Valuing postoperative recovery: validation of the SF-6D health-state utility

Background

Many surgical innovations are costly but may result in faster patient recovery. Economic analyses of these innovations require utility measures that reflect the construct of “postoperative recovery.” We investigated the validity of Short Form 6D (SF-6D) utility value as a measure of postoperative recovery in patients undergoing elective colorectal resection.

Materials and methods

Patients undergoing elective colorectal resection completed the Short Form 36 and the 6-min walk test at baseline (before surgery) and at 4 and 8 wk postoperatively. SF-6D utilities were derived from the Short Form 36. Longitudinal validity (responsiveness) was assessed using standardized response means (SRM). Construct validity was assessed by comparing the difference in mean SF-6D between patients with and without complications (discriminant) and by correlating the SF-6D with other measures of recovery (convergent).

Results

A total of 191 patients were included (58% male; mean age 63.0 (SD 14.2) y, 81% malignancy, and 54% laparoscopic). SF-6D values dropped significantly from baseline to 4 wk after surgery (SRM −0.54, P < 0.001) and returned to baseline by 8 wk (SRM −0.12, P = 0.111). At 4 wk after surgery, the SF-6D was lower in patients with complications than in those without (mean difference −0.047, 95% CI −0.088, −0.006). At all time points, the SF-6D correlated significantly with the physical and mental component scales of the SF-36 (Pearson r 0.67–0.80, all P < 0.001) and the 6-min walk test (r 0.21–0.29, all P < 0.05).

Conclusions

The SF-6D is a valid measure of postoperative recovery following elective colorectal resection and may be used to measure quality-adjusted life years for cost-effectiveness analyses of surgical technologies and interventions hypothesized to impact recovery.     

A comparison of the validity of two indirect utility instruments as measures of postoperative recovery

Background

Cost-effectiveness analyses of surgical interventions require valid measures of postoperative recovery. The objective of this study was to compare the validity of two indirect utility instruments, the Short Form 6D (SF-6D) and EuroQol 5D (EQ-5D), as measures of postoperative recovery.

Materials and methods

A prospective cohort of patients undergoing elective colorectal resection at two university-affiliated institutions from October 2012–October 2013 completed the SF-6D and EQ-5D (including the EQ-visual analog scale [EQ-VAS]) at baseline (before surgery), and at 4 and 8 wk after surgery. Responsiveness and construct validity were assessed through a priori hypotheses.

Results

A total of 165 patients were included. The SF-6D was the most responsive to the expected postoperative changes at 4 and 8 wk compared with the EQ-5D and the EQ-VAS. The 4-wk SF-6D, EQ-5D, and EQ-VAS discriminated between patients with and without complications after controlling for confounders with adjusted mean differences of −0.070 (95% confidence interval [CI] −0.126 to −0.015), −0.133 (95% CI −0.231, −0.030), and −7.91 (95% CI −14.77, −1.04), respectively. Mean SF-6D and EQ-5D values were significantly different from the US population norms at all time points, but the magnitude of change was highest for the SF-6D. The strength of correlation between all three instruments was moderate at all time points (r = 0.550–0.684, all P < 0.05).

Conclusions

The SF-6D preference-based health index appears to be a more valid measure of postoperative recovery than the EQ-5D and EQ-VAS in surgical cost-effectiveness analyses.     

加速康复外科理念下术后不输液对腹腔镜胆囊切除术患者的影响

目的 探讨腹腔镜胆囊切除术(LC)术后不输液对患者恢复及安全性的影响。方法 回顾性分析宁波市医疗中心李惠利医院2019年1月至2020年1月间接受LC术的患者临床资料。根据LC术后是否进行静脉输液,将患者分为未输液组(n=80)与常规输液组(n=80)。统计两组患者术前一般情况,对比分析两组患者术中、术后情况。结果 两组患者术前一般资料无统计学差异(P>0.05)。两组在手术时间、麻醉时间、术中出血量、术后疼痛评分方面比较,差异均无统计学意义(P>0.05)。未输液组在术后排气时间、住院时间及住院费用方面,均低于常规输液组(P<0.05)。术后共5例出现不同程度的切口感染,其中不输液组2例,输液组3例,均是在出院后1周内发现,在门诊换药后痊愈。所有患者未出现其他并发症。两组患者术后1个月复查,肝肾功能及肝胆B超均未见明显异常。结论 在加速康复外科理念下,对于胆囊炎症轻、无基础疾病、营养状况良好的患者,LC术后不进行静脉输液,可加快患者康复,临床安全可行。     

Evaluation of utility in shoulder pathology: Correlating the American Shoulder and Elbow Surgeons and Constant scores to the EuroQoL

AIM: To study whether health utility scores can be derived from shoulder-specific scores.METHODS: Authors investigated two questions:(1) do the American Shoulder and Elbow Surgeons(ASES) score and the Constant score correlate with the EuroQo L(EQ-5D), a measure of health utility?(2) can the ASES and Constant scores be obtained from a complete study sample without bias? Thirty subjects with various shoulder diagnoses completed ASES, Constant, and EQ-5D instruments. Pearson correlations were calculated to assess the associations between EQ-5D score and ASES and Constant scores.RESULTS: The correlation between EQ-5D score and ASES score was 0.60(P 0.001); it was 0.54 for EQ-5D and Constant scores(P 0.003). A multiple regression model containing ASES score, Constant score, age, and gender failed to adequately predict EQ-5D. Moreover, 25% of patients meeting the inclusion criteria did not complete the ASES questionnaire because they did not feel that specific questions, such as "do usual sport-list" and "throw ball overhand," applied to them.CONCLUSION: Authors' results do not support the use of the ASES and Constant scores in predicting EuroQ ol health utility values. However, the Constant score was more suitable for this patient population because all patients were able to complete it.     

细胞色素P450 2D6*10基因多态性对曲马多术后病人自控镇痛效果的影响

目的 探讨细胞色素P450 2D6* 10(CYP2D6* 10)基因多态性对曲马多术后病人自控镇痛(PCA)效果的影响.方法 全麻病人212例,年龄20～64岁,ASA Ⅰ或Ⅱ级.按基因型分为野生型纯合子(w/w)组,杂合子(m/w)组和突变型纯合子(m/m)组.手术结束前30 min静脉注射曲马多1.5mg/kg.清醒时VAS评分＞4分则静脉注射曲马多,若用量超过3 mg/kg则静脉注射芬太尼,至VAS评分≤4分后开始PCA,记录曲马多负荷量.曲马多PCA背景输注速率18 mg/h、16 h后降为12 mg/h、32h后降为9mg/h,PCA剂量22.5mg.记录术后6、12、24及48 h(T1～4)时曲马多累积用量.分别于T1、T3和T4时采用视觉模拟评分法(VAS)评价疼痛程度.于T4后行PCA镇痛效果评价.结果 与w/w组相比,m/m组曲马多负荷量、T1～3时曲马多累积用量均升高,清醒和T1时VAS评分升高(P＜0.05);与m/w组相比,m/m组曲马多负荷量、T3时曲马多累积用量均升高,T1时VAS评分升高(P＜0.05).结论 C YP2D6* 10基因多态性为曲马多术后镇痛药效学个体差异的因素之一.     

The Use of Short-Form Quality of Life Questionnaires to Measure the Impact of Imipramine on Women with Urge Incontinence

Short-form questionnaires were used to measure the change in quality of life (QOL) of women with urge-predominant urinary incontinence treated with imipramine hydrochloride. Short forms of the Incontinence Impact Questionnaire (IIQ-7) and the Urogenital Distress Index (UDI-6) were integrated into a patient questionnaire, which was given to 25 patients with urge-predominant urinary incontinence before and after treatment with imipramine. Demographic data and self-reports of the number of incontinent episodes were also recorded. Total and subscale QOL scores and number of incontinent episodes were recorded and compared with Wilcoxson’s signed ranks test, as well as correlated to the change in number of incontinent episodes with Pearson’s correlation coefficient. Treatment with imipramine resulted in a clinical improvement or cure in 16/22 patients (72.7%), with an average reduction in incontinent episodes of 78.7% (P<0.001). The average per cent improvement in QOL scores for total IIQ-7 was 42.1% (P<0.01) and total UDI-6 score was 44.1% (P<0.001). All subscale QOL differences were also significant (P<0.01). The incidence of side effects to imipramine was 41%, which resulted in dose changes. Fourteen per cent eventually discontinued therapy. Neither total nor subscale QOL improvement scores were correlated with improvement in number of incontinent episodes. The short form IIQ-7 and UDI-6 are effective tools to determine change in QOL, as evidenced by the effectiveness of imipramine for the treatment of urge-predominant urinary incontinence. Significant reductions in incontinent episodes and improvements in IIQ-7 and UDI-6 QOL scores were both seen, but were not correlated. Short-form QOL measures can easily be integrated into a patient questionnaire to objectively measure a very subjective topic.     

Laparoscopic endobiliary stenting: a simplified approach to the management of occult common bile duct stones

Three years ago we described laparoscopic placement of biliary stems as an adjunct to laparoscopic common bile duct exploration (LCBDE) in 16 patients. We now present a modification of our technique and experience with 48 additional patients. Laparoscopic cholecystectomy with intraoperative fluorocholangiography (LC/IOC) performed in 372 consecutive patients during a 36-month period revealed common bile duct stones (CBDS) in 48 patients (12.9%). In this series, LCBDE was not performed and no attempt was made to clear CBDS prior to transcystic stent placement. Stent placement added 9 to 26 minutes of operative time to LC/IOC alone. Forty-four patients (92%) were discharged after surgery and four (8%) were observed overnight. Outpatient endoscopic retrograde cholangiopancreatography 1 to 4 weeks later succeeded in clearing CBDS in all patients. All stents were retrieved without difficulty and 3- to 36-month follow-up demonstrates no surgical, endoscopic, or stent-related complications to date. Laparoscopic biliary stent placement for the treatment of CBDS is a safe, rapid, technically less challenging alternative to existing methods of LCBDE. It preserves the benefits of minimally invasive surgery for patients, and virtually assures success of postoperative endoscopic retrograde cholangiopancreatography with complete stone clearance. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 2l–24, 2000 (poster presentation).     

Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio

IntroductionCYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome.Materials and methodsA target NDMT/E ratio was defined as associated with an E level of 15 nM in the 161 patient Test cohort of tamoxifen-treated patients, dichotomizing them into ‘Normal’ (NM) and ‘Slow’ (SM) CYP2D6 metabolizer groups. This ratio was then tested on a validation cohort of 52 patients. Patients were phenotyped based on the standard method (ultrarapid/extensive, intermediate or poor metabolizers; UM/EM, IM, PM) or a simplified system based on whether any variant allele (V) vs wildtype (wt) was present (wt/wt, wt/V, V/V). Comprehensive CYP2D6 genotyping was undertaken on germline DNA.ResultsA target NDMT/E ratio of 35 correlated with the 15 nM E level, dichotomizing patients into NM (<35; N = 117) and SM (>35; N = 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method - sensitivity 81% and specificity 83%.ConclusionsThe simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered.     

Adjusting the dose of tamoxifen in patients with early breast cancer and CYP2D6 poor metabolizer phenotype

BackgroundCYP2D6 is a key enzyme in tamoxifen metabolism, transforming it into its main active metabolite, endoxifen. Poor CYP2D6 metabolizers (PM) have lower endoxifen plasma concentrations and possibly benefit less from treatment with tamoxifen. We evaluated tamoxifen dose adjustment in CYP2D6 PM patients in order to obtain plasma concentrations of endoxifen comparable to patients with extensive CYP2D6 metabolism (EM).Patients and methodsComprehensive CYP2D6 genotyping and plasma tamoxifen metabolite concentrations were performed among 249 breast cancer patients in adjuvant treatment with tamoxifen. Tamoxifen dose was increased in PM patients to 40 mg and to 60 mg daily for a 4-month period each, repeating tamoxifen metabolite measurements on completion of each dose increase. We compared the endoxifen levels between EM and PM patients, and among the PM patients at each dose level of tamoxifen (20, 40 and 60 mg).ResultsEleven PM patients (4.7%) were identified. The mean baseline endoxifen concentration in EM patients (11.30 ng/ml) was higher compared to the PM patients (2.33 ng/ml; p < 0.001). In relation to the 20 mg dose, increasing the tamoxifen dose to 40 and 60 mg in PM patients significantly raised the endoxifen concentration to 8.38 ng/ml (OR 3.59; p = 0.013) and to 9.30 ng/ml (OR 3.99; p = 0.007), respectively. These concentrations were comparable to those observed in EM patients receiving 20 mg of tamoxifen (p = 0.13 and p = 0.64, respectively).ConclusionIn CYP2D6 PM patients, increasing the standard tamoxifen dose two-fold or three-fold raises endoxifen concentrations to levels similar to those of patients with EM phenotype.     

Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P-450 2D6 activity

Background. Tramadol is potentially a very useful pain reliefmedication in neonates and infants. It is primarily metabolizedinto O-demethyl tramadol (M1) by CYP2D6. Data concerning tramadoldisposition and CYP2D6 activity in young infants are not available. Methods. A population pharmacokinetic analysis of tramadol andM1 time–concentration profiles was undertaken using non-linearmixed-effects models (NONMEM), based on newly collected dataon tramadol and M1 time–concentration profiles in neonatesand young infants (n=20) and published studies on intravenoustramadol in children and adults. M1 formation served as a surrogatefor CYP2D6 activity. Results. Tramadol clearance was described using a two-compartmentlinear model with zero-order input and first-order elimination.Clearance increased from 25 weeks post-conception age (PCA)(5.52 litre h^–1 [70 kg]^–1) to reach 84% of the maturevalue by 44 weeks PCA (standardized to a 70 kg adult using allometric‘1/4 power’ models). The central volume of distributiondecreased from 25 weeks PCA (256 litre [70 kg]^–1) to reach120% of its mature value by 87 weeks PCA. Formation clearanceto M1 contributed 43% of tramadol clearance, but had no relationshipwith PCA. There was a weak non-linear relationship between PCAand M1 metabolite clearance. Conclusions. Maturational clearance of tramadol is almost completeby 44 weeks PCA. A target concentration of 300 µg litre^–1is achieved after a bolus of tramadol hydrochloride 1 mg kg^–1and can be maintained by infusion of tramadol hydrochloride0.09 mg kg^–1 h^–1 at 25 weeks PCA, 0.14 mg kg^–1h^–1 at 30 weeks PCA, 0.17 mg kg^–1 h^–1 at 35weeks PCA, 0.18 mg kg^–1 h^–1 at 40 weeks, 0.19 mgkg^–1 h^–1 at 50 weeks PCA to 1 yr, 0.18 mg kg^–1h^–1 at 3 yr and 0.12 mg kg^–1 h^–1 in adulthood.CYP2D6 activity was observed as early as 25 weeks PCA, but theimpact of CYP2D6 polymorphism on the variability in pharmacokinetics,metabolism and pharmacodynamics of tramadol remains to be established.     

The Discriminatory Value of CYP2D6 Genotyping in Predicting the Dextromethorphan/Dextrorphan Phenotype in Women with Breast Cancer

BACKGROUND: The growth inhibitory effect of tamoxifen is used for the treatment of breast cancer. Tamoxifen efficacy is mediated by its biotransformation, predominantly via the cytochrome P450 2D6 (CYP2D6) isoenzyme, to the active metabolite endoxifen. We investigated the relationship of CYP2D6 genotypes to the metabolism of dextromethorphan (DM), which is frequently used as a surrogate marker for the formation of endoxifen. METHODS: The CYP2D6 genotype was determined by polymerase chain reaction (PCR) in previously untreated patients with hormone receptor-positive invasive breast cancer considered to receive antihormonal therapy. The DM/dextrorphan (DX) urinary excretion ratios were obtained in a subset of patients by high-pressure liquid chromatography (HPLC)-mediated urine analysis after intake of 25 mg DM. The relationships of genotype and corresponding phenotype were statistically analyzed for association. RESULTS: From 151 patients predicted based on their genotype data for the 'traditional' CYP2D6 phenotype classes poor, intermediate, extensive and ultrarapid, 83 patients were examined for their DM/DX urinary ratios. The genotype-based poor metabolizer status correlated with the DM/DX ratios, whereas the intermediate, extensive and ultrarapid genotypes could not be distinguished based on their phenotype. Citalopram intake did not significantly influence the phenotype. CONCLUSIONS: The DM metabolism can be reliably used to assess the CYP2D6 enzyme activity. The correlation with the genotype can be incomplete and the metabolic ratios do not seem to be compromised by citalopram. DM phenotyping may provide a standardized tool to better assess the CYP2D6 metabolic capacity.     

CYP2D6＊10等位基因多态性对胃癌术后曲马多镇痛效果的影响

目的：探讨中国人群CYP2D6＊10等位基因对胃癌术后曲马多镇痛效果的影响。方法：70例胃癌根治术患者,手术结束前30min静脉注入负荷剂量曲马多100mg,随后采用持续背景剂量-PCA量的给药模式（曲马多10mg/mL、甲氧氯普胺0.3mg/mL）进行术后镇痛。全麻诱导后抽取血样,采用聚合酶链反应-限制性片断长度多态性方法分析患者CYP2D6＊10基因多态性,根据不同CYP2D6基因型分为3组,比较不同基因组患者之间曲马多的用量。结果：CYP2D6＊10等位基因频率为52.4%,不携带CYP2D6＊10（I组）17例,CYP2D6＊10杂合子（II组）26例,CYP2D6＊10纯合子（III组）20例。48h曲马多用量,III组明显高于I组和II组,I组和II组之间差异无统计学意义。结论：在中国人群中,CYP2D6＊10等位基因对曲马多镇痛效果有显著影响。     

Determining Cost-Effectiveness of Total Hip and Knee Arthroplasty Using the Short Form-6D Utility Measure

Background

With the implementation of the Patient Protection and Affordable Care Act, cost-effectiveness analyses are becoming increasingly important for resource allocation, and particularly for the justification of costly procedures, such as total knee and total hip arthroplasties (TKAs and THAs). Therefore, using the Short Form-6D (SF-6D) utility values, the purpose of this study was to determine (1) the quality-adjusted life years (QALYs) gained and (2) and the cost-effectiveness of undergoing THA and TKA.

Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells.

BACKGROUND: Injection of maxacalcitol (OCT) directly into the parathyroid gland (PTG) is a clinically safe and effective treatment for advanced secondary hyperparathyroidism (A-SHPT) resistant to conventional medical treatment. In the present study, the degree of nuclear localization of directly injected OCT in parathyroid cells (PTC) was investigated by microautoradiography (mARG) in a model of A-SHPT. METHODS: The 5/6 nephrectomized Sprague-Dawley rats were fed a high-phosphate and low-calcium diet for 8 weeks and consequently the level of vitamin D receptor (VDR) in their PTC severely decreased. The bilateral PTG were surgically exposed and only the left gland were directly injected with 3H-OCT (DI-3H-OCT). The time course of the changes in both radioactivity and localization of 3H-OCT in the bilateral glands was analysed using a bioimaging analyser system and mARG, respectively. A very high dose of unlabelled calcitriol was administered intravenously (IV-1,25D3) prior to DI-3H-OCT, as a competitive study. RESULTS: Peak radioactivity levels in the directly injected and intact PTG occured immediately and 1 h, respectively, after DI-3H-OCT, and the difference was about 50-fold higher in the treated gland. The of mARG showed a marked concentration of silver grains in the nuclei of PTC in the gland treated with DI-3H-OCT and that concentration was significantly suppressed by IV-1,25D3. CONCLUSIONS: Direct injection of OCT into the PTG enables the administration of the highly concentrated drug for specific binding to nuclear vitamin D binding sites, including VDR of PTC, which markedly suppresses the parathyroid hormone, improves the response to calcium and vitamin D and induces apoptosis in PTC.