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Background Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children’s MUAC. Methods This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003–05) and a late period (2014–16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education. Results A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality. Conclusions From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow’s interventions.

Aims To examine the effect of childhood adversity on the development of cardiovascular disease (CVD) between ages 16 and 38, specifically focusing on ischaemic heart disease and cerebrovascular disease. Methods and results Register data on all children born in Denmark between 1 January 1980 and 31 December 2001, who were alive and resident in Denmark without a diagnosis of CVD or congenital heart disease until age 16 were used, totalling 1 263 013 individuals. Cox proportional hazards and Aalen additive hazards models were used to estimate adjusted hazard ratios (HRs) and adjusted hazard differences of CVD from ages 16 to 38 in five trajectory groups of adversity experienced between ages 0 and 15. In total, 4118 individuals developed CVD between their 16th birthday and 31 December 2018. Compared with those who experienced low levels of adversity, those who experienced severe somatic illness and death in the family (men: adjusted HR: 1.6, 95% confidence interval: 1.4–1.8, women: 1.4, 1.2–1.6) and those who experienced very high rates of adversity across childhood and adolescence (men: 1.6, 1.3–2.0, women: 1.6, 1.3–2.0) had a higher risk of developing CVD, corresponding to 10–18 extra cases of CVD per 100 000 person-years in these groups. Conclusions Individuals who have been exposed to childhood adversity are at higher risk of developing CVD in young adulthood compared to individuals with low adversity exposure. These findings suggest that interventions targeting the social origins of adversity and providing support for affected families may have long-term cardio-protective effects.

Background: Childhood adversity such as poverty, loss of a parent, and dysfunctional family dynamics may be associated with exposure to environmental and behavioral hazards, interfere with normal biological functions, and affect cancer care and outcomes. To explore this hypothesis, we assessed the cancer burden among young men and women exposed to adversity during childhood. Methods: We undertook a population-based study using Danish nationwide register data on childhood adversity and cancer outcomes. Children who were alive and resident in Denmark until their 16th birthday were followed into young adulthood (16–38 years). Group-based multi-trajectory modelling was used to categorize individuals into five distinct groups: low adversity, early material deprivation, persistent material deprivation, loss/threat of loss, and high adversity. We assessed the association with overall cancer incidence, mortality, and five-year case fatality; and cancer specific outcomes for the four most common cancers in this age group in sex-stratified survival analyses. Findings: 1,281,334 individuals born between Jan 1, 1980, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing 8229 incident cancer cases and 662 cancer deaths. Compared to low adversity, women who experienced persistent material deprivation carried a slightly lower risk of overall cancer (hazard ratio (HR) 0.90; 95% CI 0.82; 0.99), particularly due to malignant melanoma and brain and central nervous system cancers, while women who experienced high adversity carried a higher risk of breast cancer (HR 1.71; 95% CI 1.09; 2.70) and cervical cancer incidence (HR 1.82; 95% CI 1.18; 2.83). While there was no clear association between childhood adversity and cancer incidence in men, those men who had experienced persistent material deprivation (HR 1.72; 95% CI 1.29; 2.31) or high adversity (HR 2.27; 95% CI 1.38; 3.72) carried a disproportionate burden of cancer mortality during adolescence or young adulthood compared to men in the low adversity group. Interpretation: Childhood adversity is associated with a lower risk of some subtypes of cancer and a higher risk of others, particular in women. Persistent deprivation and adversity are also associated with a higher risk of adverse cancer outcomes for men. These findings may relate to a combination of biological susceptibility, health behaviors and treatment-related factors. Funding: None.

BackgroundChildren who are exposed to adversities might be more susceptible to disease development during childhood and in later life due to impaired physiological and mental development. To explore this hypothesis, we assessed hospitalisation patterns through childhood and into adult life among those exposed to different trajectories of adversities during childhood.MethodsFor this population-based cohort study, we used annually updated data from Danish nationwide registers covering more than half a million children (aged 0–15 years) born between 1994 and 2001. Children who were alive and resident in Denmark on their 16th birthday were included in the analysis. Cluster analysis was used to divide children into five distinct trajectories according to their experience of childhood adversities, including poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics. To describe comprehensively the disease patterns experienced by these groups of children, we assessed the associations of each adversity trajectory with hospital admission patterns according to the entire spectrum of disease diagnoses in the International Classification of Diseases 10th edition, from birth to 24 years of age, using survival models.Findings508 168 children born between Jan 1, 1994, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing more than 3·8 million hospital admissions from birth to early adulthood. Hospitalisation rates were consistently higher in all four adversity groups compared with the low adversity group. The high adversity group (14 577 children, 3%), who were exposed to adversities of deprivation, family loss, and negative family dynamics, had a markedly higher rate of hospitalisations across all ages. For example, we observed 243 additional hospital admissions per 1000 person-years (95% CI 238–248) in the high versus low adversity group for those aged 16–24 years. These associations were particularly strong for diagnoses related to injuries, unspecified symptoms, and factors influencing health service contacts (eg, health screening and observation). They also covered a considerable burden of respiratory and infectious diseases, congenital malformations, diseases of the nervous system (especially in early life), mental and behavioural diagnoses, and diagnoses related to pregnancy and childbirth in early adult life.InterpretationThe close linkage between childhood adversities and poor lifelong health outcomes highlights a need for public health and policy attention on improving the socioeconomic circumstances children are born into to prevent the early emergence of health inequalities.

Machine learning models applied to health data may help health professionals to prioritize resources by identifying risk factors that may reduce morbidity and mortality. However, many novel machine learning papers on this topic neither account for nor discuss biases due to calendar time variations. Often, efforts to account for calendar time (among other confounders) are necessary since patterns in health data – especially in low- and middle-income countries – may be influenced by calendar time variations such as temporal changes in risk factors and changes in the disease and mortality distributions over time (epidemiological transitions), seasonal changes in risk factors and disease and mortality distributions, as well as co-occurring artefacts in data due to changes in surveillance and diagnostics. Based on simulations, real-life data from Guinea-Bissau, and examples drawn from recent studies, we discuss how including calendar time variations in machine learning models is beneficial for generating more relevant and actionable results. In this brief report, we stress that explicitly handling temporal structures in machine learning models still remains to be considered (like in general epidemiological studies) to prevent resources from being misdirected to ineffective interventions.

OBJECTIVE Experiencing adversities in childhood may increase the risk of type 1 diabetes through hyperactivation of the stress response system, but the empirical evidence is conflicting. We aim to describe the age-specific incidence of type 1 diabetes for males and females separately in five predefined groups covering the most common trajectories of adversity among Danish children. RESEARCH DESIGN AND METHODS We included all 1,081,993 children without parental type 1 diabetes born in Denmark from 1980 to 1998. We used register data to estimate age-specific incidence rates of type 1 diabetes in five trajectory groups of adversity characterized by 1) low adversity, 2) early life material deprivation, 3) persistent material deprivation, 4) loss or threat of loss in the family, and 5) cumulative high adversity. All analyses were stratified by sex. RESULTS In total, 5,619 people developed type 1 diabetes before 2016. We found only minor differences when comparing the incidence rates of type 1 diabetes between the trajectory groups. The only clear exceptions were in the high versus low adversity group, in which males had a higher incidence of type 1 diabetes in childhood ( CONCLUSIONS Childhood adversities were generally not associated with age-specific incidence of type 1 diabetes except among those exposed to a very high and increasing annual rate of childhood adversities. Differences between highly exposed males and females seem to depend on age at onset of type 1 diabetes.

The existing vaccine paradigm assumes that vaccines only protect against the target infection, that effective vaccines reduce mortality corresponding to the target infection's share of total mortality, and that the effects of vaccines are similar for males and females. However, epidemiological vaccine research has generated observations that contradict these assumptions and suggest that vaccines have important non-specific effects on overall health in populations. These include the observations that several live vaccines reduce the incidence of all-cause mortality in vaccinated compared with unvaccinated populations far more than can be explained by protection against the target infections, and that several non-live vaccines are associated with increased all-cause mortality in females. In this Personal View we describe current observations and contradictions and define six emerging principles that might explain them. First, that live vaccines enhance resistance towards unrelated infections. Second, non-live vaccines enhance the susceptibility of girls to unrelated infections. Third, the most recently administered vaccination has the strongest non-specific effects. Fourth, combinations of live and non-live vaccines given together have variable non-specific health effects. Fifth, vaccinating children with live vaccines in the presence of maternal immunity enhances beneficial non-specific effects and reduces mortality. Finally, vaccines might interact with other co-administered health interventions, for example vitamin A supplementation. The potential implications for child health are substantial. For example, if BCG vaccination was given to children at birth, if higher measles vaccination coverage could be obtained, if diphtheria, tetanus, and pertussis-containing vaccines were not given with or after measles vaccine, or if the BCG strain with the best non-specific effects could be used consistently, then child mortality could be considerably lower. Pursuing these emerging principles could improve our understanding and use of vaccines globally.

Projekt Tilgængeligørelse af Helbredskort - også kaldet Projekt Helbredskort - har til formål at tilgængeliggøre et værdifuldt kildemateriale fra bl.a. longitudinelle højde- og vægtmålinger af danske skolebørn hørende under Landsarkivet for Nørrejylland, nu kaldet Rigsarkivet Viborg, med sigte på muligheder for kvantitative og kvalitative analyser. Helbredskort indeholder informationer over de undersøgelser, som lægen har udført på skolebørn, og de betegnes ofte som "skolelægejournaler" i videnskabelige miljøer.

PURPOSE: To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population.METHODS: Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population.RESULTS: The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed.CONCLUSIONS: LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

International audience; We examine the association between trajectories of childhood adversities and Post-Traumatic Stress Disorder (PTSD) using a register-based Danish cohort. The DANish LIFE Course (DANLIFE) cohort includes and prospectively follows all individuals born in Denmark from 1980. We estimated the rate of PTSD diagnosed from age 16, according to childhood adversity trajectories from age 0 to 16 (n = 1 277 548). Trajectories were previously defined into 5 groups: Low Adversity, Early Life Material Deprivation, Persistent Material Deprivation, Loss or Threat of Loss, And High Adversity. We then estimated adjusted relative hazard ratios (aHR), and absolute hazards differences of PTSD according to childhood adversity trajectories in adjusted survival analysis. All analyses were stratified by sex. Individuals were followed for a median of 10·1 years a fter their 16th birthday, and 4966 individuals were diagnosed with PTSD. Compared with the low adversity group, children exposed to childhood adversity were more likely to be diagnosed with PTSD. The aHR for PTSD varied from 1·4 (95% CI: 1·3-1·5) in the Early Life Material Deprivation group, to 3·7 (3·3-4·1) in the High Adversity group, which corresponds to 8·3 extra cases of PTSD per 10 000 person years. The relative associations were comparable in men and women, but approximately twice as many women compared with men were affected. We report a clear association between exposure to childhood adversities and PTSD in young adulthood. The highest burden was among women in the high adversity group.

Background Parental leave policies have been hypothesized to benefit mothers’ mental health. We assessed the impact of a 6-week extension of parental leave in Denmark on maternal mental health. Methods We linked individual-level data from Danish national registries on maternal sociodemographic characteristics and psychiatric diagnoses. A regression discontinuity design was applied to study the increase in parental leave duration after 26 March 1984. We included women who had given birth between 1 January 1981 and 31 December 1987. Our outcome was a first psychiatric diagnosis following the child’s birth, ascertained as the first day of inpatient hospital admission for any psychiatric disorder. We presented cumulative incidences for the 30-year follow-up period and reported absolute risk differences between women eligible for the reform vs not, in 5-year intervals. Results In all, 291 152 women were followed up until 2017, death, emigration or date of first psychiatric diagnosis. The median follow-up time was 29.99 years, corresponding to 10 277 547 person-years at risk. The cumulative incidence of psychiatric diagnoses at 30 years of follow-up was 59.5 (95% CI: 57.4 to 61.6) per 1000 women in the ineligible group and 57.5 (95% CI: 55.6 to 59.4) in the eligible group. Eligible women took on average 32.85 additional days of parental leave (95% CI: 29.20 to 36.49) and had a lower probability of having a psychiatric diagnosis within 5 years [risk difference (RD): 2.4 fewer diagnoses per 1000 women, 95% CI: 1.5 to 3.2] and up to 20 years after the birth (RD: 2.3, 95% CI: 0.4 to 4.2). In subgroup analyses, the risk reduction was concentrated among low-educated, low-income and single women. Conclusions Longer parental leave may confer mental health benefits to women, in particular to those from disadvantaged backgrounds.

Background Studies in low-income countries have shown that among Bacille Calmette-Guérin (BCG) vaccinated children, those who develop a BCG-scar have significantly better survival than those who do not develop a scar. In a Danish multicenter randomized clinical trial we assessed determinants for developing a BCG-scar and for BCG scar size following neonatal BCG vaccination. Methods At three Danish hospitals, newborns were randomized 1:1 to BCG vaccination or no BCG vaccination. The infants were invited for a clinical examination at the ages of 3 and 13 months. At 13 months, the scar site was inspected and scar size measured. We investigated three groups of determinants; external, parental, and individual-level determinants on relative scar prevalence and differences in median scar sizes. Results Among 2118 BCG vaccinated infants, 2039 (96 %) were examined at 13 months; 1857 of these (91 %) had developed a BCG-scar. Compared with Copenhagen University Hospital, Hvidovre (85 %), Copenhagen University Hospital, Rigshospitalet had a scar prevalence of 95 % (adjusted Prevalence ratio (aPR) = 1.24 [CI 95 %: 1.18 to 1.30]); it was 93 % at Kolding Hospital (aPR 1.27 [CI 95 %: 1.19 to 1.35]). Increasing vaccine experience was positively associated with developing a scar and with scar size. Conclusion Across multiple potential determinants of BCG scaring and size, logistical factors dominated. The results support that injection technique is an important determinant of developing a scar. Given the strong link between having a BCG scar and subsequent health, improved BCG vaccination technique could play a major role for child health., BCG vaccine; BCG scar; Non-specific effects; Heterologous immunity.

Nearly all diseases can be caused by different combinations of exposures. Yet, most epidemiological studies focus on the causal effect of a single exposure on an outcome. We present the Causes of Outcome Learning (CoOL) approach, which seeks to identify combinations of exposures (which can be interpreted causally if all causal assumptions are met) that could be responsible for an increased risk of a health outcome in population sub-groups. The approach allows for exposures acting alone and in synergy with others. It involves (a) a pre-computational phase that proposes a causal model; (b) a computational phase with three steps, namely (i) analytically fitting a non-negative additive model, (ii) decomposing risk contributions, and (iii) clustering individuals based on the risk contributions into sub-groups based on the predefined causal model; and (c) a post-computational phase on hypothesis development and validation by triangulation on new data before eventually updating the causal model. The computational phase uses a tailored neural network for the non-negative additive model and Layer-wise Relevance Propagation for the risk decomposition through this model. We demonstrate the approach on simulated and real-life data using the R package ‘CoOL’. The presentation is focused on binary exposures and outcomes but can be extended to other measurement types. This approach encourages and enables epidemiologists to identify combinations of pre-outcome exposures as potential causes of the health outcome of interest. Expanding our ability to discover complex causes could eventually result in more effective, targeted, and informed interventions prioritized for their public health impact.

To estimate the life expectancy (LE) of HIV-infected patients in the West African country Guinea-Bissau and compare it with the background population.Using data from the largest HIV outpatient clinic at the Hospital Nacional Simão Mendes in the capital Bissau, a retrospective observational cohort study was performed. The study included patients attending the clinic between June 2005 and January 2018. A total of 8958 HIV-infected patients were included. In the analysis of the background population, a total of 109,191 people were included. LE incorporating loss to follow-up (LTFU) was estimated via Kaplan-Meier estimators using observational data on adult HIV-infected patients and background population.The LE of 20-year-old HIV-infected patients was 9.8 years (95% CI 8.3-11.5), corresponding to 22.3% (95% CI 18.5-26.7%) of the LE of the background population. (LE for 20-year-olds in the background population was 44.0 years [95% CI 43.0-44.9].) Patients diagnosed with CD4 cell counts below 200 cells/µL had a LE of 5.7 years (95% CI 3.6-8.2). No increase in LE with later calendar period of diagnosis was observed.LE was shown to be markedly lower among HIV-infected patients compared with the background population. While other settings have shown marked improvements in prognosis of HIV-infected patients in recent years, no improvement in Bissau was observed over time (9.8 years (95% CI 7.6-12.2) and 9.9 years (95% CI 7.6-12.1) for the periods 2005-2010 and 2014-2016, respectively).

ObjectiveIn Guinea-Bissau, West Africa, we observed that having a smallpox vaccination scar was associated with lower HIV-1 prevalence, more strongly for women than men. If this represents a causal effect, the female/male HIV-1 prevalence ratio would increase for birth cohorts no longer receiving smallpox vaccination due to the phase-out of this vaccine.DesignAn ecological design using HIV surveys and information about smallpox vaccination coverage.SettingUrban and rural Guinea-Bissau.ParticipantsParticipants in HIV surveys were grouped into an age group with decreasing smallpox vaccination coverage (15–34 years) and an age group with steady smallpox vaccination coverage (≥35 years).InterventionsThe exposure of interest was the phase-out of the smallpox vaccine in Guinea-Bissau.Primary and secondary outcome measuresHIV-1 prevalence.ResultsAt both sites, the female/male HIV-1 prevalence ratio increased by calendar time for the age group with decreasing smallpox vaccination coverage; the combined female/male HIV-1 prevalence ratio among people aged 15–34 years was 1.00 (95% CI 0.17 to 5.99) in 1987–1990, 1.16 (95% CI 0.69 to 1.93) in 1996–1997, 2.32 (95% CI 1.51 to 3.56) in 2006–2007 (p value for no trend=0.04). There was no increase in the female-to-male HIV-1 prevalence ratio for the age group >35 years with steady smallpox vaccination coverage; 1.93 (95% CI 0.40 to 9.25) in 1987–1990, 1.32 (95% CI 0.83 to 2.10) in 1996–1997, 0.81 (95% CI 0.56 to 1.16) in 2006–2007 (p value for no trend=0.07).ConclusionsThus, data was compatible with the deduction that the phase-out of smallpox vaccination may have increased the susceptibility to HIV-1 relatively more for women than men. Hence, phasing out smallpox vaccination may have contributed to the global increase in the female/male HIV-1 prevalence ratio among young individuals. Due to the potential fallacies of ecological studies, the results should be interpreted carefully, and this hypothesis needs further assessment. If the hypothesis is true, studies of smallpox vaccination could inform HIV-1 vaccine research.

An increased risk for cholera was witnessed during both droughts and floods in sub-Saharan Africa; these findings call for increased preparedness and surveillance during droughts in addition to floods. Cholera outbreaks in Africa have been attributed to both droughts and floods, but whether the risk of a cholera outbreak is elevated during droughts is unknown. We estimated the risk of cholera outbreaks during droughts and floods compared with drought- and flood-free periods in 40 sub-Saharan African countries during 1990–2010 based on data from EM-DAT: the OFDA/CRED International Disaster Database (www.emdat.be). A cholera outbreak was registered in one of every three droughts and one of every 15 floods. We observed an increased incidence rate of cholera outbreaks during drought periods (IRR = 4.3, 95% confidence interval [CI] = 2.9–7.2) and during flood periods (IRR = 144, 95% CI = 101–208) when compared with drought/flood-free periods. Floods are more strongly associated with cholera outbreaks, yet the prevalence of cholera outbreaks is higher during droughts because of droughts’ long durations. The results suggest that droughts in addition to floods call for increased cholera preparedness.

Summary Background Childhood is a sensitive period with rapid brain development and physiological growth, and adverse events in childhood might interfere with these processes and have long-lasting effects on health. In this study, we aimed to describe trajectories of adverse childhood experiences and relate these to overall and cause-specific mortality in early adult life. Methods For this population-based cohort study, we used unselected annually updated data from Danish nationwide registers covering more than 1 million children born between 1980 and 1998. We distinguished between three different dimensions of childhood adversities: poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics such as maternal separation. We used a group-based multi-trajectory clustering model to define the different trajectories of children aged between 0 and 16 years. We assessed the associations between these trajectories and mortality rates between 16 and 34 years of age using a Cox proportional hazards model and an Aalen hazards difference model. Findings Between Jan 1, 1980 and Dec 31, 2015, 2 223 927 children were included in the Danish Life Course cohort. We excluded 1 064 864 children born after 1998, 50 274 children who emigrated before their 16th birthday, and 11 161 children who died before their 16th birthday, resulting in a final sample of 1 097 628 children. We identified five distinct trajectories of childhood adversities. Compared with children with a low adversity trajectory, those who had early-life material deprivation (hazard ratio 1·38, 95% CI 1·27–1·51), persistent deprivation (1·77, 1·62–1·93), or loss or threat of loss (1·80, 1·61–2·00) had a moderately higher risk of premature mortality. A small proportion of children (36 081 [3%]) had multiple adversities within all dimensions and throughout the entire childhood. This group had a 4·54 times higher all-cause mortality risk (95% CI 4·07–5·06) than that of children with a low adversity trajectory, corresponding to 10·30 (95% CI 9·03–11·60) additional deaths per 10 000 person-years. Accidents, suicides, and cancer were the most common causes of death in this high adversity population. Interpretation Almost half of Danish children in our study experienced some degree of adversity, and this was associated with a moderately higher risk of mortality in adulthood. Among these, a small group of children had multiple adversities across social, health, and family-related dimensions. This group had a markedly higher mortality risk in early adulthood than that of other children, which requires public health attention. Funding None.

BACKGROUND: Early smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population.METHODS: We conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965-1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers.RESULTS: The individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72-2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53-2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61-2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87-3.48) compared with none of these. Vaccination below the age of one year gave similar results.CONCLUSIONS: We found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination.

BackgroundIn addition to vaccines’ specific effects, vaccines may have non-specific effects (NSEs) altering the susceptibility to unrelated infections. Non-live vaccines have been associated with negative NSEs. In 2010, a campaign with the non-live H1N1-influenza vaccine targeted children 6–59 months in Guinea-Bissau.MethodsBandim Health Project runs a health and demographic surveillance system site in Guinea-Bissau. Using a Cox proportional hazards model, we compared all-cause consultation rates after vs. before the campaign, stratified by participation status.ResultsAmong 10 290 children eligible for the campaign, 60% had participated, 18% had not and for 22% no information was obtained. After the H1N1 campaign, the consultation rates tended to decline less for participants [HR = 0.80 (95% confidence interval, CI: 0.75; 0.85)] than for non-participants [HR = 0.68 (95% CI: 0.58; 0.79)], p = 0.06 for same effect.ConclusionThe decline in the vaccinated group may have been smaller than the decline in the non-vaccinated group consistent with H1N1-vaccine increasing susceptibility to unrelated infections.

Background and objectiveLive vaccines may have beneficial non-specific effects. We tested whether the live measles, mumps and rubella (MMR) vaccine compared with the non-live diphtheria–tetanus–acellular-pertussis–inactivated-polio–Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine as the most recent vaccine was associated with less childhood asthma and fewer acute hospital contacts for childhood asthma among boys and girls.MethodsThis study is a nationwide register-based cohort study of 338 761 Danish children born between 1999 and 2006. We compared (i) the incidence of first-registered childhood asthma based on hospital contacts and drug prescriptions and (ii) the incidence of severe asthma defined as acute hospital contacts for childhood asthma between the ages of 15 and 48 months among children whose last received vaccine was three doses of DTaP-IPV-Hib and then MMR with children whose last received vaccine was three doses of DTaP-IPV-Hib.ResultsFor boys, following the recommended vaccine schedule of MMR after DTaP-IPV-Hib3 compared with DTaP-IPV-Hib3 as the last received vaccine, MMR was associated with 8.1 (95% confidence interval 3.9–12.3) fewer childhood asthma cases per 1000 boys, corresponding to 10% (5–15%) reduction in the cumulative incidence of childhood asthma. MMR, when given last, was also associated with 16.3 (95% confidence interval 12.7–20.0) fewer acute hospital admissions for childhood asthma per 1000 boys, corresponding to a 27% (22–31%) reduction in the cumulative incidence. No associations were seen for girls.ConclusionMMR may have a protective effect against childhood asthma for boys. This calls for an understanding of whether non-specific effects of vaccines can be used to optimize our vaccine programmes.

In this article, we illustrate how to use mi impute chained with intreg to fit an analysis of covariance analysis of censored and nondetectable immunological concentrations measured in a randomized pretest–posttest design.

In low-income countries, available evidence suggests that Bacille Calmette-Guerin (BCG) vaccination reduces child mortality by at least one-third, far more than can be explained by prevention of tuberculosis (TB). In Denmark, BCG vaccination at school age was associated with strong mortality reductions into early adulthood. Hence, BCG seems to have beneficial nonspecific effects. Both in Guinea-Bissau and in Denmark, BCG was associated with a particularly beneficial effect in children whose mothers were BCG vaccinated. Hence, maternal priming may be important to elicit the beneficial nonspecific effects of BCG. Revaccination (“boosting”) with BCG has also been associated with amplification of its beneficial nonspecific effects. Strong beneficial effects of maternal priming and of boosting have also been observed for other live vaccines. We may be designed to benefit from meeting pathogens in the presence of preexisting immunity, be it from our mother or from previous exposure.

Background The live smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, human immunodeficiency virus (HIV)-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and we tested this hypothesis in both Guinea-Bissau and Denmark. Methods We conducted 2 studies: (1) a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1751 individuals and (2) a case-base study with a background population of 46239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission was almost exclusively sexually transmitted. In Denmark, we excluded intravenous drug users. Data were analyzed using logistic regression. Results Bacillus Calmette-Guérin and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval [CI], 0.36–1.07) in Guinea-Bissau and 0.70 (95% CI, 0.43–1.15) in Denmark. We combined the results from both settings in a meta-analysis (aOR = 0.66; 95% CI, 0.46–0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR = 0.27; 95% CI, 0.10–0.75) as follows: women, aOR = 0.18 (95% CI, 0.05–0.64); men, aOR = 0.52 (95% CI, 0.12–2.33); sex-differential effect, P = .29. Conclusions The studies from Guinea-Bissau and Denmark, 2 very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine.

PurposeThe DANish LIFE course (DANLIFE) cohort is a prospective register-based study set up to investigate the complex life course mechanisms linking childhood adversities to health and well-being in childhood, adolescence and young adulthood including cumulative and synergistic actions and potentially sensitive periods in relation to health outcomes.ParticipantsAll children born in Denmark in 1980 or thereafter have successively been included in the cohort totalling more than 2.2 million children. To date, the study population has been followed annually in the nationwide Danish registers for an average of 16.8 years with full data coverage in the entire follow-up period. The information is currently updated until 2015.Findings to dateDANLIFE provides information on a wide range of family-related childhood adversities (eg, parental separation, death of a parent or sibling, economic disadvantage) with important psychosocial implications for health and well-being in childhood, adolescence and young adulthood. Measurement of covariates indicating demographic (eg, age, sex), social (eg, parental education) and health-related factors (eg, birth weight) has also been included from the nationwide registers. In this cohort profile, we provide an overview of the childhood adversities and covariates included in DANLIFE. We also demonstrate that there is a clear social gradient in the exposure to childhood adversities confirming clustering of adverse experiences within individuals.Future plansDANLIFE provides a valuable platform for research into early life adversity and opens unique possibilities for testing new research ideas on how childhood adversities affect health across the life course.