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Do complication screening programs detect complications present at admission?

BACKGROUND: A study was undertaken to verify the accuracy of computer algorithms on administrative data to identify hospital complications. The assessment was based on a medical records indicator that differentiated hospital-acquired conditions from preexisting comorbidities. METHODS: The indicators for identifying potential hospital complications were applied to all secondary diagnoses to distinguish hospital-acquired from preexisting conditions for all 1997-1998 discharges. RESULTS: Of the 95 defined complication types, cases were found with secondary diagnoses that met the criteria for 71 different complications. Sixty-nine of these complications had one or more cases with the trigger diagnosis coded as an acquired condition. Thirty-five complications had at least 30 cases with acquired conditions. Hospital complications add greatly to costs; for example, postoperative septicemia increased the hospital bill by more $25,000, added 13 hospital days to the stay, and increased hospital mortality by 16.6%. CONCLUSIONS: Current complication algorithms identify many cases where the condition was actually present on hospital admission. This fact, coupled with the known variability in coding between institutions, makes comparisons between hospitals on many of the complications problematic. Collection of the present-on-admission flag significantly reduces the noise in monitoring complication rates.

Algorithms↗

Application of molecular genetics for diagnosing familial hypercholesterolemia in Norway: results from a family-based screening program.

A total of 119 different mutations in the low-density lipoprotein-receptor gene have so far been found to cause familial hypercholesterolemia (FH) among Norwegian patients. As of April 2003, 2390 patients from 959 unrelated families were provided with a molecular genetic diagnosis. Of these, 25.3% had xanthomas and 8.4% had xanthelasma. During the last 2-3 years, a systematic family-based program to identify close relatives of FH patients has been established. A total of 851 relatives of 188 index patients have undergone genetic testing. Four hundred seven people (47.9%) were affected, and 444 (52.1%) were unaffected. Only 41.5% of those affected were on lipid-lowering drugs, and only 6.1% had a value for total serum cholesterol below 193 mg/dL (5.0 mmol/L). A follow-up study was conducted in 146 of 407 affected relatives 6 months after genetic testing was performed. Of those already under treatment at the time of genetic testing, nonsignificant reductions of total serum cholesterol and low-density lipoprotein cholesterol of 3.2% and 7.1% were observed. Of those not under treatment who were aged 18 years and older, the corresponding reductions were 21.2% (p <.0001) and 30.0% (p <.0001), respectively. We conclude that molecular genetic methods represent a feasible and highly efficient tool in a family-based strategy to diagnose FH.

Biomarkers↗

DNA repair protein levels vis-à-vis anticancer drug resistance in the human tumor cell lines of the National Cancer Institute drug screening program.

Nucleotide excision repair (NER) is a multi-enzyme DNA repair pathway in eukaryotes. Several NER genes in this pathway including XPB, XPD, XPA and ERCC-1 have been implicated in anticancer drug resistance in human tumor cells. In this study, we assessed the levels of the above-mentioned proteins in the NCI panel of 60 human tumor cell lines in relation to the cytotoxicity patterns of 170 compounds that constitute the standard agent (SA) database. The database consists of drugs used in the clinic for which a mechanism of action has been at least partially defined. The ERCC-1, XPD and XPB protein expression patterns yielded significant negative Pearson correlations with 13, 32 and 17 out of the 170 compounds, respectively (using p<0.05). XPA produced a random assortment of negative and positive correlations, and did not appear to confer an overall resistance or sensitivity to these drugs. Protein expression was also compared with a pre-defined categorization of the standard agents into six mechanism-of-action groups resulting in an inverse association between XPD and alkylating agent sensitivity. Our present data demonstrate that XPD protein levels correlate with resistance to alkylating agents in human tumor cell lines suggesting that XPD is implicated in the development of this resistance. NER activity, using the in vitro cell-free system repair assay, revealed no correlation between NER activity and the level of XPD protein in four cell lines with widely varying XPD protein levels. This lack of correlation may be due to the contribution of XPD to other functions including interactions with the Rad51 repair pathway.

Antineoplastic Agents, Alkylating↗