Biomedical subjects
P K Andersen
Publications and source records attributed to P K Andersen.
Multi-state models for bleeding episodes and mortality in liver cirrhosis.
Data from a controlled clinical trial in liver cirrhosis are used to illustrate that multi-state models may be a useful tool in the analysis of data where survival is the ultimate outcome of interest but where intermediate, transient states are identified. We compare models for the marginal survival time distribution with models including transient states, both with respect to their clinical interpretation and with respect to the precision of survival probability estimates obtained from the various models.
Factors influencing the effect of age on prognosis in breast cancer: population based study.
OBJECTIVE: To investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment influences such an association. DESIGN: Retrospective cohort study based on a population based database of patients with breast cancer containing detailed information on tumour characteristics, treatment regimens, and survival. SETTING: Denmark. SUBJECTS: 10 356 women with primary breast cancer who were less than 50 years old at diagnosis. MAIN OUTCOME MEASURES: Relative risk of dying within the first 10 years after diagnosis according to age at diagnosis after adjustment for known prognostic factors and expected mortality. RESULTS: Overall, young women with low risk disease who did not receive adjuvant treatment had a significantly increased risk of dying; risk increased with decreasing age at diagnosis (adjusted relative risk: 45-49 years (reference): 1; 40-44 years: 1.12 (95% confidence interval 0.89 to 1.40); 35-39 years: 1.40 (1.10 to 1.78); <35 years: 2.18 (1.64 to 2.89). However, no similar trend was seen in patients who received adjuvant cytotoxic treatment. The increased risk in younger women who did not receive adjuvant treatment compared with those who did remained when women were grouped according to presence of node negative disease and by tumour size. CONCLUSION: The negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease who did not receive adjuvant cytotoxic treatment. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic treatment.
Thermodilution versus inert gas rebreathing for estimation of effective pulmonary blood flow.
OBJECTIVE: To compare measurements of the effective pulmonary blood flow (Qep, i.e., nonshunted fraction of cardiac output, Qt) by the inert gas rebreathing (RB) method and the thermodilution (TD) technique in critically ill patients. DESIGN: Prospective, comparative study of a noninvasive method and an established invasive technique. SETTING: An 11-bed general intensive care unit in a university hospital. PATIENTS: A total of 14 critically ill patients, all mechanically ventilated and monitored with systemic and pulmonary artery catheters. MEASUREMENTS AND MAIN RESULTS: Qep was determined in duplicate by RB using a mass spectrometer for gas analysis. For each determination, Qt was measured in triplicate by the cold water bolus TD technique and averaged. Simultaneously mixed venous and arterial blood samples were analyzed to calculate the intrapulmonary shunt fraction and thereby convert estimates of Qt to Qep. Mean difference between paired estimates (RB - TD) was 0.01 L/min, so for differences was 1.19 L/min, and 95% confidence interval for the bias was -0.45 to 0.47 L/min. Coefficients of variation for repeated Qep estimates were 8% (RB) and 12% (TD), respectively. Coefficients of variation for RB estimates of functional residual capacity and lung tissue volume were 6% and 17%, respectively. CONCLUSIONS: The RB method is a promising method for simultaneous noninvasive estimation of Qep and functional residual capacity in mechanically ventilated patients. However, further investigations are needed to evaluate potential problems of the method before it can be recommended for clinical purposes.
Reproductive history and stage of breast cancer.
A woman's reproductive history influences her risk of breast cancer. The authors hypothesized that reproductive history also influences stage of disease at the time of diagnosis. The authors analyzed a population-based cohort of 1.5 million Danish women born between 1935 and 1978 for whom individual information on births was available. Between 1978 and 1994, 10,790 incident cases of breast cancer in women under 60 years of age were identified. Nulliparous women compared with parous women and women with a late age at first birth compared with an early age were at significantly increased risk of being diagnosed with a large tumor and with cancer that had spread to regional lymph nodes. However, such an association was not seen for women diagnosed with a small tumor and women with cancer that had not spread to regional lymph nodes. Reproductive history did not appear to influence the time interval from first symptoms to first physician visit ("patient delay") or the time interval from first physician visit to surgery ("doctor delay"). The authors conclude that reproductive history is associated both with incidence of breast cancer and with stage of the disease at diagnosis, indicating possible influences on tumor progression and growth rate. Intensified awareness is warranted to achieve earlier diagnosis among nulliparous women and women with a late age at first childbirth, with the hope of improving their prognosis.
Calculating the number needed to treat for trials where the outcome is time to an event.
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Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests.
The problem of testing for a centre effect in multi-centre studies following a proportional hazards regression analysis is considered. Two approaches to the problem can be used. One fits a proportional hazards model with a fixed covariate included for each centre (except one). The need for a centre specific adjustment is evaluated using either a score, Wald or likelihood ratio test of the hypothesis that all the centre specific effects are equal to zero. An alternative approach is to introduce a random effect or frailty for each centre into the model. Recently, Commenges and Andersen have proposed a score test for this random effects model. By a Monte Carlo study we compare the performance of these two approaches when either the fixed or random effects model holds true. The study shows that for moderate samples the fixed effects tests have nominal levels much higher than specified, but the random effect test performs as expected under the null hypothesis. Under the alternative hypothesis the random effect test has good power to detect relatively small fixed or random centre effects. Also, if the centre effect is ignored the estimator of the main treatment effect may be quite biased and is inconsistent. The tests are illustrated on a retrospective multi-centre study of recovery from bone marrow transplantation.
Modelling covariate adjusted mortality relative to a standard population.
A study of long term survival of 1487 patients given an allogeneic bone marrow transplant for acute myelogenous leukaemia and 729 patients given a transplant for severe aplastic anaemia was conducted by the International Bone Marrow Transplant Registry. One aim of this study is to determine if the mortality rates of these patients return after some period of time to the same mortality rate as in the general population. To examine this question a model for the relative mortality of a bone marrow transplant patient relative to a matched individual in the general population is presented. This model allows for different relative mortality rates depending on the risk factors the patient may have. We discuss an estimation procedure for this model and construct a test that the mortality rate in the transplanted population is the same as in the reference population over a given time interval.
Multivariate competing risks.
Competing risks models can be used to compare the effect of risk factors for different causes of death or subtypes of a disease. However, sometimes more than one outcome classification is available and if two such classifications are correlated, one may speculate whether differences in the effect of a risk factor according to one classification simply may be an effect of differences according to the other correlated classification. We introduce in this paper the new concept of multivariate competing risks to test formally such a hypothesis.
Reproductive risk factors for breast cancer by receptor status, histology, laterality and location.
It is well established that a woman's reproductive history influences her risk of breast cancer. We examined whether the effect of reproductive history was similar for different sub-types of breast cancer. The study was based on a population-based cohort of 1.5 million Danish women born between 1935 and 1978, with individual information on births. Between 1978 and 1994, 10,790 incident cases of breast cancer were identified in a nationwide cancer registry, including detailed information on receptor status, histology, laterality and location of the tumour. Overall, the incidence of breast cancer was 13% lower in parous compared with nulliparous women. This reduction was significantly stronger for mucinous than for ductal carcinomas and for tumours located centrally than for those non-central in the breast. Overall, the incidence in parous women increased by 10% by each 5-year postponement of their first birth. For the incidence of lobular carcinomas this increase was significantly stronger, and for mucinous carcinomas it tended to be stronger than for ductal carcinomas. For the incidence of centrally located tumours the increase was stronger than for non-centrally located tumours. On average, there was a 10% decrease in breast-cancer risk by each additional birth. This decrease was seen in most sub-types, but not for lobular carcinomas of for centrally located tumours. According to our findings, lobular and mucinous carcinomas and centrally located tumours may have risk-factor profiles that differ from other types of breast cancer.
[The course of affective disorders--a registry study].
In recent years, studies of the risk of recurrence in affective disorder in relation to the number of prior episodes have given contradictory results. Survival analysis was used to calculate the rate of recurrence after successive episodes in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. Totally, 20,350 first-admission patients were discharged with a diagnosis of affective disorder, depressive or manic/circular type. The rate of recurrence increased with the number of previous episodes in both unipolar and bipolar disorder. Initially, the two types of disorders followed markedly different courses, but later in the course of the illness the rate of recurrence was the same for the two disorders. The course of severe unipolar and bipolar disorder seems to be progressive in nature despite the effect of treatment.
Recurrence in affective disorder: analyses with frailty models.
The risk of recurrence in affective disorder is influenced by the number of prior episodes and by a person's tendency toward recurrence. Newly developed frailty models were used to estimate the effect of the number of episodes on the rate of recurrence, taking into account individual frailty toward recurrence. The study base was the Danish psychiatric case register of all hospital admissions for primary affective disorder in Denmark during 1971-1993. A total of 20,350 first-admission patients were discharged with a diagnosis of major affective disorder. For women with unipolar disorder and for all kinds of patients with bipolar disorder, the rate of recurrence was affected by the number of prior episodes even when the effect was adjusted for individual frailty toward recurrence. No effect of episodes but a large effect of the frailty parameter was found for unipolar men. The authors concluded that the risk of recurrence seems to increase with the number of episodes of bipolar affective disorder in general and for women with unipolar disorder.
Effects of family history and place and season of birth on the risk of schizophrenia.
BACKGROUND: Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. METHODS: Using data from the Civil Registration System in Denmark, we established a population-based cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. RESULTS: The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. CONCLUSIONS: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis.
The effect of episodes on recurrence in affective disorder: a case register study.
BACKGROUND: The risk of recurrence has been found to increase with the number of episodes in both unipolar and bipolar affective disorder. The present study compared the effect of the number of episodes on the risk of recurrence in the two disorders. METHOD: A case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. The effect of the number of prior episodes on the rate of recurrence following the first discharge after 1984 was estimated. A total of 7925 unipolar patients and 2011 bipolar patients were included in the study. RESULTS: The rate of recurrence was, on average, 1.6 times greater for bipolar patients than for unipolar patients. Nevertheless, the effect of the number of episodes was greatest for unipolar patients. Thus, the rate of recurrence increased, on average, 15% with every episode for unipolar patients and 9% with every episode for bipolar patients, when adjusted for differences in age and gender. CONCLUSION: The risk of recurrence increases with every new episode in affective disorder. The effect of episodes is greater for unipolar disorder than for bipolar disorder. LIMITATIONS: The data relate to re-admissions rather than recurrence. CLINICAL RELEVANCE: The study shows that the prognosis worsens more for unipolar than for bipolar patients with each new episode and suggests the relevance of earlier and more sustained intervention.
Preterm delivery and risk of breast cancer.
To explore the risk of breast cancer in relation to the length of a pregnancy we tested whether a preterm delivery carries a higher risk of breast cancer than does a full-term delivery. Based on information from the Civil Registration System, and the National Birth Registry in Denmark, we established a population-based cohort of 474 156 women born since April 1935, with vital status and detailed parity information, including the gestational age of liveborn children and stillbirths. Information on spontaneous and induced abortions was obtained from the National Hospital Discharge Registry and the National Registry of Induced Abortions. Incident cases of breast cancer in the cohort (n = 1363) were identified through linkage with the Danish Cancer Registry. The period at risk started in 1978 and continued until a breast cancer diagnosis, death, emigration, or 31 December, 1992, whichever occurred first. After adjusting for attained age, parity, age at first birth and calendar period, we observed the following relative risks of breast cancer for different lengths of the pregnancy: < 29 gestational weeks = 2.11 (95% confidence interval 1.00-4.45); 29-31 weeks = 2.08 (1.20-3.60); 32-33 weeks = 1.12 (0.62-2.04); 34-35 weeks = 1.08 (0.71-1.66); 36-37 weeks = 1.04 (0.83-1.32); 38-39 weeks = 1.02 (0.89-1.17); 40 weeks = 1 (reference). Parous women who had a preterm delivery below 32 weeks gestation had a 1.72-fold (1.14-2.59) increased risk of breast cancer compared with other parous women. In conclusion, a preterm delivery of 32+ weeks gestation did not significantly increase a woman's risk of contracting breast cancer. Only for the very small group of women with preterm deliveries of less than 32 weeks gestation did we observe an increased risk.
We should monitor human fecundity, but how? A suggestion for a new method that may also be used to identify determinants of low fecundity.
Human fecundity may be declining, and we may need ways to monitor it. The most simple monitoring is based on measuring waiting time to pregnancy retrospectively among pregnant women. Unfortunately, this design does not provide an estimate of fecundity, because infertile couples are excluded. We suggest a novel approach that combines the measurement of waiting time for pregnant women with information on the distribution of waiting time among women waiting to become pregnant. The method is based on principles from the case-cohort design.
Adjustment for age at first birth in etiologic studies of breast cancer involving exposures that may effect age at first birth.
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Dementia in affective disorder: a case-register study.
OBJECTIVE: The aim of the study was to investigate whether patients with affective disorder have increased risk of developing dementia compared to other groups of psychiatric patients and compared to the general population. METHOD: In the Danish psychiatric central register, 3363 patients with unipolar affective disorder, 518 patients with bipolar affective disorder, 1025 schizophrenic and 8946 neurotic patients were identified according to the diagnosis at the first ever discharge from psychiatric hospital during the period from 1970 to 1974. The rate of discharge diagnosis of dementia on readmission was estimated during 21 years of follow-up. In addition, the rates were compared with the rates for admission to psychiatric hospitals with a discharge diagnosis of dementia for the total Danish population. RESULTS: Patients with unipolar and with bipolar affective disorder had a greater risk of receiving a diagnosis of dementia than patients with schizophrenia and those with neurosis. All groups of patients had a higher risk of being given a diagnosis of dementia than gender- and age-matched samples of the general population. CONCLUSION: Patients with affective disorder appear to be at increased risk of developing dementia.