[Publication of negative test results].
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Biomedical subjects
Publications and source records attributed to N Keiding.
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The incidence of myasthenia gravis (MG) was found to be constant in calendar time. The mean annual incidence rate was 4.4 per million population. Age- and sex-specific incidence rates disclosed a bimodal appearance for both sexes, with a peak age at onset located in the early-onset group and another peak for late onset of MG. Early onset of MG appeared 10 years later for male individuals than for female individuals, whereas the peak for late onset of MG was located at the same age for both sexes. It is suggested that the separation between early onset and late onset of MG should be at the age of 50 years for both sexes, rather than at 35 to 40 years as accepted in most studies. The prevalence of MG has increased in time. On January 1, 1988, the point prevalence rate was 77 per million population (female subjects, 96, and male subjects, 57). This reflects an improvement in prognosis despite the fact that life expectancy was found to be significantly lower for MG patients than that of the sex- and age-matched population. The factors causing increased mortality were found to be operative throughout the duration of the disease. Maximum severity of disease was reached within 2 years from onset in 78% of the cases, and more than 50% of all MG-related deaths occurred during the same period. In the course of MG, 70% of all patients experience generalized muscular weakness, and 30% to 40% also suffer from respiratory problems.
Based on historical regression analyses of survival one may calculate expected survival curves for patients in a study group, based on their observed covariates. This note discusses this calculation and illustrates it on a comparison of the survival of a certain group of liver transplant patients to their prognosis under conservative treatment.
In a randomized clinical trial of the effect of prednisone versus placebo on survival in patients with liver cirrhosis, follow-up visits were scheduled after 3, 6 and 12 months of treatment and thereafter once a year. At each follow-up the prothrombin index, a measure of liver function, was recorded and scored as either low or normal. The interaction between treatment and prothrombin index was analysed using a three-state illness-death model with recovery. The continuous-time Markov process model with constant or piecewise constant intensities suggested by Kay allows inference to proceed even though the status of the disease indicator, here the prothrombin index, is only known at the time of each visit and not between visits. We compare the analysis with the theoretically incorrect, but practically rather common approximation, where the status of the disease indicator is assumed to remain constant from one visit until just before the next. Under this approximation both standard parametric methods and non-parametric approaches developed by Aalen and Johansen are available.
A 13-year departmental sample of 34 patients with definite (biopsy-verified) giant cell arteritis (GCA) was reviewed. The mortality of this material was compared to sex-, age- and time-specific death rates in the Danish population. The standardized mortality ratio (SMR) was 1.8 (95% confidence limits, 1.1-2.8). During the same period 146 patients with probable (not biopsied, but clinically diagnosed in the department) GCA and 85 cases of possible (diagnosed and treated before admission) GCA had been admitted to the department. Those two groups did not differ from the biopsy-verified group with respect to SMR, sex distribution or age. In the group of patients with department-diagnosed GCA (definite + probable = 180 patients), the 95% confidence interval for the SMR of the women included 1.0. In all other subgroups there was a significant excess mortality. Excess mortality has been found in two of seven previous studies on survival in GCA. The prevailing opinion that steroid-treated GCA does not affect the life expectancy of patients is probably not correct.
A number of studies have dealt with determination of the age at onset of sperm emission (spermarche), based on observations of first occurrence of spermatozoa in urine. A major problem in this connection is the intermittent occurrence of sperm-negative urine samples after the achievement of spermarche. We have here considered an empirical Bayes approach for handling the probability of a sperm-positive urine sample after spermarche. The investigation was inspired by a concrete longitudinal study concerning 40 Scottish boys, which is used for illustration throughout. In this study, the urine was tested for spermatozoa from well before spermarche and every 3 months thereafter for at most 7 years. Some of the boys left the study earlier and techniques for handling such censoring were also developed.
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Hereditary ataxias, hereditary spastic paraplegia and Charcot-Marie-Tooth syndrome (HA) are chronic progressive neurological diseases. Epidemiologic studies of these disorders are few. In a geographically well-defined Danish population, we present incidence rates, cumulated incidence rates and prevalence for patients with HA based on modern continuous-time survival analysis techniques. From these, prevalence has been estimated to be 6.06 per 10(5) in the 10 to 50-year-old population. Combined risk of HA was found to be 0.16% for women and 0.20% for men up to their 51st birthday.
The size of the fibrillar centres (FC) in nucleoli was investigated taking the Swiss cheese effect into account. Electron microscopy was performed on the neurons of the rat supraoptic nucleus after the secretion of vasopressin had been fully suppressed by water load, after the secretion had been stimulated by water deprival and in normal rats with water ad libitum. When the secretory activity was suppressed from a normal level to approximately no activity, the size of the individual FC was doubled. Moreover, with increasing secretory activity the number of FC per cell increased.
The objective of the study was to measure the level of HIV/AIDS related anxiety among health care workers and identify its determinants. Data were obtained by means of a mailed, anonymous, self-administered questionnaire distributed to 2561 Danish medical doctors, nurses and nursing aides drawn randomly from the lists of members of the respective national associations. The data were analysed on the basis of a pre-study model including 12 variables hypothesizing a hierarchy of causal dependencies with anxiety at the top. 44% of the participants expressed HIV/AIDS related anxiety--hospital workers more than primary care workers, the older less than the younger. Anxiety was significantly associated with negative/restrictive attitudes towards HIV positives and gay men and with low levels of knowledge about HIV transmission and less education about HIV/AIDS. Negative/restrictive attitudes towards HIV positives were associated both with less knowledge regarding HIV transmission and fewer contacts with HIV positives. Similar associations were found regarding gay men. It is suggested that new kinds of training programmes be established which focus much more on attitudes and norms concerning HIV/AIDS--especially among health care workers with only occasional contact with HIV patients.
Until December 1988, 38 patients with primary biliary cirrhosis (PBC) had been transplanted in the Nordic countries. The observed survival probability in accordance with Kaplan-Meier analysis was around 75% 2-3 months after surgery, with few deaths during the next 3 years. The observed survival curve was compared with the expected survival calculated from the experience of a recent English PBC transplant series; the patterns are very similar. Secondly, the observed survival was compared with the expected survival curve, calculated from the survival experience of an international trial of medical treatment--that is, the expected survival had the patients not been transplanted; after the first 2-3 months the observed survival stayed better than the expected survival. Finally, the merits of transplantation for each particular patient was evaluated by means of the ratio of probability of survival when transplanted to probability of survival when medically treated 3, 6, and 8 months after surgery. The ratio increased with time, indicating a relative increase in the benefit of transplantation with time after surgery.
"Occupational mortality and morbidity is usually studied via standardized mortality (or morbidity) ratios, with little attention to the basic fit of the implicit underlying proportional hazards model. This paper presents a case study on unemployment and mortality, based on the complete Danish male population aged 20-64 years at the 1970 census. The effect of unemployment on the age-specific mortality rate is intermediate between additive and multiplicative and was fitted well by an additive effect on the square root of the mortality. The paper discusses and illustrates whether finer stratification or random residual variation ('frailty') is to be preferred for obtaining a statistically satisfactory fit."
Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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If the distribution of onset age of disease in a well-defined prevalent (cross-sectional) population of patients is known, disease incidence rates specific for age and calendar time period may be estimated, assuming known mortality rates and a closed population. This paper develops a method of estimation, illustrates this method on Danish diabetes data, and discusses its general applicability. The prevalent population of diabetic subjects in Fyn County on July 1, 1973 was ascertained from prescriptions, and information on disease onset was obtained from the patients' medical records. In this study only patients with onset of disease before or at age 30 years were studied. The mortality of diabetic subjects in Denmark was estimated from retrospective hospital data covering the period since 1933, and historical age-specific population sizes of Fyn County were obtained from census data. The incidence of diabetes increases with calendar time and with age for most cohorts. The variation with age for a fixed calendar year is more complicated, however, usually displaying a local maximum at about the age of puberty and a higher incidence at the upper end of the studied age range.
The recurrence-free survival rates (RFS) after one-stage mastectomy and partial axillary dissection in 1242 low risk breast cancer patients with invasive ductal carcinoma with or without residual cancer tissue (RCT) in the wall of the biopsy cavity were compared. RFS was significantly lower in patients with RCT (RCT-positive) whether premenopausal (n = 416) or postmenopausal (n = 826). By applying the Cox multivariate analysis on RCT and various known prognostic criteria, the incidence rates for RCT-positive patients relative to RCT-negative patients were estimated. The relative risk by RCT-positivity was in the order of 1.45, indicating that RCT is an independent risk factor contributing an increased risk of recurrence of about 45%.
It is noted that the bivariate exponential distribution introduced by Marshall and Olkin (1967, Journal of the American Statistical Association 62, 30-40) allows semiparametric generalizations along the lines of the Cox regression model for survival data. Partial likelihoods for the regression parameters may be derived (here illustrated by the use of the profile likelihood construction), and in most cases standard Cox regression model software may be applied for the analysis with minor modification of the input files. The study was initiated by data on occurrence of metastases from breast cancer. Metastases may occur at various sites, here grouped into ten categories, and simultaneous as well as consecutive occurrence at several sites in common. It is desired to identify and compare risk factors for development of metastases at each site, and we illustrate on some of these data that the above models may be useful for this purpose.