Henrik Møller

Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark

To explore prenatal risk factors that are common to testicular cancer and cryptorchidism, two parallel case-control studies were conducted in Denmark. Information about characteristics of the mother, the pregnancy, and the birth were obtained from the mothers of cases and controls, using a mailed self-administered questionnaire. A maternal age above 30 years was associated with odds ratios (OR) of 1.9 (95 percent confidence interval [CI]= 1.2-3.0) for cryptorchidism and 2.0 (CI = 1.2-3.6) for testicular seminoma; the latter effect was particularly high when the boy was the first child of the mother (OR = 4.1, CI = 1.1-14.6). Birth weights below 3,000 g or above4,000 g were associated with increased risks of testicular cancer, with OR sup to 2.6 (CI = 1.1-5.9) for birth weight below 2,500 g. For cryptorchidism, there was a monotonous trend in the OR from 0.4 in birth weights above 4,500 g to 2.3 in birth weights below 2,500 g. The association between cryptorchidism and testicular cancer was not attenuated by adjustment for maternal age and birthweight, indicating that all three variables are independent risk factors for testicular cancer. With the exception of high maternal age, which consistently is associated more strongly with seminoma than withnon-seminoma, it remains most likely that seminoma and non-seminoma have similar causes.

Change in male:female ratio among newborn infants in Denmark

SIR—It is well known that the human male:female ratio at birth has a slight male excess. Many factors have been identified that may affect the male:female ratio—eg, time of insemination within the cycle, birth order, age of the parents, and certain hormonal treatments and chemical exposures. James suggested that male reproductive hazards may usefully be monitored by low offspring male:female ratios, as an alternative to other indices such as sperm counts, conception waits, or hormone assays. There has electrophysiological testing or exercise is definitely lifethreatening, without being unduly alarmist. When no arrhythmia has been detected during multiple tests we also find it difficult to give categorical reassurance that the patient does not have life-threatening arrhythmia. Because of this, clinicians often feel obliged to consider antiarrhythmic therapy in patients with and without symptoms who are probably at risk of life-threatening arrhythmia. The CAST study provided the first concrete proof of the potential proarrhythmic harm of antiarrhythmic drugs. Following this, the licence for flecainide restricted its use only to treatment of life-threatening arrhythmia. If all other antiarrhythmic agents prescribable for non-life-threatening arrhythmia were put through the same protocol as flecainide in the CAST study, it is likely that several would also be found dangerous. We therefore arrive at a dilemma: although it may seem unethical to include patients in drug trials, such as CAST and SWORD (July 6, p 7), for fear of recording more deaths in the treatment arm, failure to conduct such studies would result in many patients being continually prescribed (for seemingly valid reasons) antiarrhythmic agents which may, because of their unspecified proarrhythmic potential, cause death. The latter mortality may be substantially greater than that which might be recorded in the trials. Equally worrying is Sanderson’s suggestion that only patients with symptomatic arrhythmia should be treated with antiarrhythmic agents. If strictly followed this could render some patients with symptomless but life-threatening arrhythmia unprotected. The alternative—the implantable defibrillator—is still prohibitively expensive for most patients. For the present, we have to accept that all drug trials can result in iatrogenic deaths. Obviously, safeguards must be incorporated in the trial designs to minimise mortality risk. In so identifying and characterising the harmful potential of drugs, clinicians can avoid the possibly greater and unquantifiable harm of uninformed prescribing. Decisions by ethics committees, for example, to prevent drug trials from proceeding may result in a greater general harm to patients.

Risks of testicular cancer and cryptorchidism in relation to socio-economic status and related factors: case-control studies in Denmark.

To explore risk factors for testicular cancer and cryptorchidism, 2 parallel case‐control studies were conducted in Denmark. The testicular‐cancer study was population‐based and included 514 cases and 720 controls. The cryptorchidism study included 387 cases and 416 controls and was based on 2 hospital series of men treated for cryptorchidism and a control group sampled among residents in the Copenhagen area. The 2037 men were interviewed by telephone, and self‐administered questionnaires were sent to their mothers. A strong association was seen between low social class and cryptorchidism, with sons of unskilled workers having a 3‐fold higher risk of cryptorchidism than sons of self‐employed men. Testicular cancer was only moderately associated with high‐social‐class indicators, and only with such indicators pertaining to the mother. Both testicular cancer and cryptorchidism tended to occur more frequently in first‐born men and in sons of older women, but these associations were not statistically significant. Late puberty was associated with reduced risk of testicular cancer. The effect of age at puberty may be due both to advanced age at diagnosis and to the existence of common determinants of age at puberty and testicular cancer. Men who had been treated for cryptorchidism entered puberty later than other men, possibly because of impaired hormonal function of the testes. There was no indication of increased risk of testicular cancer or cryptorchidism in sons of mothers who smoked around the time of conception or during the pregnancy.

Trends in sex‐ratio, testicular cancer and male reproductive hazards: Are they connected?

In the last few decades, the male proportion of newborn babies has been decreasing in several populations. The changes are very small and without practical importance per se, but the underlying biological mechanisms are not known. In the same period, testicular cancer incidence has increased, and there has been indications of decreasing sperm counts in men in several populations. The available knowledge on factors that influence the sex‐ratio in humans supports the idea that an excess of girls in the offspring of a man may be an indicator of reproductive hazards. Data from a Danish case‐control study show strong associations between testicular cancer, low fertility and a low M:F sex‐ratio in the offspring. It is proposed as a hypothesis that there may exist common aetiological factors for testicular cancer, low fertility and low offspring sex‐ratio, and that a search for the causal factors involved may focus on agents that can act prenatally to disrupt the normal development and differentiation of the male reproductive organs.

Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation

PURPOSEnAtrial fibrillation is an important risk factor for stroke. We analyzed stroke risk over time in patients discharged from the hospital with a diagnosis of incident atrial fibrillation as compared with the risk of stroke in the Danish population.nnnSUBJECTS AND METHODSnIn a random sample of half of the Danish population, we identified 13,625 men and 13,577 women, aged 50 to 89 years, with a hospital diagnosis of atrial fibrillation and no prior diagnosis of stroke during 1980 to 1993. Data on other medical conditions were also available from 1977 to 1993, but medication data were not available. Patients were followed from the diagnosis of atrial fibrillation until the first diagnosis of stroke (nonfatal or fatal cerebral ischemic infarct and cerebral hemorrhage), death, or the end of 1993. The risk of stroke in these patients was compared with the risk in the Danish population using Poisson regression modeling to estimate relative risks (RR) and 95% confidence intervals (CI).nnnRESULTSnFor men with atrial fibrillation, the stroke rates increased by age, from 13 per 1,000 person-years in those ages 50 to 59 years, to 22 per 1,000 person-years in those ages 60 to 69 years, to 42 per 1,000 person-years in those ages 70 to 79 years, to 51 per 1,000 person-years in those ages 80 to 89 years. Age-specific stroke rates were similar in women with atrial fibrillation. Patients with a hospital diagnosis of atrial fibrillation had an increased risk of stroke (RR = 2.4; 95% CI, 2.3 to 2.5 in men and RR = 3.0; 95% CI, 2.9 to 3.2 in women) compared with the Danish population. Stroke risk was greatest during the first year after discharge and decreased thereafter. Hypertension, diabetes, and peripheral atherosclerosis were also associated with an increased risk of stroke among patients with atrial fibrillation. Ischemic heart disease and heart failure were risk factors in men only. There was no reduction in the risk of stroke from 1980 to 1993.nnnCONCLUSIONSnMen and women with atrial fibrillation are at a substantially increased risk of stroke, particularly in the first year after the diagnosis.

Does a discrepancy between gestational age determined by biparietal diameter and last menstrual period sometimes signify early intrauterine growth retardation

Objective To assess the association between gestational age estimated from the last menstrual period (GALMP) or from the biparietal diameter (GABPD), and the subsequent birthweight for gestational age.

Testicular neoplasia in cryptorchid boys at primary surgery: case series

Cryptorchidism is associated with testicular cancer; the lifetime risk of 2-3% is about four times higher than in the general population.1 2 Some groups of cryptorchid patients may have an especially high risk of testicular cancer.3 Testicular carcinoma in situ is a well described histological pattern that precedes germ cell tumours.1 4 We investigated whether it is possible at primary surgery to identify cryptorchid boys who have testicular neoplasia and therefore are at high risk of testicular cancer.nnWe examined 1535 consecutive specimens of testicular tissue that were obtained from undescended testes at surgery for cryptorchidism in 1249 boys between 1971 and 1998. Previous reports have described 1026 of the biopsies in detail.2 4 No patient had fallopian tubes or a uterus.nnThe table shows the total occurrence of testicular neoplasia at surgery for cryptorchidism. There was one case …

Changes in risk of hospital readmission among asthmatic children in Denmark, 1978-93

The management of asthma in children has changed over the two most recent decades, with increasing emphasis on early anti-inflammatory treatment and complete disease control with inhaled steroids.1 2 We estimated the changes in hospital readmission rates for asthma in children in Denmark in 1978-93 with a view to evaluating concomitant changes in disease control.nnData on hospital admissions and subsequent readmissions with asthma in children aged 5-14 at first admission were obtained from the Danish National Board of Health for the period 1978-93. Readmission was defined as any subsequent admission related to asthma that was separated by 12 months or more from the first admission.nnThe age standardised incidence of admission to hospital for asthma was calculated by dividing the number …

Increased adverse pregnancy outcomes with unreliable last menstruation

Objective To estimate the risk of adverse outcomes in women whose first day of the last menstrual period (LMP) was unreliable. Methods Among 20,244 singleton pregnancies with measurements of biparietal diameter between 12 and 22 weeks gestation, LMP was registered as unreliable in 3775 (18.6%) and reliable in 16,469 (81.4%). Adverse outcomes were defined as spontaneous or missed abortions after 12 weeks gestation, stillbirth or postnatal death within 1 year, preterm birth, birth weight less than 2500 g, and low birth weight (LBW) for gestation (lower than 22% below sex-specific expected weight). Logistic regression analysis and Kaplan-Meier survival analysis were used to analyze the risk of adverse outcomes. Results The risk of death was doubled in pregnant women with unreliable LMPs compared with those with reliable LMPs (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.5, 2.6). This risk was highest with respect to stillbirth (OR 2.7; 95% CI 1.7, 4.3). The risks of preterm birth, LBW, and LBW for gestation were also significantly increased (ORs 1.5, 1.4, and 1.2; 95% CIs 1.3, 1.7; 1.2, 1.6; and 1.0, 1.4, respectively). Conclusion An unreliable LMP is associated with increased risk of adverse outcomes, especially fetal death.

F96A discrepancy between gestational age estimated by last menstrual period and biparietal diameter may indicate an increased risk of fetal death and adverse outcomes of pregnancy

Objective