Marko Merikukka

Sex differences in age-related cardiovascular mortality.

Introduction Sex-related physiological differences result in different expressions of diseases for men and women. Data are contradicting regarding the increase in the female risk for cardiovascular disease (CVD) at mid-life. Thus, we studied possible sex differences in age-adjusted mortality for CVD and non-vascular diseases stratifying our findings by specific age groups. Methods Over one million deaths (1 080 910) reported to the Finnish nationwide Causes of Death Register in 1986–2009 were analyzed. A total of 247 942 male deaths and 278 752 female deaths were of CVD origin, the remaining deaths were non-vascular. The annual mortality rates were calculated per 100 000 mid-year population, separately for men and women in 5-year age categories. Results The age-standardized risk of death from CVD was 80% higher for men (442/100 000) than for women (246/100 000). After age 45–54 the male CVD mortality rate elevated parallel to the non-vascular mortality, whereas in women the CVD mortality elevated considerably more rapidly than the non-vascular mortality from age 60 years onwards. Conclusions Heart disease mortality in men accelerates at a relatively young age, but in women the risk shows a steep increase at approximately 60 years of age. These data emphasize the need to identify and prevent risk factors for CVD, especially in women in their mid-life years.

Social determinants of mental health: a Finnish nationwide follow-up study on mental disorders

Background Most mental disorders start in childhood and adolescence. Risk factors are prenatal and perinatal, genetic as well as environmental and family related. Research evidence is, however, insufficient to explain the life-course development of mental disorders. This study aims to provide evidence on factors affecting mental health in childhood and adolescence. Data and methods The 1987 Finnish Birth Cohort covers all children born in Finland in 1987 (N=59 476) who were followed up until the age of 21 years. The study covers detailed health, social welfare and sociodemographic data of the cohort members and their parents from Finnish registers. Results Altogether, 7578 (12.7%) cohort members had had a diagnosed mental disorder. Several prenatal, perinatal and family-related risk factors for mental disorders were found, with sex differences. The main risk factors for mental disorders were having a young mother (OR 1.30 (1.16 to 1.47)), parents’ divorce (OR 1.33 (1.26 to1.41)), death of a parent (OR 1.27 (1.16 to 1.38)), parents’ short education (OR 1.23(1.09 to 1.38)), childhood family receiving social assistance (OR 1.61 (1.52 to 1.71)) or having a parent treated at specialised psychiatric care (OR 1.47 (1.39 to 1.55)). Perinatal problem (OR 1.11 (1.01 to 1.22)) and prenatal smoking (OR 1.09 (1.02 to 1.16)) were risk factors for mental disorders, even after controlling for background factors. Elevated risk was seen if the cohort member had only basic education (OR 3.37 (3.14 to 3.62)) or had received social assistance (OR 2.45 (2.30 to 2.60)). Conclusions Mental disorders had many social risk factors which are interlinked. Although family difficulties increased the risk for mental disorders, they were clearly determined by the cohort members low education and financial hardship. This study provides evidence for comprehensive preventative and supporting efforts. Families with social adversities and with parental mental health problems should be supported to secure childrens development.

Differences in incidence and co-occurrence of vaccine and nonvaccine human papillomavirus types in Finnish population before human papillomavirus mass vaccination suggest competitive advantage for HPV33

To understand likelihood of type replacement after vaccination against the high‐risk human papillomavirus (HPV) types, we evaluated competition of the seven most common genital HPV types in a population sample of unvaccinated, fertile‐aged Finnish women. First trimester sera from two consecutive pregnancies were retrieved from 3,183 Finnish women (mean age, 23.1 years) of whom 42.3% had antibodies to at least one HPV type (6/11/16/18/31/33/45) at the baseline. Antibody positivity to more than one HPV types by the second pregnancy was common among the baseline HPV seropositives. However, compared to baseline HPV‐seronegative women, significantly increased incidence rate ratios (IRRs), indicating an increased risk to seroconvert for another HPV type, were consistently noted only for HPV33 among baseline HPV16 or HPV18 antibody (ab)‐positive women: HPV16ab only → 16&33ab IRR 2.9 [95% confidence interval (CI) 1.6–5.4] and HPV18ab only → 18&33ab IRR 2.5 (95% CI 1.1–6.0), irrespectively of the presence of antibodies to other HPV types at baseline: HPV16ab → 16&33ab IRR 3.2 (95% CI 2.0–5.2) and HPV18ab → 18&33ab IRR 3.6 (95% CI 2.1–5.9). Our findings suggest a possible competitive advantage for HPV33 over other genital HPV types in the unvaccinated population. HPV33 should be monitored for type replacement after HPV mass vaccination.

Order of HPV/Chlamydia infections and cervical high-grade precancer risk: a case-cohort study.

Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high‐grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C. trachomatis were measured in paired sera of the cases and a subcohort of 2,796 women with a minimum of two pregnancies. HPV16‐adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0, 4.4) and 10 (95% CI 1.8, 57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3, 190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk.

Evaluation of Type Replacement Following HPV16/18 Vaccination: Pooled Analysis of Two Randomized Trials.

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs). Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)—two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine—to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided. Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = −0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70. Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.

Order of HPV/Chlamydia infections and cervical high-grade precancer risk: A case-cohort study

Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high‐grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C. trachomatis were measured in paired sera of the cases and a subcohort of 2,796 women with a minimum of two pregnancies. HPV16‐adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0, 4.4) and 10 (95% CI 1.8, 57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3, 190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk.

Mental disorder diagnoses of offspring affected by parental cancer before early adulthood: the 1987 Finnish Birth Cohort study

The purpose of this study is to investigate psychiatric diagnoses given to children affected by parental cancer in psychiatric and somatic specialized health care settings.

Parents' traumatic brain injury increases their children's risk for use of psychiatric care: the 1987 Finnish Birth Cohort study

OBJECTIVE Traumatic brain injury (TBI) of a parent causes significant changes in their family life and parent-children relationships. However, the number of children affected by parental TBI and the long-term consequences for these children remain unknown. We estimated the prevalence of children affected by parental TBI and investigated whether these children had greater use of psychiatric services than their peers. METHODS This a retrospective population-based register study. All 60,069 children born in Finland in 1987 were followed up through national health and social registers from 1987 to 2008. RESULTS During the 21-year follow-up, 1532 (2.6%) children had a parent with TBI. Overall, 22.5% of those having a parent with TBI were treated in specialized psychiatric care. Use of psychiatric care was significantly increased among those cohort members with a parent with mild [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.37-2.38] or severe (OR 1.49, 95% CI 1.12-1.98) TBI compared to their peers. CONCLUSIONS Parental TBI is associated with increased use of specialized psychiatric services by children. Adult health care services must have appropriate systems in place to address the psychosocial needs and support the welfare and development of children of patients with TBI.

Determinants of underage induced abortion - the 1987 Finnish Birth Cohort study

Although underage pregnancies often end in induced abortion, data on girls who undergo termination of pregnancy are lacking. Our aim was to identify determinants of underage induced abortion and compare them with those of childbirth.

Impact of smoking on the quantity and quality of antibodies induced by human papillomavirus type 16 and 18 AS04-adjuvanted virus-like-particle vaccine – a pilot study

BackgroundThe AS04-adjuvanted bivalent L1 virus-like-particle (VLP) vaccine (Cervarix™) against infection with human papillomavirus (HPV) types 16/18 holds great promise to prevent HPV16/18 infections and associated neoplasias, but it is important to rule out significant co-factors of the neoplasias like smoking.MethodsWe conducted a pilot study to compare the quantity and quality of HPV16/18 antibody response at baseline and 7 months post vaccination in 104 non-smoking and 112 smoking female participants vaccinated at 0, 1 and 6 months with Cervarix™ (55 and 48 study participants) or with Hepatitis A vaccine (HAVRIX™) (48 and 64 participants, respectively). These 216 women were a sub-sample of 4808 baseline 16- to 17-year old Finnish women initially enrolled in the double-blind, randomized controlled phase III PATRICIA trial. Following end-of-study unblinding in 2009 they were randomly chosen out of all the participants of the three major Finnish PATRICIA study sites in the Helsinki metropolitan area (University of Helsinki, N = 535, and Family Federation Finland, N = 432) and Tampere (University of Tampere, N = 428). Following enrolment, serum samples were collected at month 0 and month 7 post 1st vaccination shot, and were analysed for levels and avidity of IgG antibodies to HPV16 and HPV18 using standard and modified (4 M urea elution) VLP ELISAs.ResultsWe found that at month 7 post vaccination women who smoked (cotinine level > 20 ng/ml) had levels of anti-HPV16/18 antibodies comparable to those of non-smoking women. Low-avidity HPV16/18 IgG antibodies were observed in 16% of the vaccinated women, and active smoking conferred a three-fold increased risk (95% CI 1.0-9.3) of having the low-avidity antibodies.ConclusionOur data suggest that while smoking does not interfere with the quantity of vaccine-induced peak IgG levels, it may affect the avidity of IgG induced by HPV16/18 vaccination.