the Canadian Institute for Health Information domains. Forty measures could be calculated. Conclusions: The measures represent a comprehensive set of performance measures suitable for the evaluation of services for people with a first‐episode psychosis. The measures could be used by other services in order to establish standards and norms for routine clinical practice.     

The influence of partnership centrality on organizational perceptions of support: a case study of the AHLN structure

Background  

Knowledge of the structure and character of inter-organizational relationships found among health promotion organizations is a prerequisite for the development of evidence-based network-level intervention activities. The Alberta Healthy Living Network (AHLN) mapped the inter-organizational structure of its members to examine the effects of the network environment on organizational-level perceptions. This exploratory analysis examines whether network structure, specifically partnership ties among AHLN members, influences organizational perceptions of support after controlling for organizational-level attributes.     

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.     

Induction of 8-hydroxydeoxyguanosine in Ah-responsive mouse liver by iron and Aroclor 1254.

Treatment of Ah-responsive C57BL/10ScSn mice with iron greatly sensitizes them to induction of hepatic porphyria and tumour formation by the polychlorinated biphenyl mixture Aroclor 1254. In the present studies, male C57BL/10ScSn mice received a single dose of iron-dextran (600 mg Fe/kg) and were fed a diet containing 0.01% Aroclor 1254 for 1, 3 and 5 weeks. By use of HPLC with electrochemical detection, 8-hydroxydeoxyguanosine (8-OHdG) was then measured in liver DNA as a marker for oxidative damage. Treatments with iron or Aroclor alone did not result in a significant increase in 8-OHdG except at 3 weeks following iron treatment. At 1 and 3 weeks 8-OHdG levels were induced approximately 3- and 5-fold above control groups respectively in iron- and Aroclor-treated animals. Although there was an apparent 5- to 10-fold increase in the level of 8-OHdG at 5 weeks, this was partially attributed to the in vitro effects of porphyrins, levels of which were massively elevated in liver at this time point. The iron/Aroclor-induced synergistic elevation of 8-OHdG at 1 and 3 weeks was concluded to be due to in vivo damage, thus suggesting the importance of DNA oxidation in the early events of carcinogenesis in this system.     

Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.