Effectiveness of anti-osteoporotic drugs to prevent secondary fragility fractures: systematic review and meta-analysis.

Patients with osteoporotic fractures have an increased risk for secondary fractures. However, a rigorous study that assesses the effectiveness of individual osteoporotic drugs in preventing subsequent fractures is lacking. The purpose of this review was to analyze the effectiveness of anti-osteoporotic drugs in preventing secondary fractures. We searched for randomized controlled trials that showed the incidence of secondary fractures while using anti-osteoporotic drugs (bisphosphonates, selective estrogen receptor modulators, parathyroid hormone (PTH), or calcitonin) in MEDLINE, Embase.com , and Cochrane Central Register databases. We estimated risk ratios (RR) and numbers needed to treat (NNT) to prevent secondary fractures. Twenty-six studies met our eligibility criteria. There was a significant reduction in RR (0.38-0.77) after the use of anti-osteoporotic drugs for secondary vertebral fractures. Bisphosphonates and PTH significantly reduced the risk of a secondary non-vertebral fracture (RR 0.59 and 0.64). PTH needed the fewest number of patients to be treated to prevent a secondary vertebral fracture (NNT: 56). Our study demonstrated the effectiveness of anti-osteoporotic agents included in our systematic review in preventing secondary vertebral fractures. Bisphosphonates and PTH were most effective in preventing non-vertebral fractures. We suggest that clinicians should prescribe these drugs to prevent secondary vertebral/non-vertebral fractures.

Reconstructive procedures for treating peri-implantitis: a systematic review.

This review aimed at evaluating the effectiveness of reconstructive procedures for treating peri-implantitis. Searches of electronic databases and cross-referencing were performed for human comparative clinical trials with ≥ 10 implants for ≥ 12 months of follow-up, reporting radiographic defect fill and at least one of the following parameters: probing depth reduction, clinical attachment level gain, bleeding on probing reduction, and mucosal recession. The searches retrieved 430 citations. Only 1 randomized controlled trial was identified, which compared reconstructive therapy and open flap debridement. Case series studies were also included to evaluate the overall performance of the reconstructive procedures. Twelve studies were finally included. Meta-analysis revealed that the weighted mean radiographic defect fill was 2.17 mm (95% confidence interval [CI]: 1.46-2.87 mm), probing depth reduction was 2.97 mm (95% CI: 2.38-3.56 mm), clinical attachment level gain was 1.65 mm (95% CI: 1.17-2.13 mm), and bleeding on probing reduction was 45.8% (95% CI: 38.5%-53.3%). Great variability in reparative outcomes was found, attributed to patient factors, defect morphology, and reconstructive agents used. Currently, there is a lack of evidence for supporting additional benefit of reconstructive procedures to the other treatment modalities for managing peri-implantitis.

Modeling global and focal hyperarticulation during human-computer error resolution.

When resolving errors with interactive systems, people sometimes hyperarticulate--or adopt a clarified style of speech that has been associated with increased recognition errors. The primary goals of the present study were: (1) to provide a comprehensive analysis of acoustic, prosodic, and phonological adaptations to speech during human-computer error resolution after different types of recognition error; and (2) to examine changes in speech during both global and focal utterance repairs. A semi-automatic simulation method with a novel error-generation capability was used to compare speech immediately before and after system recognition errors. Matched original-repeat utterance pairs then were analyzed for type and magnitude of linguistic adaption during global and focal repairs. Results indicated that the primary hyperarticulate changes in speech following all error types were durational, with increases in number and length of pauses most noteworthy. Speech also was adapted toward a more deliberate and hyperclear articulatory style. During focal error repairs, large durational effects functioned together with pitch and amplitude to provide selective prominence marking of the repair region. These results corroborate and generalize the computer-elicited hyperarticulate adaptation model (CHAM). Implications are discussed for improved error handling in next-generation spoken language and multimodal systems.

Identification of an indirectly presented epitope in a mouse model of skin allograft rejection.

BACKGROUND: The indirect pathway of allorecognition involves the processing and presentation of donor molecules by recipient antigen-presenting cells to alloreactive CD4+ T cells. Our objective was to assess the occurrence and significance of the indirect presentation of allogeneic major histocompatibility complex molecules in the rejection of major histocompatibility complex class I-disparate skin. METHODS: A mouse model of allograft rejection was developed in which tail skin from C57.BL/10 (H2b) donors was transplanted onto B10.A(5R) recipients resulting in an allogeneic mismatch at the D locus. T-cell depletion studies were used to characterize T-cell subset involvement in rejection. B10.A(5R) mice were immunized with pools of overlapping peptides spanning the polymorphic region of Db in order to identify Db-derived epitopes involved in rejection. The relevance of these epitopes was assessed through immunization of recipient mice with peptides before skin grafting to observe the effect of presensitization on the kinetics of rejection. RESULTS: Rejection of Db-disparate skin by B10.A(5R) was delayed by CD4 and CD8+ T-cell depletion, indicating the significance of both cell types in rejection. At least six immunogenic peptides were identified, all of which contained a cryptic T-cell epitope. One peptide, however, was able to accelerate the rejection of Db-disparate skin. Presensitization of B10.A(5R) mice with this peptide also resulted in an increase in alloantibody, indicating the presence of a physiological as well as a cryptic epitope. Presensitization of mice with a peptide containing a distinct cryptic epitope, however, failed to influence rejection. CONCLUSIONS: These findings demonstrate a significant role for the indirect pathway of antigen presentation in allograft rejection.

Circulating erythropoietic precursors assessed in culture: characterization in normal men and patients with hemoglobinopathies.

Circulating erythropoietic precursors in normal men and patients with hemoglobinopathies were characterized in culture. Blood mononuclear cells harvested with a modification of the Ficoll-Isopaque technique were cultured in methylcellulose for 14 days. The majority of erythropoietic colonies consisted of several subcolonies assuming the morphology of erythropoietic "bursts" described in murine marrow cultures. Time course studied of colony formation from marrow and blood nucleated cells confirmed that the circulating erythropoietic precursors represented only early stages of development. Peak sedimentation velocity of the circulating precursors analyzed using a Staput apparatus averaged 5.31 mm/hr and corresponded with that of the early erythropoietic precursors in human marrow. One ml of blood yielded an average of 153 colonies in normal men and 785 colonies in patients with hemoglobinopathies. No correlation was observed between colony formation and reticulocyte indices of individual patients. Examination of the proliferative state of the erythropoietic precursors using high specific activity tritium-labeled thymidine revealed that almost none of the cells in normal men or patients with hemoglobinopathies were in the DNA synthetic phase.