The impact of personal functional goal achievement on patient satisfaction with progress one year following completion of a functional restoration program for chronic disabling spinal disorders.

STUDY DESIGN: This prospective cohort study investigated personal goal achievement and satisfaction with progress in patients with chronic disabling spinal disorders (CDSD). OBJECTIVE: This study examined the relationships between satisfaction with progress and several alternative outcome measures for CDSD patients at least 1 year after completing a functional restoration program (FRP). SUMMARY OF BACKGROUND DATA: Treatment outcome measures for CDSD commonly include pain, physical capacities, and functional/vocational status. These factors are weakly correlated and may not reflect individual patients' perspectives and priorities. METHODS: On enrollment in the FRP, patients' pretreatment functional, work, and recreation goals were recorded. Pre- and end-of-program clinical measures included: pain, disability, fear avoidance, lifting, trunk flexibility, and treadmill endurance. At least 1 year after program completion surveys were mailed to consecutive FRP graduates. Nonresponders were surveyed by telephone when possible. Surveys included each patient's personal pretreatment goals, and assessed Average Pain, SF-36 Physical Function, and satisfaction "with the progress made with your pain problem." Each patient indicated levels of importance and achievement for each personal goal, and these scores were integrated to yield a goal achievement score (GAS). Linear regression was used to test the relationships between 1-year satisfaction with progress and the following variables: baseline to end-of-program change in clinical measures, and 1-year pain, physical function, and GAS. RESULTS: Of the 106 surveys mailed, 89 (84%) were returned and 86 (81%) had complete data for analysis. None of the pre-post-program clinical measures was significantly correlated with satisfaction (overall R2 = 0.013, P < 0.74). In contrast, year-end Average Pain (R2= 0.28), Physical Function (R2 = 0.29), and GAS (R2 = 0.29) were each significantly correlated (P < 0.0001) with satisfaction, with a combined R2 = 0.43, P < 0.0001. Of these variables, GAS had the highest unique contribution to satisfaction. CONCLUSION: For CDSD patients 1 year after completing rehabilitation, compared to more traditional outcomes, GAS provided the greatest unique contribution to patient satisfaction. Goal achievement may be a valuable patient-centered measure of treatment outcome.

High-performance liquid chromatographic determination of N-[2-(hydroxyethyl)-N-(2-(7-guaninyl)ethyl)]methylamine, a reaction product between nitrogen mustard and DNA and its application to biological samples.

Nitrogen mustard (HN2) is a bifunctional alkylating agent which is thought to cause cytotoxicity by covalently binding to DNA. Most studies to date have looked at qualitatively determining the presence of DNA-HN2 adducts from reactions with native DNA. The adduct which is predominately formed in these reactions is N-[2-(hydroxyethyl)-N-(2-(7-guaninyl)ethyl]methylamine (N7G). A simple and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of N7G from DNA using ultraviolet detection is described. DNA samples having been exposed to HN2 treatment were hydrolyzed and preseparated from high-molecular-mass material by filtration using a molecular mass cut-off of 3000. The mobile phase consisted of methanol-26 mM ammonium formate, pH 6.5 (24:76, v/v). N7G, as well as the internal standard, methoxyphenol, were separated within 30 min. The recovery of N7G after hydrolysis of the DNA reaction product was quantitative and limits of detection and quantification of 10 and 20 ng/ml, respectively, were calculated. The method was validated in DNA-HN2 dose response experiments. The N7G reaction product appears to be the first reaction product formed at lower ratios of HN2/DNA but its production plateaus at higher ratios of HN2/DNA probably due to increased formation of hitherto unknown adducts. The method is simple and sensitive and for this reason, may be suited for the determination of DNA/HN2 reaction products.

Pharmacokinetics and kinetic-dynamic modelling of aminophenones as methaemoglobin formers.

Methaemoglobin, the oxidized form of haemoglobin, can be formed by a variety of agents, most of which act to oxidize haemoglobin directly or indirectly. Cyanide has a higher affinity for methaemoglobin than for mitochondrial cytochromes, making methaemoglobin formation a basis for the treatment of cyanide poisoning. We used the beagle dog model to investigate the relationship between drug concentration and methaemoglobin levels for two candidate anti-cyanide compounds. The compounds studied were the aminophenones p-aminopropiophenone (PAPP) and p-aminoheptylphenone (PAHP). Both PAPP and PAHP were given as intravenous boluses and as two different oral formulations. The kinetics of both compounds appeared to follow a three-compartment open model for intravenous bolus administration and a two-compartment open model for oral administration. The first distribution phase seen with the intravenous administration was obscured by the absorption phase during oral administration. Bioavailability for all formulations varied between 20 and 47%. For both compounds there was a delay between the appearance of drug in the plasma and the appearance of methaemoglobin (counter-clockwise hysteresis) which is suggestive of an active metabolite causing methaemoglobin formation. The pharmacodynamics were fit with an effect-compartment kinetic-dynamic model linked to a sigmoid Emax pharmacodynamic model. Maximum amounts of methaemoglobin occurred between 2 and 4 h for PAHP and between 1 and 3 h for PAPP. When administered intravenously estimates of EC50 were lower than the estimates of EC50 from oral administration for both compounds. This might be because of oral first-pass inactivation or a 'first-pass' activation through the lungs contributing to the formation of an active metabolite. The phenones as a class appear to have the drug cleared and methaemoglobin return to near baseline within 12 h. Both compounds seem to produce sufficient methaemoglobin to treat acute cyanide poisoning and to serve as prophylactic agents against acute cyanide poisoning in a military setting.