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The authors reflect on the state of care for older people in the intensive care unit (ICU) of hospitals. They mention the study by C. Brandberg, H. Blomqvist, and M. Jirwe, which shows that most older patients that are over 80 years old received much lesser treatment and increase in limitation of care. They also mention the study in Sweden which shows reduction of age inequalities in the health-care system of the country.

Although Denmark and Sweden have close cultural and historical ties, lifespans for Danes have generally been lower than those of Swedes. Recent improvements in Danish mortality after a period of stagnation have led to the suspicion that there may be positive trends at the very high ages at death within that population and that these trends could be quite different from those observed in Sweden. Although the mean ages at death for Danish and Swedish centenarians have been relatively constant at about 102 years for the cohorts born 1870-1904, the oldest-old in Denmark have been getting older, but no evidence has suggested any increase in lifespan for Swedes. Using quantile regression, we show that Danish centenarian lifespans in the 90th percentile have been lengthening, with those in 94th percentile (6 % longest-lived individuals) having a trend that is statistically significant at the 5 % level. We demonstrate that the increase observed is not due to the increasing sizes of birth cohorts and thus must be due to improving survival among this select top tier. We postulate that this super-select group in Denmark is best able to take advantage of the factors driving mortality reduction, whereas the majority of centenarians are not.

The Nordic countries have comprehensive, population-based health and medical registries linkable on individually unique personal identity codes, enabling complete long-term follow-up. The aims of this study were to describe the NorTwinCan cohort established in 2010 and assess whether the cancer mortality and incidence rates among Nordic twins are similar to those in the general population. We analyzed approximately 260,000 same-sexed twins in the nationwide twin registers in Denmark, Finland, Norway and Sweden. Cancer incidence was determined using follow-up through the national cancer registries. We estimated standardized incidence (SIR) and mortality (SMR) ratios with 95% confidence intervals (CI) across country, age, period, follow-up time, sex and zygosity. More than 30,000 malignant neoplasms have occurred among the twins through 2010. Mortality rates among twins were slightly lower than in the general population (SMR 0.96; CI 95% [0.95, 0.97]), but this depends on information about zygosity. Twins have slightly lower cancer incidence rates than the general population, with SIRs of 0.97 (95% CI [0.96, 0.99]) in men and 0.96 (95% CI [0.94, 0.97]) in women. Testicular cancer occurs more often among male twins than singletons (SIR 1.15; 95% CI [1.02, 1.30]), while cancers of the kidney (SIR 0.82; 95% CI [0.76, 0.89]), lung (SIR 0.89; 95% CI [0.85, 0.92]) and colon (SIR 0.90; 95% CI [0.87, 0.94]) occur less often in twins than in the background population. Our findings indicate that the risk of cancer among twins is so similar to the general population that cancer risk factors and estimates of heritability derived from the Nordic twin registers are generalizable to the background populations.

Background: Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood., Methods: In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79 years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks., Findings: A model incorporating additive genetic (A) and person-specific environmental (E) influences best explained the variation in both clocks. Heritability was estimated at 55% at baseline and at 51% at follow-up for the Horvath clock and 34% at baseline and 41% at follow-up for the Levine clock. For the Horvath clock, new sources of A influences emerged at follow-up, whereas for the Levine clock, the same A influences accounted for the genetic variance at both measurement occasions. The cross-time phenotypic correlations, 0·52 for the Horvath clock and 0·36 for the Levine clock, were mediated primarily by genetic factors, whereas the person-specific environmental factors were completely different at the two measurement occasions., Interpretation: For both clocks, new sources of person-specific environmental influences emerge with age. The epigenetic clocks might thus be responsive to new environmental stimuli even at old age. FUND: NIH (R01;AG04563;AG10175;AG028555) the MacArthur Foundation Research Network on Successful Aging, FAS/FORTE (97:0147:1B;2009-0795), Swedish Research Council (825-2007-7460;825-2009-6141;521-2013-8689;2015-03255;2015-06796;2018-02077), FORTE (2013-2292), the Strategic Research Program in Epidemiology at KI, VELUX FOUNDATION, NIA (P01-AG08761), the EU (FP7/2007-2011;259679) and The Danish National Program for Research Infrastructure 2007 (9-063256)., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction., Objective: To estimate familial risk and heritability of cancer types in a large twin cohort., Design, Setting, and Participants: Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up., Exposures: Shared environmental and heritable risk factors among pairs of twins., Main Outcomes and Measures: The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death., Results: A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%)., Conclusions and Relevance: In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Background: Increasing evidence shows that some cancers originate in utero. It is hypothesized that elevated exposure to some steroid hormones might increase cancer risk and that hormone transfer between twin fetuses could result in different prenatal exposure to testosterone., Methods: This large-scale prospective twin study compared opposite-sex (OS) and same-sex (SS) twins to test the impact of intrauterine exposures on cancer risk. On the basis of the Danish and Swedish twin and cancer registries, we calculated incidence rate ratios for OS and SS twins, whereas standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for OS/SS twins compared with the general population., Results: A total of 18,001 cancers were identified during 1943-2009. No significant differences were observed between OS and SS twins, neither for the sex-specific cancers nor for cancer at all sites. All-cause cancer was slightly reduced for OS and SS twins compared with the general population, significant for OS males (SIR, 0.95; 95% CI, 0.92-0.98) and for SS males and females (SIR, 0.97; 95% CI, 0.94-0.99)., Conclusions: Our data suggest that having a male co-twin-which may entail higher exposure to prenatal testosterone-does not increase the risk of sex-specific cancers in OS females. Furthermore, the study supports that twinning per se is not a risk factor of cancer., Impact: Findings are reassuring, as they fail to provide evidence for the hypothesis that endocrine or other difference in the in utero milieu affects the risk of sex-specific cancers., (©2015 American Association for Cancer Research.)

Purpose: In Utah, the prevalence of unhealthy male risk behaviors are lower than in most other male populations, whereas women experience higher mortality risk because of higher fertility rates. Therefore, we hypothesize that the Utah sex differential in mortality would be small and less than in Sweden and Denmark., Methods: Life tables from Utah, Denmark, and Sweden were used to calculate cohort life expectancies for men and women born in 1850-1910., Results: The sex difference in cohort life expectancy was similar or larger in Utah when compared with Denmark and Sweden. The change over time in the sex differences in cohort life expectancy was approximately 2 years smaller for active Mormons in Utah than for other groups suggesting lifestyle as an important component for the overall change seen in cohort life expectancy. Sex differences in cohort life expectancy at the age of 50 years were similar for individuals actively affiliated with the Church of Jesus Christ of Latter-day Saints and for Denmark and Sweden., Conclusions: The hypothesis that a smaller sex difference in cohort life expectancies in Utah would be detected in relation to Denmark and Sweden was not supported. In Utah, the male-female differences in life expectancy remain substantial pointing toward biological mechanisms or other unmeasured risk factors., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Purpose: It would be essential to clinicians, familial aneurysm study groups, and aneurysm families to understand the genetic basis of subarachnoid hemorrhage (SAH), but there are no large population-based heritability estimates assessing the relative contribution of genetic and environmental factors to SAH., Methods: We constructed the largest twin cohort to date, the population-based Nordic Twin Cohort, which comprised 79 644 complete twin pairs of Danish, Finnish, and Swedish origin. The Nordic Twin Cohort was followed up for 6.01 million person-years using nationwide cause-of-death and hospitalization registries., Results: One hundred eighty-eight fatal and 321 nonfatal SAH cases were recorded in the Nordic Twin Cohort. Thus, SAH incidence was 8.47 cases per 100,000 follow-up years. Data for pairwise analyses were available for a total of 504 SAH cases, of which 6 were concordant (5 monozygotic and 1 opposite sex) and 492 discordant twin pairs for SAH. The concordance for SAH in monozygotic twins was 3.1% compared with 0.27% in dizygotic twins, suggesting at most a modest role for genetic factors in the etiology of SAH. The population-based probability estimate for SAH in dizygotic siblings of a patient with SAH is 0.54%, and only 1 of 185 full siblings experience familial SAH. The corresponding risk of SAH in monozygotic twins is 5.9%. Model-fitting, which was based on the comparison of the few monozygotic and dizygotic pairs, suggested that the estimated heritability of SAH is 41%., Conclusions: SAH appears to be mainly of nongenetic origin, and familial SAHs can mostly be attributed to environmental risk factors.

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.

Stroke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.

Previous twin studies have indicated that approximately 25% of the variation in life span can be attributed to genetic factors and recent studies have also suggested a moderate clustering of extreme longevity within families. Here we discuss various definitions of extreme longevity and some analytical approaches with special attention to the challenges due to censored data. Lexis diagrams are provided for the Danish, Dutch, Finnish, Italian, Norwegian, and Swedish Twin registries hereby outlining possibilities for longevity studies within GenomEUtwin. We extend previous analyses of lifespan for the Danish 1870-1900 twin cohorts to include the new 1901-1910 cohorts, which are consistent with the previous findings. The size of the twin cohorts in GenomEUtwin and the existence of population-based, nationwide health and death registers make epidemiological studies of longevity very powerful. The combined GenomEUtwin sample will also allow detailed age-specific heritability analyses of lifespan. Finally, it will provide a resource for identifying unusual sibships (i.e., dizygotic twin pairs) where both survived to extreme ages, as a basis for discovering genetic variants of importance for extreme survival.

The safety and efficacy of isoprinosine in HIV-infected individuals were assessed in a multicentre, randomized, double-blind, 24-week study phase, followed by an optional 24-week open treatment phase. The results of the double-blind phase have been reported separately. Of 866 HIV-seropositive individuals randomized, 832 were eligible for efficacy analysis. On completion of the double-blind phase, 596 patients started open treatment. All patients were evaluated with regard to progression to AIDS. Within 48 weeks, 10/412 patients (2.4%) assigned isoprinosine and 27/420 (6.4%) assigned placebo progressed to AIDS (p = 0.005; odds ratio: 2.8, 95% CI: 1.3-6.2). Intention-to-treat analysis showed identical results. No severe adverse reactions or toxicities were observed. We conclude that HIV-infected individuals without AIDS may be safely and effectively treated with isoprinosine.

Streptococcus agalactiae transmitted to infants from the vagina during birth is an important cause of invasive neonatal infection. We have done a prospective, randomised, double-blind, placebo-controlled, multi-centre study of chlorhexidine prophylaxis to prevent neonatal disease due to vaginal transmission of S agalactiae. On arrival in the delivery room, swabs were taken for culture from the vaginas of 4483 women who were expecting a full-term single birth. Vaginal flushing was then done with either 60 ml chlorhexidine diacetate (2 g/l) (2238 women) or saline placebo (2245) and this procedure was repeated every 6 h until delivery. The rate of admission of babies to special-care neonatal units within 48 h of delivery was the primary end point. For babies born to placebo-treated women, maternal carriage of S agalactiae was associated with a significant increase in the rate of admission compared with non-colonised mothers (5.4 vs 2.4%; RR 2.31, 95% CI 1.39-3.86; p = 0.002). Chlorhexidine reduced the admission rate for infants born of carrier mothers to 2.8% (RR 1.95, 95% CI 0.94-4.03), and for infants born to all mothers to 2.0% (RR 1.48, 95% CI 1.01-2.16; p = 0.04). Maternal S agalactiae colonisation is associated with excess early neonatal morbidity, apparently related to aspiration of the organism, that can be reduced with chlorhexidine disinfection of the vagina during labour.

In a kindergarten with 42 children and 17 female staff members, an epidemic of group B streptococcal carriage in the upper respiratory tract occurred. In the middle of February 1978, 6 children and 5 adults carried type I b streptococci in the throat while only 2 of these 11 were carriers 2 weeks later. Only one other streptococcus, belonging to type II, was found in the throat specimens. Five strains other than type I b were found in the urogenital tract of the staff. Three type I b throat carriers were also urogenital carriers of this type. The spread of type I b streptococci could have resulted from co-spreading with other upper respiratory tract pathogens found, including group A streptococci of type 12. Haemophilus influenzae, Branhamella catarrhalis and pneumococci. Estimation of antibodies with radiolabelled protein A indicated an immune response to type I b, but not to types I a, II or III group B streptococci in the staff compared with healthy blood donors.

During a 15-month period, all 34 infants delivered at the department of obstetrics and gynecology at University Hospital in Lund, Sweden, who died perinatally or neonatally were included in a prospective study of causes of death. Autopsies--including extensive culturing of specimens for bacteria, chlamydia, fungi, mycoplasmas, and viruses--were performed for all infants. Maternal sera obtained during pregnancy and after delivery were examined regarding titers against a number of microorganisms. During the study period, the perinatal mortality rate was 0.60% and the neonatal mortality rate 0.56%. It was found that 37% of the deaths were caused by lethal malformations, 17% by idiopathic respiratory distress syndrome, and 9% by ablatio placentae. However, no less than 21% occurred as a direct consequence of infections, including 2 deaths caused by group B streptococci, 2 by Coxsackie B virus, and 3 deaths each by Hemophilus influenzae, Pseudomonas pyocyanea, and Candida albicans. A 6-month study of late abortions revealed another case of intrauterine group B streptococcal infection. The study has demonstrated that autopsy, including microbial examination, is recommended in all cases of perinatal and neonatal deaths.

Since 1976, all cases of neonatal group B streptococcal (GBS) septicemia/meningitis have been registered at two Swedish University Hospitals. A significant increase in the number of infants contracting early-onset GBS-septicemia was noticed at one clinic in 1981, from 1-3 cases per yr to 8 cases. Six months prior to this increase the number of deliveries increased from about 1500 per yr to nearly 3000 per yr. It is suggested that external factors, e.g., subtle changes in the nursing combined with an extended disadvantage at the ward might influence the development of early-onset GBS septicemia.

Thirty-four mothers to infants seriously infected with group B streptococci (GBS) were investigated for G1m (1) and G3m(5) allotype markers. The frequency of Gm (1, -5) was 14.7%, of Gm(1,5) 20.6% and Gm (-1, 5) 64.7%. There was a marked deficit Gm (1) individuals and the distribution significantly differed from that in the normal Swedish populations.