European Journal of Epidemiology

Researchers often attempt to categorize tumors into more homogeneous subtypes to better predict prognosis or understand pathogenic mechanisms. In clinical research, typically the focus is on prognosis: the tumor subtypes are intended to be associated with specific responses to treatment and/or different clinical outcomes. In aetiological research, the focus is on identifying distinct pathogenic mechanisms, which may involve different risk factors. We used directed acyclic graphs to present a framework for considering potential biases arising in aetiological research of tumor subtypes, when there is incomplete correspondence between the identified subtypes and the underlying pathogenic mechanisms. We identified two main scenarios: (1) weak effect, when the tumor subtypes are identified through combinations of characteristics and some of these characteristics are affected by factors that are unrelated with the underlying pathogenic mechanisms; and (2) lack of causality, when the set of characteristics corresponds with a mechanism that is actually not a cause of the tumor of interest. Examples of the magnitude of bias that can be introduced in these situations are provided. Although categorization of tumors into homogenous subtypes may have important implications for aetiological research and identification of risk factors, the characteristics used to classify tumors into subtypes should be as close as possible to the actual pathogenic mechanisms to avoid interpretative biases. Whenever our knowledge of these mechanisms is limited, research into risk factors for tumor subtypes should first aim to causally link the characteristics to the pathogenic mechanisms.

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.

Objective: To assess changes in consultation rates, medication use and work absences due to migraine and tension-type headache (TTH) in Denmark over a 12-year period. Methods: Surveys of the general population in 1989 and 2001. Medical doctors conducted all headache diagnostic interviews based on ICDH-I and II. The participation rate was 76% (740) in 1989 and 74% (711) in 2001. Headache status was categorized as pure migraine, pure frequent TTH (frequent episodic or chronic TTH), coexisting migraine and frequent TTH, and healthy subjects (no primary headache or only infrequent TTH). Results: Headache-related consultation rates (OR=1.6 (1.1–2.2)), especially specialist consultations (OR=3.6 (2.3–5.6)), increased for all headache groups. Use of prescription medication because of headache increased moderately (OR=2.1 (1.1–3.9)) while the use of prophylactic medication was stable (OR=1.1 (0.3–4.0)). Both headache-related (OR=1.1 (0.7–1.7)) and overall (OR=0.9 (0.7–1.2)) absence rates were largely unchanged. Headache-related absence rates were higher for subjects with both headache types (OR= 7.5 (4.3–13.1)) or with pure migraine (OR=3.6 (2.0–6.6)) than for subjects with frequent TTH alone. Triptans users had higher migraine headache frequency and tended to have higher absence rates than non-users. Overall absence rates were higher for subjects with both headache types (OR=2.3 (1.3–4.0)) or with frequent TTH (OR=1.9 (1.4–2.7)) than for healthy subjects. Pure migraine was not associated with higher overall absence rates (OR=1.0 (0.6–1.6)). Conclusion: Despite an increase in headache consultation rates and in use of prescription medication and triptans, no improvement in work absence rates was observed. Consultations, medication use, and absence rates were highest for individuals with both migraine and frequent TTH.

To evaluate the role of nutritional factors in the etiology of endometrial cancer, we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a subcohort was constructed by selecting a 10% random sample from the 56,837 women in the dietary cohort. Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31, 1993 and ascertained by record linkage to the Canadian Cancer Database. Information on usual diet at enrolment and other epidemiological variables was collected by means of self-administered questionnaires. Hazard ratios were obtained from proportional hazards regression models, with estimation of robust standard errors. We found a strong association of endometrial cancer with body mass index >25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06–3.50). Endometrial cancer risk was not associated significantly with intakes of total energy, carbohydrates, proteins, total fat and major fatty acids, total dietary fiber and various types of fibers, vitamin C, E and A, folic acid, β-carotene, lutein, or cryptoxanthin. Some decrease in risk was noted with relatively high intakes of saturated fat, animal fat or lycopene. The associations observed in the study were independent of total energy intake and most non-dietary risk factors. The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women.

Obesity during pregnancy may be correlated with an adverse nutritional status affecting pregnancy and offspring outcomes. We examined the associations of prepregnancy body mass index and gestational weight gain with plasma fatty acid concentrations in mid-pregnancy. This study was embedded in a population-based prospective cohort study among 5636 women. We obtained prepregnancy body mass index and maximum weight gain during pregnancy by questionnaires. We measured concentrations of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 polyunsaturated fatty acid (n-3 PUFA) and n-6 polyunsaturated fatty acid (n-6 PUFA) at a median gestational age of 20.5 (95 % range 17.1–24.9) weeks. We used multivariate linear regression models. As compared to normal weight women, obese women had higher total SFA concentrations [difference: 0.10 standard deviation (SD) (95 % Confidence Interval (CI) 0, 0.19)] and lower total n-3 PUFA concentrations [difference: − 0.11 SD (95 % CI − 0.20, − 0.02)]. As compared to women with sufficient gestational weight gain, those with excessive gestational weight gain had higher SFA concentrations [difference: 0.16 SD (95 % CI 0.08, 0.25)], MUFA concentrations [difference: 0.16 SD (95 % CI 0.08, 0.24)] and n-6 PUFA concentrations [difference: 0.12 SD (95 % CI 0.04, 0.21)]. These results were not materially affected by adjustment for maternal characteristics. Our results suggest that obesity and excessive weight gain during pregnancy are associated with an adverse fatty acids profile. Further studies are needed to assess causality and direction of the observed associations.

Previous studies have found an association between recessions and increased rates of suicide. In the present study we widened the focus to examine the association between economic uncertainty and suicides. We used monthly suicide data from the US at the State level from 2000 to 2017 and combined them with the monthly economic uncertainty index. We followed a panel data econometric approach to study the association between economic uncertainty and suicide, controlling for unemployment and other indicators. Economic uncertainty is positively associated with suicide when controlling for unemployment [coeff: 8.026; 95% CI: 3.692–12.360] or for a wider range of economic and demographic characteristics [coeff: 7.478; 95% CI: 3.333–11.623]. An increase in the uncertainty index by one percent is associated with an additional 11–24.4 additional monthly suicides in the US. Economic uncertainty is likely to act as a trigger, which underlines the impulsive nature of some suicides. This highlights the importance of providing access to suicide prevention interventions (e.g. hotlines) during periods of economic uncertainty.

Within the last four years, we have observed five patients with epidemiological, clinical, and serological features that were consistent with Q fever meningoencephalitis. Attempts to isolate Coxiella burnetii from the cerebrospinal fluid of two patients were unsuccessful. Neurological features ranged from coma, general seizures, confusion, to palsy and meningitis. All patients were febrile. These patients were neuroradiologicaly investigated. Since 1984, four other cases have been reported in the literature. Antibiotics with good penetration into the cerebrospinal fluid, such as new quinolones, may be useful for treatment of confirmed cases. Q fever should be considered as a possible etiology of meningitis in endemic areas, and diagnosis should be confirmed by serology.