RESUMO
BACKGROUND: Numerous surgical options exist to treat chondral lesions in the knee, including microfracture (MFx), osteochondral autograft transplantation (OAT), first-generation autologous chondrocyte implantation (ACI-1), and next-generation ACI (ACI-2). PURPOSE: To compare the cost-effectiveness of MFx, OAT, and ACI-1. The secondary purpose of this study was to compare the functional outcomes of MFx, OAT, ACI-1, and ACI-2. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: Two independent reviewers conducted an online literature search of 2 databases for level 1 and 2 studies using the Lysholm, International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), and/or Hospital for Special Surgery (HSS) Knee Score. A weighted mean difference in pre- to postoperative functional outcome score was calculated for each treatment. The mean per-patient costs associated with MFx, OAT, and ACI-1 were determined from a recent publication based on review of a national private insurance database. The cost for each procedure was then divided by the weighted mean difference in functional outcome score to give the cost-per-point change in outcome score. RESULTS: A total of 12 studies (6 level 1, 6 level 2) met the inclusion criteria for the functional outcome analysis, including 730 knees (MFx, n = 300; OAT, n = 90; ACI-1, n = 68; ACI-2, n = 272). The mean follow-up was not significantly different between groups (MFx, 29.4 months; OAT, 38.3 months; ACI-1, 19.0 months; ACI-2, 26.7 months). The mean increase in functional outcome score was 23 for MFx, 19 for OAT, 20 for ACI-1, and 35 for ACI-2. The change in functional outcome score was significantly greater for ACI-2 when compared with all other treatments (P < .0001). The cost-per-point change in functional outcome score was $200.59 for MFx, $313.84 for OAT, and $536.59 for ACI-1. CONCLUSION: MFx, OAT, ACI-1, and ACI-2 are effective surgical procedures for the treatment of cartilage defects in the knee. All 4 treatments led to an increase in functional outcome scores postoperatively with a short-term follow-up. ACI-2 had a statistically greater improvement in functional outcome scores as compared with the other 3 procedures. MFx was found to be the most cost-effective treatment option and ACI-1 the least cost-effective.
RESUMO
The genetics of Alzheimer's disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org ) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case-control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes.