Health Promotion and Preventive Care Intervention for Older Community-Dwelling People: Long-Term Effects of a Randomised Controlled Trial (RCT) within the LUCAS Cohort.

OBJECTIVES: An RCT of a health promotion and preventive care intervention was done in 2001-2002. Here, long-term analyses based on 12 years of follow-up of survival and of change in functional competence between intervention and control group are presented. Positive 1-year results (significantly higher use of preventive services and better health behaviour) were presented earlier. DESIGN: Parallel group randomised controlled trial (RCT) with 878 participants in the intervention and 1,702 participants in the control group. SETTING: The study took place in Hamburg, Germany and made use of health care structures and professionals of a geriatrics centre. PARTICIPANTS: Study participants were initially community-dwelling, aged 60 years and older and without B-ADL-restrictions, cognitive impairment, or need of nursing care, with sufficient command of the German language. INTERVENTIONS: Health promotion and preventive care interventions relied on an extensive health questionnaire and the subsequent offer to participate in multi-topic personal reinforcement performed in small group sessions or at preventive home visits. MEASUREMENTS: Primary outcome: Survival time; in some analyses, adjustments were made for gender, age and self-perceived health. Secondary outcome: Functional competence (LUCAS Functional Ability Index) based on responses to self-administered questionnaires at 1-year follow-up and 12 years after 1-year follow-up (2013/2014). RESULTS: Mean time under observation was 10.3 years. 38.3% (987/2,580) of the participants died; intervention group (IG): 35.7% (313/878), control group (CG): 39.6% (674/1,702); HR=0.89; p=0.09. Functional competence at 1-year follow-up: IG: ROBUST 67.4% (391/580), FRAIL 11.9% (69/580) vs. CG: ROBUST 62.9% (861/1,368), FRAIL 14.8% (203/1,368); p=0.12. 12-years after 1-year follow-up: IG: ROBUST 50.0% (160/320), FRAIL 30.9% (99/320) vs. CG: ROBUST 48.9% (307/628), FRAIL 34.1% (214/628); p=0.56. CONCLUSIONS: Insignificant but consistent effects on survival and the dynamics of functional competence suggest effectivity of the complex intervention. We plan to take a closer look at the effect of each reinforcement separately.

[Acceptance of preventive home visits among frail elderly persons : Participants an non-participants in a Follow-up after 2 and 4 years within the LUCAS longitudinal study]. / Akzeptanz des präventiven Hausbesuchs bei älteren Personen mit Frailty : Teilnehmende und Nichtteilnehmende im Zwei- und Vierjahres-Follow-up im Rahmen der LUCAS-Langzeitstudie.

BACKGROUND: The objective of preventive home visits (PHV) is to support independent living of elderly people. The target group is a matter of discussion and acceptance so far seems to have been low. The target group favored in studies were persons with functional impairments living independently; therefore, acceptance of this offer by frail persons and characteristics of participants and non-participants were studied. MATERIAL AND METHODS: All participants classified as frail in the longitudinal urban cohort ageing study (LUCAS; BMBF Fkz 01ET0708-13/01, ET1002A-D/01EL1407) were randomized (RCT) in 2007/2008 into an intervention group (174 persons) and a control group (379 persons). Participants in the intervention group were offered the option of a PHV. Sociodemographic and health-related characteristics were compared between the participants with a PHV, non-participants and controls at baseline and after 2 and 4 years. Non-participants who refused the offer of the PHV were asked about their reasons. RESULTS: There were 64 persons (36.8 %) in the intervention group classified as frail who accepted the offer of a PHV. Of these, significantly more lived alone, tended to be female with a higher educational level and with less need of care. After 2 years significantly more persons in the group without PHV had died and after 4 years more participants with PHV reported a depressive mood. There were no other significant differences between the groups. Half of the reasons not to accept the PHV that were reported by the non-participants were because of health-related or psychological problems and one third because of lack of interest or need for PHV. CONCLUSION: The offer of PHV to frail elderly persons with an unlimited age was associated with a relatively high acceptance. The high number of refusals by non-participants with functional impairments is remarkable and needs further investigation.

[Resources and risks in old age: the LUCAS-I marker set for a classification of elderly people as fit, pre-frail and frail. First results on validity from the Longitudinal Urban Cohort Ageing Study (LUCAS), Hamburg]. / Ressourcen und Risiken im Alter: Die LUCAS-I Marker zur Klassifizierung älterer Menschen als FIT, pre-FRAIL und FRAIL. Validierung und erste Ergebnisse aus der Longitudinalen Urbanen Cohorten-Alters-Studie (LUCAS).

BACKGROUND: There is a need for a simple self-administered instrument to assess frailty in community-dwelling seniors. METHODS: We present a new marker set to assess the functional state of seniors. Contrary to current literature, we focus not only on risks, but also include resources. The questions relate to facts (ways to do things), rather than on subjective information (e.g. exhaustion). It was developed in the context of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Hamburg, Germany. RESULTS: The classification based on these questions proposes operational definitions of the terms fit, pre-frail and frail and is predictive for need for nursing care as well as mortality. A wealth of results establishes the validity of the categorisation compared to other health questions. One of the classification questions concerns cycling. For areas where cycling is not suitable, we propose to replace this question with one about independently walking 500 m. However, the cycling question appears to indicate frailty earlier. CONCLUSION: The self-administered questionnaire provides a simple, cost-effective way to screen seniors for early signs of declining function in order to start preventive action.

[Health and competence: detection and decoding using comprehensive assessments in the Longitudinal Urban Cohort Ageing Study (LUCAS)]. / Grauzonen von Gesundheit und Handlungsfähigkeit: Erfassung und Aufschlüsselung durch erweiterte Assessments in der Longitudinalen Urbanen Cohorten-Alters-Studie (LUCAS).

PURPOSE: The goal of this work was to characterise and distinguish persons without (fit), with earliest signs (pre-frail) or accelerated functional decline (frail) during self-referral (geriatric centre) or preventive home visits. METHODS: After screening independently living older people in an urban longitudinal cohort (n = 1,995) using a self-administered questionnaire, they were functionally classified as fit, pre-frail or frail. In 10% randomly selected samples of these cohort parts a comprehensive extended gerontological-geriatric assessment (EGGA) was administered. RESULTS: Fit, pre-frail and frail samples are significantly different regarding comorbidity, medication, mobility, fall risk, instrumental activities of daily living and use of social support but not nutrition. The best indicator to discriminate fit versus frail was exhaustion (mobility tiredness). CONCLUSION: Competence is essential regarding health in old age. Identification of resources and risks by comprehensive assessment is useful before planning interventions to prevent frailty or its progression.

On Graphically Checking Goodness-of-fit of Binary Logistic Regression Models.

OBJECTIVES: This paper is concerned with checking goodness-of-fit of binary logistic regression models. For the practitioners of data analysis, the broad classes of procedures for checking goodness-of-fit available in the literature are described. The challenges of model checking in the context of binary logistic regression are reviewed. As a viable solution, a simple graphical procedure for checking goodness-of-fit is proposed. METHODS: The graphical procedure proposed relies on pieces of information available from any logistic analysis; the focus is on combining and presenting these in an informative way. RESULTS: The information gained using this approach is presented with three examples. In the discussion, the proposed method is put into context and compared with other graphical procedures for checking goodness-of-fit of binary logistic models available in the literature. CONCLUSION: A simple graphical method can significantly improve the understanding of any logistic regression analysis and help to prevent faulty conclusions.

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis.

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category 'missing by design', rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models.

Distinguishing phenotypes of childhood wheeze and cough using latent class analysis.

Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions. From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age. The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels. This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.

Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients.

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder in the heme biosynthetic pathway caused by a partial deficiency of porphobilinogen (PBG) deaminase. Clinically, AIP is characterized as acute neurovisceral attacks that are often precipitated by exogenous factors such as drugs, hormones, and alcohol. An early detection of mutation carriers is essential for prevention of acute attacks by avoiding precipitating factors. This study was aimed at analyzing genetic defects causing AIP among Swiss families to further investigate aspects concerning the clinical expression of the disease. MATERIALS AND METHODS: The PBGD gene of index patients from 21 Swiss AIP families was systematically analyzed by denaturing gradient gel electrophoresis of polymerase chain reaction (PCR) amplified DNA fragments and direct sequencing. RESULTS: Five new mutations insA503, del L170, T190I, P241S, and R321H, as well as three known mutations (R26H, R173Q and W283X) were detected. Twelve of the 21 index patients (57%) carried the prevalent mutation W283X previously found among the Swiss AIP population. Family-specific mutations were then screened among relatives of the index patients. Among the 107 studied individuals, 58 carried a PBGD gene mutation--30 were overt AIP patients and 28 were asymptomatic carriers. The apparent rate of overt disease in the study cohort was 52%, which is significantly higher than the previously reported penetrance of 10-20%. To further examine the clinical expression of AIP, the cumulative life-time risk was calculated among 58 mutation-positive individuals after stratifying for age. The result shows a linear increase of the percentage of the symptomatic patients with age, reaching up to 75% among carriers aged over 60. Moreover, statistical analysis of the gender distribution among patients and asymptomatic carriers indicated that the disease was more frequently expressed among females than males (Fisher's exact test two sided, p= (0.001). CONCLUSIONS: This comprehensive search for genetic defects in the PBGD gene confirmed the existence of a prevalent mutation W283X among Swiss AIP patients, as well as a number of family-private mutations. Genetic analysis laid a groundwork for further studies such as the effects of gender and age on the clinical expression of AIP.

[Test-retest reliability of a German language multidimensional assessment instrument in elderly probands]. / Test-Retest-Reliabilität eines deutschsprachigen multidimensionalen Assessmentinstruments bei älteren Personen.

Most geriatric assessment instruments have been developed in the English language. Translated versions might differ in their psychometric properties. We analyzed the test-retest reliability and internal consistency of a German instrument for multidimensional geriatric assessment that was based on a newly developed English version. A group of 100 over 75-year-old community-dwelling persons (mean age 83.0 years, 81% women) in Hamburg (n = 26) and Ulm (n = 51), Germany, and Berne (n = 23), Switzerland was interviewed twice by the same trained interviewers with a one week interval. We administered questions on general health, chronic disorders, basic and instrumental activities of daily living, urinary incontinence, nutrition, falls, pain, the social support/network and preventive care measures. In addition, the Functional Status Questionnaire, the Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the Elderly and the Geriatric Depression Scale were administered. Cohen's kappa was good to excellent (0.64 < or = kappa < or = 0.89) with only three exceptions (pain questions, kappa = 0.53; questions on preventive care services, kappa = 0.51; and one of the questions on recent falls, kappa = 0.44). Cronbach alpha (internal consistency) was good to excellent for all domains (0.76 < or = alpha < or = 0.95). The study results confirm good test-retest reliability of the German version of this multidimensional geriatric assessment instrument. Adapted versions of this instrument can be used for different purposes, e.g., preventive home visits, outpatient geriatric assessments or epidemiological studies in older persons.

Leukemia, brain tumors, and exposure to extremely low frequency electromagnetic fields in Swiss railway employees.

Railway engineers provide excellent opportunities for studying the relation between exposure to extremely low frequency magnetic fields and leukemia or brain tumors. In a cohort study of Swiss railway personnel with 2.7 x 10(5) person-years of follow-up (1972--1993), the authors compared occupations with high average exposures (line engineers: 25.9 microT) to those with medium and low exposures (station masters: 1 microT). The mortality rate ratio for leukemia was 2.4 (95% confidence interval (CI): 1.0, 6.1) among line engineers (reference category: station masters). The mortality rate ratio for brain tumors was 1.0 (95% CI: 0.2, 4.6) among line engineers and 5.1 (95% CI: 1.2, 21.2) among shunting yard engineers (compared with station masters). Two exposure characteristics were evaluated: cumulative exposure in microT-years and years spent under exposure to magnetic fields of > or =10 microT. There was a significant increase in leukemia mortality of 0.9% (95% CI: 0.2, 1.7) per microT-year of cumulative exposure to extremely low frequency magnetic fields. The increase by years spent under exposure of > or =10 microT was even stronger: 62% per year (95% CI: 15, 129). Brain cancer risk did not show a dose-response relation. This study contributes to the evidence for a link between heavy exposure to extremely low frequency magnetic fields and leukemia. Its strengths include reliable measurements and reliable historical reconstruction of exposures.

Health services utilization of elderly Swiss: evidence from panel data.

The demand for health care services by the elderly is a topic of growing importance because of changes in the demographic structure in many countries. This paper provides estimates of the determinants of the demand for physician visits by the elderly, including the impact of a disability prevention intervention. We control for unobserved heterogeneity across individuals and the count data structure of the data by estimating random effects negative binomial models for all primary physician and specialist visits.

[A multidimensional questionnaire as a component of preventive geriatric assessment: comparison of self-assessment version with the interview version]. / Ein multidimensionaler Fragebogen als Bestandteil eines präventiven geriatrischen Assessments: Vergleich der Selbstausfüllerversion mit der Interviewversion.

In an earlier study we have shown good internal consistency and test-retest-reliability of a newly developed German-language instrument in the interviewer-administered version. The aim of this study was to test the reliability of a self-administered version compared to the original interviewer-administered version of our newly developed German-language instrument. We recruited a group of 50 over 75-year-old community-dwelling persons in Hamburg, Germany (N = 25) and Berne, Switzerland (N = 25). The questionnaire contains items on: self-perceived health, chronic conditions, basic and instrumental activities of daily living, urinary incontinence, nutrition, recent falls, pain, the social support/network and preventive-care measures. In addition, the Functional Status Questionnaire, the Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the Elderly and the Geriatric Depression Scale were administered. Cohen's Kappa (self-administered version compared to the interviewer-administered version) was good to excellent (0.69-1.0) with only three exceptions (physical activity kappa = 0.49, basic activities kappa = 0.54 and oral health kappa = 0.54). For the domains activities of daily living, oral health, visual function and depression the self-administered version detected significantly more problems than the interview. In the future the self-administered version of this assessment instrument can be used for various purposes, e.g. (annual) preventive geriatric assessment for outpatients and other community-dwelling persons and epidemiological studies in older persons.

[Preventive home visits for elderly patients: development and pilot testing of a multidimensional assessment instrument]. / Präventive Hausbesuche im Alter: Entwicklung und Pilottestung eines multidimensionalen Abklärungsinstruments.

Preventive home visits with multidimensional geriatric assessment have been shown to delay or prevent the onset of disability and reduce nursing home admissions in older people. The purpose of the present study was to develop and test a multidimensional instrument for in-home preventive assessments in older persons. In developing the instrument, we conducted a systematic literature review of risk factors for functional status decline and of appropriate instruments for measuring these risk factors. Based on an Expert Panel using a modified Delphi process [1] the risk factor domains for functional status decline were chosen, [2] the instruments for evaluating each of the included risk factor domains were selected, and [3] the individual instruments were combined into one comprehensive assessment instrument. A German language version of the original English version of the instrument was developed based on translation, backtranslation, and cultural adaptation. The feasibility of use of the new instrument was evaluated in a field test in 150 people aged 75 years and older in Hamburg, Ulm, Germany, and Bern, Switzerland. The instrument was well accepted by the older persons. The prevalence of risk factors for functional status decline in these populations (e.g., physical inactivity, urinary incontinence, vision impairment) was high. There was also a high prevalence of underuse of preventive care measures (e.g., no pneumococcal vaccination in over 95 percent of persons). These preliminary results support the possible usefulness of this instrument for conducting preventive home visits or for epidemiological purposes (e.g., prevention surveillance). In a next phase, the test-retest reliability of the instrument, and the feasibility and reliability of self-administration as compared to interviewer administration will be described in a separate paper.

A randomized trial of in-home visits for disability prevention in community-dwelling older people at low and high risk for nursing home admission.

BACKGROUND: In-home preventive visits with multidimensional geriatric assessments can delay the onset of disabilities in older people. METHODS: This was a stratified randomized trial. There were 791 participants, community-dwelling people in Bern, Switzerland, older than 75 years. The participants' risk status was based on 6 baseline predictors of functional deterioration. The intervention consisted of annual multidimensional assessments and quarterly follow-up in-home visits by 3 public health nurses (nurses A, B, and C), who, in collaboration with geriatricians, evaluated problems, gave recommendations, facilitated adherence with recommendations, and provided health education. Each nurse was responsible for conducting the home visits in 1 ZIP code area. RESULTS: After 3 years, surviving participants at low baseline risk in the intervention group were less dependent in instrumental activities of daily living (ADL) compared with controls (odds ratio, 0.6; 95% confidence interval, 0.3-1.0; P = .04). Among subjects at high baseline risk, there were no favorable intervention effects on ADL and an unfavorable increase in nursing home admissions (P= .02). Despite the similar health status of subjects, nurse C identified fewer problems in the subjects who were visited compared with those assessed by nurses A and B. Subgroup analysis revealed that among low-risk subjects visited by nurses A and B, the intervention had favorable effects on instrumental ADL (P = .005) and basic ADL (P = .009), reduced nursing home admissions (P = .004), and resulted in net cost savings in the third year (US $1403 per person per year). Among low-risk subjects visited by nurse C, the intervention had no favorable effects. CONCLUSIONS: These data suggest that this intervention can reduce disabilities among elderly people at low risk but not among those at high risk for functional impairment, and that these effects are likely related to the home visitor's performance in conducting the visits.

Are safety committees really safe?

In an increasing number of recent major clinical trials, independent safety committees or safety monitors have been involved. Their role and function is not yet defined and continues to evolve. The aim of this paper is to discuss the role and tasks of safety committees as a result of our collective experience as members of three safety committees of studies evaluating antithrombotic prophylaxis against postoperative deep vein thrombosis. We believe that the type of pharmacological intervention used is of less importance than the general experiences gained, which can be extrapolated to other studies and should stimulate a more general debate.

Comparison of responses to an asthma symptom questionnaire (ISAAC core questions) completed by adolescents and their parents. SCARPOL-Team. Swiss Study on Childhood Allergy and Respiratory Symptoms with respect to Air Pollution.

The primary objective of the study was to determine the impact of the identity of the respondent (parents versus adolescents) on prevalence estimates of asthma symptoms in Swiss adolescents. In addition, factors influencing agreement between parents' and adolescents' responses to the same questions were analysed. One thousand three hundred and seventy-four (78.4%) adolescents, aged 14 years, self-completed a questionnaire at school based on the International Study of Asthma and Allergy in Childhood (ISAAC) core questions on wheezing and asthma. The same questions were incorporated into a questionnaire to be completed by the parents at home. The adolescents' self-reported prevalence rates of current asthma symptoms and "asthma ever" were significantly higher than those obtained from the parental questionnaires. 856 (62.6%) parental questionnaires were filled in by parents without the help of the adolescents, 460 (37.4%) were completed by parents and adolescents and 51 (3.7%) were completed by the adolescents without the parents. Prevalence rates were higher when parents and adolescents completed the questionnaire jointly than when questionnaires were completed by parents alone. The level of agreement between parental and self-completed questionnaires was moderate to low (kappa coefficients 0.22-0.68). Agreement between parental and adolescents reports of asthma symptoms was best when questionnaires were completed jointly by parents and adolescents, when the adolescent was a girl, when a family history of asthma was recorded, when the adolescent was a non-smoker, and when the parental education was high. We conclude that the higher reporting of prevalence rates of current asthma symptoms by adolescents compared to reporting by their parents demonstrates the need to take the respondent to a questionnaire into account when comparisons are made between prevalence studies. The results also suggest that factors related to the family milieu influence symptom reporting.

Effects of exposure to 16.7 Hz magnetic fields on urinary 6-hydroxymelatonin sulfate excretion of Swiss railway workers.

The aim of our study was to examine the effects of 16.7 Hz electromagnetic-field exposure on pineal melatonin production in healthy humans. The study was based on comparing urinary 6-hydroxymelatonin sulfate (6-OHMS) levels of 108 male railway workers between leisure periods and days following the start of service on electrically powered engines (66 engineers) or working beneath transmission lines (42 railway employees such as train attendants and station managers; controls). A repeated measures design was used, i.e., each volunteer served as his own control. The exposure averaged 20 muTesla in the most exposed workers and around 1 muTesla in the least exposed. Apart from magnetic exposure the workers were subject to a shift work schedule with daily advances between 15 min and 1 hr. Melatonin was assessed by sampling urinary 6-OHMS both in the morning and the early evening. Evening 6-OHMS values appeared to be lowered by a factor of 0.81 (95%CI: 0.73-0.90) during work days compared to leisure days among engine drivers, but not in the controls. The lowering was not confined to certain types of shift work such as early, normal, or late shifts. During subsequent leisure periods evening values recovered significantly, mean ratio = 1.27 (95%CI: 1.03-1.56), i.e., the effects appeared to be reversible. In contrast, morning 6-OHMS samples of engineers and controls did not differ much between work and leisure days. There was, however, a tendency for a rebound of morning values in a leisure period following a work period both for engineers and controls. The observed pattern appears to be in line with predictions of the "phase response curve." No evidence for a dose-response relation was found. The results support the hypothesis that 16.7 Hz magnetic fields alter 6-OHMS excretion in humans exposed to magnetic fields. An alternative explanation that cannot be excluded in this study is that the difference between engineers and controls is due to differential exposure to day light at work.

A robust method for proportional hazards regression.

In this paper we give an informal introduction to a robust method for survival analysis which is based on a modification of the usual partial likelihood estimator (PLE). Large sample results lead us to expect reduced bias for this robust estimator compared with the PLE whenever there are even slight violations of the model. In this paper we investigate three types of violation: (a) varying dependency structure of survival time and covariates over the sample; (b) omission of influential covariates, and (c) errors in the covariates. The simulations presented support the above expectation. Analyses of data sets from cancer epidemiology and from a clinical trial in lung cancer illustrate that a better fit and additional insights may be gained using robust estimators.

Intravesical versus intravesical plus intradermal bacillus Calmette-Guerin: a prospective randomized study in patients with recurrent superficial bladder tumors.

PURPOSE: Intravesical instillation of bacillus Calmette-Guerin (BCG) induces various immunological reactions and decreases the recurrence rate of superficial bladder tumors. To determine whether additional immune stimulation with concomitant intradermal BCG applications could further lower the recurrence rate, 154 patients with superficial bladder tumors at high risk for recurrence were randomized to receive either 6 intravesical instillations of 120 mg. Pasteur strain BCG alone or combined with intradermal application. MATERIALS AND METHODS: A total of 76 patients received intravesical and intradermal BCG, while 78 received intravesical BCG only. Median followup was 41 months (range 2 to 89) and 36 months (range 2 to 86), respectively. Both treatment groups were comparable regarding patient age and number of previous transurethral bladder tumor resections, as well as tumor recurrence rate, stage and grade before BCG therapy. RESULTS: A highly significant decrease in the monthly tumor recurrence rate was observed in both arms after BCG compared to the pretreatment recurrence rates (p < 0.0001). Recurrence rate decreased from 0.73 +/- 1.07 (standard deviation) to 0.06 +/- 0.13 in the combined treatment group and from 0.71 +/- 0.90 to 0.074 +/- 0.17 in the intravesical treatment only group. However, we were unable to find any difference between the 2 groups regarding interval to initial recurrence or recurrence rates after BCG treatment. Changes in the purified protein derivative skin test performed before and after BCG therapy were not useful to predict response to treatment because 44% of our patients already had a positive test before treatment. Also, interpretation of the skin test was difficult and not always reliable. In the multivariate analysis, however, fever was an important prognostic factor. Patients with increased body temperature greater than 37.5C had a significantly lower recurrence rate than those without fever (37.5C or less) after BCG instillation (p = 0.009). Moreover, fever after BCG instillation was observed significantly more frequently in patients with a positive purified protein derivative skin test before treatment (p = 0.021). CONCLUSIONS: The therapeutic benefit from intravesical BCG apparently was not substantially improved by simultaneous intradermal BCG vaccination. Fever following intravesical BCG instillation is an important prognostic factor regarding superficial bladder tumor recurrence. Fever occurs predominantly in patients who were previously sensitized to mycobacteria (by BCG vaccination or infection) as shown by a positive pretreatment purified protein derivative skin test. This finding suggests that previously sensitized patients respond significantly better to a single course of intravesical BCG.