Inferring glaucoma status from prescriptions, diagnoses, and operations data: A Danish nationwide study.

PURPOSE: To assess a new method for inferring glaucoma status using prescriptions data. METHODS: The study population comprised all individuals living in Denmark in the period 1995 to 2018 and included 6,930,571 individuals. We used information from The National Prescription Registry on claimed prescriptions as the basis for our study (N = 223,592). We inferred glaucoma status using data on claimed prescriptions, in-hospital ICD-10 diagnoses, and in-hospital glaucoma surgeries. We infer glaucoma status in three ways using the prescription pattern: glaucoma inferred by (i) the use of a first claimed prescription, (ii) the use of a second claimed prescription with a gap of at least 90 days, and (iii) the use of a third claimed prescription for glaucoma medication, again with a gap of at least 90 days between prescriptions. Furthermore, we compared the results with alternative indications for glaucoma, namely in-hospital ICD-10-diagnosed glaucoma and in-hospital glaucoma surgery. RESULTS: We first determined that glaucoma status could be inferred from claimed prescription data and found that a single claimed prescription was highly correlated with the more restricted composite measure of glaucoma (R2 = 0.80, p <0.0001), with a kappa coefficient of 80%. Focusing on individuals with a confirmed in-hospital glaucoma diagnosis, we found a high sensitivity of 88% using anti-glaucomatous prescriptions as a surrogate marker for primary open-angle glaucoma (POAG). We then derived several descriptive insights. The prevalence of glaucoma increased during the period from 1996 to 2018, while the incidence was constant. We also found a decreasing trend in the ratio of the number of people diagnosed annually in hospitals to the number of people filling prescriptions. This indicated a relative increase in the number of patients treated or managed in the secondary sector. Finally, using data on diagnoses and claimed prescriptions, we found that the proportion of total noncompliant patients, i.e., patients who do not claim their prescription at any time in the study period (two decades) was at most 11.8%. This share is calculated on the basis of diagnosed patients who did not have surgery. The results was not sensitive to the glaucoma inference rule. CONCLUSION: Anti-glaucomatous medicine prescriptions can be used to infer glaucoma status, with useful implications for epidemiological research. The sensitivity is particularly high for primary open-angle glaucoma (POAG).

Male Fertility Before and After Androgen Abuse.

PURPOSE: Previous research has found that male users of androgens are diagnosed approximately twice as often with infertility. We therefore set out to investigate the fertility in men using androgens. METHODS: The study included 545 males who tested positive for androgens in an anti-doping test program in Danish fitness centers during the period from January 3, 2006, to March 1, 2018. The confirmed androgen users were matched by birth year with 5450 male controls. We followed this cohort from 10 years prior to testing positive until the end of follow-up in May 2018. RESULTS: During the 10-year period prior to testing positive, the group of androgen users experienced a 26% lower fertility rate than the controls (rate ratio [RR] 0.74; 95% CI, 0.60-0.90; P = 0.0028). However, in the years following the doping sanction, they made a significant catch-up, and at completed follow-up the total fertility rate was only 7% lower than expected (RR 0.93, 95% CI, 0.84-1.03). The prevalence of assisted reproduction was 5.69% in the group of androgen users and 5.28% in the control group (P = 0.69). CONCLUSION: Androgen use was associated with a temporary decline in fertility and most androgen users achieved parenthood without any help from the health care system. Overall, the fertility rate and the prevalence of assisted reproduction among androgen users were close to those in the background population.

Diversity and Conflict.

This research advances the hypothesis and establishes empirically that interpersonal population diversity, rather than fractionalization or polarization across ethnic groups, has been pivotal to the emergence, prevalence, recurrence, and severity of intrasocietal conflicts. Exploiting an exogenous source of variations in population diversity across nations and ethnic groups, as determined predominantly during the exodus of humans from Africa tens of thousands of years ago, the study demonstrates that population diversity, and its impact on the degree of diversity within ethnic groups, has contributed significantly to the risk and intensity of historical and contemporary civil conflicts. The findings arguably reflect the contribution of population diversity to the non-cohesivnesss of society, as reflected partly in the prevalence of mistrust, the divergence in preferences for public goods and redistributive policies, and the degree of fractionalization and polarization across ethnic, linguistic, and religious groups.

Brain Responses to Passive Sensory Stimulation Correlate With Intelligence.

This study investigates the association between intelligence and brain power responses to a passive audiovisual stimulation. We measure the power of gamma-range steady-state responses (SSRs) as well as intelligence and other aspects of neurocognitive function in 40 healthy males born in 1953. The participants are a part of a Danish birth cohort study and the data therefore include additional information measured earlier in life. Our main power measure is the difference in power between a visual stimulation and a combined audiovisual stimulation. We hypothesize and establish empirically that the power measure is associated with intelligence. In particular, we find a highly significant correlation between the power measure and present intelligence scores. The association is robust to controlling for size-at-birth measures, length of education, speed of processing as well as a range of other potentially confounding factors. Interestingly, we find that intelligence scores measured earlier in life (childhood, youth, late midlife), are also correlated with the present-day power measure, suggesting a deep connection between intelligence and the power measure. Finally, we find that the power measure has a high sensitivity for detection of an intelligence score below the average.

Further Evidence of Within-Marriage Fertility Control in Pre-Transitional England.

The identification of parity effects on the hazard of a next birth in cross-family data requires accounting for heterogeneity in fecundity across couples. In a previously published article, Cinnirella et al. Demography, 54, 413-436 (2017), we stratified duration models at the maternal level for this purpose and found that the hazard of a next birth decreases with rising parity in historical England. Clark and Cummins Demography, 56 (2019) took issue with this finding, claiming that the result is a statistical artifact caused by stratification at the maternal level. This reply documents that our previous finding is robust to addressing Clark and Cummins' critique.

Author Correction: Human genealogy reveals a selective advantage to moderate fecundity.

In the version of this article initially published, several sentences contained errors. The sentence "Moreover, the analysis further suggests that evolutionary forces decreased the level of fecundity in the population over this period, consistent with an additional finding that the level of fecundity that maximized long-run reproductive success was above the population mean" contained an error. The word "above" should have been "below". Also, the sentence "Interestingly, the PI associated with the peak of the hump is above the mean and median PI in the population (Supplementary Table 3), in accordance with the finding that evolutionary forces decreased the mean PI in the population over the time period" contained an error. The word "decreased" should have been "increased". Finally, the sentence "Hence, consistent with the finding that the level of fecundity that maximized long-run reproductive success was above the population mean (that is, 62 weeks), as well as the population median (that is, 53 weeks), evolutionary forces operated towards an increase in the mean PI over these 4 generations from 62.4 to 66.2 weeks" contained an error. The word "fecundity" should have instead been "PI". The errors have been corrected in the HTML and PDF versions of the article.

Human genealogy reveals a selective advantage to moderate fecundity.

Life-history theory suggests that the level of fecundity of each organism reflects the effect of the trade-off between the quantity and quality of offspring on its long-run reproductive success. The present research provides evidence that moderate fecundity was conducive to long-run reproductive success in humans. Using a reconstructed genealogy for nearly half a million individuals in Quebec during the 1608-1800 period, the study establishes that, while high fecundity was associated with a larger number of children, perhaps paradoxically, moderate fecundity maximized the number of descendants after several generations. Moreover, the analysis further suggests that evolutionary forces decreased the level of fecundity in the population over this period, consistent with an additional finding that the level of fecundity that maximized long-run reproductive success was above the population mean. The research identifies several mechanisms that contributed to the importance of moderate fecundity for long-run reproductive success. It suggests that, while individuals with lower fecundity had fewer children, the observed hump-shaped effect of fecundity on long-run reproductive success reflects the beneficial effects of lower fecundity on various measures of child quality, such as marriageability and literacy, and thus on the reproductive success of each child.

The prognosis following amphetamine poisoning.

AIMS: This study investigated the long-term mortality following poisoning by amphetamine or substituted amphetamines. Furthermore, we examined the social problems and somatic and psychiatric co-morbidity related to amphetamine poisoning, and their impact on the long-term survival. METHODS: We identified amphetamine poisoned patients from the Danish Poison Information Centre database and correlated their personal identification numbers with seven Danish national registries related to different social and health aspects. For each case, we sampled 100 age and gender matched controls from the background population. RESULTS: From August 2006 to December 2013 we identified 1444 patients (70% males) who experienced amphetamine poisoning; 52% of the cases were classified as mixed poisonings and the average age at first contact was 24.8 years (SD 8.6). The prevalence of psychiatric disorders, HIV, viral hepatitis, and previous prison incarceration was approximately 10 times higher than among healthy controls. After seven years 11% were deceased as opposed to 0.6% in the control group, and 64% of the patients died from unnatural causes. Male gender (HR 2.29, 95% CI (1.07-4.90)), age (HR 1.06, 95% CI (1.03-1.09)), opioid dependence (HR 2.88, 95% CI (1.42-5.85)), schizophrenia (HR 3.09,95% CI (1.63-5.86)), affective disorders (HR 2.65, 95% CI (1.44-4.90)) and HIV (HR 5.45, 95% CI (1.19-24.90)) were associated with a high mortality. Furthermore, a significant proportion of these patients experienced social and health related deterioration in the years following poisoning. CONCLUSIONS: Amphetamine poisoning is associated with a poor long-term prognosis and is complicated by additional social and health related issues.

Visual steady state in relation to age and cognitive function.

Neocortical gamma activity is crucial for sensory perception and cognition. This study examines the value of using non-task stimulation-induced EEG oscillations to predict cognitive status in a birth cohort of healthy Danish males (Metropolit) with varying cognitive ability. In particular, we examine the steady-state VEP power response (SSVEP-PR) in the alpha (8Hz) and gamma (36Hz) bands in 54 males (avg. age: 62.0 years) and compare these with 10 young healthy participants (avg. age 27.6 years). Furthermore, we correlate the individual alpha-to-gamma difference in relative visual-area power (ΔRV) with cognitive scores for the older adults. We find that ΔRV decrease with age by just over one standard deviation when comparing young with old participants (p<0.01). Furthermore, intelligence is significantly negatively correlated with ΔRV in the older adult cohort, even when processing speed, global cognition, executive function, memory, and education (p<0.05). In our preferred specification, an increase in ΔRV of one standard deviation is associated with a reduction in intelligence of 48% of a standard deviation (p<0.01). Finally, we conclude that the difference in cerebral rhythmic activity between the alpha and gamma bands is associated with age and cognitive status, and that ΔRV therefore provide a non-subjective clinical tool with which to examine cognitive status in old age.

Malthus in the Bedroom: Birth Spacing as Birth Control in Pre-Transition England.

We use duration models on a well-known historical data set of more than 15,000 families and 60,000 births in England for the period 1540-1850 to show that the sampled families adjusted the timing of their births in accordance with the economic conditions as well as their stock of dependent children. The effects were larger among the lower socioeconomic ranks. Our findings on the existence of parity-dependent as well as parity-independent birth spacing in England are consistent with the growing evidence that marital birth control was present in pre-transitional populations.

Antihypertensive Medication Postpones the Onset of Glaucoma: Evidence From a Nationwide Study.

The aim was to investigate the impact of antihypertensive medication on the onset of glaucoma. Data from the complete Danish population between 40 and 95 years of age were used in the period from 1996 to 2012, covering >2.6 million individuals. The National Danish Registry of Medicinal Products Statistics was used to identify all claimed prescriptions for glaucoma medication and antihypertensive drugs. We first investigated basic correlations in the data and found that patients treated with antihypertensive medication, at any time during the study period, had a significantly higher overall relative risk (RR) of glaucoma, even when controlling for age and sex (with a RR of 1.31 and P<0.0001). Furthermore, our data confirm the well-known positive association between age and glaucoma. To investigate the causal effect of antihypertensive treatment on the onset of treatment for glaucoma, we used a regression discontinuity study design. This analysis provides our main finding, namely that prescription of antihypertensive medication leads to a significant reduction in the risk of developing glaucoma. Therefore, although hypertension-as indicated by the use of antihypertensive medication-is positively correlated with glaucoma, our study indicates that antihypertensive medication itself may have a preventive effect on the development of glaucoma.