PubMed Health⌕ Search

Biomedical subjects

R B Geskus

Publications and source records attributed to R B Geskus.

13 recordsLinked to original sources

Tutorial in biostatistics: competing risks and multi-state models.

Standard survival data measure the time span from some time origin until the occurrence of one type of event. If several types of events occur, a model describing progression to each of these competing risks is needed. Multi-state models generalize competing risks models by also describing transitions to intermediate events. Methods to analyze such models have been developed over the last two decades. Fortunately, most of the analyzes can be performed within the standard statistical packages, but may require some extra effort with respect to data preparation and programming. This tutorial aims to review statistical methods for the analysis of competing risks and multi-state models. Although some conceptual issues are covered, the emphasis is on practical issues like data preparation, estimation of the effect of covariates, and estimation of cumulative incidence functions and state and transition probabilities. Examples of analysis with standard software are shown.

Biometry↗

Distribution and clustering of Oesophagostomum bifurcum and hookworm infections in northern Ghana.

Human Oesophagostomum infections are locally common in northern Ghana. The present study describes the results of a cross-sectional survey involving 1011 subjects, selected by a compound-based random sampling method from 1227 compounds in 24 villages. Selected persons were examined by both Kato and coproculture methods. Hookworm-like eggs, representing ova of Oesophagostomum bifurcum and hookworm were detected in 87.5% of the Kato smears. The geometric mean egg count of the infected subjects was 1018. Upon coproculture, third-stage larvae of O. bifurcum and hookworm were detected in 53.0% and 86.9% of subjects respectively. Oesophagostomum infections were clustered but no clear explanation for aggregation of infections could be found as yet. Subjects infected with hookworm had a 5-fold higher risk of being infected with O. bifurcum. Infection rates in adult women were higher than in adult men. No association was found with family size, level of hygiene or with the presence of animals in the compounds. Representatives of the Bimoba-tribe were significantly more infected than those of the other tribes. It appears, however, that this tribal association is a geographical phenomenon: Bimoba are mostly living in villages with the highest infection rates.

Adolescent↗

Primary Souter-Strathclyde total elbow prosthesis in rheumatoid arthritis. Surgical technique.

BACKGROUND: Total elbow arthroplasty is a well-established treatment for the painful elbow joint in patients with rheumatoid arthritis. We present the results of what we believe to be the first prospective study of the Souter-Strathclyde total elbow prosthesis. METHODS: Between June 1982 and December 2000, 204 primary total elbow prostheses were inserted in 166 patients who had rheumatoid arthritis. No patient was lost to follow-up. The mean duration of follow-up was 6.4 years. All patients were examined preoperatively, at one and two years postoperatively, and at regular intervals thereafter. RESULTS: Six of the 204 elbows had pain at rest at the time of the latest follow-up. Ten patients (ten elbows) without previous neurological symptoms had development of paresthesias in the distribution of the ulnar nerve postoperatively. Patients who had pain at rest or at night and those who had ulnar nerve symptoms preoperatively were found to have a significant chance of having the same complaints postoperatively. Pain at rest or at night and a decrease in function during the follow-up period were associated with humeral loosening. Twenty-four elbows had revision of the total elbow prosthesis because of loosening of the humeral component (ten), loosening after fracture (six), dislocation (four), infection (two), restricted range of motion (one), or fracture of the middle part of the humeral shaft, proximal to the prosthesis (one). One prosthesis was removed because of humeral loosening, and eight were removed because of deep infection. Another five prostheses were radiographically loose at the time of the latest follow-up. The rate of implant survival, according to the method of Kaplan-Meier, was 77.4% after ten years and 65.2% after eighteen years. CONCLUSIONS: Total elbow replacement is associated with a high complication rate and therefore may be warranted only for seriously disabled patients. Currently, the results associated with the Souter-Strathclyde total elbow prosthesis are comparable with the results associated with other prostheses, but loosening of the humeral component remains a concern.

Arthritis, Rheumatoid↗

Influence of previous open synovectomy on the outcome of Souter-Strathclyde total elbow prosthesis.

OBJECTIVES: Open synovectomy of the elbow joint is often performed in early stages of rheumatoid arthritis. Because of poor long-term results after synovectomy, insertion of a total elbow prosthesis is commonly used as a secondary procedure. The aim of this study is to evaluate the influence of previous synovectomy on the outcome after placement of a total elbow prosthesis. METHODS: We inserted 204 primary Souter-Strathclyde total elbow prostheses for rheumatoid arthritis. Two groups could be distinguished: group A with previous synovectomy 3.9 yr (mean) before the elbow replacement (n = 33) and group B without previous synovectomy (n = 171). The mean follow-up was 5.8 yr for group A and 6.3 yr for group B. All patients were assessed clinically and radiologically before the operation, 1 and 2 years later and then at regular intervals. The effect of previous synovectomy was analysed via a Cox model and a generalized linear mixed model for binomial data with multivariate normal random effects. RESULTS: No statistically significant effect of previous synovectomy on pain, function or complaints of the ulnar nerve could be found post-operatively. The post-operative flexion was significantly higher in group B than in group A. The complication-rates were similar for both groups. The overall survival rate for respectively group A and B with revision as endpoint was 66.9% (s.e. 13.4) versus 79.6 (s.e. 4.3) after 10 yr. CONCLUSIONS: Previous synovectomy does not diminish the outcome after total elbow prosthesis in this series and could therefore be considered in early, painful stages of rheumatoid destruction of the elbow joint.

Arthritis, Rheumatoid↗

Primary Souter-Strathclyde total elbow prosthesis in rheumatoid arthritis.

BACKGROUND: Total elbow arthroplasty is a well-established treatment for the painful elbow joint in patients with rheumatoid arthritis. We present the results of what we believe to be the first prospective study of the Souter-Strathclyde total elbow prosthesis. METHODS: Between June 1982 and December 2000, 204 primary total elbow prostheses were inserted in 166 patients who had rheumatoid arthritis. No patient was lost to follow-up. The mean duration of follow-up was 6.4 years. All patients were examined preoperatively, at one and two years postoperatively, and at regular intervals thereafter. RESULTS: Six of the 204 elbows had pain at rest at the time of the latest follow-up. Ten patients (ten elbows) without previous neurological symptoms had development of paresthesias in the distribution of the ulnar nerve postoperatively. Patients who had pain at rest or at night and those who had ulnar nerve symptoms preoperatively were found to have a significant chance of having the same complaints postoperatively. Pain at rest or at night and a decrease in function during the follow-up period were associated with humeral loosening. Twenty-four elbows had revision of the total elbow prosthesis because of loosening of the humeral component (ten), loosening after fracture (six), dislocation (four), infection (two), restricted range of motion (one), or fracture of the middle part of the humeral shaft, proximal to the prosthesis (one). One prosthesis was removed because of humeral loosening, and eight were removed because of deep infection. Another five prostheses were radiographically loose at the time of the latest follow-up. The rate of implant survival, according to the method of Kaplan-Meier, was 77.4% after ten years and 65.2% after eighteen years. CONCLUSIONS: Total elbow replacement is associated with a high complication rate and therefore may be warranted only for seriously disabled patients. Currently, the results associated with the Souter-Strathclyde total elbow prosthesis are comparable with the results associated with other prostheses, but loosening of the humeral component remains a concern. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence.

Activities of Daily Living↗

Markers and residual time to AIDS.

The value of immunological and virological markers as predictors of progression to AIDS, or death by AIDS, is a topic of much current interest. Mostly, the influence of markers is investigated in a time-dependent or a baseline proportional hazard model, relating time-varying or baseline marker values to the instantaneous AIDS risk. Low CD4 numbers have been shown to increase the AIDS risk. Based on this finding, the decision to start treatment has mainly been based on a person's CD4 count. Over the last couple of years, high viral load has been added as a criterion to start treatment. Relative hazards do not directly reveal information on time to AIDS. A better approach is to base the decision to start treatment on an estimate of a person's residual time to AIDS or death by AIDS. Discrimination and calibration are introduced as criteria to compare prediction models. Two models to predict residual time to AIDS are discussed. One is a proportional hazards model based on baseline marker values; the other one is a combined model of a time-dependent proportional hazards model and a longitudinal model for marker development.

Acquired Immunodeficiency Syndrome↗

[Roaming through methodology. XXXV. Bias in prevalent cohort studies of the natural course of disease].

The natural history of infectious diseases with a long asymptomatic incubation period has mainly been studied in cohorts of individuals already infected at study entry: the so-called prevalent cohort study. Because the time of infection is usually unknown in the prevalent cohort, in standard survival analysis it is common to use the time since entry into the cohort instead of the time since infection to study risk factors for disease progression. However, the use of the time since study entry may bias results. The two most important sources of bias are onset confounding and differential length-bias sampling. Because bias may occur, results derived from a prevalent cohort are not directly comparable to results derived from an incident cohort where the moment of infection is known.

Bias↗

Methods for estimating the AIDS incubation time distribution when date of seroconversion is censored.

In most cohort studies on HIV infection and AIDS, data on time from seroconversion to AIDS or death are doubly censored, both at the time origin and at the endpoint of interest. In epidemiological research, the most frequently adopted approach is to restrict the analysis to persons with narrow seroconversion intervals and to impute the midpoint of this interval as date of seroconversion. For many cohort studies, the consequence is that a substantial proportion of the data is not used. We consider four methods that are expected to be less biased when all cohort data are used: two imputation methods, conditional mean and multiple imputation, and two likelihood maximization methods. We derive the likelihood structure of the cohort data and clarify its dependence on study design. All methods are applied to data from the Amsterdam cohort study among injection drug users. In a simulation study the data generation process of this cohort study is imitated. The performance of midpoint, conditional mean and multiple imputation are compared. With midpoint imputation, both an analysis using the full data set, as well as one restricted to the cases with small seroconversion intervals, is performed. Conditional mean imputation comes out as the preferred method. It gives best results with respect to mean squared error. Moreover, when confidence intervals are computed through standard methods that ignore the uncertainty in the imputed date of seroconversion, coverage probabilities are almost correct.

Acquired Immunodeficiency Syndrome↗

On the inclusion of prevalent cases in HIV/AIDS natural history studies through a marker-based estimate of time since seroconversion.

In most cohort studies of HIV infection and AIDS, seroprevalent cases provide a substantial amount of information. Inclusion of these people in natural history studies requires a fairly unbiased method to estimate their seroconversion distribution. When a cohort-based estimate is not feasible, an alternative is to estimate individual seroconversion distributions, based on marker values at entry. In this paper, a non-parametric marker-based estimation method is developed. The method is applied to data from the Amsterdam cohort study on homosexual men. For seroprevalent cases who entered the study between October 1984 and April 1985, individual seroconversion distributions are estimated based on their first measured CD4 count. In subsequent survival analyses, dates of seroconversion are estimated via conditional mean imputation. Inclusion of these seroprevalent cases greatly improves the quality of the data. Age at seroconversion is a significant cofactor for disease progression, a result not found when analysis is restricted to those who seroconvert. To incorporate the uncertainty in the imputed date of seroconversion, a bootstrap procedure is developed for the computation of p-values and confidence intervals. In our analyses, standard procedures, which ignore the uncertainty in the imputed date of seroconversion, perform almost as well.

Acquired Immunodeficiency Syndrome↗

Risk factors for human herpesvirus 8 seropositivity and seroconversion in a cohort of homosexual men.

Sexual and nonsexual modes of transmission of human herpesvirus 8 (HHV8) have been suggested, but specific routes remain unclear. Therefore, the objective of this study was to assess risk factors for HHV8 seropositivity and determine specific sexual practices associated with HHV8 seroconversion. Sera from 1,458 homosexual men (Amsterdam Cohort Study, 1984-1996) were tested for antibodies to HHV8 with a modified version of an enzyme immunoassay, using recombinant HHV8 lytic phase capsid (ORF65) and latent phase nuclear (ORF73) proteins. HHV8 seroprevalence at study entry was 20.9% (305/1,458); was highest among those with positive human immunodeficiency virus (HIV) status, no steady partner, and southern European or Latin American nationality; and increased with older age and higher number of sexual partners. During follow-up, 215 men seroconverted for HHV8 (incidence: 3.6/100 person-years). Both prevalence and incidence rates remained more or less stable during the study period. Orogenital insertive sex (odds ratio (OR) = 5.95; 95% confidence interval (CI): 2.88, 12.29) or orogenital receptive sex (OR = 4.29; 95% CI: 2.11, 8.71) with more than five partners in the past 6 months, older age (OR = 2.89; 95% CI: 1.13, 7.34, when older than 45 years), and preceding HIV infection (OR = 2.47; 95% CI: 1.53, 3.99) were independent predictors for HHV8 seroconversion. The authors found strong evidence for orogenital transmission of HHV8 among homosexual men.

Adult↗

Differences in progression to AIDS between injection drug users and homosexual men with documented dates of seroconversion.

We compared rates of progression to AIDS for 99 injection drug users and 120 homosexual men with documented dates of HIV-1 seroconversion. The crude risk of developing AIDS was higher among homosexual men than injection drug users [relative hazard (RH) = 2.4; 95% confidence interval (CI) = 1.3-4.4]. The relative hazard was slightly smaller among participants with a seroconversion interval of < or = 1 year (RH = 2.2; 95% CI = 1.0-5.2). The effect was partially explained by the inclusion of Kaposi's sarcoma in the AIDS case definition. Excluding those with Kaposi's sarcoma, the relative hazard was 2.0 (95% CI = 1.1-3.8). Using the 1993 AIDS case definition decreased the effect (RH = 1.9; 95% CI = 1.1-3.4). Finally, the high pre-AIDS mortality among injection drug users could partially explain the difference in progression rate between injection drug users and homosexual men. Combining the effect of the above-mentioned factors resulted in a relative hazard of 1.3 (95% CI = 0.7-2.6). Thus, the slower progression to AIDS among injection drug users compared with homosexual men was largely explained by differences in the spectrum of AIDS-defining illnesses, pre-AIDS mortality, and length of seroconversion interval.

Acquired Immunodeficiency Syndrome↗

Summary of track C: epidemiology and public health.

AIM: To review Track C on epidemiology and public health. DESCRIPTIVE EPIDEMIOLOGY: Recent trends in the descriptive epidemiology are reported, for example, the rapid spread of HIV in certain Asian countries and the more precise insights in the spread thanks to subtyping of HIV-1 (and HIV-2). TRANSMISSION: There is now ample evidence that sexually transmitted diseases enhance the rate of transmission. Viral load in the plasma of the mother is highly predictive for perinatal transmission. PROGRESSION: Natural history studies have shown that true non-progressors are probably rare. Preliminary evidence indicates that the progression rate to AIDS and death does not differ by HIV-1 subtype. Some genetic factors are associated with the rate of disease progression and a few with susceptibility to HIV infection. INTERVENTIONS AND PREVENTION: Needle-exchange programmes as an intervention measure for injecting drug users were hotly debated and so were HIV (home) testing and counselling. Successes in prevention were reported from Thailand and Uganda, and also from small scale programmes.

Female↗