Maternal risk factors and testicular cancer in the offspring : A nested case-control study

Väitöskirja, liitteenä alkuperäisartikkelit (verkkoversiossa ei alkuperäisartikkeleita

HPV-type distribution and reproducibility of histological diagnosis in cervical neoplasia in Poland

This study was performed to assess attribution of high grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) to human papillomavirus (HPV) genotypes and secondarily to assess reproducibility of HG-CIN/ICC diagnosis obtained in Poland. Formaldehyde fixed, paraffin embedded blocks of HG-CIN/ICC from two distant institutions were sent to a central laboratory together with original histological diagnoses. Central/expert review of histopathological specimens was performed and agreement between local and central/expert diagnoses was calculated. HPV detection and genotyping in the samples was carried out with the use of SPF10-LiPA25 technology. Results were analyzed for 205 HG-CIN and 193 ICC cases with centrally confirmed diagnoses. Kappa coefficients and 95 % confidence intervals for HG-CIN and ICC diagnoses were: 0.13 (0.09;0.17) and 0.19 (0.11;0.26) respectively. Cohen’s kappa coefficients for lesions with representative number of samples ranged from 0.01 for cervical intraepithelial neoplasia grade 2 to 0.75 for adenocarcinoma. HPV DNA was detected in 96.1 and 91.2 % of the confirmed HG-CIN and ICC specimens respectively. HPV positive HG-CIN was most commonly attributed to HPV types: 16 (62.8), 33 (7.8), 31 (6.6), 52 (3.7), 45 (2.6) and 58 (2.6 %). HPV positive ICC was most commonly attributed to HPV types: 16 (72.1), 18 (10.8), 33 (5.7), 45 (3.4) and 31 (1.7 %). Reproducibility of histological diagnosis of HG-CIN/ICC obtained in Poland generally increases with the severity of lesion and is lowest for cervical intraepithelial neoplasia grade 2 and highest for adenocarcinoma. Over 80 % of ICC cases are vaccine-preventable in Poland

The impact of childhood varicella vaccination on the incidence of herpes zoster in the general population: modelling the effect of exogenous and endogenous varicella-zoster virus immunity boosting

Background A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination. Methods An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo–0%Endo, 75%Exo–25%Endo, 50%Exo–50%Endo, 25%Exo–75%Endo, 0%Exo–100%Endo. Results HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively. Conclusions Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence

Additional file 1: of Coverage, efficacy or dosing interval: which factor predominantly influences the impact of routine childhood vaccination for the prevention of varicella? A model-based study for Italy

Technical appendix - dynamic transmission model for Italy. (DOCX 299 kb

Poor outcome of patients with pulmonary arterial hypertension with insufficient response to phosphodiesterase-5 inhibitors alone or in combination with other specific therapy : a registry-based study

Phosphodiesterase-5 inhibitors are commonly used in pulmonary arterial hypertension but, as suggested by the RESPITE study, phosphodiesterase-5 inhibitor therapy (mono-/combination) does not always have a satisfactory treatment effect. This study aimed to investigate the clinical course of pulmonary arterial hypertension patients not at treatment goal after at least 90 days of treatment with phosphodiesterase-5 inhibitors, alone or in combination with other pulmonary arterial hypertension therapies. The study included 106 incident patients from the Swedish Pulmonary Arterial Hypertension Registry, treated with phosphodiesterase-5 inhibitors for >= 90 days, who were not at a pre-specified treatment goal, i.e. in World Health Organisation functional class III, with 6-min walking distance 165-440 m, and N-terminal prohormone of brain natriuretic peptide >300 ng/L. Changes in World Health Organisation functional class, 6-min walking distance, N-terminal prohormone of brain natriuretic peptide, and risk group between index and follow-up were assessed. Of patients with complete follow-up data, (n = 53) 77% were on combination therapy and risk assessment yielded 98% at intermediate risk at index. At follow-up, 11 patients transitioned from World Health Organisation functional class III to World Health Organisation functional class II, the median (Q1; Q3) change in 6-min walking distance was 6 (-30; 42) meters and in N-terminal prohormone of brain natriuretic peptide 47 (-410; 603) ng/L, while 89% remained at an intermediate risk. Of those without complete follow-up data, 11 patients died and 2 underwent lung transplantation. In conclusion, pulmonary arterial hypertension patients treated with phosphodiesterase-5 inhibitors, as single or combination therapy and not achieving the pre-specified treatment goals after >= 90 days have an unfavourable clinical course

Incidence of acute otitis media in children below 6 years of age seen in medical practices in five East European countries

Background: Although acute otitis media (AOM) remains a major public health problem worldwide and brings economic burden on health care system and caregivers, little information is available about its epidemiology in Eastern Europe. Methods: We conducted an epidemiological, prospective, observational, multi-centre cohort study (NCT01365390) in five East European countries (Estonia, Lithuania, Poland, Romania and Slovenia) between June 2011 and January 2013 to determine the incidence and clinical characteristics of AOM among children aged < 6 years during 1 year. Results: AOM incidence was 160.7 cases (95 % confidence interval [CI]: 144.7–177.9) per 1000 person-years (PY) being the lowest in the < 1 year age group (92.3 cases [95 % CI: 59.7–136.2] per 1000 PY) and the highest in the 3– < 4 years age group (208.9 cases [95 % CI: 165.1–260.7] per 1000 PY). AOM incidence was similar across the countries, with the exception of Slovenia (340.3 cases [95 % CI: 278.3–412.0] per 1000 PY). There was a lower risk in breastfed children and a higher risk in those attending school/childcare or with allergies. AOM required 521 visits to the doctor. Antibiotics were prescribed for 276 (74.8 %) episodes with the lowest prescription rate in Estonia (51.4 %) and the highest in Romania (83.7 %). Complications were rare and hospitalisations occurred in 2 % of the cases. Conclusions: The disease burden of AOM in Eastern Europe is relevant and public health initiatives to reduce it should be considered