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Biomedical subjects

Lothar A J Heinemann

Publications and source records attributed to Lothar A J Heinemann.

16 recordsLinked to original sources
PubMed2006

Breast cancer risk associated with different HRT formulations: a register-based case-control study.

BACKGROUND: Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations--particularly concerning different progestins. METHODS: A case-control study was performed within Germany in collaboration with regional cancer registries and tumor centers. Up to 5 controls were matched breast cancer cases. Conditional logistic regression analysis was applied to estimate crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Stratified analyses were performed to compare the risk of different estrogens, progestins, and combinations. RESULTS: A total of 3593 cases of breast cancer were identified and compared with 9098 controls. The adjusted overall risk estimate for breast cancer (BC) associated with current or past use of HRT was 1.2 (1.1-1.3), and almost identical for lag times from 6 months to 6 years prior to diagnosis. No significant trend of increasing BC risk was found with increasing duration of HRT use, or time since first or last use in aggregate. Many established BC risk factors significantly modified the effect of HRT on BC risk, particularly first-degree family history of BC, higher age, lower education, higher body mass index (BMI), and never having used oral contraceptives (OCs) during lifetime. Whereas the overall risk estimates were stable, the numbers in many of the sub-analyses of HRT formulation groups (estrogens, progestins, and combinations) were too small for strong conclusions. Nevertheless, the BC risk seems not to vary much across HRT formulation subgroups. In particular, no substantial difference in BC risk was observed between HRT containing conjugated equine estrogens (CEE) or medroxyprogesterone acetate (MPA) and other formulations more common in Europe. CONCLUSION: The BC risk of HRT use is rather small. Low risk estimates for BC and a high potential for residual confounding and bias in this observational study do not permit causal conclusions. Apparently, there is not much variation of the BC risk across HRT formulations (estrogens, progestins). However, the small numbers and the overlapping nature of some of the subgroups suggest cautious interpretation.

Journal Article↗
PubMed2006

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.

Journal Article↗
PubMed2005

Case-control study on analgesics and nephropathy (SAN): protocol.

BACKGROUND: The association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria. METHODS/DESIGN: The objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations. A targeted sample of 1000 new (incident) dialysis patients, aged less than 50 years, was planned to recruit between January 1, 2001 and December 31, 2004. The age limit was chosen to avoid contamination of the study population with phenacetin-containing analgesics to the extent possible. Four control subjects per ESRD case, matched by age, sex, and region were selected from the population living in the region the case came from. Lifetime exposure to analgesics and potential renal risk factors were recorded in a single face-to-face interview. A set of aids was introduced to reinforce the memory of study participants. A standardized, pre-tested interview questionnaire (participants), a medical documentation sheet (physicians in dialysis centres), a logbook for all activities (dialysis centres) were used to collect the necessary data. Quality management consisted of the standardized procedures, (re-) training and supervision of interviewers, regular checks of all incoming data for completeness and plausibility. The study is scientifically independent and governed by a international Scientific Advisory Committee that bridged the gap between the sponsoring companies and the investigators. Also other advisory groups assisted the managing committee of the study. All relevant German and Austrian nephrological associations supported the study, and the study design was carefully reviewed and approved by the Kidney Foundation of Germany. DISCUSSION: The study is expected to answer the main research question by end 2005. There is however a high potential for various biases that we tried to address with adequate measure. One limitation however cannot be overcome: The methodologically needed age-limitation of the study will make it not easy to generalize the results to age groups over 50 years. It might be suggested to repeat the study for persons over 50 years in 10 years when contamination with phenacetin use early in life is likely to be outgrown.

Analgesics↗
PubMed2005

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.

Journal Article↗
PubMed2005

Scale for Quality of Sexual Function (QSF) as an outcome measure for both genders?

BACKGROUND: For years, there has been interest in sexual dysfunction and its impact on quality of life but usually focused on one gender. Therapeutic options that became available raised the interest to evaluate effects on the other partner but there is no standardized instrument applicable for both genders. This paper reports first data regarding the development of a new general "Quality of Sexual Function" (QSF) scale. METHODS: The raw scale was based on our own gender-specific scales and the pertinent literature. The scale was applied in over 700 persons of a cross-sectional survey in Germany. Factorial analyses were performed to describe the internal structure (domains) of the scale and for item reduction. Internal consistency reliability and some aspects of validity were analyzed with the same community sample preliminary reference values determined. RESULTS: The scale consists of 32 specific items and eight general questions. Four dimensions were identified: "psycho-somatic quality of life,""sexual activity,""sexual (dys)function-self-reflection," and "sexual (dys)function-partner's view." The internal consistency reliability coefficients of the total scale and the subscales were good as were the total-domain correlations. Content validity was promising. CONCLUSION: This self-administrable 40-item QSF scale can measure and compare quality of sexual function for both genders. The scale was well accepted by the respondents. It is easy to answer and the evaluation is simple. Only a few results of reliability and validity have been established in this early stage of the development of the new instrument. Further research is needed to complete many missing aspects of reliability and the construct validity, particular its sensitivity to treatment effects.

Adult↗
PubMed2004

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.

Adult↗
PubMed2004

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.

Adult↗
PubMed2004

The Aging Males' Symptoms scale (AMS) as outcome measure for treatment of androgen deficiency.

INTRODUCTION: No clinical study data in which the AMS scale was applied as outcome measure has been reported until today. METHOD: An open post-marketing study was performed by office-based urologists in Germany in 2000/01. We analysed data of 1174 androgen-deficient males who were treated with testosterone enanthate. The AMS scale was applied prior to and after 12 weeks treatment. RESULTS: The improvement of complaints during treatment relative to the baseline score was 32% on average. Patients with little or no symptoms before therapy improved by 11%, those with mild complaints at entry by 24%, with moderate by 31%, 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. We also demonstrated that the AMS results can predict the independent (physician's) opinion about the individual treatment effect. The positive predictive value was 89%, the negative predictive value 59%, sensitivity (correct prediction of a positive assessment by the urologist) 96%, however, the specificity (correct prediction of a negative assessment by the physician) was only 30%. CONCLUSION: The AMS scale showed a convincing ability to measure treatment effects on quality of life across the full range of severity of complaints. In addition, results of the scale can predict the subjective clinical expert opinion on the treatment efficiency.

Adolescent↗
PubMed2004

Safety of a new oral contraceptive containing drospirenone.

New chemical entities must undergo rigorous, and preferably independent, safety and efficacy assessments before entry into the market. This is also true for oral contraceptives (OCs) given their extensive usage by healthy women and the safety concerns highlighted by the so-called 'third generation pill scare' in Europe a decade ago. This scare heightened patient and physician awareness of the increased risk of thromboembolic complications (mainly venous thromboembolism [VTE]) associated with OC use. Yasmin (ethinylestradiol 30 microg/drospirenone 3 mg [EE/DRSP]) is a novel OC that was demonstrated in clinical phase I-III studies to be highly effective in preventing pregnancy and to have a good safety profile. Nonetheless, clinical trials are not usually sufficiently powered to detect rare adverse events such as VTE to enable comparison with other OCs, which could allay fears and concerns about their inherent risks. Therefore, an extensive assessment of the VTE risk associated with EE/DRSP has been undertaken by reviewing data from the clinical development programme, postmarketing surveillance and spontaneous worldwide reporting, as well as information from other sources. Spontaneous worldwide reporting has revealed a VTE reporting rate of 5.1/100 000 women-years with EE/DRSP use. In contrast, 3-year interim results from a large, controlled, prospective postmarketing surveillance study suggest a VTE rate of 61/100 000 women-years for EE/DRSP, which is similar to the rates of 60/100 000 and 73/100 000 women-years for levonorgestrel-containing OCs and other OCs, respectively. When placed in context with potential biases and confounding factors that would inflate the perceived risk of VTEs with a novel OC, the VTE rate with EE/DRSP does not highlight any safety concerns. Furthermore, the risk of VTE with EE/DRSP or other OCs is far less than that associated with pregnancy and delivery (up to 800/100 000 women-years) or than other risks of daily living. Available data indicate that EE/DRSP is not associated with any increased risk of other serious adverse events such as hyperkalaemia, cardiac arrhythmia or birth defects. Nonetheless, caution should be exerted in prescribing EE/DRSP to women with conditions that predispose to hyperkalaemia.Overall, the safety data with EE/DRSP and other OCs indicate that these products have no negative impact on the risk of VTE (and other adverse events) in women who receive OCs for contraception.

Adult↗
PubMed2003

The Aging Males' Symptoms (AMS) scale: review of its methodological characteristics.

BACKGROUND: The current paper reviews data from different sources to get a closer impression on the psychometric and other methodological characteristics of the Aging Males' Symptoms (AMS) scale gathered recently. The scale was designed and standardized as self-administered scale to (a) to assess symptoms of aging (independent from those which are disease-related) between groups of males under different conditions, (b) to evaluate the severity of symptoms over time, and (c) to measure changes pre- and post androgen replacement therapy. The scale is in widespread use (14 languages). METHOD: Original data from different studies in many countries were centrally analysed to evaluate reliability and validity of the AMS. RESULTS: Reliability measures (consistency and test-retest stability) were found to be good across countries, although the sample size was sometimes small. VALIDITY: The internal structure of the AMS in healthy and androgen deficient males, and across countries was sufficiently similar to conclude that the scale really measures the same phenomenon. The sub-scores and total score correlations were high (0.8-0.9) but lower among the sub-scales (0.5-0.7). This however suggests that the subscales are not fully independent. The comparison with other scales for aging males or screening instruments for androgen deficiency showed sufficiently good correlations, illustrating a good criterion-oriented validity. The same is true for the comparison with the generic quality-of-life scale SF36 where also high correlation coefficients have been shown. Methodological analyses of a treatment study of symptomatic males with testosterone demonstrated the ability of the AMS scale to measure treatment effect, irrespective of the severity of complaints before therapy. It was also shown that the AMS result can predict the independently generated (physician's) opinion about the individual treatment effect. CONCLUSION: The currently available methodological evidence points towards a high quality of the AMS scale to measure and to compare HRQoL of aging males over time or before/after treatment, it suggests a high reliability and high validity as far as the process of construct validation could be pressed ahead yet. But certainly more data will become available, particularly from ongoing clinical studies.

Adult↗
PubMed2003

International versions of the Menopause Rating Scale (MRS).

BACKGROUND: Symptom scales for aging women have clinically been used for years and the interest in measuring health-related quality of life (HRQoL) has increased in recent years. The Menopause Rating Scale (MRS) is a formally validated scale according to the requirements for quality of life instruments. The aim of this paper is to review the current state of the instrument particularly concerning versions of the scale in different languages. MRS VERSIONS AVAILABLE: The translations were performed following international methodological recommendations for the linguistic & cultural adaptation of HRQoL instruments. The first translation was done from the German original scale into English (UK & USA). The English version was used as the source language for the translations into French, Spanish, Swedish, Mexican/Argentine, Brazilian, Turkish, and Indonesian languages (attached as additional PDF files). CONCLUSION: The MRS scale is obviously a valuable tool for assessing health related quality of life of women in the menopausal transition and is used worldwide. The currently available 9 language versions have been translated following international standards for the linguistic and cultural translation of quality of life scales. Assistance is offered to help interested parties in the translation process.

Factor Analysis, Statistical↗
PubMed2003

The Aging Males' Symptoms (AMS) scale: update and compilation of international versions.

BACKGROUND: The interest of clinical research in aging males increased in recent years and thereby the interest to measure health-related quality of life (HRQoL) and symptoms of aging men. The Aging Males' Symptoms scale (AMS) became the most commonly used scale to measure HRQoL and symptoms in aging males in many countries worldwide. The aim of this paper is to review the current state of the instrument particularly concerning versions of the scale in different languages in the light of the quality of the translation process. AMS VERSIONS AVAILABLE: Most of the translations were performed following international methodological recommendations for linguistic & cultural adaptation of HRQoL instruments. Mainly the English version was used as source language for the translation into Dutch, Spanish, Portuguese, Italian, Swedish, and Japanese (attached as additional PDF-files). Preliminary versions that were derived only from forward translations are of secondary quality and available in Finnish, Flemish, and Russian. It is recommended to complete the translation process for the latter languages before using them in international studies. TRANSLATIONS IN PROCESS: The AMS scale is in the process of consensus finding of two existing French versions, and the versions in the Korean, Thai, and Indonesian languages have not yet been completed in the translation process. CONCLUSION: The AMS scale is obviously a valuable tool for assessing health related quality of life in aging men, because it is used worldwide. It is a standardized scale according to psychometric norms. Most of the currently available language versions were translated following international standards for linguistic and cultural translation of quality of life scales. Assistance is offered to help interested parties in the translation process.

Aged↗
PubMed2003

Benign gynecological tumors: estimated incidence. Results of the German Cohort Study on Women's Health.

OBJECTIVE: To analyze the lifetime incidence of benign gynecological tumors. STUDY DESIGN: The German Cohort Study on Women's Health was launched in 1998 as historic cohort study with prospective follow up. The study ascertained self-reported information on tumors by calendar time. The incidence of benign gynecological tumors was calculated from the data of the first cohort period. RESULTS: The cohort comprised 396000 women-years of observation and 1676 benign tumors were observed. This lead to incidence estimates of 27.0, 18.6, and 23.3 per 100000 women-years of observation for all benign tumors of the uterus, ovary, and breast respectively. CONCLUSION: In absence of other data, it is reasonable to use incidence rates generated by a large cohort of German women as a best estimate for the population up to 65 years of age.

Adolescent↗
PubMed2002

Case-control studies on venous thromboembolism: bias due to design? A methodological study on venous thromboembolism and steroid hormone use.

This study addressed methodological issues of epidemiologic studies on venous thromboembolism (VTE) to show how design decisions can affect the results. It examines the influence of a restricting to hospitalized and to "idiopathic" cases of VTE in case-control studies on VTE risk and oral contraceptive (OC) use and thereby the bias potential. The diagnostic processes and OC exposures of 1068 suspected cases of VTE were followed in 21 German centers from 1994 to 1999 and evaluated compared to population and hospital controls. Of 606 confirmed cases, 385 (65.5%) were hospitalized, 168 (27.7%) were "idiopathic." Comparing users versus nonusers of OCs, the odds ratio (OR) for VTE risk for all cases and controls was 3.38 and 5.44 for "idiopathic" VTE. For hospital cases and controls, the OR was 3.72 and 9.1 for "idiopathic" VTE. The risk ratio for third- vs. second-generation OCs was increased in the hospital base but not in the population base. It was concluded that restriction to hospitalized events and exclusions of certain cases overestimate the VTE risk of OCs. An evidence-based consensus on methodological standards and definitions in case-control studies on VTE and steroid hormone use is required.

Adult↗
PubMedDate not supplied

Experiences with the French Aging Males' Symptoms (AMS) scale.

INTRODUCTION: The aim of this paper is to report on experiences gained from the application of the French version of the Aging Males' Symptoms (AMS) scale, to show correlations with other relevant scales and to provide population reference values for France. METHODS: A representative survey based on an existing, representative population panel was performed in France (963 males, aged 15 + years). Other AMS data from Europe were then used for comparison. Mean scores of the French AMS scale do not systematically differ from the data of other European studies. The population reference values obtained for France strongly suggest that the scale measures can appreciate the level of well-being whatever the patients' age; however, some variables, such as age and family income, can influence the total AMS scores. Comparisons with the generic quality-of-life scale, SF-12, and a depression scale, HAD, have shown good correlations, as have comparisons with the ADAM questionnaire. CONCLUSION: The French AMS scale is a standardized, valid and simple health-related quality of life (HRQoL) scale, with results comparable to other published European findings. The results also indicate that the AMS scale can be used to measure and compare HRQoL in those less than 40 years of age.

Adolescent↗