Quality of life and hormone use: new validation results of MRS scale

BACKGROUND: The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. Recently the MRS scale was validated as outcomes measure for hormone therapy. The suspicion however was expressed that the data were too optimistic due to methodological problems of the study. A new study became available to check how founded this suspicion was. METHOD: An open post-marketing study of 3282 women with pre- and post- treatment data of the self-administered version of the MRS scale was analyzed to evaluate the capacity of the scale to detect hormone treatment related effects with the MRS scale. The main results were then compared with the old study where the interview-based version of the MRS scale was used. RESULTS: The hormone-therapy related improvement of complaints relative to the baseline score was about or less than 30% in total or domain scores, whereas it exceeded 30% improvement in the old study. Similarly, the relative improvement after therapy, stratified by the degree of severity at baseline, was lower in the new than in the old study, but had the same slope. Although we cannot exclude different treatment effects with the study method used, this supports our hypothesis that the individual MRS interviews performed by the physician biased the results towards over-estimation of the treatment effects. This hypothesis is underlined by the degree of concordance of physician's assessment and patient's perception of treatment success (MRS results): Sensitivity (correct prediction of the positive assessment by the treating physician) of the MRS and specificity (correct prediction of a negative assessment by the physician) were lower than the results obtained with the interview-based MRS scale in the previous publication. CONCLUSION: The study confirmed evidence for the capacity of the MRS scale to measure treatment effects on quality of life across the full range of severity of complaints before treatment. The difference of the relative improvement after therapy between the old and current study as well as the observed different sensitivity/specificity is – as a matter of probability – more likely to be caused by a bias introduced by the different application of the MRS scale than by real differences in the efficacy of the therapy. A randomized clinical trial would be needed to test the impact of the latter. The message for future studies is: The MRS scale should be only used as self-administered tool where the suggestive effect of questions raised by health professionals ("therapeutic optimism") can be largely excluded

The Menopause Rating Scale (MRS) scale: A methodological review

BACKGROUND: This paper compiles data from different sources to get a first comprehensive picture of psychometric and other methodological characteristics of the Menopause Rating Scale (MRS) scale. The scale was designed and standardized as a self-administered scale to (a) to assess symptoms/complaints of aging women under different conditions, (b) to evaluate the severity of symptoms over time, and (c) to measure changes pre- and postmenopause replacement therapy. The scale became widespread used (available in 10 languages). METHOD: A large multinational survey (9 countries in 4 continents) from 2001/ 2002 is the basis for in depth analyses on reliability and validity of the MRS. Additional small convenience samples were used to get first impressions about test-retest reliability. The data were centrally analyzed. Data from a postmarketing HRT study were used to estimate discriminative validity. RESULTS: Reliability measures (consistency and test-retest stability) were found to be good across countries, although the sample size for test-retest reliability was small. Validity: The internal structure of the MRS across countries was astonishingly similar to conclude that the scale really measures the same phenomenon in symptomatic women. The sub-scores and total score correlations were high (0.7–0.9) but lower among the sub-scales (0.5–0.7). This however suggests that the subscales are not fully independent. Norm values from different populations were presented showing that a direct comparison between Europe and North America is possible, but caution recommended with comparisons of data from Latin America and Indonesia. But this will not affect intra-individual comparisons within clinical trials. The comparison with the Kupperman Index showed sufficiently good correlations, illustrating an adept criterion-oriented validity. The same is true for the comparison with the generic quality-of-life scale SF-36 where also a sufficiently close association has been shown. CONCLUSION: The currently available methodological evidence points towards a high quality of the MRS scale to measure and to compare HRQoL of aging women in different regions and over time, it suggests a high reliability and high validity as far as the process of construct validation could be completed yet

Non-phenacetin analgesics and analgesic nephropathy: Clinical assessment of high users from a case-control study [1]*

Background. A recent large-scale case-control study on analgesic nephropathy (SAN) [1] found no increased risk of end-stage renal disease (ESRD) in users of combined or single formulations of phenacetin-free analgesics. In a subgroup of 22 high users, however, a dose-dependent increased risk was found, which raised the question if these patients presented or not with analgesic nephropathy (AN). Methods. The individual questionnaires of this subgroup of high users were reviewed, and the total lifetime intake of different types of analgesics was calculated. For evidence of AN, the following data were considered: (1) the amount and type of analgesics consumed, (2) the cause of ESRD, as diagnosed by the nephrologist in charge of the patient and (3) renal imaging and other relevant laboratory data. Results. This group of ESRD patients consumed on average 7.8 kg of antipyretic analgesics (range 30.8-2.7 kg) over an average of 21.5 years (range 35-6 years). Single analgesics were exclusively used by 12 patients (54.5%) and combined analgesics by 5 patients (22.7%), while 5 patients used both. None of the patients was diagnosed as having AN, and a review of the questionnaires did not disclose evidence suggestive of AN. The possibility that, irrespective of AN, the analgesic (ab)use contributed to the progression of existing renal diseases cannot be answered in the absence of well-defined criteria. The data supporting the existence of such an analgesic-associated nephropathy (AAN) are, however, not consistent and most likely due to confounding by indication. Conclusion. In a group of ESRD patients with high use of non-phenacetin analgesics, no evidence of AN was found. There is no evidence that (ab)use of analgesics or NSAIDs other than phenacetin leads to a pathologically or clinically defined renal disease that could be named AN or AA

Comparison of incidence/risk of venous thromboembolism (VTE) among selected clinical and hereditary risk markers: A community-based cohort study

BACKGROUND: Little information is available from community-based long-term VTE cohort studies to compare the absolute thrombosis risk of established clinical and genetic risk factors. MATERIALS AND METHODS: The occurrence of venous thromboembolism (VTE) was observed during a 10-year observation period in the BAvarian ThromboEmbolic Risk (BATER) study, a cohort study of 4337 women (age 18–55 years). We collected data on demographics, reproductive life, lifestyle, conditions/diseases, and particularly potential risk factors for VTE with a self-administered questionnaire. The objective was to present incidence rates of VTE and to show relative risk estimated associated with different clinical and genetic risk factors. RESULTS: 34 new, by diagnostic means confirmed VTE events occurred during the observation time of 32,656 women-years (WY). The overall incidence of VTE was 10.4 per 10(4 )WY. The incidence rates varied markedly among different risk cohorts. The highest incidence was observed in women with previous history of VTE, followed by family history of VTE. None of the measured "genetically-related risk markers" (antithrombin, protein C, FVL, prothrombin mutation, or MTHFR) showed a significant VTE risk. CONCLUSION: Most of the discussed VTE risk factors showed no significant association with the occurrence of new VTEs due to smallness of numbers. Only first-degree family history of VTE and own history of a previous VTE event depicted a significant association with future VTE. Clinical information seems to be more important to determine future VTE risk than genetically related laboratory tests

The Menopause Rating Scale (MRS) as outcome measure for hormone treatment? A validation study

BACKGROUND: The Menopause Rating Scale is a health-related Quality of Life scale developed in the early 1990s and step-by-step validated since then. No methodologically detailed work on the utility of the scale to assess health-related changes after treatment was published before. METHOD: We analysed an open, uncontrolled post-marketing study with over 9000 women with pre- and post-treatment data of the MRS scale to critically evaluate the capacity of the scale to measure the health-related effects of hormone treatment independent from the severity of complaints at baseline. RESULTS: The improvement of complaints during treatment relative to the baseline score was 36% in average. Patients with little/no complaints before therapy improved by 11%, those with mild complaints at entry by 32%, with moderate by 44%, and with severe symptoms by 55% – compared with the baseline score. We showed that the distribution of complaints in women before therapy returned to norm values after 6 months of hormone treatment. We also provided weak evidence that the MRS results may well predict the assessment of the treating physician. Limitations of the study, however, may have lead to overestimating the utility of the MRS scale as outcome measure. CONCLUSION: The MRS scale showed some evidence for its ability to measure treatment effects on quality of life across the full range of severity of complaints in aging women. This however needs confirmation in other and better-designed clinical/outcome studies

VTE Risk assessment – a prognostic Model: BATER Cohort Study of young women

BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18–55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 10(4 )WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool – containing clinical information (and if available also genetic data) – seems to be worthwhile testing in medical practice in order to confirm or refute the positive findings of this study. Our cohort study will be continued to include more VTE cases and to increase predictive value of the model

European active surveillance study of women taking HRT (EURAS-HRT): study protocol [NCT00214903]

BACKGROUND: The post marketing safety surveillance program for a drug containing a new chemical entity should assess both, the safety outcomes that relate specifically to the targeted population, as well as those that could potentially be related to special pharmacological characteristics of the drug. Active safety surveillance using valid epidemiological study designs has been proven to be a pertinent and reliable method to approach this endeavor. METHODS/DESIGN: The primary objective of the study is to compare incidence rates of serious adverse events in users of all types of newly prescribed oral HRT products. This active surveillance study will assess pertinent cardiovascular outcomes - in particular venous and arterial thromboembolism - and other serious adverse events (SAEs) in new HRT users over a period of several years. One product under surveillance is Angeliq(®), which contains the novel progestagen drospirenone (DRSP) combined with estradiol. In addition, all other oral combined HRT products with a novel progestagen or estrogen that will be newly marketed during the study period will be studied. These new HRT products will be compared with established HRT products. The combined cohort will include at least 30,000 women recruited in several European countries. At least 90,000 years of observation are expected from the field work which started in early 2002 and will end around 2008. The participating women will complete a baseline survey using a self-administered questionnaire to describe the baseline risk. After 6 months, 12 months, and then on an annual basis, they will fill out a questionnaire in which they record complaints and events during the use of the prescribed HRTs. All adverse outcomes occurring during the observational period will be evaluated. DISCUSSION: A complete lifetime medical history, individually validated SAEs over time, and a low loss to follow-up rate are essential for a robust safety assessment. Therefore, the lifetime history of diseases and relevant medications will be documented. Reported SAEs will be validated and analyzed. A four level, multi-faceted follow-up process was established to ensure low loss to follow-up rates (e.g., 3–5% after three years of follow up). Multivariate methods will be used to adjust for confounding

Sensitivity as outcome measure of androgen replacement: the AMS scale

BACKGROUND: The capacity of the AMS scale as clinical utility and as outcome measure still needs validation. METHODS: An open post-marketing study was performed by office-based physicians in Germany in 2004. We analysed data of 1670 androgen-deficient males who were treated with testosterone gel. The AMS scale was applied prior to and after 3 months treatment. RESULTS: The improvement of complaints under treatment relative to the baseline score was 30.7% (total score), 27.3% (psychological domain), 30.5% (somatic domain), and 30.7% (sexual domain), respectively. Patients with little or no symptoms before therapy improved by 9%, those with mild complaints at entry by 24%, with moderate by 32%, and with severe symptoms by 39% – compared with the baseline score. We showed that the distribution of complaints of testosterone deficient men before therapy almost returned to norm values after 12 weeks of testosterone treatment. Age, BMI, and total testosterone level at baseline did not modify the positive effect of androgen therapy. We also demonstrated that the AMS results can predict the independent (physician's) opinion about the individual treatment effect. Both, sensitivity (correct prediction of a positive assessment by the physician) and specificity (correct prediction of a negative assessment by the physician) were over 70%, if about 22% improvement of the AMS total score was used as cut-off point. CONCLUSION: The AMS scale showed a convincing ability to measure treatment effects on quality of life across the full range of severity of complaints. Effect modification by other variables at baseline was not observed. In addition, results of the scale can predict the subjective clinical expert opinion on the treatment efficiency