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Biomedical subjects

I Guggenmoos-Holzmann

Publications and source records attributed to I Guggenmoos-Holzmann.

At least 19 recordsLinked to original sources

Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestation in longitudinally followed early Bacille Calmette-Guérin-vaccinated and nonvaccinated children.

BACKGROUND: Bacille Calmette-Guérin (BCG) is a strong T helper 1 incentive and, thus, may contribute to a decreased risk of T helper 2-dependent atopic disease. OBJECTIVE: To investigate the natural course of specific immunoglobulin E (IgE) responses and atopic disease in BCG-vaccinated and nonvaccinated children. PARTICIPANTS: Seven hundred seventy-four children from a prospectively followed birth cohort. OUTCOME MEASURES: Physical examination and case history were performed at 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months of age. Total and specific serum IgE levels to 9 common inhalant and food allergens were determined (CAP; Pharmacia, Freiburg, Germany) at 12, 24, 36, 60, 72, and 84 months of age. Purified protein derivative (PPD) skin testing was performed at 84 months. RESULTS: Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life, whereas no such trend was found after the second birthday or for allergic rhinitis. The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time. No statistically significant differences were found for total IgE levels (median). Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life. The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of >/=5 mm and those with a smaller diameter. CONCLUSION: These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy. In addition, PPD skin test reactivity was not impaired in atopic individuals.

BCG Vaccine↗

The (in)validity of sensitivity and specificity.

This paper is a legacy of the first author, and after her untimely death reconstructed by the second author as a tribute to Irene Guggenmoos's contribution to biostatistics. It discusses two different views on diagnostic testing: the classical view in which sensitivity and specificity of a diagnostic test are considered universal constants, and the more statistical point of view that focuses on predictive values. The differences between the two paradigms are outlined and practical examples are discussed to show that the familiar concepts of sensitivity and specificity must be handled with care and not used indiscriminately.

Data Interpretation, Statistical↗

Effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food and inhalant allergens during the first 3 years of life. Multicenter Allergy Study Group, Germany.

BACKGROUND: The study aimed to assess the effect of pre- and postnatal tobacco smoke exposure on specific sensitization to food allergens and inhalant allergens during the first 3 years of life. METHODS: A total of 342 children of a prospective and observational birth cohort study on atopy (MAS) were included on the basis of a complete follow-up of specific IgE measurements at the ages of 1, 2, and 3 years with available questionnaire information about the parental smoking habit at birth, 18 months, and 3 years of age. Study children were grouped into four exposure categories representing in utero and postnatal environmental tobacco smoke (ETS) exposure, and according to the number of cigarettes smoked by the parents. The effect on the development of allergic sensitization to food, outdoor, and indoor allergens by 3 years of age was determined by multiple logistic regression analyses. RESULTS: At the age of 3, children who were pre- and postnatally exposed to tobacco smoke had a significantly higher risk of sensitization to food allergens (odds ratio: 2.3, 95% C.I.: 1.1-4.6) than unexposed children. Children who were only postnatally exposed by a smoking mother also had a 2.2 times higher risk (95% C.I.: 0.9-5.9) of sensitization than unexposed children. These two categories (pre- and/or postnatal exposure) contribute to the significant overall effect of the tobacco smoke exposure (P< or =0.02). No significant association between tobacco smoke exposure and specific sensitization to inhalant allergens was observed. The determining risk factors for this type of sensitization were atopic family history and mite- and cat-allergen exposure levels. CONCLUSIONS: During the first 3 years of life, both prenatal and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization which seems to be restricted to allergens to which children are mainly exposed, in combination with the peak of the ETS exposure around the first birthday.

Child, Preschool↗

Kappa-like indices of observer agreement viewed from a latent class perspective.

It is common practice to assess consistency of diagnostic ratings in terms of 'agreement beyond chance'. To explore the interpretation of such a term we consider relevant statistical techniques such as Cohen's kappa and log-linear models for agreement on nominal ratings. We relate these approaches to a special latent class concept that decomposes observed ratings into a class of systematically consistent and a class of fortuitous ratings. This decomposition provides a common framework in which the specific premises of Cohen's kappa and of log-linear models can be identified and put into perspective. As a result it is shown that Cohen's kappa may be an inadequate and biased index of chance-corrected agreement in studies of intra-observer as well as inter-observer consistency. We suggest a more critical use and interpretation of measures gauging observer reliability by the amount of agreement beyond chance.

Adult↗

Thromboembolic stroke in young women. A European case-control study on oral contraceptives. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

A matched case-control study was performed between 1993 and 1996 in 16 centers in the United Kingdom, Germany, France, Switzerland, and Austria. The objective was to determine the influence of oral contraceptives (OC), particularly those containing modern progestins, on the risk for ischemic stroke in women aged 16-44 years. A total of 220 women who had had an incident ischemic stroke and were compared with 775 control subjects who were unaffected by stroke. At least one hospital and one community control subject per patient was matched and interviewed with the corresponding patient for 5-year age band and for area of residence. Crude odds ratios (95% confidence intervals [CI]) for ischemic stroke were as follows. For current use of any OC versus no use 2.3 (1.7-3.2), the adjusted odds ratio (OR) 3.6 (2.4-5.4). The OC associated risk was higher for first generation than for second or third generation OC. The risk estimates for patients versus community control subjects were always lower than for hospital control subjects. No major regional difference of the risk estimates was found. Compared with nonusers of OC without hypertension, women with hypertension who used OC had an almost 10-fold increased risk. However, OC users who had had a blood pressure check before OC prescription had a lower risk than did those without such a check. Smoking > 10 cigarettes/day is associated with higher risk of stroke, particularly for OC users. No significant effect was found for duration of OC use. We conclude that although there is a small relative risk of occlusive stroke for healthy women currently using OC, the attributable risk is very small because the incidence in this age group is very low. The small increase in risk of OC use may be further reduced by preventive efforts for cardiovascular risk factors, particularly hypertension and smoking.

Adolescent↗

Long-lasting sensitization to food during the first two years precedes allergic airway disease. The MAS Study Group, Germany.

The purpose of the study was to investigate whether the duration of sensitization to food allergens during early childhood is related to later development of IgE mediated hypersensitivity to inhalant allergens and of allergic rhinitis and asthma in 5-year-old children and whether long-lasting food-sensitization may be used to predict subsequent allergic airway diseases. Five hundred and eight children of a prospective birth cohort study with available serum samples at one and two years of age were included and followed up until five years of age. Specific sensitization to food and inhalant allergens and the occurrence of subsequent allergic airway diseases were determined. Children with a long-lasting sensitization to food allergens (persistently sensitized for more than one year) produced significantly higher total IgE and specific IgE levels than children who were only transiently food-sensitized by two years of age. Children persistently sensitized to food had a 3.4 fold higher risk of developing allergic rhinitis and a 5.5 fold higher risk of developing asthma than infants who were only transiently food sensitized. Persistent food sensitization in combination with a positive atopic family history was a strong predictor for the development of allergic rhinitis and asthma at five years of age. The risks for these children are up to 50%, and 67% respectively. Persistently detectable sensitization to food over more than one year in early childhood is a strong prognostic factor for subsequent allergic airway disease. Persistently food-sensitized children especially in atopic families have to be regarded as a high-risk group and should be considered for preventive measures against respiratory atopy.

Administration, Inhalation↗

Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women.

OBJECTIVE: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16-44 years. DESIGN: Matched case-control study. SETTING: 16 Centres in the United Kingdom, Germany, France, Switzerland, and Austria. SUBJECTS: Cases were 220 women aged 16-44 who had an incident ischaemic stroke. Controls were 775 women (at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analysis and unconditional logistic regression to adjust for potential confounding. RESULTS: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 (2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription. CONCLUSION: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure.

Adolescent↗

[Meta-analysis].

Explore the source record for details and available documents.

Clinical Trials as Topic↗

Sensitization to hen's egg at the age of twelve months is predictive for allergic sensitization to common indoor and outdoor allergens at the age of three years.

BACKGROUND: Specific predictors for atopic sensitization in early infancy are prerequisites for preventive intervention studies. OBJECTIVE: To identify predictors of allergic sensitization to common aeroallergens in infancy, 1314 children in five German cities were followed up from birth (1990) to the age of 3 years. METHODS: Blood samples were taken from cord blood and at follow-up visits at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to common food and inhalant allergens were determined. RESULTS: Among our study population, risk factors for sensitization to indoor and/or outdoor allergens at the age of 3 years were a positive family history, the presence of hen's egg-specific IgE antibodies (> or = 0.35 kU/L), and increased log- [total IgE] levels at the age of 12 months. Elevated cord blood IgE was not associated with sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE greater than 2 kU/L in combination with a positive family history of atopy was a highly specific (specificity, 99%) and predictive (positive predictive value, 78%) marker for sensitization to inhalant allergens at 3 years of age. CONCLUSIONS: Hen's egg-specific IgE at the age of 12 months is a valuable marker for subsequent allergic sensitization to allergens that cause asthma, allergic rhinitis, and atopic dermatitis.

Allergens↗

Indoor allergen exposure is a risk factor for sensitization during the first three years of life.

BACKGROUND: The purpose of the study was to investigate the influence of environmental allergen exposure on allergic sensitization in infancy and early childhood. METHODS: A cohort of 1314 newborns was recruited and followed up prospectively at the ages 12, 24, and 36 months. The levels of major mite (Der p 1 and Der f 1) and cat (Fel d 1) allergens were determined from domestic carpet dust samples by sandwich ELISA. Specific serum IgE antibodies to mite and cat allergens were determined by CAP fluoroimmunoassay (Pharmacia). Logistic regression was used to assess the effects of allergen exposure, age, family history, and cord blood IgE simultaneously on the risk of sensitization. RESULTS: Children, who had been found to be sensitized at least once during the first 3 years of life, were found to be exposed to significantly higher house dust mite (median, 868 ng/gm vs 210 ng/mg; p = 0.001) and cat (median, 150 ng/gm vs 64 ng/gm; p = 0.011) allergen concentrations in domestic carpet dust compared with the group without sensitization. In homes with low (< or = 25th percentile) dust concentrations, the risk of sensitization to mite (1.6%), and cat (2.0%) is low, compared with 6.5% for mite and 6.3% for cat if the domestic exposure is above the 75th percentile. The dose-response relationships between allergen levels and sensitization indicate that the increase in sensitization risk at low allergen levels is more pronounced in cat allergy (p = 0.002) than in mite allergy (p = 0.026). In the group with a positive family history, lower mite and cat allergen concentrations are needed to achieve specific sensitization compared with the group with a negative family history. CONCLUSION: Our data indicate that avoidance measures in the domestic environment aimed at the primary prevention of allergen-driven sensitization should be introduced at the earliest possible stage, if possible during infancy.

Air Pollution, Indoor↗

Problems in defining cutoff points of continuous prognostic factors: example of tumor thickness in primary cutaneous melanoma.

Continuous prognostic factors are often categorized by defining optimized cutoff points. One component of criticism of this approach is the problem of multiple testing that leads to an overestimation of the true prognostic impact of the variable. The present study focuses on another crucial point by investigating the dependence of optimized cutoff points on the observed distribution of the continuous variable. The continuous variable investigated was the vertical tumor thickness according to Breslow, which is known to be the most important prognostic factor in primary melanoma. Based on the data of 5093 patients, stratified random samples were drawn out of six artificially created distributions of tumor thickness. For each of these samples, Cox models were calculated to explore optimized cutoff points for tumor thickness together with other prognostic variables. The optimized cutoff points for tumour thickness varied considerably with the underlying distribution. Even in samples from the same distribution, the range of cutoff points was amazingly broad and, for some of the distributions, covered the whole region of possible values. The results of the present study demonstrate that optimized cutoff points are extremely data dependent and vary notably even if prerequisites are constant. Therefore, if the classification of a continuous prognostic factor is necessary, it should not be based on the results of one single study, but on consensus discussions including the findings of several investigations.

Female↗

Distinct central anticholinergic syndrome following general anaesthesia.

The purpose of this prospective study was to identify the incidence of a distinct central anticholinergic syndrome following routine anaesthesia. For 2 months, all inpatients aged more than 15 years scheduled for elective procedures and cared for in the recovery room were investigated for symptoms of the syndrome. Patients with neuropsychiatric disease or other disorders that could alter consciousness were excluded. Prolonged action of anaesthetics or relaxants, respiratory depression and metabolic disorder were ruled out before making the diagnosis. Out of 962 patients (366 men, 596 women), 18 (4 men, 14 women) developed the syndrome. The difference between men and women was not statistically significant. Six out of 60 women developed the syndrome after a hysterectomy with or without adnectomy/oophorectomy, and this high incidence was significantly different from that observed after all other procedures in women (P = 0.003) or all other gynaecological procedures (P = 0.013). The reason for this is unknown. In six of the 18 cases, untreated prolonged somnolence lasted for more than 2 h. All patients woke up after an injection of physostigmine, but six of them relapsed into somnolence and needed a second, and in one case a third, injection. The findings of the study emphasize that, when there is delayed recovery from anaesthesia, the diagnosis of central anticholinergic syndrome should be considered if other accessible causes for that condition have been excluded.

Adolescent↗

History of syringe sharing in prison and risk of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection among injecting drug users in Berlin.

BACKGROUND: Injecting drug users (IDU) are at risk of parenterally transmitted diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. We investigated whether a history of syringe sharing in prison is a risk factor for these infections. In the longitudinal part of the study, HBV, HCV, and HIV seroincidence rates were determined. METHODS: The participants were recruited by multisite-sampling at different agencies for IDU. Data on risk behaviour were obtained by a standardized questionnaire. Serological markers for HBV, HCV, and HIV were determined. Logistic regression analysis was performed to adjust for confounding effects. RESULTS: A history of syringe sharing in prison was significantly associated with HBV (adjusted prevalence odds ratio [POR] = 3.9, 95% confidence interval [CI]: 2-10), HCV (POR = 9.7, 95% CI: 3-33), and HIV infection (POR = 10.4, 95% CI: 4-29). The HIV seroincidence rate was 5.9 per 100 person-years. None of the IDU receiving methadone maintenance treatment (MMT) seroconverted whereas the HIV incidence was 8.5 among IDU not in MMT (P = 0.01). CONCLUSIONS: The increased risk of HBV, HCV, and HIV infection among IDU who had shared syringes in prison warrants specific preventive action. The longitudinal data suggest that IDU in MMT have a lower risk of HIV infection.

Adult↗

Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.

Adolescent↗

Predictability of early atopy by cord blood-IgE and parental history.

BACKGROUND: Atopic family history and cord blood IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least for cord blood IgE the sensitivity has been shown to be very low. The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. METHODS: A total of 1314 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. RESULTS: The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.53, 95%CI 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value > 0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood IgE was of low accuracy. CONCLUSION: The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth.

Adult↗

Could preferential prescribing and referral behaviour of physicians explain the elevated thrombosis risk found to be associated with third generation oral contraceptives?

BACKGROUND: Recently published case-control studies on third versus second generation oral contraceptives showed a slightly increased risk for venous thromboembolism (VTE) and led to a discussion about biases or confounders external to the study such as, preferential prescribing of third generation pills to women at higher risk and differential diagnostic behaviour. METHODS: An interview survey with 102 physicians was performed in 2 weeks of December 1995 in Germany and 1209 of their patients were included in a retrospective cohort analysis of drug utilization and risk markers. RESULTS: German physicians previously preferred to prescribe third generation pills whenever an increased risk was perceived, i.e. risk for VTE and for arterial thrombosis (risk factors, personal or family history of cardiovascular diseases). Almost all predefined risk scenarios were associated with an increased attention to non-specific venous symptoms and patients were more frequently sent for intensive diagnostic search for venous thromboses. The behaviour was not directly dependent on the type of OC; however the third generation pills were indirectly associated with higher risk in the pill-taking women. The physicians' view was confirmed by the analysis of the cohorts of patients: preferential prescribing was also found in this data set, although it was not as impressive as in the physicians responses. CONCLUSION: The possibility cannot be excluded that preferential prescribing and differential diagnostic behaviour alone could have explained the roughly two-fold increased odds ratios from case-control studies recently published, had this information been available among the study variables.

Journal Article↗