Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion.

OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

Stability and predictiveness of multiple trigger and episodic viral wheeze in preschoolers.

BACKGROUND: In 2008, the European Respiratory Society Task Force proposed the terms multiple-trigger wheeze (MTW) and episodic (viral) wheeze (EVW) for children with wheezing episodes. We determined MTW and EVW prevalence, their 24-month stability and predictiveness for asthma. METHODS: In total, 565 preschoolers (1-, 2- and 3-year-olds) in primary care with respiratory symptoms were followed until the age of 6 years when asthma was diagnosed. MTW status and EVW status were determined using questionnaire data collected at baseline and after one and 2 years. We distinguished 3 phenotypes and determined their 24-month stability, also accounting for treatment with inhaled corticosteroids (ICS). Logistic regression was used to analyse the phenotypes' associations with asthma. RESULTS: Two hundred and eighty-one children had complete information. MTW and EVW were stable in 10 of 281 (3.6%) and 24 of 281 (8.5%), respectively. The odds of developing asthma for children with stable MTW and stable EVW were 14.4 (1.7-119) and 3.6 (1.2-11.3) times greater than those for children free of wheeze (for at least 1 year). ICS was associated with increased stability of MTW and EVW. CONCLUSIONS: Stable multiple-trigger and stable episodic viral wheeze are relatively uncommon. However, 1- to 3-year-olds with stable MTW are at much increased risk of asthma.

BMI, male sex and IL28B genotype associated with persistently high hepatitis C virus RNA levels among chronically infected drug users up to 23 years following seroconversion.

The natural course of serum HCV RNA levels during chronic infection remains unclear. We investigated HCV RNA levels and factors associated with HCV RNA levels for the entire course from HCV seroconversion. We measured HCV RNA levels of 54 HCV seroconverters from the Amsterdam Cohort Studies among drug users at yearly intervals up to 23 years using bDNA (VERSANT 3.0, lower limit of detection 615 IU/mL). Samples below the cut-off of the assay were tested by TMA (Siemens VERSANT, detection limit 5 IU/mL). We used a latent class linear mixed model to examine the HCV RNA patterns and factors associated with HCV RNA levels. The median follow-up time was 10.8 years (IQR 6.5-14.9). We found two distinct HCV RNA patterns characterized by 45/54 cases and 9/54 cases. In multivariable analyses, HCV RNA levels were 0.41 log(10) IU/mL (95% confidence interval (CI) 0.06-0.75) higher for males as compared to females. Individuals with the IL28B CC genotype had 0.40 log(10) IU/mL (95% 0.08-0.73) higher HCV RNA levels than individuals with IL28B CT/TT genotypes. Body mass index (BMI) was associated with higher HCV RNA levels, 0.055 log(10) IU/mL per BMI point (95% CI 0.027-0.083). In this unique study, which examines the HCV RNA patterns over an extended period and following seroconversion, male sex, IL28B CC genotype and BMI were independently associated with higher average HCV RNA levels. These results contribute to defining the natural history of HCV infection and could play an important part in clinical decision-making.

Factors associated with hepatitis C virus RNA levels in early chronic infection: the InC3 study.

Improved understanding of natural history of hepatitis C virus (HCV) RNA levels in chronic infection provides enhanced insights into immunopathogenesis of HCV and has implications for the clinical management of chronic HCV infection. This study assessed factors associated with HCV RNA levels during early chronic infection in a population with well-defined early chronic HCV infection. Data were from an international collaboration of nine prospective cohorts studying acute HCV infection (InC(3) study). Individuals with persistent HCV and detectable HCV RNA during early chronic infection (one year [±4 months] postinfection) were included. Distribution of HCV RNA levels during early chronic infection was compared by selected host and virological factors. A total of 308 individuals were included. Median HCV RNA levels were significantly higher among males (vs females; 5.15 vs 4.74 log IU/mL; P < 0.01) and among individuals with HIV co-infection (vs no HIV; 5.89 vs 4.86; P = 0.02). In adjusted logistic regression, male sex (vs female, adjusted odds ratio [AOR]: 1.93; 95%CI: 1.01, 3.69), interferon lambda 4 (IFNL4) rs12979860 CC genotype (vs TT/CT; AOR: 2.48; 95%CI: 1.42, 4.35), HIV co-infection (vs no HIV; AOR: 3.27; 95%CI: 1.35, 7.93) and HCV genotype G2 (vs G3; AOR: 5.40; 95%CI: 1.63, 17.84) were independently associated with high HCV RNA levels (>5.6 log IU/mL = 400 000 IU/mL). In conclusion, this study demonstrated that IFNL4 rs12979860 CC genotype, male sex, HIV co-infection and HCV genotype G2 are associated with high HCV RNA levels in early chronic infection. These factors exert their role as early as one year following infection.

Appropriate antibiotic use for patients with complicated urinary tract infections in 38 Dutch Hospital Departments: a retrospective study of variation and determinants.

BACKGROUND: Appropriate antibiotic use in patients with complicated urinary tract infections can be measured by a valid set of nine quality indicators (QIs). We evaluated the performance of these QIs in a national setting and investigated which determinants influenced appropriate antibiotic use. For the latter, we distinguished patient, department and hospital characteristics, including organizational interventions aimed at improving the quality of antibiotic use (antibiotic stewardship elements). METHODS: A retrospective, observational multicentre study included 1964 patients (58% male sex) with a complicated urinary tract infection treated at Internal Medicine and Urology departments of 19 Dutch university and non-university hospitals. Data of 50 patients per department were extracted from medical charts. QI performance scores were calculated using previously constructed algorithms. Department and hospital characteristics were collected using questionnaires filled in by an internal medicine physician and an urologist. Regression analysis was performed to identify determinants of QI performance. Clustering at department and hospital level was taken into account through inclusion of random effects in a multi-level model. RESULTS: Median QI performance of departments varied between 31% ('Treat urinary tract infection in men according to local guideline') and 77% ('Perform urine culture'). The patient characteristics non-febrile urinary tract infection, female sex and presence of a urinary catheter were negatively associated with performance on many QIs. The presence of an infectious diseases physician and an antibiotic formulary were positively associated with 'Prescribe empirical therapy according to guideline'. No other department or hospital characteristics, including stewardship elements, were consistently associated with better QI performance. CONCLUSIONS: A large inter-department variation was demonstrated in the appropriateness of antibiotic use. In particular certain patient characteristics (more than department or hospital characteristics) influenced the quality of antibiotic use. Some, but not all antibiotic stewardship elements did translate into better QI performance.

Correcting for the dependent competing risk of treatment using inverse probability of censoring weighting and copulas in the estimation of natural conception chances.

When estimating the probability of natural conception from observational data on couples with an unfulfilled child wish, the start of assisted reproductive therapy (ART) is a competing event that cannot be assumed to be independent of natural conception. In clinical practice, interest lies in the probability of natural conception in the absence of ART, as this probability determines the need for therapy. We thus want to estimate the marginal cumulative pregnancy distribution. Without assumptions on the dependence structure between the two competing events, this marginal distribution is not identifiable. We first use inverse probability of censoring weighting assuming that the factors influencing the choice to start ART are known. Then, we parameterize the event distributions for conception and for start of ART and use copulas to account for the dependency between both events. By using these two ways of correcting for the dependent risk of treatment, we obtain a plausible estimation region for the cumulative pregnancy curve and for the prognostic effect of tubal tests.

Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma.

BACKGROUND: Tumor location of extrahepatic cholangiocarcinoma (CCA) might influence survival after resection. METHODS: A consecutive series of 175 patients who had undergone a potentially curative resection of extrahepatic CCA was analyzed. We calculated concordance indices of different constructed prognostic models for survival including TNM (tumour-node-metastasis) staging and developed a nomogram of the most sensitive model. RESULTS: Overall cancer-specific survival rates were 83%, 58%, and 26% at 1, 2, and 5 years, respectively. Cancer-specific survival according to location was 42% for proximal, 23% for mid, and 19% for distal CCA after 5 years. Tumor location was not an independent significant predictor (P = 0.06). A prognostic model using all potential prognostic variables predicted survival better compared with TNM staging (concordance index 0.65 versus 0.63). A reduced model containing only lymph node status, microscopically residual tumor status, and tumor differentiation grade, also outperformed TNM staging (concordance index 0.66). CONCLUSIONS: Tumor location of extrahepatic CCA does not independently predict cancer-specific survival after resection. We developed a nomogram, based on a prognostic model with lymph node status, microscopically residual tumor status of resection margins, and tumor differentiation grade, that predicted survival better than TNM staging.

Low yield of routine screening for thyroid dysfunction in asymptomatic patients with vitiligo.

BACKGROUND: Nonsegmental vitiligo is considered to be an autoimmune disease and is known to be associated with other autoimmune diseases, particularly affecting the thyroid. Screening patients with nonsegmental vitiligo for thyroid function and for the presence of thyroid autoantibodies has been recommended. OBJECTIVE: To investigate the prevalence of thyroid dysfunction and thyroid peroxidase-specific (TPO) antibodies in a large cohort of patients with nonsegmental vitiligo in order to help decide whether routine screening is justified. METHODS: A total of 434 adults with nonsegmental vitiligo who were referred to our institute were enrolled. Thyroid function and anti-TPO antibody titres were assessed in those patients who had no history of thyroid disease or recent thyroid screening. RESULTS: Forty-three patients had already been diagnosed with thyroid dysfunction, and in 27 patients the general practitioner had performed a thyroid function test with negative results <3months previously. In these patients, thyroid function assessment was not repeated. The remaining 364 patients were screened for thyroid dysfunction. Overt hypothyroidism was newly diagnosed in three (0·8%) patients; subclinical disease was found in 10 (2·7%) patients and increased levels of TPO antibodies, without thyroid disease, were found in 49 (13·5%) patients. An elevated risk for thyroid disease was found among older women and in women with a positive family history of thyroid disease. CONCLUSION: The overall prevalence of thyroid dysfunction in adult patients with nonsegmental vitiligo was higher than reported in the general population. However, the number of newly diagnosed cases with overt and subclinical thyroid dysfunction in our population was low. Most patients had already been diagnosed by their general practitioner and had symptoms indicative for thyroid disease. Thyroid disease was found predominantly among older women and in subjects with a positive family history of thyroid disease. Thyroid screening including anti-TPO antibodies is advisable in these high-risk subpopulations.

Ongoing transmission of a single hepatitis B virus strain among men having sex with men in Amsterdam.

For the past decade, a specific hepatitis B virus (HBV) genotype A strain has been prevalent among men having sex with men (MSM) in Amsterdam, the Netherlands. At what point in time this strain was introduced in the MSM population, and why only this specific strain continues to be transmitted, remains unclear. Between 1984 and 2003, sera of 1862 MSM were retrospectively screened for anti-HBc in the context of the Amsterdam Cohort studies. After 2003, most MSM participating in this study were vaccinated, making further testing less useful. HBV DNA from anti-HBc seroconverters was amplified and sequenced. Poisson regression was used to test for temporal trends in HBV and HIV incidence. Of the 1042 MSM who were negative for anti-HBc at entry, 64 had seroconverted during follow-up at a median age of 32. At the point of seroconversion, 31 MSM were HIV positive. HBV incidence declined dramatically in the first years and then remained stable throughout the study period. The HBV and HIV incidence ran almost in parallel. With the exception of three MSM, all were infected with genotype A. Fifteen of these (41%) were infected with an identical genotype A strain. For the past two decades, an identical genotype A strain has been circulating among MSM in the Netherlands. Although HBV is generally considered more infectious than HIV, this study shows that the trend and magnitude in HBV and HIV incidence among MSM are similar.

A simple G-computation algorithm to quantify the causal effect of a secondary illness on the progression of a chronic disease.

Progression of a chronic disease can lead to the development of secondary illnesses. An example is the development of active tuberculosis (TB) in HIV-infected individuals. HIV disease progression, as indicated by declining CD4 + T-cell count (CD4), increases both the risk of TB and the risk of AIDS-related mortality. This means that CD4 is a time-dependent confounder for the effect of TB on AIDS-related mortality. Part of the effect of TB on AIDS-related mortality may be indirect by causing a drop in CD4. Estimating the total causal effect of TB on AIDS-related mortality using standard statistical techniques, conditioning on CD4 to adjust for confounding, then gives an underestimate of the true effect. Marginal structural models (MSMs) can be used to obtain an unbiased estimate. We describe an easily implemented algorithm that uses G-computation to fit an MSM, as an alternative to inverse probability weighting (IPW). Our algorithm is simplified by utilizing individual baseline parameters that describe CD4 development. Simulation confirms that the algorithm can produce an unbiased estimate of the effect of a secondary illness, when a marker for primary disease progression is both a confounder and intermediary for the effect of the secondary illness. We used the algorithm to estimate the total causal effect of TB on AIDS-related mortality in HIV-infected individuals, and found a hazard ratio of 3.5 (95 per cent confidence interval 1.2-9.1).

Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study.

OBJECTIVES: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease. METHODS: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients >or=50 years who in 2003 were dispensed >or=2 prescriptions of daily used inhaled beta(2) agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared using Kaplan-Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis. RESULTS: Of 49,599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to 0.98). CONCLUSION: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.

Migrants travelling to their country of origin: a bridge population for HIV transmission?

BACKGROUND: By having unprotected heterosexual contact in both The Netherlands and their homeland, migrants who travel to their homeland might form a bridge population for HIV and sexually transmitted infection (STI) transmission. We studied the determinants for such a population in two large migrant communities in The Netherlands. METHODS: From 2003 to 2005, 1938 people of Surinamese and Antillean origin were recruited at social venues in two large cities, interviewed and their saliva samples tested for HIV antibodies. We used multivariate multinomial logistic regression to explore characteristics of groups with four risk levels (no, low, moderate and high) for cross-border transmission. RESULTS: 1159/1938 (60%) participants had travelled from The Netherlands to their homeland in the previous 5 years and 1092 (94%) of them reported partnerships and condom use in both countries. Of these 9.2% reported having unprotected sex with partners in both countries. People in this high-risk or bridge population group were more likely to be male, frequent travellers and older compared with people who had no sex or had sexual contact solely in one country in the past 5 years. CONCLUSIONS: Older male travellers of Surinamese and Antillean origin are at high risk for cross-border heterosexual transmission of HIV/STIs. They should be targeted by prevention programmes, which are focused on sexual health education and HIV/STI testing, to raise their risk awareness and prevent transmission.

Dynamic prediction of recurrent events data by landmarking with application to a follow-up study of patients after kidney transplant.

This paper extends dynamic prediction by landmarking to recurrent event data. The motivating data comprised post-kidney transplantation records of repeated infections and repeated measurements of multiple markers. At each landmark time point ts, a Cox proportional hazards model with a frailty term was fitted using data of individuals who were at risk at landmark s. This model included the time-updated marker values at ts as time-fixed covariates. Based on a stacked data set that merged all landmark data sets, we considered supermodels that allow parameters to depend on the landmarks in a smooth fashion. We described and evaluated four ways to parameterize the supermodels for recurrent event data. With both the study data and simulated data sets, we compared supermodels that were fitted on stacked data sets that consisted of either overlapping or non-overlapping landmark periods. We observed that for recurrent event data, the supermodels may yield biased estimates when overlapping landmark periods are used for stacking. Using the best supermodel amongst the ones considered, we dynamically estimated the probability to remain infection free between ts and a prediction horizon thor, conditional on the information available at ts.

HLA-identical haematopoietic stem cell transplantation for acute leukaemia in children: less relapse with higher biologically effective dose of TBI.

To examine relapse, survival and transplant-related complications in relationship to disease- and pre-treatment-related characteristics, we evaluated 132 children, who consecutively received an allogeneic HLA-identical SCT for acute leukaemia in our centre: ALL in first remission (n=24), ALL in second remission (n=53) and AML in first remission (n=55). The source of the stem cells was bone marrow in all but three cases. Most patients (89%) were pre-treated with cyclophosphamide and an age-related dose of TBI. Initially, GVHD prophylaxis consisted of long-course MTX only (n=24), later short-course MTX and CsA (n=102) was given. All patients were nursed in strictly protective isolation and received total gut decontamination to suppress their potentially pathogenic enteric microflora. The 5-year probability of overall survival was 63, 53 and 74% for ALL1, ALL2 and AML1, respectively (median follow-up: 10.6 years). The overall transplant-related mortality was 6%. The incidence of acute GVHD was 17%; 6% was grades II-IV. A higher total biologically effective TBI dose (BED) resulted in a decreased relapse frequency (P=0.034) and increased overall survival. AML patients with acute GVHD got no relapse (P=0.02); this was not the case in ALL patients. Fractionated TBI regimens with higher BED should be evaluated in prospective studies.

[Better antibiotic use in complicated urinary tract infections; multicentre cluster randomised trial of 2 improvement strategies]. / Beter antibioticagebruik bij gecompliceerde urineweginfecties.

OBJECTIVE: To compare the effectiveness of two strategies to improve antibiotic use in patients with a complicated urinary tract infection. DESIGN: Multicentre cluster randomised unblinded trial. METHOD: The departments of Internal Medicine and Urology from 19 hospitals in the Netherlands took part in this trial. Based on retrospective patient record investigations we performed baseline measurements on the scores of a validated set of quality indicators for antibiotic use in a minimum of 50 patients with a complicated urinary tract infection per department in 2009. A similar post-trial measurement took place in 2012. In 2010 we randomised the hospitals between 2 improvement strategies: a multifaceted strategy that included results of the baseline measurements, education, reminders and assistance with optional improvement interventions, and a competitive feedback strategy, in which the departments only received results of the baseline measurements and non-anonymous results from the other departments in this study arm. The primary outcome measure was improvement of the quality indicator scores. Secondary outcome measures were determinants of improvement of the indicators. (Netherlands Trial Register: NTR1742) RESULTS: The baseline and post-trial measurements were performed on 1,964 patients and 2,027 patients, respectively. Post-trial measurements revealed a significant, but limited, improvement of several indicators compared with baseline measurements. We found no significant difference in improvement between the two strategies for any indicator. The intensity with which the departments implemented improvement strategies was mostly suboptimal, but intensive implementation of a strategy was associated with greater improvement. CONCLUSION: The effectiveness of both improvement strategies was comparable, but limited. For real improvement in antibiotic use in patients with complicated urinary tract infections, improvement interventions should be developed and applied by local professionals themselves.

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.

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.

PIP: More than 1500 abstracts were submitted in the Epidemiology and Public Health Track of the XI International Conference on Acquired Immunodeficiency Syndrome (AIDS). Summarized, in this article, are papers on recent trends in the descriptive epidemiology of AIDS, the interaction between human immunodeficiency virus (HIV) and sexually transmitted diseases (STDs), determinants of perinatal transmission, aspects of the natural history of HIV (including non-progression), and intervention issues related to intravenous drug users. The data confirm that persons with STDs transmit HIV more easily through heterosexual contact than those without STDs; however, STD treatment lowers the viral load and reduces the risk of HIV transmission. The recommendation that HIV-infected women in developing countries continue to breast feed may be retracted in light of evidence that significantly more breast-fed infants become infected than bottle-fed infants.

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.

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.

[Roaming through methodology. XXXV. Bias in prevalent cohort studies of the natural course of disease]. / Dwalingen in de methodologie. XXXV. Bias in het prevalentiecohort-onderzoek naar het natuurlijke ziektebeloop.

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.